FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Baugher, JD Baugher, BD Shirley, MD Pevsner, J AF Baugher, Joseph D. Baugher, Benjamin D. Shirley, Matthew D. Pevsner, Jonathan TI Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method SO BMC GENOMICS LA English DT Article DE Mosaicism; Parent-of-origin; Trio; Parent-child; Software; Microarray; Autism; Cleft; HapMap ID DETECTABLE CLONAL MOSAICISM; DENSITY SNP ARRAYS; COPY NUMBER; ANEUPLOIDY; CANCER; HETEROZYGOSITY; IDENTIFICATION; SEGMENTATION; INHERITANCE; VARIANTS AB Background: Mosaic somatic alterations are present in all multi-cellular organisms, but the physiological effects of low-level mosaicism are largely unknown. Most mosaic alterations remain undetectable with current analytical approaches, although the presence of such alterations is increasingly implicated as causative for disease. Results: Here, we present the Parent-of-Origin-based Detection (POD) method for chromosomal abnormality detection in trio-based SNP microarray data. Our software implementation, triPOD, was benchmarked using a simulated dataset, outperformed comparable software for sensitivity of abnormality detection, and displayed substantial improvement in the detection of low-level mosaicism while maintaining comparable specificity. Examples of low-level mosaic abnormalities from a large autism dataset demonstrate the benefits of the increased sensitivity provided by triPOD. The triPOD analyses showed robustness across multiple types of Illumina microarray chips. Two large, clinically-relevant datasets were characterized and compared. Conclusions: Our method and software provide a significant advancement in the ability to detect low-level mosaic abnormalities, thereby opening new avenues for research into the implications of mosaicism in pathogenic and non-pathogenic processes. C1 [Baugher, Joseph D.; Shirley, Matthew D.; Pevsner, Jonathan] Johns Hopkins Sch Med, Program Biochem Cellular & Mol Biol, Baltimore, MD 21205 USA. [Baugher, Benjamin D.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA. [Pevsner, Jonathan] Johns Hopkins Sch Med, Program Human Genet, Baltimore, MD 21205 USA. [Pevsner, Jonathan] Johns Hopkins Med Inst, Hugo W Moser Res Inst, Dept Neurol, Baltimore, MD 21205 USA. [Pevsner, Jonathan] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Pevsner, J (reprint author), Johns Hopkins Sch Med, Program Biochem Cellular & Mol Biol, Baltimore, MD 21205 USA. EM pevsner@kennedykrieger.org FU Autism Genetic Resource Exchange is a program of Autism Speaks [1U24MH081810]; National Institute of Mental Health; National Institute of Dental and Craniofacial Research (NIDCR); Iowa Comprehensive Program to Investigate Craniofacial and Dental Anomalies (Murray) [R01-DE-09886, R01-DE-012472, R01-DE-014677, R01-DE-016148, R21-DE-016930, R01-DE-013939]; [R21-DE-01370]; [R01-DE-014581]; [R37-DE-08559]; [P50-DE-016215] FX We thank Eric L. Stevens for critical review of the manuscript. 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). We thank Dr. Cathy Laurie for providing sample identifiers for previously reported mosaic abnormalities within the cleft lip/palate dataset. We thank Drs. Terri H. Beaty, Alan F. Scott, Ingo Ruczinski, and Robert Scharpf for facilitating access to the cleft dataset. Funding support for the study entitled "International Consortium to Identify Genes and Interactions Controlling Oral Clefts" was provided by several previous grants from the National Institute of Dental and Craniofacial Research (NIDCR). Data and samples were drawn from several studies performed by members of this consortium. Funding to support original data collection, previous genotyping, and analysis was provided to individual investigators from several sources. Funding for individual investigators included: R21-DE-013707 and R01-DE-014581 (Beaty); R37-DE-08559 and P50-DE-016215 (Murray, Marazita); the Iowa Comprehensive Program to Investigate Craniofacial and Dental Anomalies (Murray); R01-DE-09886 (Marazita); R01-DE-012472 (Marazita); R01-DE-014677 (Marazita); R01-DE-016148 (Marazita); R21-DE-016930 (Marazita); and R01-DE-013939 (Scott). Parts of this research were supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Wilcox, Lie). Additional recruitment was supported by the Smile Train Foundation for recruitment in China (Jabs, Beaty, Shi) and a grant from the Korean government (Jee). The genomewide association study, also known the International Cleft Consortium, is part of the Gene Environment Association Studies (GENEVA) program of the trans-NIH Genes, Environment, and Health Initiative [GEI] supported by U01-DE- 018993. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health (NIH) to The Johns Hopkins University, contract number HHSN268200782096C. Funds for genotyping were provided by the NIDCR through CIDR's NIH contract. Assistance with genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01-HG-004446) and by the National Center for Biotechnology Information (NCBI). We sincerely thank all of the patients and families at each recruitment site for participating in this study, and we gratefully acknowledge the invaluable assistance of all clinical, field, and laboratory staff who contributed to this effort over the years. 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Mari, Frank Godenschwege, Tanja A. TI New Tools for Targeted Disruption of Cholinergic Synaptic Transmission in Drosophila melanogaster SO PLOS ONE LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; LARVAL NEUROMUSCULAR-JUNCTION; LIGAND-BINDING DOMAIN; GIANT FIBER SYSTEM; LONG-TERM-MEMORY; L-GLUTAMATE; EXPRESSION; D-ALPHA-7; NEURONS; ACHBP AB Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. The alpha 7 subtype of nAChRs is involved in neurological pathologies such as Parkinson's disease, Alzheimer's disease, addiction, epilepsy and autism spectrum disorders. The Drosophila melanogaster alpha 7 (D alpha 7) has the closest sequence homology to the vertebrate alpha 7 subunit and it can form homopentameric receptors just as the vertebrate counterpart. The D alpha 7 subunits are essential for the function of the Giant Fiber circuit, which mediates the escape response of the fly. To further characterize the receptor function, we generated different missense mutations in the D alpha 7 nAChR's ligand binding domain. We characterized the effects of targeted expression of two UAS-constructs carrying a single mutation, D197A and Y195T, as well as a UAS-construct carrying a triple D77T, L117Q, I196P mutation in a D alpha 7 null mutant and in a wild type background. Expression of the triple mutation was able to restore the function of the circuit in D alpha 7 null mutants and had no disruptive effects when expressed in wild type. In contrast, both single mutations severely disrupted the synaptic transmission of D alpha 7-dependent but not glutamatergic or gap junction dependent synapses in wild type background, and did not or only partially rescued the synaptic defects of the null mutant. These observations are consistent with the formation of hybrid receptors, consisting of D197A or Y195T subunits and wild type D alpha 7 subunits, in which the binding of acetylcholine or acetylcholine-induced conformational changes of the D alpha 7 receptor are altered and causes inhibition of cholinergic responses. Thus targeted expression of D197A or Y195T can be used to selectively disrupt synaptic transmission of D alpha 7-dependent synapses in neuronal circuits. Hence, these constructs can be used as tools to study learning and memory or addiction associated behaviors by allowing the manipulation of neuronal processing in the circuits without affecting other cellular signaling. C1 [Mejia, Monica] Florida Atlantic Univ, Dept Biol Sci, Boca Raton, FL 33431 USA. [Heghinian, Mari D.; Mari, Frank] Florida Atlantic Univ, Dept Chem & Biochem, Boca Raton, FL 33431 USA. [Godenschwege, Tanja A.] Florida Atlantic Univ, Dept Biol Sci, Jupiter, FL USA. RP Godenschwege, TA (reprint author), Florida Atlantic Univ, Dept Biol Sci, John D Mac Arthur Campus, Jupiter, FL USA. EM godensch@fau.edu FU National Institute for Neurological Disorders and Stroke [R21NS06637]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD050725] FX This work was funded by the National Institute for Neurological Disorders and Stroke grant R21NS06637 to F.M. and T.A.G. and the Eunice Kennedy Shriver National Institute of Child Health and Human Development R01HD050725 to T.A.G. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Heinimaa, Markus Cheslack-Postava, Keely Suominen, Auli Sourander, Andre TI Parental psychiatric disorders and autism spectrum disorders SO PSYCHIATRY RESEARCH LA English DT Article DE Schizophrenia; Affective; Childhood autism; Asperger's syndrome; Pervasive developmental disorders-unspecified; Risk factors; Epidemiology ID FINNISH PERINATAL HEALTH; ASPERGER-SYNDROME; BIPOLAR DISORDER; INFANTILE-AUTISM; CONDUCT PROBLEMS; RISK-FACTORS; FOLLOW-UP; SOCIOECONOMIC DIFFERENCES; CHILDHOOD AUTISM; BIRTH COHORT AB The present population-based, case-control study examines associations between specific parental psychiatric disorders and autism spectrum disorders (ASD) including childhood autism, Asperger's syndrome and pervasive developmental disorder (PDD-NOS). The cohort includes 4713 children born between 1987 and 2005 with diagnoses of childhood autism, Asperger's syndrome or PDD-NOS. Cases were ascertained from the Finnish Hospital Discharge Register, and each was matched to four controls by gender, date of birth, place of birth, and residence in Finland. Controls were selected from the Finnish Medical Birth Register. Parents were identified through the Finnish Medical Birth Register and Finnish Central Population Register. Parental psychiatric diagnoses from inpatient care were collected from the Finnish Hospital Discharge Register. Conditional logistic regression models were used to assess whether parents' psychiatric disorders predicted ASD after controlling for parents' age, smoking during pregnancy and weight for gestational age. In summary, parental schizophrenia spectrum disorders and affective disorders were associated with the risk of ASD regardless of the subgroup. PDD-NOS was associated with all parental psychiatric disorders investigated. Further studies are needed to replicate these findings. These results may facilitate the investigation of shared genetic and familial factors between ASD and other psychiatric disorders. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Jokiranta, Elina; Suominen, Auli; Sourander, Andre] Univ Turku, Dept Child Psychiat, Turku 20014, Finland. [Jokiranta, Elina; Suominen, Auli; Sourander, Andre] Turku Univ Hosp, FIN-20520 Turku, Finland. [Brown, Alan S.; Sourander, Andre] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, Dept Psychiat,Mailman Sch Publ Hlth, New York, NY USA. [Heinimaa, Markus] Univ Turku, Dept Psychiat, Turku 20014, Finland. [Cheslack-Postava, Keely] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Sourander, Andre] Univ Tromso, Fac Hlth Sci, RKBU, N-9001 Tromso, Norway. RP Jokiranta, E (reprint author), Univ Turku, Dept Child Psychiat, Itainen Pitkakatu 1 Varia, Turku 20014, Finland. EM ekjoki@utu.fi FU Jane & Aatos Erkko Foundation; Finnish Pediatric Research Foundation; National Institute for Environmental Health Sciences (NIEHS); National Institute of Mental Health FX This study was supported by grants from the Jane & Aatos Erkko Foundation, and the Finnish Pediatric Research Foundation (E. Jokiranta) and by the National Institute for Environmental Health Sciences (NIEHS) and by the National Institute of Mental Health (A. Brown, PI). None of the funding sources played a role in the conduct of the research. 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PD MAY 30 PY 2013 VL 207 IS 3 BP 203 EP 211 DI 10.1016/j.psychres.2013.01.005 PG 9 WC Psychiatry SC Psychiatry GA 165OF UT WOS:000320492500009 PM 23391634 ER PT J AU Ji, WD Li, T Pan, YS Tao, H Ju, K Wen, ZJ Fu, YC An, ZG Zhao, Q Wang, T He, L Feng, GY Yi, QZ Shi, YY AF Ji, Weidong Li, Tao Pan, Yaosheng Tao, Hua Ju, Kang Wen, Zujia Fu, Yingchun An, Zhiguo Zhao, Qian Wang, Ti He, Lin Feng, Guoyin Yi, Qizhong Shi, Yongyong TI CNTNAP2 is significantly associated with schizophrenia and major depression in the Han Chinese population SO PSYCHIATRY RESEARCH LA English DT Article DE Bipolar disorder; Schizophrenia; Major depression; Single nucleotide polymorphism (SNP); CNTNAP2 ID DISORDERS; PREVALENCE; LINKAGE; SHESIS; GENE AB CNTNAP2, located on 7q35-36.1, encodes a single-pass transmembrane protein mediating cell-cell interactions in the nervous system. CNTNAP2 has been suggested to play an important role in mental diseases such as autism and language disorder. However, we still do not know whether it also confers risk to major psychiatric disorders such as schizophrenia, major depression and bipolar disorder. We analysed single nucleotide polymorphisms (SNPs) previously reported to be associated with autism or language impairment in 1135 schizophrenia patients, 1135 unrelated major depression patients, 1135 unrelated bipolar disorder patients and 1135 unrelated normal controls recruited from the Han Chinese population. We found that the genotypes of rs17236239 were significantly associated with schizophrenia and the alleles of rs2710102 and rs2710117 were significantly associated with major depression. According to the location of significant signals, our study indicated that exon 13-15 of CNTNAP2 may play important roles in both schizophrenia and major depression in the Han Chinese population. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Ji, Weidong; Pan, Yaosheng; Tao, Hua; Ju, Kang; Fu, Yingchun; He, Lin; Shi, Yongyong] Shanghai Changning Mental Hlth Ctr, Shanghai 200042, Peoples R China. [Ji, Weidong; Li, Tao; Pan, Yaosheng; Tao, Hua; Ju, Kang; Wen, Zujia; Fu, Yingchun; He, Lin; Shi, Yongyong] Shanghai Jiao Tong Univ, Inst Neuropsychiat Sci & Syst Biol Med, Shanghai 200042, Peoples R China. [Ji, Weidong; Li, Tao; Pan, Yaosheng; Tao, Hua; Ju, Kang; Wen, Zujia; Fu, Yingchun; Zhao, Qian; Wang, Ti; He, Lin; Shi, Yongyong] Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai 200030, Peoples R China. [Feng, Guoyin] Shanghai Inst Mental Hlth, Shanghai 200030, Peoples R China. [Yi, Qizhong] Xinjiang Med Univ, Teaching Hosp 1, Dept Psychiat, Urumqi 830002, Peoples R China. RP Shi, YY (reprint author), Shanghai Jiao Tong Univ, Bio X Insititutes, Little White Bldg,55 Guangyuan Xi Rd, Shanghai 200030, Peoples R China. EM shiyongyong@gmail.com FU Natural Science Foundation of China [81130022, 81272302, 31000553, 81121001]; National 863 project [2012AA02A515]; 973 Program [2010CB529600]; Program for Changjiang Scholars and Innovative Research Team in University [IRT1025]; Foundation for the Author of National Excellent Doctoral Dissertation of China [201026]; Program for New Century Excellent Talents in University [NCET-09-0550]; Shanghai Science and Technology Development Funds [12QA1401900]; Shanghai Changning Health Bureau program [20094Y06001] FX We warmly thank all patients and healthy individuals who participated in our study. This work was supported by the Natural Science Foundation of China (81130022, 81272302, 31000553 and 81121001), the National 863 project (2012AA02A515), the 973 Program (2010CB529600), Program for Changjiang Scholars and Innovative Research Team in University (IRT1025), the Foundation for the Author of National Excellent Doctoral Dissertation of China (201026), the Program for New Century Excellent Talents in University (NCET-09-0550), Shanghai Science and Technology Development Funds (12QA1401900) and the Shanghai Changning Health Bureau program (20094Y06001). 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Mutations in the GRIN2B gene (MRD6, MIM613970) have been identified as a common cause of ID (prevalence of 0.5 - 1% in individuals with ID) associated with EEG and behavioral problems. Methods: We assessed five GRIN2B mutation carriers aged between 3 and 14 years clinically and via standardized questionnaires to delineate a detailed behavioral phenotype. Parents and teachers rated problem behavior of their affected children by completing the Developmental Behavior Checklist (DBC) and the Conners' Rating Scales Revised (CRS-R:L). Results: All individuals had mild to severe ID and needed guidance in daily routine. They showed characteristic behavior problems with prominent hyperactivity, impulsivity, distractibility and a short attention span. Stereotypies, sleeping problems and a friendly but boundless social behavior were commonly reported. Conclusion: Our observations provide an initial delineation of the behavioral phenotype of GRIN2B mutation carriers. C1 [Freunscht, Inga; Hebebrand, Johannes] Univ Duisburg Essen, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-45147 Essen, Germany. [Popp, Bernt; Endele, Sabine; Reis, Andre; Zenker, Martin] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Blank, Rainer] Kinderzentrum Maulbronn gGmbH, Klin Kinderneurol & Sozialpadiatrie, Maulbronn, Germany. [Moog, Ute] Heidelberg Univ, Inst Human Genet, Heidelberg, Germany. [Petri, Holger] DRK Kinderklin, Siegen, Germany. [Prott, Eva-Christina; Wieczorek, Dagmar] Univ Duisburg Essen, Univ Hosp Essen, Inst Humangenet, Essen, Germany. [Ruebo, Jochen] St Antonius Hosp Kleve, Klin Kinder & Jugendmed, Kleve, Germany. [Zabel, Bernhard] Univ Hosp Freiburg, Ctr Pediat & Adolescent Med, Freiburg, Germany. [Zenker, Martin] Univ Magdeburg, Inst Humangenet, Magdeburg, Germany. RP Freunscht, I (reprint author), Univ Duisburg Essen, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-45147 Essen, Germany. EM Inga.Freunscht@lvr.de RI Reis, Andre/D-2309-2009 OI Reis, Andre/0000-0002-6301-6363 FU German Federal Ministry of Education and Research (BMBF) as a part of the National Genome Research Network (NGFN) [01GS08164, 01GS0816, 01GS08168] FX We are grateful to the families for their participation in the study. The Institutes for Human Genetics Essen, Erlangen and Heidelberg, Germany, are members of the 'German Mental Retardation Network' (MRNET), which is funded by the German Federal Ministry of Education and Research (BMBF) as a part of the National Genome Research Network (NGFN) (http://www.ngfn.de/en/retardierung.html, project reference numbers 01GS08164, 01GS0816, 01GS08168). We thank Nicholas Wagner for critically reading this manuscript. 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PD MAY 29 PY 2013 VL 9 AR 20 DI 10.1186/1744-9081-9-20 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 165UQ UT WOS:000320511300001 PM 23718928 ER PT J AU Kajiume, A Aoyama-Setoyama, S Saito-Hori, Y Ishikawa, N Kobayashi, M AF Kajiume, Aiko Aoyama-Setoyama, Shiori Saito-Hori, Yuri Ishikawa, Nobutsune Kobayashi, Masao TI Reduced brain activation during imitation and observation of others in children with pervasive developmental disorder: a pilot study SO BEHAVIORAL AND BRAIN FUNCTIONS LA English DT Article DE Pervasive developmental disorder; Imitation; Mirror neuron systems; Near-infrared spectroscopy ID MIRROR-NEURON SYSTEM; AUTISM SPECTRUM DISORDERS; RECOGNITION; DYSFUNCTION; HYPOTHESIS AB Background: Children with pervasive developmental disorder (PDD) are thought to have poor imitation abilities. Recently, this characteristic has been suggested to reflect impairments in mirror neuron systems (MNS). We used near-infrared spectroscopy (NIRS) to examine the brain activity of children with PDD during tasks involving imitation and observations of others. Findings: The subjects were 6 male children with PDD (8-14 years old) and 6 age- and gender-matched normal subjects (9-13 years old). A video in which a woman was opening and closing a bottle cap was used as a stimulus. Hemoglobin concentration changes around the posterior part of the inferior frontal gyrus and the adjacent ventral premotor cortex were measured with a 24-channel NIRS machine during action observation and action imitation tasks. Regional oxygenated hemoglobin concentration changes were significantly smaller in the PDD group than in the control group. Moreover, these differences were clearer in the action observation task than in the action imitation task. Conclusions: Dysfunction in the MNS in children with PDD was suggested by the reduced activation in key MNS regions during tasks involving observations and imitations of others. These preliminary results suggest that further studies are needed to verify MNS dysfunction in children with PDD. C1 [Kajiume, Aiko; Aoyama-Setoyama, Shiori; Ishikawa, Nobutsune; Kobayashi, Masao] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Pediat, Minami Ku, Hiroshima 7348551, Japan. [Saito-Hori, Yuri] Sendai Seiyo Gakuin Collage, Dept Child Studies, Wakabayashi Ku, Sendai, Miyagi 9840022, Japan. RP Kajiume, A (reprint author), Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Pediat, Minami Ku, 1-2-3 Kasumi, Hiroshima 7348551, Japan. EM aimaru@triton.ocn.ne.jp FU Japan Society for the Promotion of Science (JSPS) FX This research was supported by the Grants-in-Aid for Scientific Research by Japan Society for the Promotion of Science (JSPS). We thank children and their parents for their interested participation. We would like to thank Dr. Junko Tanaka (Hiroshima University Graduate School of Biomedical and Health Sciences) for helpful comments about statistical analysis. 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Brain Funct. PD MAY 29 PY 2013 VL 9 AR 21 DI 10.1186/1744-9081-9-21 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 157MV UT WOS:000319901600001 PM 23718943 ER PT J AU Davis, DA Bortolato, M Godar, SC Sander, TK Iwata, N Pakbin, P Shih, JC Berhane, K McConnell, R Sioutas, C Finch, CE Morgan, TE AF Davis, David A. Bortolato, Marco Godar, Sean C. Sander, Thomas K. Iwata, Nahoko Pakbin, Payam Shih, Jean C. Berhane, Kiros McConnell, Rob Sioutas, Constantinos Finch, Caleb E. Morgan, Todd E. TI Prenatal Exposure to Urban Air Nanoparticles in Mice Causes Altered Neuronal Differentiation and Depression-Like Responses SO PLOS ONE LA English DT Article ID TAIL-SUSPENSION TEST; POLYCYCLIC AROMATIC-HYDROCARBONS; DIESEL EXHAUST EXPOSURE; N-TERMINAL KINASE; ULTRAFINE PARTICLES; HIPPOCAMPAL-NEURONS; AXON FORMATION; CITY CHILDREN; LOS-ANGELES; AUTISM AB Emerging evidence suggests that excessive exposure to traffic-derived air pollution during pregnancy may increase the vulnerability to neurodevelopmental alterations that underlie a broad array of neuropsychiatric disorders. We present a mouse model for prenatal exposure to urban freeway nanoparticulate matter (nPM). In prior studies, we developed a model for adult rodent exposure to re-aerosolized urban nPM which caused inflammatory brain responses with altered neuronal glutamatergic functions. nPMs are collected continuously for one month from a local freeway and stored as an aqueous suspension, prior to re-aerosolization for exposure of mice under controlled dose and duration. This paradigm was used for a pilot study of prenatal nPM impact on neonatal neurons and adult behaviors. Adult C57BL/6J female mice were exposed to re-aerosolized nPM (350 mu g/m(3)) or control filtered ambient air for 10 weeks (3x5 hour exposures per week), encompassing gestation and oocyte maturation prior to mating. Prenatal nPM did not alter litter size, pup weight, or postnatal growth. Neonatal cerebral cortex neurons at 24 hours in vitro showed impaired differentiation, with 50% reduction of stage 3 neurons with long neurites and correspondingly more undifferentiated neurons at Stages 0 and 1. Neuron number after 24 hours of culture was not altered by prenatal nPM exposure. Addition of exogenous nPM (2 mu g/ml) to the cultures impaired pyramidal neuron Stage 3 differentiation by 60%. Adult males showed increased depression-like responses in the tail-suspension test, but not anxiety-related behaviors. These pilot data suggest that prenatal exposure to nPM can alter neuronal differentiation with gender-specific behavioral sequelae that may be relevant to human prenatal exposure to urban vehicular aerosols. C1 [Davis, David A.; Iwata, Nahoko; Finch, Caleb E.; Morgan, Todd E.] USC, Davis Sch Gerontol, Los Angeles, CA USA. [Godar, Sean C.; Shih, Jean C.] USC, Sch Pharm, Los Angeles, CA USA. [Sander, Thomas K.] USC, Dornsife Coll Letters Arts & Sci, Los Angeles, CA USA. [Pakbin, Payam; Sioutas, Constantinos] USC, Viterbi Sch Engn, Los Angeles, CA USA. [Finch, Caleb E.] USC, Dornsife Coll, Dept Neurobiol, Los Angeles, CA USA. [Berhane, Kiros; McConnell, Rob] USC, Keck Sch Med, Los Angeles, CA USA. [Bortolato, Marco] Univ Kansas, Sch Pharm, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA. RP Finch, CE (reprint author), USC, Davis Sch Gerontol, Los Angeles, CA USA. EM cefinch@usc.edu FU National Institutes of Health [R21AG040683, R21AG040753, R21HD070611, P30ES007048, T32AG000037] FX The authors are grateful for National Institutes of Health support (R21AG040683, R21AG040753, R21HD070611, P30ES007048). D.A.D. was supported by NIH grant T32AG000037. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Coffey-Corina, Sharon Padden, Denise Munson, Jeffrey Estes, Annette Dawson, Geraldine TI Brain Responses to Words in 2-Year-Olds with Autism Predict Developmental Outcomes at Age 6 SO PLOS ONE LA English DT Article ID EARLY LANGUAGE-ACQUISITION; EVENT-RELATED POTENTIALS; SPECTRUM DISORDERS; VOCABULARY GROWTH; CEREBRAL SPECIALIZATION; PRESCHOOL-CHILDREN; SOCIAL-INTERACTION; SPEECH-PERCEPTION; 2ND YEAR; INFANTS AB Autism Spectrum Disorder (ASD) is a developmental disability that affects social behavior and language acquisition. ASD exhibits great variability in outcomes, with some individuals remaining nonverbal and others exhibiting average or above average function. Cognitive ability contributes to heterogeneity in autism and serves as a modest predictor of later function. We show that a brain measure (event-related potentials, ERPs) of word processing in children with ASD, assessed at the age of 2 years (N = 24), is a broad and robust predictor of receptive language, cognitive ability, and adaptive behavior at ages 4 and 6 years, regardless of the form of intensive clinical treatment during the intervening years. The predictive strength of this brain measure increases over time, and exceeds the predictive strength of a measure of cognitive ability, used here for comparison. These findings have theoretical implications and may eventually lead to neural measures that allow early prediction of developmental outcomes as well as more individually tailored clinical interventions, with the potential for greater effectiveness in treating children with ASD. C1 [Kuhl, Patricia K.; Padden, Denise] Univ Washington, Inst Learning & Brain Sci, Seattle, WA 98195 USA. [Coffey-Corina, Sharon] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95616 USA. [Munson, Jeffrey] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Estes, Annette] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. [Dawson, Geraldine] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Dawson, Geraldine] Autism Speaks Fdn, New York, NY USA. RP Kuhl, PK (reprint author), Univ Washington, Inst Learning & Brain Sci, Seattle, WA 98195 USA. EM pkkuhl@u.washington.edu FU National Institutes of Health; National Institute of Mental Health (NIMH) [U54MH066399]; National Institute of Child Health and Human Development (NICHD) [P50 HD55782]; NIH UW Research Core Grant; University of Washington [P30 DC04661] FX This research was supported by the National Institutes of Health (www.nih.gov), funded by grants from The National Institute of Mental Health (NIMH) (U54MH066399) and National Institute of Child Health and Human Development (NICHD) (P50 HD55782). This work was facilitated by P30 HD02274 from the NICHD and an NIH UW Research Core Grant, University of Washington P30 DC04661. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Baving, Lioba TI Sleep Promotes Consolidation of Emotional Memory in Healthy Children but Not in Children with Attention-Deficit Hyperactivity Disorder SO PLOS ONE LA English DT Article ID AUTISM SPECTRUM DISORDER; SLOW-WAVE ACTIVITY; DEFICIT/HYPERACTIVITY DISORDER; CORTICAL MATURATION; DECLARATIVE MEMORY; YOUNG-ADULTS; ADHD; AMYGDALA; METAANALYSIS; ADOLESCENTS AB Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline-corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD. C1 [Prehn-Kristensen, Alexander; Munz, Manuel; Molzow, Ina; Wiesner, Christian D.; Baving, Lioba] Univ Kiel, Sch Med, Ctr Integrat Psychiat, Dept Child & Adolescent Psychiat & Psychotherapy, Kiel, Germany. [Wilhelm, Ines] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany. [Wilhelm, Ines] Univ Childrens Hosp Zurich, Child Dev Ctr, Zurich, Switzerland. RP Prehn-Kristensen, A (reprint author), Univ Kiel, Sch Med, Ctr Integrat Psychiat, Dept Child & Adolescent Psychiat & Psychotherapy, Kiel, Germany. EM a.prehn@zip-kiel.de FU German research foundation [SFB 654] FX This study was supported by a grant of the German research foundation (SFB 654, Plasticity and Sleep). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Washbourne, Philip TI Neuroligin1 Drives Synaptic and Behavioral Maturation through Intracellular Interactions SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MORRIS WATER MAZE; AUTISM SPECTRUM DISORDERS; D-ASPARTATE RECEPTORS; NMDA RECEPTORS; GLUTAMATERGIC SYNAPSES; INHIBITORY SYNAPSES; OBJECT RECOGNITION; BURST STIMULATION; MOUSE MODEL; MICE AB In vitro studies suggest that the intracellular C terminus of Neuroligin1 (NL1) could play a central role in the maturation of excitatory synapses. However, it is unknown how this activity affects synapses in vivo, and whether it may impact the development of complex behaviors. To determine how NL1 influences the state of glutamatergic synapses in vivo, we compared the synaptic and behavioral phenotypes of mice overexpressing a full-length version of NL1 (NL1FL) with mice overexpressing a version missing part of the intracellular domain (NL1 Delta C). We show that overexpression of full-length NL1 yielded an increase in the proportion of synapses with mature characteristics and impaired learning and flexibility. In contrast, the overexpression of NL1 Delta C increased the number of excitatory postsynaptic structures and led to enhanced flexibility in mnemonic and social behaviors. Transient overexpression of NL1FL revealed that elevated levels are not necessary to maintain synaptic and behavioral states altered earlier in development. In contrast, overexpression of NL1FL in the fully mature adult was able to impair normal learning behavior after 1 month of expression. These results provide the first evidence that NL1 significantly impacts key developmental processes that permanently shape circuit function and behavior, as well as the function of fully developed neural circuits. Overall, these manipulations of NL1 function illuminate the significance of NL1 intracellular signaling in vivo, and enhance our understanding of the factors that gate the maturation of glutamatergic synapses and complex behavior. This has significant implications for our ability to address disorders such as autism spectrum disorders. C1 [Hoy, Jennifer L.; Constable, John R. L.; Arias, Renee J.; McCallum, Raluca; Kyweriga, Michael; Wehr, Michael; Washbourne, Philip] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. [Haeger, Paola A.; Castillo, Pablo E.] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA. [Schnell, Eric] Portland VA Med Ctr, Portland, OR 97239 USA. [Schnell, Eric] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Davis, Lawrence] Univ Oregon, Dept Phys, Eugene, OR 97403 USA. RP Washbourne, P (reprint author), 1254 Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. EM pwash@uoneuro.uoregon.edu RI Kyweriga, Michael/H-3226-2013 OI Kyweriga, Michael/0000-0003-3511-6292 FU National Institute of Neurological Disorders and Stroke [R01 NS065795]; Autism Speaks [1368]; National Institute of Mental Health [R01 MH081935]; American Psychological Association [DPN T32 MH18882-22]; National Science Foundation [GK-12]; Oregon Center for Optics; Biomedical Sciences Chile; Becas Chile FX This work was supported by National Institute of Neurological Disorders and Stroke R01 NS065795 and Autism Speaks 1368 to P.W., by National Institute of Mental Health R01 MH081935 to P.E.C., the American Psychological Association DPN T32 MH18882-22 to J.L.H, National Science Foundation GK-12 program to L.D., and the Oregon Center for Optics to J.L.H. and L.D.P.A.H. is a PEW Latin American Fellow in the Biomedical Sciences and Becas Chile recipient. We thank Keith Beadle for establishing the immunolabeling technique in thinly sectioned brain tissue; Sheryl Moy (University of North Carolina) for excellent guidance in conducting the appropriate behavioral tests and initial characterization of our transgenic mice, and providing critical feedback on this manuscript; Cris Niell and Victoria Herman for providing comments on previous versions of this manuscript; Gary Westbrook (OHSU) for generously providing his lab's reagents and support; Miriam Deutsch (University of Oregon Physics Department) for providing lab support for extended data analysis techniques; Shawn Brown and Sebastien Valverde for technical assistance in preparation of synaptosomal fractions and Western blot generation; and Sebastien Valverde and Leah Deblander for additional assistance in training mice in the water maze and social tasks. 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Neurosci. PD MAY 29 PY 2013 VL 33 IS 22 BP 9364 EP 9384 DI 10.1523/JNEUROSCI.4660-12.2013 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 152XV UT WOS:000319566300014 PM 23719805 ER PT J AU Ribeiro, TC Valasek, CA Minati, L Boggio, PS AF Ribeiro, Tatiane C. Valasek, Claudia A. Minati, Ludovico Boggio, Paulo S. TI Altered semantic integration in autism beyond language: a cross-modal event-related potentials study SO NEUROREPORT LA English DT Article DE autism spectrum disorders; event-related potentials; late positive potential; music; N400 component; semantic priming ID BRAIN POTENTIALS; DISORDERS; CHILDREN; VERSION; MUSIC AB Autism spectrum disorders (ASDs) are characterized by impaired communication, particularly pragmatic and semantic language, resulting in verbal comprehension deficits. Semantic processing in these conditions has been studied extensively, but mostly limited only to linguistic material. Emerging evidence, however, suggests that semantic integration deficits may extend beyond the verbal domain. Here, we explored cross-modal semantic integration using visual targets preceded by musical and linguistic cues. Particularly, we have recorded the event-related potentials to evaluate whether the N400 and late positive potential (LPP) components, two widely studied electrophysiological markers of semantic processing, are differently sensitive to congruence with respect to typically developing children. Seven ASD patients and seven neurotypical participants matched by age, education and intelligence quotient provided usable data. Neuroelectric activity was recorded in response to visual targets that were related or unrelated to a preceding spoken sentence or musical excerpt. The N400 was sensitive to semantic congruence in the controls but not the patients, whereas the LPP showed a complementary pattern. These results suggest that semantic processing in ASD children is also altered in the context of musical and visual stimuli, and point to a functional decoupling between the generators of the N400 and LPP, which may indicate delayed semantic processing. These novel findings underline the importance of exploring semantic integration across multiple modalities in ASDs and provide motivation for further investigation in large clinical samples. NeuroReport 24:414-418 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Valasek, Claudia A.; Boggio, Paulo S.] Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Social & Cognit Neurosci Lab, BR-01241001 Sao Paulo, Brazil. [Valasek, Claudia A.; Boggio, Paulo S.] Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Dev Disorders Program, BR-01241001 Sao Paulo, Brazil. [Ribeiro, Tatiane C.] Univ Fed Sao Paulo UNIFESP, Dept Psychiat, Sao Paulo, Brazil. [Ribeiro, Tatiane C.] Univ Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. [Minati, Ludovico] Ist Nazl Neurol Carlo Besta, Dept Sci, Milan, Italy. RP Boggio, PS (reprint author), Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Social & Cognit Neurosci Lab, 181 Piaui St, BR-01241001 Sao Paulo, Brazil. EM boggio@mackenzie.br FU MackPesquisa; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [305718/2009-6]; Master Grant [FAPESP 2010/14656-7] FX This manuscript is dedicated to the memory of friend and coinvestigator Prof. Marcos T. Mercadante, who contributed to study design and data acquisition. This research was supported by MackPesquisa. P. S. B. was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (305718/2009-6). C. A. V. was supported by a Master Grant (FAPESP 2010/14656-7). The authors thank Ana Carolina Alem Giglio and Lucas Murrins for assistance in the preparation of illustrations. 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Banerjee, Probal Flory, Michael Cohen, Ira L. London, Eric Brown, W. Ted Hare, Carolyn Komich Wisniewski, Thomas TI Contribution of olivofloccular circuitry developmental defects to atypical gaze in autism SO BRAIN RESEARCH LA English DT Article DE Autism; Atypical gaze; Cerebellum; Flocculus; Dysplasia ID UNIPOLAR BRUSH CELL; DEVELOPING CEREBELLAR CORTEX; DEVELOPING RAT CEREBELLUM; EYE-MOVEMENT CONTROL; PURKINJE-CELLS; BERGMANN GLIA; VESTIBULOOCULAR REFLEX; NEURONAL MIGRATION; HEAD MOVEMENTS; STELLATE CELLS AB Individuals with autism demonstrate atypical gaze, impairments in smooth pursuit, altered movement perception and deficits in facial perception. The olivofloccular neuronal circuit is a major contributor to eye movement control. This study of the cerebellum in 12 autistic and 10 control subjects revealed dysplastic changes in the flocculus of eight autistic (67%) and two control (20%) subjects. Defects of the oculomotor system, including avoidance of eye contact and poor or no eye contact, were reported in 88% of autistic subjects with postmortem-detected floccular dysplasia. Focal disorganization of the flocculus cytoarchitecture with deficit, altered morphology, and spatial disorientation of Purkinje cells (PCs); deficit and abnormalities of granule, basket, stellate and unipolar brush cells; and structural defects and abnormal orientation of Bergmann glia are indicators of profound disruption of flocculus circuitry in a dysplastic area. The average volume of PCs was 26% less in the dysplastic region than in the unaffected region of the flocculus (p<0.01) in autistic subjects. Moreover, the average volume of PCs in the entire cerebellum was 25% less in the autistic subjects than in the control subjects (p<0.001). Findings from this study and a parallel study of the inferior olive (IO) suggest that focal floccular dysplasia combined with IO neurons and PC developmental defects may contribute to oculomotor system dysfunction and atypical gaze in autistic subjects. Published by Elsevier B.V. C1 [Wegiel, Jerzy; Kuchna, Izabela; Nowicki, Krzysztof; Imaki, Humi; Wegiel, Jarek; Ma, Shuang Yong] New York State Inst Basic Res Dev Disabil, Dept Dev Neurobiol, Staten Isl, NY 10314 USA. [Azmitia, Efrain C.] NYU, Dept Biol Psychiat & CNS, New York, NY USA. [Banerjee, Probal] CUNY Coll Staten Isl, Neurosci Program, Staten Isl, NY USA. [Flory, Michael; Cohen, Ira L.; London, Eric] New York State Inst Basic Res Dev Disabil, Dept Psychol, Staten Isl, NY 10314 USA. [Brown, W. Ted] New York State Inst Basic Res Dev Disabil, Dept Human Genet, Staten Isl, NY 10314 USA. [Hare, Carolyn Komich] Autism Speaks, Autism Tissue Program, Princeton, NJ USA. [Wisniewski, Thomas] NYU, Dept Neurol, Sch Med, New York, NY 10016 USA. [Wisniewski, Thomas] NYU, Dept Pathol, Sch Med, New York, NY 10016 USA. [Wisniewski, Thomas] NYU, Dept Psychiat, Sch Med, New York, NY 10016 USA. RP Wegiel, J (reprint author), New York State Inst Basic Res Dev Disabil, Dept Dev Neurobiol, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. EM jerzy.wegiel@opwdd.ny.gov FU New York State Office for People with Developmental Disabilities; Department of Defense Autism Spectrum Disorders Research Program [AS073234]; Autism Speaks (Princeton); PHS [R24-MH 068855]; Brain and Tissue Bank for Developmental Disorders of the National Institute of Child Health and Human Development at the University of Maryland; Brain and Tissue Bank at 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 for People with Developmental Disabilities, a grant from the Department of Defense Autism Spectrum Disorders Research Program (AS073234; J.W., T.W.), and a grant from Autism Speaks (Princeton, N.J.; J.W.). Tissue and clinical records acquisition was coordinated by The Autism Tissue Program (Princeton; Director: Jane Pickett, 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 Brain and Tissue Bank for Developmental Disorders of the National Institute of Child Health and Human Development at the University of Maryland, and the Brain and Tissue Bank at the New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY. 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PD MAY 28 PY 2013 VL 1512 BP 106 EP 122 DI 10.1016/j.brainres.2013.03.037 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 160AG UT WOS:000320087800011 PM 23558308 ER PT J AU Theodoridou, A Rowe, AC Mohr, C AF Theodoridou, Angeliki Rowe, Angela C. Mohr, Christine TI Men perform comparably to women in a perspective taking task after administration of intranasal oxytocin but not after placebo SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE oxytocin; empathy; perspective taking; sex differences; self-report ID EMPATHY ALTRUISM HYPOTHESIS; OWN-BODY TRANSFORMATIONS; HIGH-FUNCTIONING AUTISM; ADRENAL AXIS RESPONSES; SEX-DIFFERENCES; IMAGINED TRANSFORMATIONS; INDIVIDUAL-DIFFERENCES; PSYCHOSOCIAL STRESS; HEALTHY-VOLUNTEERS; EMOTIONAL EMPATHY AB Oxytocin (OT) is thought to play an important role in human interpersonal information processing and behavior. By inference, OT should facilitate empathic responding, i.e., the ability to feel for others and to take their perspective. In two independent double-blind, placebo-controlled between-subjects studies, we assessed the effect of intranasally administered OT on affective empathy and perspective taking, whilst also examining potential sex differences (e.g., women being more empathic than men). In study 1, we provided 96 participants (48 men) with an empathy scenario and recorded self-reports of empathic reactions to the scenario, while in study 2, a sample of 120 individuals (60 men) performed a computerized implicit perspective taking task. Whilst results from Study 1 showed no influence of OT on affective empathy, we found in Study 2 that OT exerted an effect on perspective taking ability in men. More specifically, men responded faster than women in the placebo group but they responded as slowly as women in the OT group. We conjecture that men in the OT group adopted a social perspective taking strategy, such as did women in both groups, but not men in the placebo group. On the basis of results across both studies, we suggest that self-report measures (such as used in Study 1) might be less sensitive to OT effects than more implicit measures of empathy such as that used in Study 2. If these assumptions are confirmed, one could infer that OT effects on empathic responses are more pronounced in men than women, and that any such effect is best studied using more implicit measures of empathy rather than explicit self-report measures. C1 [Theodoridou, Angeliki; Rowe, Angela C.] Univ Bristol, Sch Expt Psychol, Bristol BS8 1TU, Avon, England. [Mohr, Christine] Univ Lausanne, Inst Psychol, Lausanne, Switzerland. RP Theodoridou, A (reprint author), Univ Bristol, Sch Expt Psychol, 12A Priory Rd, Bristol BS8 1TU, Avon, England. EM at4194@bristol.ac.uk FU ESRC FX We wish to thank the ESRC for funding this study in way of a studentship to the lead author, Angeliki Theodoridou. 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Hum. Neurosci. PD MAY 27 PY 2013 VL 7 AR 197 DI 10.3389/fnhum.2013.00197 PG 11 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 151HW UT WOS:000319452300001 PM 23754995 ER PT J AU Mrozek-Budzyn, D Kieltyka, A Majewska, R Augustyniak, M AF Mrozek-Budzyn, Dorota Kieltyka, Agnieszka Majewska, Renata Augustyniak, Malgorzata TI Measles, mumps and rubella (MMR) vaccination has no effect on cognitive development in children - The results of the Polish prospective cohort study SO VACCINE LA English DT Article DE Children; MMR vaccine; Cognitive development ID PRENATAL EXPOSURE; AUTISM; CHILDHOOD; DISORDERS; VACCINES AB Objectives: The aim of the study was to examine the hypothesis that MMR exposure has a negative influence on cognitive development in children. Furthermore, MMR was compared to single measles vaccine to determine the potential difference of these vaccines safety regarding children's cognitive development. Methods: The prospective birth cohort study with sample consisted of 369 infants born in Krakow. Vaccination history against measles (date and the type of the vaccine) was extracted from physicians' records. Child development was assessed using the Bayley Scales of Infant Development (BSID-II) up to 3rd year of life, Raven test in 5th and 8th year and Wechsler (WISC-R) in 6th and 7th year. Data on possible confounders came from mothers' interview, medical records and analyses of lead and mercury level at birth and at the end of 5th year of life. Linear and logistic regression models adjusted for potential confounders were used to assess the association. Results: No significant differences in cognitive and intelligence tests results were observed between children vaccinated with MMR and those not vaccinated up to the end of the 2nd year of life. Children vaccinated with MMR had significantly higher Mental BSID-II Index (MDI) in the 36th month than those vaccinated with single measles vaccine (103.8 +/- 10.3 vs. 97.2 +/- 11.2, p = 0.004). Neither results of Raven test nor WISC-R were significantly different between groups of children vaccinated with MMR and with single measles vaccine. After standardization to child's gender, maternal education, family economical status, maternal IQ, birth order and passive smoking all developmental tests were statistically insignificant. Conclusion: The results suggest that there is no relationship between MMR exposure and children's cognitive development. Furthermore, the safety of triple MMR is the same as the single measles vaccine with respect to cognitive development. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Mrozek-Budzyn, Dorota; Kieltyka, Agnieszka; Majewska, Renata; Augustyniak, Malgorzata] Jagiellonian Univ, Coll Med, PL-31034 Krakow, Poland. RP Mrozek-Budzyn, D (reprint author), Jagiellonian Univ, Coll Med, Kopernika 7A, PL-31034 Krakow, Poland. EM dorota.mrozek-budzyn@uj.edu.pl; mykielty@cyf-kr.edu.pl; rmajewska@cm-uj.krakow.pl; malgorzata.augustyniak@uj.edu.pl FU NIEHS [R01ES010165, R01ES015282]; Lundin Foundation; John and Wendy Neu Family Foundation; Gladys and Roland Harriman Foundation FX The study received funding from a NIEHS R01 grants entitled "Vulnerability of the Fetus/Infant to PAH, PM2.5 and ETS" and "Developmental effects of early-life exposure to airborne PAH" (R01ES010165 and R01ES015282) and from The Lundin Foundation, The John and Wendy Neu Family Foundation, and The Gladys and Roland Harriman Foundation. Principal investigator: Prof. FP Perera; co-investigator: Prof. W Jedrychowski. 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Kennedy, Hayley A. Rinehart, Nicole J. Bradshaw, John L. Tonge, Bruce J. Daskalakis, Zafiris J. Fitzgerald, Paul B. TI Interpersonal motor resonance in autism spectrum disorder: evidence against a global "mirror system" deficit SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE mirror neurons; interaction; transcranial magnetic stimulation; primary motor cortex; electromyography ID NEURON SYSTEM; EXCITABILITY; DYSFUNCTION; PERCEPTION; MODULATION; FACILITATION; INDIVIDUALS; IMPAIRMENTS; ACTIVATION; CHILDREN AB The mirror neuron hypothesis of autism is highly controversial, in part because there are conflicting reports as to whether putative indices of mirror system activity are actually deficient in autism spectrum disorder (ASD). Recent evidence suggests that a typical putative mirror system response may be seen in people with an ASD when there is a degree of social relevance to the visual stimuli used to elicit that response. Individuals with ASD (n = 32) and matched neurotypical controls (n = 32) completed a transcranial magnetic stimulation (TMS) experiment in which the left primary motor cortex (M1) was stimulated during the observation of static hands, individual (i.e., one person) hand actions, and interactive (i.e., two person) hand actions. Motor-evoked potentials (MEP) were recorded from the contralateral first dorsal interosseous, and used to generate an index of interpersonal motor resonance (IMR; a putative measure of mirror system activity) during action observation. There was no difference between ASD and NT groups in the level of IMR during the observation of these actions. These findings provide evidence against a global mirror system deficit in ASD, and this evidence appears to extend beyond stimuli that have social relevance. Attentional and visual processing influences may be important for understanding the apparent role of IMR in the pathophysiology of ASD. C1 [Enticott, Peter G.; Kennedy, Hayley A.; Fitzgerald, Paul B.] Monash Univ, Alfred & Cent Clin Sch, Monash Alfred Psychiat Res Ctr, Melbourne, Vic 3004, Australia. [Enticott, Peter G.; Rinehart, Nicole J.; Bradshaw, John L.; Tonge, Bruce J.] Monash Univ, Sch Psychol & Psychiat, Ctr Dev Psychiat & Psychol, Clayton, Vic, Australia. [Daskalakis, Zafiris J.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. RP Enticott, PG (reprint author), Monash Alfred Psychiat Res Ctr, Level 4,607 St Kilda Rd, Melbourne, Vic 3004, Australia. EM peter.enticott@monash.edu RI Daskalakis, Zafiris/J-5503-2013 OI Daskalakis, Zafiris/0000-0001-9502-0538 FU National Health and Medical Research Council (NHMRC, Australia) Project Grant [545811]; NHMRC Clinical Training Fellowship; Canadian Institutes of Health Research Clinician Scientist Award; NHMRC Practitioner Fellowship; National Alliance for Research on Schizophrenia and Depression Lieber Young Investigator award FX The authors wish to thank all those who took part in the study and those who assisted with participant recruitment, including Prof. Tony Attwood, Ms. Tracel Devereux (Alpha Autism), Dr. Richard Eisenmajer, Mr. Dennis Freeman (Wesley College Melbourne), Ms. Pam Langford, Dr. Kerryn Saunders, Ms. Linke Smedts-Kreskas (Supporting Parents of Children with Autism and Asperger's Syndrome, Community Living and Respite Services Inc.), Autism Victoria, Autism Asperger's Advocacy Australia, Autism Spectrum Australia, and the Asperger Syndrome Support Network. The authors also wish to thank Mrs. Felina Theburge for assisting with stimulus production, and Dr. Bernadette Fitzgibbon and Ms. Sara Arnold for their helpful comments on the manuscript. This work was supported by a National Health and Medical Research Council (NHMRC, Australia) Project Grant (545811). Peter G. Enticott is supported by a NHMRC Clinical Training Fellowship. Zafiris J. Daskalakis is supported by a Canadian Institutes of Health Research Clinician Scientist Award and by Constance and Stephen Lieber through a National Alliance for Research on Schizophrenia and Depression Lieber Young Investigator award. Paul B. Fitzgerald is supported by a NHMRC Practitioner Fellowship. 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Hum. Neurosci. PD MAY 23 PY 2013 VL 7 AR 218 DI 10.3389/fnhum.2013.00218 PG 8 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 149OS UT WOS:000319331000001 PM 23734121 ER PT J AU O'Connell, G Christakou, A Haffey, AT Chakrabarti, B AF O'Connell, Garret Christakou, Anastasia Haffey, Anthony T. Chakrabarti, Bhismadev TI The role of empathy in choosing rewards from another's perspective SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE empathy; reward; temporal discounting; social distance; simulation ID PRISONERS-DILEMMA GAME; PREFRONTAL CORTEX; NEURAL RESPONSES; SOCIAL ANXIETY; DELAY; OTHERS; IMPULSIVITY; CHOICE; AUTISM; INTELLIGENCE AB As social animals, we regularly act in the interest of others by making decisions on their behalf. These decisions can take the form of choices between smaller short-term rewards and larger long-term rewards, and can be effectively indexed by temporal discounting (TD). In a TD paradigm, a reward loses subjective value with increasing delay presumably because it becomes more difficult to simulate how much the recipient (e.g., future self) will value it. If this is the case, then the value of delayed rewards should be discounted even more steeply when we are choosing for someone whose feelings we do not readily simulate, such as socially distant strangers. Second, the ability to simulate shows individual differences and is indexed by trait empathy. We hypothesized that individuals high in trait empathy will more readily simulate, and hence discount less steeply for distant others, compared to those who are low on trait empathy. To test these predictions, we asked 63 participants from the general population to perform a TD task from the perspectives of close and distant others, as well as their own. People were found to discount less steeply for themselves, and the steepness of TD increased with increasing distance from self. Additionally, individuals who scored high in trait empathy were found to discount less steeply for distant others compared to those who scored low. These findings confirm the role of empathy in determining how we choose rewards for others. C1 [O'Connell, Garret; Christakou, Anastasia; Haffey, Anthony T.; Chakrabarti, Bhismadev] Univ Reading, Sch Psychol & Clin Language Sci, Ctr Integrat Neurosci & Neurodynam, Reading RG6 6AL, Berks, England. RP Chakrabarti, B (reprint author), Univ Reading, Sch Psychol & Clin Language Sci, Ctr Integrat Neurosci & Neurodynam, Reading RG6 6AL, Berks, England. EM b.chakrabarti@reading.ac.uk RI Christakou, Anastasia/B-7838-2008 OI Christakou, Anastasia/0000-0002-4267-3436 FU University of Reading doctoral studentship; Human Frontier Science Program; Medical Research Council UK FX Garret O'Connell is supported by a University of Reading doctoral studentship. Anastasia Christakou is supported by the Human Frontier Science Program. Anthony T. Haffey and Bhismadev Chakrabarti are supported by the Medical Research Council UK. CR AINSLIE G, 1975, PSYCHOL BULL, V82, P463, DOI 10.1037/h0076860 Alessi SM, 2003, BEHAV PROCESS, V64, P345, DOI 10.1016/S0376-6357(03)00150-5 Baron-Cohen S, 2004, J AUTISM DEV DISORD, V34, P163, DOI 10.1023/B:JADD.0000022607.19833.00 Bartels DM, 2010, J EXP PSYCHOL GEN, V139, P49, DOI 10.1037/a0018062 Beisswanger AH, 2003, BASIC APPL SOC PSYCH, V25, P121, DOI 10.1207/S15324834BASP2502_3 Bickel WK, 1999, PSYCHOPHARMACOLOGY, V146, P447, DOI 10.1007/PL00005490 Chakrabarti B, 2006, SOC NEUROSCI-UK, V1, P364, DOI 10.1080/17470910601041317 Cheng YW, 2010, NEUROIMAGE, V51, P923, DOI 10.1016/j.neuroimage.2010.02.047 Christakou A, 2011, NEUROIMAGE, V54, P1344, DOI 10.1016/j.neuroimage.2010.08.067 DAMASIO AR, 1991, FRONTAL LOBE FUNCTION AND DYSFUNCTION, P217 Davis M., 1980, JASA CATALOGUE SELEC, V44, P113 de Wit H, 2007, PERS INDIV DIFFER, V42, P111, DOI 10.1016/j.paid.2006.06.026 Dichter G. 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Hum. Neurosci. PD MAY 23 PY 2013 VL 7 AR 174 DI 10.3389/fnhum.2013.00174 PG 5 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 149NV UT WOS:000319328600001 PM 23734112 ER PT J AU Sarachana, T Hu, VW AF Sarachana, Tewarit Hu, Valerie W. TI Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder SO MOLECULAR AUTISM LA English DT Article DE RORA; Autism; Nuclear hormone receptor; Transcriptional targets; Chromatin immunoprecipitation; Promoter microarray ID COPY-NUMBER VARIATION; ORPHAN NUCLEAR RECEPTOR; STAGGERER MUTANT MICE; CEREBELLAR DEVELOPMENT; NEURONAL DEVELOPMENT; MENTAL-RETARDATION; ABNORMAL-BEHAVIOR; ASPERGER-SYNDROME; OXIDATIVE STRESS; FRONTAL-CORTEX AB Background: We have recently identified the nuclear hormone receptor RORA (retinoic acid-related orphan receptor-alpha) as a novel candidate gene for autism spectrum disorder (ASD). Our independent cohort studies have consistently demonstrated the reduction of RORA transcript and/or protein levels in blood-derived lymphoblasts as well as in the postmortem prefrontal cortex and cerebellum of individuals with ASD. Moreover, we have also shown that RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting the possibility that RORA may contribute to the male bias of ASD. However, little is known about transcriptional targets of this nuclear receptor, particularly in humans. Methods: Here we identify transcriptional targets of RORA in human neuronal cells on a genome-wide level using chromatin immunoprecipitation (ChIP) with an anti-RORA antibody followed by whole-genome promoter array (chip) analysis. Selected potential targets of RORA were then validated by an independent ChIP followed by quantitative PCR analysis. To further demonstrate that reduced RORA expression results in reduced transcription of RORA targets, we determined the expression levels of the selected transcriptional targets in RORA-deficient human neuronal cells, as well as in postmortem brain tissues from individuals with ASD who exhibit reduced RORA expression. Results: The ChIP-on-chip analysis reveals that RORA1, a major isoform of RORA protein in human brain, can be recruited to as many as 2,764 genomic locations corresponding to promoter regions of 2,544 genes across the human genome. Gene ontology analysis of this dataset of genes that are potentially directly regulated by RORA1 reveals statistically significant enrichment in biological functions negatively impacted in individuals with ASD, including neuronal differentiation, adhesion and survival, synaptogenesis, synaptic transmission and plasticity, and axonogenesis, as well as higher level functions such as development of the cortex and cerebellum, cognition, memory, and spatial learning. Independent ChIP-quantitative PCR analyses confirm binding of RORA1 to promoter regions of selected ASD-associated genes, including A2BP1, CYP19A1, ITPR1, NLGN1, and NTRK2, whose expression levels (in addition to HSD17B10) are also decreased in RORA1-repressed human neuronal cells and in prefrontal cortex tissues from individuals with ASD. Conclusions: Findings from this study indicate that RORA transcriptionally regulates A2BP1, CYP19A1, HSD17B10, ITPR1, NLGN1, and NTRK2, and strongly suggest that reduction of this sex hormone-sensitive nuclear receptor in the brain causes dysregulated expression of these ASD-relevant genes as well as their associated pathways and functions which, in turn, may contribute to the underlying pathobiology of ASD. C1 [Sarachana, Tewarit; Hu, Valerie W.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Med, Washington, DC 20037 USA. RP Hu, VW (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Med, 2300 I St NW, Washington, DC 20037 USA. EM valhu@gwu.edu FU The George Washington University; Office of the Commission on Higher Education of the Royal Thai Government, Thailand, through Faculty of Allied Health Sciences, Chulalongkorn University FX This study was supported in part by a generous gift from the LIFE Foundation (Aspen, CO, USA) and by an intramural grant from The George Washington University (Medical Faculty Associates award). Neither of the funding sources played any role in the study design, collection, analysis, and interpretation of data, writing of the manuscript, or decision to submit this study for publication. TS was a predoctoral student in the Institute for Biomedical Sciences at the George Washington University, who was supported by the Higher Educational Strategic Scholarship for Frontier Research Network (SFR scholarship) from the Office of the Commission on Higher Education of the Royal Thai Government, Thailand, through the Faculty of Allied Health Sciences, Chulalongkorn University. 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The objective of the current study was to compare verbal working memory, acquisition and delayed recall in children with High-Functioning Autism (HFA) to children with ADHD and typically developing children (TDC). Thirty-eight children with HFA, 79 with ADHD and 50 TDC (age 8-17) were assessed with a letter/number sequencing task and a verbal list-learning task. To investigate the possible influence of attention problems in children with HFA, we divided the HFA group into children with (HFA+) or without (HFA2) "attention problems'' according to the Child Behaviour Checklist 6-18. The children with HFA+ displayed significant impairment compared to TDC on all three neurocognitive measures, while the children with HFA2 were significantly impaired compared to TDC only on the working memory and acquisition measures. In addition, the HFA+ group scored significantly below the HFA2 group and the ADHD group on the verbal working memory and delayed recall measures. The results support the proposition that children with HFA+, HFA2, and ADHD differ not only on a clinical level but also on a neurocognitive level which may have implications for treatment. C1 [Andersen, Per Normann; Hovik, Kjell Tore; Skogli, Erik Winther; Oie, Merete] Innlandet Hosp Trust, Div Mental Hlth Care, Lillehammer, Norway. [Andersen, Per Normann; Hovik, Kjell Tore; Skogli, Erik Winther; Egeland, Jens; Oie, Merete] Univ Oslo, Inst Psychol, Oslo, Norway. [Egeland, Jens] Vestfold Hosp Trust, Div Mental Hlth & Addict, Tonsberg, Norway. RP Andersen, PN (reprint author), Innlandet Hosp Trust, Div Mental Hlth Care, Lillehammer, Norway. EM per.normann.andersen@sykehuset-innlandet.no FU Innlandet Hospital Trust [150170]; Regional Resource Center for Autism; ADHD; Tourette's syndrome; Narcolepsy; Oslo University Hospital [150182] FX The work was supported by grants from Innlandet Hospital Trust, www.sykehuset-innlandet.no, (grant number 150170) and from Regional Resource Center for Autism, ADHD, Tourette's syndrome, and Narcolepsy, Oslo University Hospital http://www.oslo-universitetssykehus. no/omoss/avdelinger/rfm/Sider/ enhet.aspx (grant number 150182). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Luna, Beatriz Kay-Stacey, Margaret Nowinski, Caralynn V. Rubin, Leah H. Scudder, Charles Minshew, Nancy Sweeney, John A. TI Saccade Adaptation Abnormalities Implicate Dysfunction of Cerebellar-Dependent Learning Mechanisms in Autism Spectrum Disorders (ASD) SO PLOS ONE LA English DT Article ID PURKINJE-CELLS; SUPERIOR COLLICULUS; OCULOMOTOR VERMIS; INFANTILE-AUTISM; EYE-MOVEMENTS; COMMUNICATION DEFICITS; ADAPTIVE MODIFICATION; POSTERIOR-FOSSA; MOTOR; CHILDREN AB The cerebellar vermis (lobules VI-VII) has been implicated in both postmortem and neuroimaging studies of autism spectrum disorders (ASD). This region maintains the consistent accuracy of saccadic eye movements and plays an especially important role in correcting systematic errors in saccade amplitudes such as those induced by adaptation paradigms. Saccade adaptation paradigms have not yet been used to study ASD. Fifty-six individuals with ASD and 53 age-matched healthy controls performed an intrasaccadic target displacement task known to elicit saccadic adaptation reflected in an amplitude reduction. The rate of amplitude reduction and the variability of saccade amplitude across 180 adaptation trials were examined. Individuals with ASD adapted slower than healthy controls, and demonstrated more variability of their saccade amplitudes across trials prior to, during and after adaptation. Thirty percent of individuals with ASD did not significantly adapt, whereas only 6% of healthy controls failed to adapt. Adaptation rate and amplitude variability impairments were related to performance on a traditional neuropsychological test of manual motor control. The profile of impaired adaptation and reduced consistency of saccade accuracy indicates reduced neural plasticity within learning circuits of the oculomotor vermis that impedes the fine-tuning of motor behavior in ASD. These data provide functional evidence of abnormality in the cerebellar vermis that converges with previous reports of cellular and gross anatomic dysmorphology of this brain region in ASD. C1 [Mosconi, Matthew W.; Sweeney, John A.] Univ Texas Southwestern, Dept Psychiat, Dallas, TX USA. [Mosconi, Matthew W.; Sweeney, John A.] Univ Texas Southwestern, Dept Pediat, Dallas, TX USA. [Luna, Beatriz] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Luna, Beatriz] Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA USA. [Kay-Stacey, Margaret] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL USA. [Nowinski, Caralynn V.] Univ Illinois, Off Vice President Res, Urbana, IL 61801 USA. [Rubin, Leah H.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Scudder, Charles] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA USA. [Scudder, Charles] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA USA. [Minshew, Nancy] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Minshew, Nancy] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. RP Mosconi, MW (reprint author), Univ Texas Southwestern, Dept Psychiat, Dallas, TX USA. EM Matt.Mosconi@UTSouthwestern.edu FU NIMH [MH092696]; NICHD Collaborative Program of Excellence in Autism [HD35469]; Autism Center of Excellence [HD055751, HD055748]; Autism Speaks and the National Alliance for Autism Research FX This study was supported by NIMH MH092696, the NICHD Collaborative Program of Excellence in Autism HD35469, Autism Center of Excellence awards HD055751 and HD055748, Autism Speaks and the National Alliance for Autism Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Several genetic studies found an association between RELN gene and increased risk of autism suggesting that reelin deficiency may be a vulnerability factor in its etiology. Moreover, a reduced reelin expression has been observed in several brain regions of subjects with Autism Spectrum Disorders. Since a number of reports have documented presence of vocal and neuromotor abnormalities in patients with autism and suggested that these dysfunctions predate the onset of the syndrome, we performed a fine-grain characterization of the neonatal vocal and motor repertoire in reelin mutant mice to explore the developmental precursors of the disorder. Our findings evidence a general delay in motor and vocal development in heterozygous (50% reduced reelin) and reeler (lacking reelin gene) mutant mice. As a whole, an increased number of calls characterized heterozygous pup's emission. Furthermore, the typical ontogenetic peak in the number of calls characterizing wild-type pups on postnatal day 4 appeared slightly delayed in heterozygous pups (to day 6) and was quite absent in reeler littermates, which exhibited a flat profile during development. We also detected a preferential use of a specific call category (two-components) by heterozygous and reeler mice at postnatal days 6 and 8 as compared to their wild-type littermates. With regard to the analysis of spontaneous movements, a differential profile emerged early in development among the three genotypes. While only slight coordination difficulties are exhibited by heterozygous pups, all indices of motor development appear delayed in reeler mice. Overall, our results evidence a genotype-dependent deviation in ultrasonic vocal repertoire and a general delay in motor development in reelin mutant pups. C1 [Romano, Emilia; Laviola, Giovanni] Ist Super Sanita, Behav Neurosci Sect, Dept Cell Biol & Neurosci, Rome, Italy. [Michetti, Caterina; Caruso, Angela; Scattoni, Maria Luisa] Ist Super Sanita, Neurotoxicol & Neuroendocrinol Sect, Dept Cell Biol & Neurosci, Rome, Italy. [Romano, Emilia] Ist Ricovero & Cura Carattere Sci, Bambino Gesu Childrens Hosp, Rome, Italy. RP Scattoni, ML (reprint author), Ist Super Sanita, Neurotoxicol & Neuroendocrinol Sect, Dept Cell Biol & Neurosci, Rome, Italy. EM marialuisa.scattoni@iss.it FU Italian Ministry of Health Grant, Young Researcher, GR3-"Non-invasive tools for early detection of Autism Spectrum Disorders'; ERAnet "PrioMedChild'', Italian Ministry of Health; IRE-IFO [RF2008] FX This work has been supported by the Italian Ministry of Health Grant, Young Researcher 2008, GR3-"Non-invasive tools for early detection of Autism Spectrum Disorders'' (MLS, CM and AC); by the ERAnet "PrioMedChild'', Italian Ministry of Health (ER) and IRE-IFO (RF2008) "MECP2 phosphorilation and related kinase in Rett syndrom'' (GL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Sciences SC Science & Technology - Other Topics GA 149OK UT WOS:000319330200132 PM 23700474 ER PT J AU Cao, Y Zhao, QD Hu, LJ Sun, ZQ Sun, SP Yun, WW Yuan, YG AF Cao, Yin Zhao, Quan-Di Hu, Li-Jun Sun, Zhi-Qin Sun, Su-Ping Yun, Wen-Wei Yuan, Yong-Gui TI Theory of mind deficits in patients with esophageal cancer combined with depression SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Esophageal cancer combined with depression; Theory of mind; Social perceptual component; Social cognitive component ID QUALITY-OF-LIFE; PSYCHOLOGICAL DISTRESS; ADULTS; SURVIVORS; DISORDER; AUTISM AB AIM: To characterize the two components of theory of mind (ToM) in patients with esophageal cancer combined with depression. METHODS: Sixty-five patients with esophageal cancer combined with depression (depressed group) and 62 normal controls (control group) were assessed using reading the mind in the eyes test, faux pas task, verbal fluency test, digit span test and WAIS IQ test. The depressed group was divided into two subgroups including psychotic depressed (PD) group (32 cases) and nonpsychotic depressed (NPD) group (33 cases).The clinical symptoms of patients were assessed using Beck depression inventory version. and brief psychiatric reacting scale (BPRS). RESULTS: There was a significant difference between the depressed group and the control group on tasks involving ToM social perceptual components (mind reading: t = 7.39, P < 0.01) and tests involving ToM social cognitive components (faux pas questions: t = 13.75, P < 0.01), respectively. A significant difference was also found among the PD group, the NPD group and the control group on mind reading (F = 32.98, P < 0.01) and faux pas questions (chi(2) = 78.15, P < 0.01), respectively. The PD group and NPD group performed worse than normal group controls both on mind reading and faux pas questions (P < 0.05). The PD group performed significantly worse than the NPD group on tasks involving ToM (mind reading: F = 18.99, P < 0.01; faux pas questions: F = 36.01, P < 0.01). In the depressed group, there was a negative correlation between ToM performances and BPRS total score (mind reading: r = -0.35, P < 0.01; faux pas questions: r = -0.51, P < 0.01), and between ToM performances and hostile suspiciousness factor score (mind reading: r = -0.75, P < 0.01; faux pas questions: r = -0.73, P < 0.01), respectively. CONCLUSION: The two components of ToM are both impaired in patients with esophageal cancer combined with depression. This indicates that there may be an association between ToM deficits and psychotic symptoms in clinical depression. (C) 2013 Baishideng. All rights reserved. C1 [Cao, Yin; Yun, Wen-Wei] Nanjing Med Univ, Changzhou Peoples Hosp 2, Dept Internal Med, Changzhou 213003, Jiangsu, Peoples R China. [Zhao, Quan-Di; Hu, Li-Jun; Sun, Su-Ping] Nanjing Med Univ, Changzhou Peoples Hosp 2, Dept Radiotherapy, Changzhou 213003, Jiangsu, Peoples R China. [Sun, Zhi-Qin] Nanjing Med Univ, Changzhou Peoples Hosp 2, Dept Nursing, Changzhou 213003, Jiangsu, Peoples R China. [Yuan, Yong-Gui] Southeast Univ, Dept Psychol, Zhongda Hosp, Nanjing 210009, Jiangsu, Peoples R China. RP Yuan, YG (reprint author), Southeast Univ, Dept Psychol, Zhongda Hosp, 87 Dingjiaqiao, Nanjing 210009, Jiangsu, Peoples R China. 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Gastroenterol. PD MAY 21 PY 2013 VL 19 IS 19 BP 2969 EP 2973 DI 10.3748/wjg.v19.i19.2969 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 149PT UT WOS:000319334100014 PM 23704831 ER PT J AU Wataya-Kaneda, M Tanaka, M Hamasaki, T Katayama, I AF Wataya-Kaneda, Mari Tanaka, Mari Hamasaki, Toshimitsu Katayama, Ichiro TI Trends in the Prevalence of Tuberous Sclerosis Complex Manifestations: An Epidemiological Study of 166 Japanese Patients SO PLOS ONE LA English DT Article ID ACQUIRED PERIUNGUAL FIBROKERATOMA; UTERINE LEIOMYOMA; DIAGNOSTIC-CRITERIA; MUTATIONAL ANALYSIS; MENTAL-RETARDATION; CLINICAL-FEATURES; EPILEPSY; LYMPHANGIOLEIOMYOMATOSIS; CHILDREN; TSC1 AB Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with multi-system involvement and variable manifestations. There has been significant progress in TSC research and the development of technologies used to diagnose this disorder. As a result, individuals with mild TSC are now being diagnosed, including many older adults who have not developed seizures or cognitive abnormalities. We conducted a statistical analysis of the frequency of TSC manifestations in a population of Japanese adults and children, comparing our findings with historical data. The chi-square test was used to examine the frequency of each manifestation by age. A total of 166 outpatients at the Department of Dermatology of Osaka University Hospital during the period from January 2001 to March 2011 were included in the study. Compared to previous reports, the frequency of neurologic manifestations (excepting autism) was lower in this cohort, and the frequency of skin manifestations (excepting hypomelanotic macules) was higher in this cohort. The frequencies of pulmonary lymphangioleiomyomatosis and renal manifestations were not significantly different from those previously reported. Regarding the association of each manifestation with age, the frequency of neurologic manifestations (excepting subependymal giant cell astrocytoma) was significantly higher in younger patients than in older patients. The frequency of skin manifestations and renal angiomyolipoma were significantly higher in older patients than in younger patients. Because of their high frequency and visibility, skin manifestations are useful in the diagnosis of TSC. Moreover, uterine perivascular epithelioid cell tumor was also characterized as a new findings associated with TSC. C1 [Wataya-Kaneda, Mari; Tanaka, Mari; Katayama, Ichiro] Osaka Univ, Grad Sch Med, Dept Dermatol, Suita, Osaka, Japan. [Hamasaki, Toshimitsu] Osaka Univ, Grad Sch Med, Dept Biomed Stat, Suita, Osaka, Japan. RP Wataya-Kaneda, M (reprint author), Osaka Univ, Grad Sch Med, Dept Dermatol, Suita, Osaka, Japan. EM mkaneda@derma.med.osaka-u.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Ministry of Health, Labor and Welfare of Japan FX This study was supported by the grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the grant from the Ministry of Health, Labor and Welfare of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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However, the neural correlates of deception processing, which requires mentalizing, remain unclear. Using functional magnetic resonance imaging (fMRI), we examined the neural correlates of deception, including mentalization, in social contexts in normally developing children. Healthy right-handed children (aged 8-9 years) were scanned while performing interactive games involving deception. The games varied along two dimensions: the type of reply (deception and truth) and the type of context (social and less social). Participants were instructed to deceive a witch and to tell the truth to a girl. Under the social-context conditions, participants were asked to consider what they inferred about protagonists' preferences from their facial expressions when responding to questions. Under the less-social-context conditions, participants did not need to consider others' preferences. We found a significantly greater response in the right precuneus under the social-context than under less-social-context conditions. Additionally, we found marginally greater activation in the right inferior parietal lobule (IPL) under the deception than under the truth condition. These results suggest that deception in a social context requires not only inhibition of prepotent responses but also engagement in mentalizing processes. This study provides the first evidence of the neural correlates of the mentalizing processes involved in deception in normally developing children. C1 [Yokota, Susumu; Tanaka, Mari] Tohoku Univ, Grad Sch Educ, Sendai, Miyagi 9808576, Japan. [Yokota, Susumu] Japan Soc Promot Sci, Tokyo, Japan. [Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Thyreau, Benjamin; Kawashima, Ryuta] Tohoku Univ, IDAC, Div Dev Cognit Neurosci, Sendai, Miyagi 9808576, Japan. RP Yokota, S (reprint author), Tohoku Univ, Grad Sch Educ, Aoba Ku, 27-1 Kawauchi, Sendai, Miyagi 9808576, Japan. EM susumuyokota38@gmail.com FU Japan Society for the Promotion of Science FX This study was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science Fellows. We would like to thank our participants and their parents for their participation in the present study. We thank K. Asano and M. Asano for collecting MR data and K. Sato, Y. Kurita, Y. Matsuzaki, N. Hosozima, K. Nagase, Y. Takegahara, and K. Takenoshita for cognitive testing. 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PD MAY 17 PY 2013 VL 7 AR 206 DI 10.3389/fnhum.2013.00206 PG 8 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 145UH UT WOS:000319043100001 PM 23730281 ER PT J AU Lim, L Marquand, A Cubillo, AA Smith, AB Chantiluke, K Simmons, A Mehta, M Rubia, K AF Lim, Lena Marquand, Andre Cubillo, Ana A. Smith, Anna B. Chantiluke, Kaylita Simmons, Andrew Mehta, Mitul Rubia, Katya TI Disorder-Specific Predictive Classification of Adolescents with Attention Deficit Hyperactivity Disorder (ADHD) Relative to Autism Using Structural Magnetic Resonance Imaging SO PLOS ONE LA English DT Article ID DEFICIT/HYPERACTIVITY DISORDER; SPECTRUM DISORDER; LIKELIHOOD ESTIMATION; ALZHEIMERS-DISEASE; BRAIN STRUCTURE; METAANALYSIS; MRI; CHILDREN; ABNORMALITIES; NEUROANATOMY AB Objective: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, but diagnosed by subjective clinical and rating measures. The study's aim was to apply Gaussian process classification (GPC) to grey matter (GM) volumetric data, to assess whether individual ADHD adolescents can be accurately differentiated from healthy controls based on objective, brain structure measures and whether this is disorder-specific relative to autism spectrum disorder (ASD). Method: Twenty-nine adolescent ADHD boys and 29 age-matched healthy and 19 boys with ASD were scanned. GPC was applied to make disorder-specific predictions of ADHD diagnostic status based on individual brain structure patterns. In addition, voxel-based morphometry (VBM) analysis tested for traditional univariate group level differences in GM. Results: The pattern of GM correctly classified 75.9% of patients and 82.8% of controls, achieving an overall classification accuracy of 79.3%. Furthermore, classification was disorder-specific relative to ASD. The discriminating GM patterns showed higher classification weights for ADHD in earlier developing ventrolateral/premotor fronto-temporo-limbic and stronger classification weights for healthy controls in later developing dorsolateral fronto-striato-parieto-cerebellar networks. Several regions were also decreased in GM in ADHD relative to healthy controls in the univariate VBM analysis, suggesting they are GM deficit areas. Conclusions: The study provides evidence that pattern recognition analysis can provide significant individual diagnostic classification of ADHD patients and healthy controls based on distributed GM patterns with 79.3% accuracy and that this is disorder-specific relative to ASD. Findings are a promising first step towards finding an objective differential diagnostic tool based on brain imaging measures to aid with the subjective clinical diagnosis of ADHD. C1 [Lim, Lena; Cubillo, Ana A.; Smith, Anna B.; Chantiluke, Kaylita; Rubia, Katya] Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London WC2R 2LS, England. [Lim, Lena] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Psychol Med, Singapore 117595, Singapore. [Marquand, Andre; Simmons, Andrew; Mehta, Mitul] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London WC2R 2LS, England. [Simmons, Andrew] South London & Maudsley Fdn NHS Trust, NIHR Biomed Res Ctr, London, England. [Simmons, Andrew] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. RP Rubia, K (reprint author), Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London WC2R 2LS, England. EM katya.rubia@kcl.ac.uk RI Simmons, Andrew/B-8848-2008; Mehta, Mitul/F-3960-2010; Marquand, Andre/B-6050-2012 OI Simmons, Andrew/0000-0003-2306-5811; Marquand, Andre/0000-0001-5903-203X FU NIHR Biomedical Research Centre (BRC) for Mental Health at South London; Maudsley NHS Foundation Trust; Institute of Psychiatry, Kings College London; Lilly Pharmaceuticals; National Medical Research Council (Singapore); NIHR BRC; King's College London Centre of Excellence in Medical Engineering; Wellcome Trust; EPSRC [WT088641/Z/09/Z] FX Data collection was supported by grants by the NIHR Biomedical Research Centre (BRC) for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Kings College London and Lilly Pharmaceuticals. LL was supported by the National Medical Research Council (Singapore). A, Smith, AC, A. Simmonds and KC were supported by the NIHR BRC. AM was supported by the King's College London Centre of Excellence in Medical Engineering, funded by the Wellcome Trust and EPSRC under grant no. WT088641/Z/09/Z. Lilly Pharmaceuticals had no input into the design, analysis, data interpretation or write-up. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Chen, John W. Stemmer-Rachamimov, Anat Kwiatkowski, David J. Breakefield, Xandra O. TI Stochastic Model of Tsc1 Lesions in Mouse Brain SO PLOS ONE LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; MTOR PATHWAY; GIANT-CELLS; RAPAMYCIN; ACTIVATION; MANAGEMENT; SURVIVAL; DEFICITS; MICE AB Tuberous sclerosis complex (TSC) is an autosomal dominant disorder due to mutations in either TSC1 or TSC2 that affects many organs with hamartomas and tumors. TSC-associated brain lesions include subependymal nodules, subependymal giant cell astrocytomas and tubers. Neurologic manifestations in TSC comprise a high frequency of mental retardation and developmental disorders including autism, as well as epilepsy. Here, we describe a new mouse model of TSC brain lesions in which complete loss of Tsc1 is achieved in multiple brain cell types in a stochastic pattern. Injection of an adeno-associated virus vector encoding Cre recombinase into the cerebral ventricles of mice homozygous for a Tsc1 conditional allele on the day of birth led to reduced survival, and pathologic findings of enlarged neurons, cortical heterotopias, subependymal nodules, and hydrocephalus. The severity of clinical and pathologic findings as well as survival was shown to be dependent upon the dose and serotype of Cre virus injected. Although several other models of TSC brain disease exist, this model is unique in that the pathology reflects a variety of TSC-associated lesions involving different numbers and types of cells. This model provides a valuable and unique addition for therapeutic assessment. C1 [Prabhakar, Shilpa; Zuang, Xuan; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Prabhakar, Shilpa; Zuang, Xuan; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Prabhakar, Shilpa; Zuang, Xuan; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Goto, June; Kwiatkowski, David J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Translat Med Div,Dept Med, Boston, MA 02115 USA. [Sena-Esteves, Miguel; Gianni, Davide] Univ Massachusetts, Sch Med, Dept Neurol, Gene Therapy Ctr, Worcester, MA USA. [Bronson, Roderick] Harvard Univ, Sch Med, Rodent Histopathol Core Facil, Boston, MA USA. [Brockmann, Jillian; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wojtkiewicz, Gregory R.; Chen, John W.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Wojtkiewicz, Gregory R.; Chen, John W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. EM breakefield@hms.harvard.edu FU NIH/NINDS [NS24279-23, R01NS070835, R01NS072167]; DOD Army Grant [W81XWH-13-1-0076] FX NIH/NINDS NS24279-23, R01NS070835, R01NS072167 and DOD Army Grant W81XWH-13-1-0076 for the Award Mechanism: Exploration - Hypothesis Development Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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However, the performance of various methods developed so far lacks accuracy, and more robust methods need to be developed to identify the emotional pattern associated with ECG signals. Methods: Emotional ECG data was obtained from sixty participants by inducing the six basic emotional states (happiness, sadness, fear, disgust, surprise and neutral) using audio-visual stimuli. The non-linear feature 'Hurst' was computed using Rescaled Range Statistics (RRS) and Finite Variance Scaling (FVS) methods. New Hurst features were proposed by combining the existing RRS and FVS methods with Higher Order Statistics (HOS). The features were then classified using four classifiers - Bayesian Classifier, Regression Tree, K- nearest neighbor and Fuzzy K-nearest neighbor. Seventy percent of the features were used for training and thirty percent for testing the algorithm. Results: Analysis of Variance (ANOVA) conveyed that Hurst and the proposed features were statistically significant (p < 0.001). Hurst computed using RRS and FVS methods showed similar classification accuracy. The features obtained by combining FVS and HOS performed better with a maximum accuracy of 92.87% and 76.45% for classifying the six emotional states using random and subject independent validation respectively. Conclusions: The results indicate that the combination of non-linear analysis and HOS tend to capture the finer emotional changes that can be seen in healthy ECG data. This work can be further fine tuned to develop a real time system. C1 [Selvaraj, Jerritta; Murugappan, Murugappan; Wan, Khairunizam; Yaacob, Sazali] Univ Malaysia Perlis, Sch Mechatron Engn, Arau 02600, Perlis, Malaysia. RP Selvaraj, J (reprint author), Univ Malaysia Perlis, Sch Mechatron Engn, Kampus Ulu Pauh, Arau 02600, Perlis, Malaysia. EM sn.jerritta@gmail.com RI MURUGAPPAN, MURUGAPPAN/E-2402-2014 OI MURUGAPPAN, MURUGAPPAN/0000-0002-5839-4589 FU Fundamental Research Grant Scheme (FRGS), Ministry of Higher Education (MOHE), Malaysia [9003-00341]; Ministry of Science, Technology and Innovation (MOSTI), Malaysia [9005-00053] FX This research is supported by the Fundamental Research Grant Scheme (FRGS), Ministry of Higher Education (MOHE), Malaysia. Grant number: 9003-00341 and Ministry of Science, Technology and Innovation (MOSTI), Malaysia. Grant number: 9005-00053. 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Eng. Online PD MAY 16 PY 2013 VL 12 AR 44 DI 10.1186/1475-925X-12-44 PG 18 WC Engineering, Biomedical SC Engineering GA 161KS UT WOS:000320192400001 PM 23680041 ER PT J AU Buxbaum, JD Baron-Cohen, S AF Buxbaum, Joseph D. Baron-Cohen, Simon TI DSM-5: the debate continues SO MOLECULAR AUTISM LA English DT Editorial Material AB We are fortunate to have invited commentaries from the laboratories of Dr Cathy Lord and Dr Fred Volkmar offering their perspectives on the new Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for the autism spectrum. Both commentaries note how DSM-5 collapses the earlier diagnostic categories of the pervasive developmental disorders into a single category of autism spectrum disorder. In addition, DSM-5 collapses social and communication domains into a single combined domain. The commentaries go on to discuss the positive aspects of these changes and raise some areas of potential concern. We support the evidence-based changes to autism diagnosis found in DSM-5, and look forward to further studies on the autism phenotype as this has implications for diagnosis and treatment. As our mechanistic understanding of autism improves, diagnoses based on behavioral parameters will continue to provide opportunities for interventions targeting the behaviors, while etiological diagnoses will provide opportunities for interventions tailored to etiology. C1 [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Seaver Autism Ctr Res & Treatment, Dept Psychiat, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Seaver Autism Ctr Res & Treatment, Dept Neurosci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Seaver Autism Ctr Res & Treatment, Dept Genet & Genom Sci, New York, NY 10029 USA. [Baron-Cohen, Simon] Univ Cambridge, Autism Res Ctr, Cambridge CB2 8AH, England. RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, Seaver Autism Ctr Res & Treatment, Dept Psychiat, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu; sb205@cam.ac.uk NR 0 TC 5 Z9 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2040-2392 J9 MOL AUTISM JI Mol. Autism PD MAY 15 PY 2013 VL 4 AR 11 DI 10.1186/2040-2392-4-11 PG 2 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 254VC UT WOS:000327195500001 PM 23676181 ER PT J AU Grzadzinski, R Huerta, M Lord, C AF Grzadzinski, Rebecca Huerta, Marisela Lord, Catherine TI DSM-5 and autism spectrum disorders (ASDs): an opportunity for identifying ASD subtypes SO MOLECULAR AUTISM LA English DT Review ID PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC INTERVIEW; ASPERGER-SYNDROME; YOUNG-CHILDREN; LANGUAGE IMPAIRMENT; EARLY-CHILDHOOD; SENSORY ABNORMALITIES; GENETIC INFLUENCES; PDD-NOS; POPULATION AB The heterogeneous clinical presentations of individuals with autism spectrum disorders (ASDs) poses a significant challenge for sample characterization and limits the interpretability and replicability of research studies. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnostic criteria for ASD, with its dimensional approach, may be a useful framework to increase the homogeneity of research samples. In this review, we summarize the revisions to the diagnostic criteria for ASD, briefly highlight the literature supporting these changes, and illustrate how DSM-5 can improve sample characterization and provide opportunities for researchers to identify possible subtypes within ASD. C1 [Grzadzinski, Rebecca; Huerta, Marisela; Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Dev Brain, New York, NY USA. [Grzadzinski, Rebecca; Huerta, Marisela; Lord, Catherine] New York Presbyterian Hosp, Westchester Div, New York, NY USA. [Grzadzinski, Rebecca] Columbia Univ, Teachers Coll, New York, NY 10027 USA. RP Grzadzinski, R (reprint author), Weill Cornell Med Coll, Ctr Autism & Dev Brain, New York, NY USA. 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Autism PD MAY 15 PY 2013 VL 4 AR 12 DI 10.1186/2040-2392-4-12 PG 6 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 254VC UT WOS:000327195500002 PM 23675638 ER PT J AU Volkmar, FR Reichow, B AF Volkmar, Fred R. Reichow, Brian TI Autism in DSM-5: progress and challenges SO MOLECULAR AUTISM LA English DT Review DE Autism spectrum disorders; diagnosis; DSM-IV; DSM-5 ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDER; DIAGNOSTIC-CRITERIA; FIELD TRIALS; IV-TR; CLASSIFICATION; SPECIFICITY; SENSITIVITY AB Background: Since Kanner's first description of autism there have been a number of changes in approaches to diagnosis with certain key continuities. Since the Fourth edition of the Diagnostic and Statistical Manual (DSM-IV) appeared in 1994 there has been an explosion in research publications. The advent of changes in DSM-5 presents some important moves forward as well as some potential challenges. Methods: The various relevant studies are summarized. Results: If research diagnostic instruments are available, many (but not all) cases with a DSM-IV diagnosis of autism continue to have this diagnosis. The overall efficiency of this system falls if only one source of information is available and, particularly, if the criteria are used outside the research context. The impact is probably greatest among the most cognitively able cases and those with less classic autism presentations. Conclusions: Significant discontinuities in diagnostic practice raise significant problems for both research and clinical services. For DSM-5, the impact of these changes remains unclear. C1 [Volkmar, Fred R.; Reichow, Brian] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA. RP Volkmar, FR (reprint author), Yale Univ, Sch Med, Ctr Child Study, POB 207900, New Haven, CT 06520 USA. EM fred.volkmar@yale.edu FU NIMH [P50 MH081756] FX FRV was supported by NIMH P50 MH081756. 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Autism PD MAY 15 PY 2013 VL 4 AR 13 DI 10.1186/2040-2392-4-13 PG 6 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 254VC UT WOS:000327195500003 PM 23675688 ER PT J AU Ueda, S Negishi, M Katoh, H AF Ueda, Shuhei Negishi, Manabu Katoh, Hironori TI Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SMALL GTPASES; ARP2/3 COMPLEX; CELL-MIGRATION; NMDA RECEPTOR; RHO GTPASES; ACTIN; AUTISM; MORPHOGENESIS; SCHIZOPHRENIA; MAINTENANCE AB In neuronal development, dendritic spine formation is important for the establishment of excitatory synaptic connectivity and functional neural circuits. Developmental deficiency in spine formation results in multiple neuropsychiatric disorders. Dock4, a guanine nucleotide exchange factor (GEF) for Rac, has been reported as a candidate genetic risk factor for autism, dyslexia, and schizophrenia. We previously showed that Dock4 is expressed in hippocampal neurons. However, the functions of Dock4 in hippocampal neurons and the underlying molecular mechanisms are poorly understood. Here we show that Dock4 is highly concentrated in dendritic spines and implicated in spine formation via interaction with the actin-binding protein cortactin. In cultured neurons, short hairpin RNA (shRNA)-mediated knockdown of Dock4 reduces dendritic spine density, which is rescued by coexpression of shRNA-resistant wild-type Dock4 but not by a GEF-deficient mutant of Dock4 or a truncated mutant lacking the cortactin-binding region. On the other hand, knockdown of cortactin suppresses Dock4-mediated spine formation. Taken together, the results show a novel and functionally important interaction between Dock4 and cortactin for regulating dendritic spine formation via activation of Rac. C1 [Ueda, Shuhei; Negishi, Manabu; Katoh, Hironori] Kyoto Univ, Grad Sch Biostudies, Mol Neurobiol Lab, Sakyo Ku, Kyoto 6068501, Japan. RP Katoh, H (reprint author), Kyoto Univ, Grad Sch Biostudies, Mol Neurobiol Lab, Sakyo Ku, Kyoto 6068501, Japan. EM hirokato@pharm.kyoto-u.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan [23370085, 23390019, 24659031, 236767] FX We thank M. Matsuda for the Dock180 expression plasmid and J. Miyazaki and T. Saito for the EYFP expression plasmid. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan: Scientific Research (B) 23370085 (to H.K.), 23390019 (to M.N.), Challenging Exploratory Research 24659031 (to H.K.), and Research Fellowship for Young Scientists (DC) 236767 (to S.U.). 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Biol. Cell PD MAY 15 PY 2013 VL 24 IS 10 BP 1602 EP 1613 DI 10.1091/mbc.E12-11-0782 PG 12 WC Cell Biology SC Cell Biology GA 174ZS UT WOS:000321198700010 PM 23536706 ER PT J AU Dinsdale, NL Hurd, PL Wakabayashi, A Elliot, M Crespi, BJ AF Dinsdale, Natalie L. Hurd, Peter L. Wakabayashi, Akio Elliot, Mick Crespi, Bernard J. TI How Are Autism and Schizotypy Related? Evidence from a Non-Clinical Population SO PLOS ONE LA English DT Article ID SPECTRUM QUOTIENT AQ; HIGH-FUNCTIONING AUTISM; GENERAL-POPULATION; MAGICAL IDEATION; MIXED-HANDEDNESS; HAND PREFERENCE; SEX-DIFFERENCES; SOCIAL BRAIN; SCHIZOPHRENIA; DISORDERS AB Both autism spectrum conditions (ASCs) and schizophrenia spectrum conditions (SSCs) involve altered or impaired social and communicative functioning, but whether these shared features indicate overlapping or different etiological factors is unknown. We outline three hypotheses (overlapping, independent, and diametric) for the possible relationship between ASCs and SSCs, and compare their predictions for the expected relationships between autistic and schizotypal phenotypes using the Autism Spectrum Quotient and the Schizotypal Personality Questionnaire-Brief Revised from a large non-clinical sample of undergraduate students. Consistent with previous research, autistic features were positively associated with several schizotypal features, with the most overlap occurring between interpersonal schizotypy and autistic social and communication phenotypes. The first component of a principal components analysis (PCA) of subscale scores reflected these positive correlations, and suggested the presence of an axis (PC1) representing general social interest and aptitude. By contrast, the second principal component (PC2) exhibited a pattern of positive and negative loadings indicative of an axis from autism to positive schizotypy, such that positive schizotypal features loaded in the opposite direction to core autistic features. These overall PCA patterns were replicated in a second data set from a Japanese population. To evaluate the validity of our interpretation of the PCA results, we measured handedness and mental rotation ability, as these are established correlates of SSCs and ASCs, respectively. PC2 scores were significantly associated with hand preference, such that increasingly 'schizotypal' scores predicted reduced strength of handedness, which is consistent with previous research. PC1 scores were positively related to performance on the mental rotation task, suggesting trade-offs between social skills and visual-spatial ability. These results provide novel evidence for an autism-positive schizotypy axis, and highlight the importance of recognizing that psychological variation involving reduced social interest and functioning may have diverse causes. C1 [Dinsdale, Natalie L.; Elliot, Mick; Crespi, Bernard J.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Hurd, Peter L.] Univ Alberta, Edmonton, AB, Canada. [Wakabayashi, Akio] Chiba Univ, Chiba, Japan. RP Crespi, BJ (reprint author), Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. EM crespi@sfu.ca RI Hurd, Peter/A-4342-2009 OI Hurd, Peter/0000-0002-4389-0846 FU NSERC [31-611569] FX This research was funded by NSERC Discovery Grant 31-611569 (www.nserc-crsng.gc.ca/index_eng.asp). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Quach, Susan Dao, Huy Hao Kwong, Jeffrey C. Deeks, Shelley L. Crowcroft, Natasha S. Quan, Sherman D. Guay, Maryse CA Public Hlth Agcy Canada Canadian I Evaluation Grp TI Contagious Comments: What Was the Online Buzz About the 2011 Quebec Measles Outbreak? SO PLOS ONE LA English DT Article ID VACCINATION AB Background: Although interruption of endemic measles was achieved in the Americas in 2002, Quebec experienced an outbreak in 2011 of 776 reported cases; 80% of these individuals had not been fully vaccinated. We analyzed readers' online responses to Canadian news articles regarding the outbreak to better understand public perceptions of measles and vaccination. Methods: We searched Canadian online English and French news sites for articles posted between April 2011 and March 2012 containing the words "measles" and "Quebec". We included articles that i) concerned the outbreak or related vaccination strategies; and ii) generated at least ten comments. Two English and two bilingual researchers coded the unedited comments, categorizing codes to allow themes to emerge. Results: We analyzed 448 comments from 188 individuals, in response to three French articles and six English articles; 112 individuals expressed positive perceptions of measles vaccination (2.2 comments/person), 38 were negative (4.2 comments/person), 11 had mixed feelings (1.5 comments/person), and 27 expressed no opinion (1.1 comments/person). Vaccine-supportive themes involved the success of vaccination in preventing disease spread, societal responsibility to vaccinate for herd immunity, and refutation of the autism link. Those against measles vaccination felt it was a personal rather than societal choice, and conveyed a distrust of vaccine manufacturers, believing that measles infection is not only safe but safer than vaccination. Commenters with mixed feelings expressed uncertainty of the infection's severity, and varied in support of all vaccines based on perceived risk/benefit ratios. Conclusion: The anti-vaccine minority's volume of comments translates to a disproportionately high representation on online boards. Public health messages should address concerns by emphasizing that immunization is always a personal choice in Canada, and that the pharmaceutical industry is strictly controlled. Illustrating the dangers of measles through personal stories, rather than scientific data only, may also serve to strengthen messaging. C1 [Pereira, Jennifer A.; Quach, Susan; Kwong, Jeffrey C.; Deeks, Shelley L.; Crowcroft, Natasha S.] Publ Hlth Ontario, Toronto, ON, Canada. [Dao, Huy Hao; Guay, Maryse] Univ Sherbrooke, Dept Sci Sante Communautaire, Longueuil, PQ, Canada. [Kwong, Jeffrey C.; Deeks, Shelley L.; Crowcroft, Natasha S.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Kwong, Jeffrey C.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Kwong, Jeffrey C.] Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada. [Kwong, Jeffrey C.; Quan, Sherman D.] Univ Hlth Network, Toronto, ON, Canada. [Crowcroft, Natasha S.] Univ Toronto, Lab Med & Pathobiol, Toronto, ON, Canada. [Guay, Maryse] Inst Natl Sante Publ Quebec, Longueuil, PQ, Canada. [Guay, Maryse] Ctr Rech Hop Charles LeMoyne, Longueuil, PQ, Canada. RP Pereira, JA (reprint author), Publ Hlth Ontario, Toronto, ON, Canada. EM jennifer.pereira@oahpp.ca FU Public Health Agency of Canada; Canadian Institutes of Health Research; Public Health Ontario FX The Canadian Association for Immunization Research and Evaluation provided networking assistance. The Public Health Agency of Canada, the Canadian Institutes of Health Research, and the Public Health Ontario provided funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Here we show that EPAC binds directly to the intracellular loop of an ATP-sensitive potassium (K-ATP) channel type-1 sulfonylurea receptor (SUR1) receptor consisting of amino acids 859-881 (SUR1(859-881)). Ablation of EPAC or expression of SUR1(859-881), which intercepts EPAC-SUR1 binding, increases the open probability of K-ATP channels consisting of the Kir6.1 subunit and SUR1. Opening of K-ATP channels inhibits glutamate release and reduces seizure vulnerability in adult mice. Therefore, EPAC interaction with SUR1 controls seizure susceptibility and possibly acts via regulation of glutamate release. C1 [Zhao, Kunpeng; Wen, Ruojian; Wang, Xiaoxi; Pei, Lei; Yang, Ying; Zhu, Ling-Qiang; Tian, Qing; Lu, Youming] Huazhong Univ Sci & Technol, Tongji Med Coll, Key Lab Neurol Dis, Minist Educ, Wuhan 430030, Peoples R China. [Shang, You; Lu, Youming] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Translat Res Ctr, Wuhan 430022, Peoples R China. [Yang, Ying; Bazan, Nicolas; Lu, Youming] Louisiana State Univ, Sch Med, Neurosci Ctr Excellence, New Orleans, LA 70112 USA. [Yang, Ying; Bazan, Nicolas; Lu, Youming] Louisiana State Univ, Sch Med, Dept Neurol, New Orleans, LA 70112 USA. RP Zhu, LQ (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Key Lab Neurol Dis, Minist Educ, Wuhan 430030, Peoples R China. EM zhulq@mail.hust.edu.cn; tianq@mail.hust.edu.cn; lym@mail.hust.edu.cn FU National Natural Science Foundation of China [81130079, 91232302, 81200863, 81271404]; New Century Excellent Talent [NCET-10-0241]; Ministry of Science and Technology of China [2011DFG33250]; National Institute on Aging-National Institutes of Health [R01AG033282] FX This work was supported by National Natural Science Foundation of China (Grants 81130079 and 91232302 to Y.L., 81200863 to L.P., and 81271404 to Q.T.), New Century Excellent Talent (Grant NCET-10-0241 to L.-Q.Z.), Ministry of Science and Technology of China (Grant 2011DFG33250 to L.-Q.Z.), and the National Institute on Aging-National Institutes of Health (Grant R01AG033282 to Y.L.). 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Here, we show evidence of upregulated proteasome activity in PHTS-derived lymphoblasts, Pten knock-in mice and cell lines expressing missense and nonsense PTEN mutations. Notably, elevated nuclear proteasome activity occurred in cells expressing the nuclear mislocalized PTEN-K62R mutant, whereas elevated cytosolic proteasome activity was observed in cells expressing the cytosolic-predominant mutant PTEN (M3M4 and C136R). Treatment with proteasome inhibitor MG-132 was able to restore both nonsense and missense mutant PTEN protein levels in vitro. PHTS patients with destabilizing PTEN mutations and proteasome hyperactivity are more susceptible to develop neurologic symptoms such as mental retardation and autism than mutation-positive patients with normal proteasome activity. A detailed molecular and functional analysis shows that PTEN mutants most likely cause proteasome hyperactivity via 2 different mechanisms, namely, induction of proteotoxic stress and loss of protein phosphatase activity. These results provide novel insights into the cellular functions of PTEN and reveal molecular mechanisms whereby PTEN mutations increase proteasome activity and lead to neurologic phenotypes. Cancer Res; 73(10); 3029-40. (C) 2013 AACR. C1 [He, Xin; Arrotta, Nicholas; Radhakrishnan, Deepa; Wang, Yu; Romigh, Todd; Eng, Charis] Cleveland Clin, Genom Med Inst, Cleveland, OH 44195 USA. [Eng, Charis] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44195 USA. [Eng, Charis] Cleveland Clin, Stanley Shalom Zielony Inst Nursing Excellence, Cleveland, OH 44195 USA. [Eng, Charis] Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, Cleveland, OH USA. [Eng, Charis] Case Western Reserve Univ, Sch Med, CASE Comprehens Canc Ctr, Cleveland, OH USA. 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BTBR-T(+)tf/J (BTBR) mice, a mouse strain with behaviors that resemble autism and with elevated levels of anti-brain antibodies (Abs), have enhanced activation of peripheral B cells and CD4(+) T cells and an expanded percentage of CD4(+) T cells expressing V(beta)6 chains. The CD4(+)CD25(+)V(beta)6(+) and V(beta)6-splenic cells of BTBR mice have elevated levels of IL-4, IFN-gamma and IL-17, but there appears to be no preferential CD4(+) T subset skewing/polarization. The high level of IgG production by BTBR B cells was dependent on T cells from BTBR mice. The CD4(+) T cells of BTBR mice, especially those expressing V(beta)6 become spontaneously activated and expanded in an autoimmune-like manner, which occurred in both BTBR and B6 hosts that received an equal number of BTBR and B6 bone marrow cells. BTBR mice also have an elevated percentage of peripheral blood neutrophils, which may represent their elevated inflammatory state. B6 offspring derived from B6 dams that were gestationally injected with purified IgG from sera of BTBR mice, but not IgG of B6 mice, developed significantly impaired social behavior. Additionally, B6 offspring that developed in BTBR dams had impaired social behavior, while BTBR offspring that developed in B6 dams had improved social behavior. All of the immunological and behavioral parameters of BTBR mice were compared with those of B6 mice, which have relatively normal behaviors. The results indicate maternal Abs and possibly other maternal influences affect the social behavior of offspring. (C) 2013 Elsevier B.V. All rights reserved. C1 [Zhang, Yubin; Gao, Donghong; Kluetzman, Kerri; Mendoza, Alvaro; Bolivar, Valerie J.; Reilly, Andrew; Jolly, Jane K.; Lawrence, David A.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12208 USA. [Zhang, Yubin; Bolivar, Valerie J.; Lawrence, David A.] SUNY Albany, Sch Publ Hlth, Albany, NY 12208 USA. 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Neuroimmunol. PD MAY 15 PY 2013 VL 258 IS 1-2 BP 51 EP 60 DI 10.1016/j.jneuroim.2013.02.019 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 143AC UT WOS:000318837700007 PM 23537887 ER PT J AU Iqbal, Z Vandeweyer, G van der Voet, M Waryah, AM Zahoor, MY Besseling, JA Roca, LT Vulto-van Silfhout, AT Nijhof, B Kramer, JM Van der Aa, N Ansar, M Peeters, H Helsmoortel, C Gilissen, C Vissers, LELM Veltman, JA de Brouwer, APM Kooy, RF Riazuddin, S Schenck, A van Bokhoven, H Rooms, L AF Iqbal, Zafar Vandeweyer, Geert van der Voet, Monique Waryah, Ali Muhammad Zahoor, Muhammad Yasir Besseling, Judith A. Roca, Laura Tomas Vulto-van Silfhout, Anneke T. Nijhof, Bonnie Kramer, Jamie M. Van der Aa, Nathalie Ansar, Muhammad Peeters, Hilde Helsmoortel, Celine Gilissen, Christian Vissers, Lisenka E. L. M. Veltman, Joris A. de Brouwer, Arjan P. M. Kooy, R. Frank Riazuddin, Sheikh Schenck, Annette van Bokhoven, Hans Rooms, Liesbeth TI Homozygous and heterozygous disruptions of ANK3: at the crossroads of neurodevelopmental and psychiatric disorders SO HUMAN MOLECULAR GENETICS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; GENOME-WIDE ASSOCIATION; MENTAL-RETARDATION; BIPOLAR DISORDER; AXONAL LOCALIZATION; MEMORY DEFICITS; CELL-ADHESION; AUTISM; DROSOPHILA AB AnkyrinG, encoded by the ANK3 gene, is involved in neuronal development and signaling. It has previously been implicated in bipolar disorder and schizophrenia by association studies. Most recently, de novo missense mutations in this gene were identified in autistic patients. However, the causative nature of these mutations remained controversial. Here, we report inactivating mutations in the Ankyrin 3 (ANK3) gene in patients with severe cognitive deficits. In a patient with a borderline intelligence, severe attention deficit hyperactivity disorder (ADHD), autism and sleeping problems, all isoforms of the ANK3 gene, were disrupted by a balanced translocation. Furthermore, in a consanguineous family with moderate intellectual disability (ID), an ADHD-like phenotype and behavioral problems, we identified a homozygous truncating frameshift mutation in the longest isoform of the same gene, which represents the first reported familial mutation in the ANK3 gene. The causality of ANK3 mutations in the two families and the role of the gene in cognitive function were supported by memory defects in a Drosophila knockdown model. Thus we demonstrated that ANK3 plays a role in intellectual functioning. In addition, our findings support the suggested association of ANK3 with various neuropsychiatric disorders and illustrate the genetic and molecular relation between a wide range of neurodevelopmental disorders. C1 [Iqbal, Zafar; van der Voet, Monique; Besseling, Judith A.; Roca, Laura Tomas; Vulto-van Silfhout, Anneke T.; Nijhof, Bonnie; Kramer, Jamie M.; Ansar, Muhammad; Gilissen, Christian; Vissers, Lisenka E. L. M.; Veltman, Joris A.; de Brouwer, Arjan P. M.; Schenck, Annette; van Bokhoven, Hans] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Iqbal, Zafar; van der Voet, Monique; Besseling, Judith A.; Roca, Laura Tomas; Nijhof, Bonnie; Kramer, Jamie M.; Schenck, Annette; van Bokhoven, Hans] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, NL-6525 ED Nijmegen, Netherlands. [Iqbal, Zafar; van der Voet, Monique; Besseling, Judith A.; Roca, Laura Tomas; Nijhof, Bonnie; Kramer, Jamie M.; Schenck, Annette; van Bokhoven, Hans] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [de Brouwer, Arjan P. M.] Radboud Univ Nijmegen, Med Ctr, Inst Genet & Metab Dis, NL-6525 ED Nijmegen, Netherlands. [Vandeweyer, Geert; Van der Aa, Nathalie; Helsmoortel, Celine; Kooy, R. Frank; Rooms, Liesbeth] Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium. [Vandeweyer, Geert; Van der Aa, Nathalie; Helsmoortel, Celine; Kooy, R. Frank; Rooms, Liesbeth] Univ Antwerp Hosp, Antwerp, Belgium. [Waryah, Ali Muhammad; Zahoor, Muhammad Yasir; Ansar, Muhammad; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. [Waryah, Ali Muhammad; Zahoor, Muhammad Yasir; Riazuddin, Sheikh] Allama Iqbal Med Coll, Lahore 54550, Pakistan. [Waryah, Ali Muhammad] Liaquat Univ Med & Hlth Sci, Mol Biol & Genet Dept, Med Res Ctr, Jamshoro, Pakistan. [Ansar, Muhammad] King Edward Med Univ, Adv Ctr Biomed Sci, Lahore, Pakistan. [Peeters, Hilde] Katholieke Univ Leuven Hosp, Ctr Human Genet, Louvain, Belgium. RP Schenck, A (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. EM A.Schenck@gen.umcn.nl; H.vanBokhoven@gen.umcn.nl; liesbeth.rooms@ua.ac.be RI Gilissen, Christian/E-5246-2012; Schenck, Annette/E-4514-2012; Vissers, Lisenka/A-2598-2015; Veltman, Joris/F-5128-2010; van der Voet, Monique/F-5772-2012 OI Gilissen, Christian/0000-0003-1693-9699; Schenck, Annette/0000-0002-6918-3314; van der Voet, Monique/0000-0002-8829-1767 FU European Union [241995]; project GENCODYS; Dutch Brain Foundation [2010(1)-30]; brain and cognition excellence program [433-09-229]; Netherlands Organization for Health Research and Development (ZonMW) [VIDI 917-96-346]; Belgian Nation Fund for Scientific Research - Flanders (FWO); Marguerite-Marie Delacroix foundation; Higher Education Commission (HEC), Islamabad, Pakistan FX This work was supported by the European Union's Seventh Framework Program (grant agreement number 241995), project GENCODYS (to A. S., S. R. and H. v. B.), by the Dutch Brain Foundation (2010(1)-30 to A.d.B.) and brain and cognition excellence program (433-09-229 to M.v.d.V and A. S.) and by the Netherlands Organization for Health Research and Development (ZonMW; VIDI 917-96-346 to A. S.). This work was further supported by the Belgian Nation Fund for Scientific Research - Flanders (FWO) (to R. F. K., L. R. and N.V.A.) and the Marguerite-Marie Delacroix foundation. Z.I. was supported by Higher Education Commission (HEC), Islamabad, Pakistan. 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Mol. Genet. PD MAY 15 PY 2013 VL 22 IS 10 BP 1960 EP 1970 DI 10.1093/hmg/ddt043 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 139CL UT WOS:000318559000005 PM 23390136 ER PT J AU Natarajan, R Trivedi-Vyas, D Wairkar, YP AF Natarajan, Rajalaxmi Trivedi-Vyas, Deepti Wairkar, Yogesh P. TI Tuberous sclerosis complex regulates Drosophila neuromuscular junction growth via the TORC2/Akt pathway SO HUMAN MOLECULAR GENETICS LA English DT Article ID TUMOR-SUPPRESSOR PROTEINS; MAMMALIAN TARGET; CELL-GROWTH; ACTIVE ZONE; RAPAMYCIN TREATMENT; SYNAPTIC GROWTH; GENE-PRODUCTS; AKT; KINASE; TSC1 AB Mutations in the tuberous sclerosis complex (TSC) are associated with various forms of neurodevelopmental disorders, including autism and epilepsy. The heterodimeric TSC complex, consisting of Tsc1 and Tsc2 proteins, regulates the activity of the TOR (target of rapamycin) complex via Rheb, a small GTPase. TOR, an atypical serine/threonine kinase, forms two distinct complexes TORC1 and TORC2. Raptor and Rictor serve as specific functional components of TORC1 and TORC2, respectively. Previous studies have identified Tsc1 as a regulator of hippocampal neuronal morphology and function via the TOR pathway, but it is unclear whether this is mediated via TORC1 or TORC2. In a genetic screen for aberrant synaptic growth at the neuromuscular junctions (NMJs) in Drosophila, we identified that Tsc2 mutants showed increased synaptic growth. Increased synaptic growth was also observed in rictor mutants, while raptor knockdown did not phenocopy the TSC mutant phenotype, suggesting that a novel role exists for TORC2 in regulating synapse growth. Furthermore, Tsc2 mutants showed a dramatic decrease in the levels of phosphorylated Akt, and interestingly, Akt mutants phenocopied Tsc2 mutants, leading to the hypothesis that Tsc2 and Akt might work via the same genetic pathway to regulate synapse growth. Indeed, transheterozygous analysis of Tsc2 and Akt mutants confirmed this hypothesis. Finally, our data also suggest that while overexpression of rheb results in aberrant synaptic overgrowth, the overgrowth might be independent of TORC2. Thus, we propose that at the Drosophila NMJ, TSC regulates synaptic growth via the TORC2-Akt pathway. C1 [Wairkar, Yogesh P.] Univ Texas Med Branch, Dept Neurol, Galveston, TX 77555 USA. Univ Texas Med Branch, George & Cynthia Mitchell Ctr Neurodegenerat Dis, Galveston, TX 77555 USA. RP Wairkar, YP (reprint author), Univ Texas Med Branch, Dept Neurol, Rte 1045,301 Univ Blvd, Galveston, TX 77555 USA. EM yowairka@utmb.edu FU University of Texas system; University of Texas Medical Branch FX This project was started in the laboratory of Aaron DiAntonio at the Washington University Medical School. A STARS award from the University of Texas system and startup funds from the University of Texas Medical Branch to Y.P.W. supported this work. We would like to thank the fly stock center at Bloomington for the flies used in this study and Dr(s) Jongkyeong Chung and Tian Xu for the gift of rictor mutant flies and raptor RNAi lines and UAS-gig lines. We thank the Hybridoma Bank at University of Iowa for many antibodies used in this study and Aaron DiAntonio, Ben Eaton, Cathy Collins, George Jackson, Rakez Kayed, N. Muge Kuyumcu-Martinez and Shreyasi Chatterjee for critical reading of the manuscript. We also wish to thank Xiaolu Sun, Lhia Dolores and Shramika Adhikary for their excellent technical help. 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Mol. Genet. PD MAY 15 PY 2013 VL 22 IS 10 BP 2010 EP 2023 DI 10.1093/hmg/ddt053 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 139CL UT WOS:000318559000009 PM 23393158 ER PT J AU Lionel, AC Vaags, AK Sato, D Gazzellone, MJ Mitchell, EB Chen, HY Costain, G Walker, S Egger, G Thiruvahindrapuram, B Merico, D Prasad, A Anagnostou, E Fombonne, E Zwaigenbaum, L Roberts, W Szatmari, P Fernandez, BA Georgieva, L Brzustowicz, LM Roetzer, K Kaschnitz, W Vincent, JB Windpassinger, C Marshall, CR Trifiletti, RR Kirmani, S Kirov, G Petek, E Hodge, JC Bassett, AS Scherer, SW AF Lionel, Anath C. Vaags, Andrea K. Sato, Daisuke Gazzellone, Matthew J. Mitchell, Elyse B. Chen, Hong Yang Costain, Gregory Walker, Susan Egger, Gerald Thiruvahindrapuram, Bhooma Merico, Daniele Prasad, Aparna Anagnostou, Evdokia Fombonne, Eric Zwaigenbaum, Lonnie Roberts, Wendy Szatmari, Peter Fernandez, Bridget A. Georgieva, Lyudmila Brzustowicz, Linda M. Roetzer, Katharina Kaschnitz, Wolfgang Vincent, John B. Windpassinger, Christian Marshall, Christian R. Trifiletti, Rosario R. Kirmani, Salman Kirov, George Petek, Erwin Hodge, Jennelle C. Bassett, Anne S. Scherer, Stephen W. TI Rare exonic deletions implicate the synaptic organizer Gephyrin (GPHN) in risk for autism, schizophrenia and seizures SO HUMAN MOLECULAR GENETICS LA English DT Article ID MOLYBDENUM COFACTOR DEFICIENCY; SCAFFOLDING PROTEIN SHANK3; TEMPORAL-LOBE EPILEPSY; COPY NUMBER VARIATION; SPECTRUM DISORDERS; MENTAL-RETARDATION; MOLECULAR CHARACTERIZATION; PSYCHIATRIC-DISORDERS; BIPOLAR DISORDER; CANDIDATE GENES AB The GPHN gene codes for gephyrin, a key scaffolding protein in the neuronal postsynaptic membrane, responsible for the clustering and localization of glycine and GABA receptors at inhibitory synapses. Gephyrin has well-established functional links with several synaptic proteins that have been implicated in genetic risk for neurodevelopmental disorders such as autism spectrum disorder (ASD), schizophrenia and epilepsy including the neuroligins (NLGN2, NLGN4), the neurexins (NRXN1, NRXN2, NRXN3) and collybistin (ARHGEF9). Moreover, temporal lobe epilepsy has been linked to abnormally spliced GPHN mRNA lacking exons encoding the G-domain of the gephyrin protein, potentially arising due to cellular stress associated with epileptogenesis such as temperature and alkalosis. Here, we present clinical and genomic characterization of six unrelated subjects, with a range of neurodevelopmental diagnoses including ASD, schizophrenia or seizures, who possess rare de novo or inherited hemizygous microdeletions overlapping exons of GPHN at chromosome 14q23.3. The region of common overlap across the deletions encompasses exons 35, corresponding to the G-domain of the gephyrin protein. These findings, together with previous reports of homozygous GPHN mutations in connection with autosomal recessive molybdenum cofactor deficiency, will aid in clinical genetic interpretation of the GPHN mutation spectrum. Our data also add to the accumulating evidence implicating neuronal synaptic gene products as key molecular factors underlying the etiologies of a diverse range of neurodevelopmental conditions. C1 [Lionel, Anath C.; Vaags, Andrea K.; Sato, Daisuke; Gazzellone, Matthew J.; Mitchell, Elyse B.; Chen, Hong Yang; Walker, Susan; Thiruvahindrapuram, Bhooma; Merico, Daniele; Prasad, Aparna; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada. [Lionel, Anath C.; Vaags, Andrea K.; Sato, Daisuke; Gazzellone, Matthew J.; Chen, Hong Yang; Walker, Susan; Thiruvahindrapuram, Bhooma; Merico, Daniele; Prasad, Aparna; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1L7, Canada. [Lionel, Anath C.; Gazzellone, Matthew J.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1L7, Canada. [Lionel, Anath C.; Gazzellone, Matthew J.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5G 1L7, Canada. [Costain, Gregory; Bassett, Anne S.] Ctr Addict & Mental Hlth, Neurogenet Sect, Clin Genet Res Program, Toronto, ON M5S 2S1, Canada. [Egger, Gerald; Vincent, John B.] Ctr Addict & Mental Hlth, Neurogenet Sect, Mol Neuropsychiat & Dev Lab, Toronto, ON M5S 2S1, Canada. [Anagnostou, Evdokia] Univ Toronto, Bloorview Res Inst, Toronto, ON M4G 1R8, Canada. [Fombonne, Eric] Montreal Childrens Hosp, Dept Psychiat, Montreal, PQ H3Z 1P2, Canada. [Fombonne, Eric] McGill Univ, Montreal, PQ H3Z 1P2, Canada. [Zwaigenbaum, Lonnie] Univ Alberta, Dept Pediat, Edmonton, AB T5G 0B7, Canada. [Roberts, Wendy] Hosp Sick Children, Autism Res Unit, Toronto, ON M5G 1X8, Canada. [Szatmari, Peter] McMaster Univ, Dept Psychiat & Behav Neurosci, Offord Ctr Child Studies, Hamilton, ON L8S 4K1, Canada. [Fernandez, Bridget A.] Mem Univ Newfoundland, Discipline Genet, St John, NF A1B 3V6, Canada. [Fernandez, Bridget A.] Mem Univ Newfoundland, Discipline Med, St John, NF A1B 3V6, Canada. [Vincent, John B.] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada. [Mitchell, Elyse B.; Hodge, Jennelle C.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Kirmani, Salman; Hodge, Jennelle C.] Mayo Clin, Dept Med Genet, Rochester, MN 55905 USA. [Trifiletti, Rosario R.] UMDNJ New Jersey Med Sch, Dept Neurol, Newark, NJ 07101 USA. [Brzustowicz, Linda M.] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA. [Egger, Gerald; Windpassinger, Christian; Petek, Erwin] Med Univ Graz, Inst Human Genet, A-8036 Graz, Austria. [Roetzer, Katharina; Kaschnitz, Wolfgang] Med Univ Graz, Univ Klin Kinder & Jugendheilkunde, A-8036 Graz, Austria. [Georgieva, Lyudmila; Kirov, George] Cardiff Univ, Dept Psychol Med & Neurol, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF14 4XN, S Glam, Wales. RP Scherer, SW (reprint author), Hosp Sick Children, Ctr Appl Genom, MaRS Ctr, East Tower,101 Coll St,Room 14-704, Toronto, ON M5G 1L7, Canada. EM stephen.scherer@sickkids.ca RI Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU NeuroDevNet; University of Toronto McLaughlin Centre; Genome Canada; Ontario Genomics Institute; Canadian Institutes for Health Research (CIHR); Canadian Institute for Advanced Research; Canada Foundation for Innovation; Government of Ontario; Autism Speaks; Hospital for Sick Children Foundation; ONB Jubilaumsfonds [13226]; NeuroDevNet doctoral fellowship; CIHR Autism Training Program; CIHR [MOP-89066, MOP-111238] FX This work was supported by grants from NeuroDevNet, the University of Toronto McLaughlin Centre, Genome Canada and the Ontario Genomics Institute, the Canadian Institutes for Health Research (CIHR), the Canadian Institute for Advanced Research, the Canada Foundation for Innovation, the Government of Ontario, Autism Speaks, The Hospital for Sick Children Foundation and ONB Jubilaumsfonds (Project Number: 13226). The control data sets were obtained, along with permission for use, from the database of Genotype and Phenotype database (dbGaP) found at http://www.ncbi.nlm.nih.gov/gap through accession numbers phs000143.v1.p1 (Starr County Study), phs000091.v2.p1 (GENEVA NHS/HPFS study) and phs000169.v1.p1 (HABC study). A. C. L. holds a NeuroDevNet doctoral fellowship. A. P. was supported by a fellowship from the CIHR Autism Training Program. A.S.B. holds the Canada Research Chair in Schizophrenia Genetics and Genomic Disorders and received funding support from CIHR grants MOP-89066 and MOP-111238. S. W. S. holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children. 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PD MAY 15 PY 2013 VL 22 IS 10 BP 2055 EP 2066 DI 10.1093/hmg/ddt056 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 139CL UT WOS:000318559000012 PM 23393157 ER PT J AU Whitney, J Howe, M Shoemaker, V Li, S Sanders, EM Dijamco, C Acquaye, T Phillips, J Singh, M Chang, K AF Whitney, Jane Howe, Meghan Shoemaker, Virginia Li, Sherrie Sanders, Erica Marie Dijamco, Cheri Acquaye, Tenah Phillips, Jennifer Singh, Manpreet Chang, Kiki TI Socio-emotional processing and functioning of youth at high risk for bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Pediatric bipolar disorder; Bipolar offspring; Social reciprocity; Theory of mind; Affect recognition ID EMOTION LABELING DEFICITS; ANXIETY DISORDERS; SPECTRUM DISORDER; RATING-SCALE; CHILDREN; AUTISM; MOOD; ADOLESCENTS; RELIABILITY; ONSET AB Background: The goal of this study was to investigate differences in socio-emotional processing and functioning in children and adolescents at high risk for bipolar disorder (BD) and healthy control participants. Methods: Children and adolescents with a parent with bipolar disorder, who had mood dysregulation but not fully syndromal BD (high risk, HR, n=24), were compared to participants with no personal or family history of psychopathology (healthy control, HC, n=27) across several neuropsychological domains. Social reciprocity was measured by the Social Responsiveness Scale, theory of mind was measured by use of the NEPSY, and affect recognition was measured by the NEPSY and the Diagnostic Test of Nonverbal Accuracy 2 (DANVA). Results: The HR group demonstrated significant impairment in social reciprocity, including impairments in social awareness, social cognition, social communication, social motivation, and autistic mannerisms. There were no significant group differences in performance on theory of mind or affect recognition tasks. Limitations: Lack of impairment in tasks associated with theory of mind or affect recognition indicate that social functioning difficulties are not likely due to impairments in these areas, or that the measures employed were not sufficiently sensitive to detect group differences. Conclusions: Youth at high risk for BD demonstrated impairments in numerous social domains, which may be due to innate differences in brain development governing socio-emotional functioning or may be due to disruptions in normal development caused by mood regulation difficulties. (C) 2012 Elsevier B.V. All rights reserved. C1 [Whitney, Jane; Howe, Meghan; Shoemaker, Virginia; Li, Sherrie; Sanders, Erica Marie; Dijamco, Cheri; Acquaye, Tenah; Singh, Manpreet; Chang, Kiki] Stanford Univ, Pediat Bipolar Disorders Program, Stanford, CA 94305 USA. [Howe, Meghan; Shoemaker, Virginia; Li, Sherrie; Sanders, Erica Marie; Dijamco, Cheri; Acquaye, Tenah; Phillips, Jennifer; Singh, Manpreet; Chang, Kiki] Stanford Univ, Div Child & Adolescent Psychiat, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Whitney, J (reprint author), 401 Quarry Rd, Stanford, CA 94305 USA. EM jane.whitney@gmail.com FU National Institute of Mental Health [R01 MH077047, K23 MH085919]; Stanford Medical Scholars Fellowship Program; GlaxoSmithKline; Merck FX Funding to support this study was provided by the National Institute of Mental Health (R01 MH077047; K23 MH085919) and the Stanford Medical Scholars Fellowship Program.Dr. Chang is a consultant for GlaxoSmithKline, Eli Lilly and Company, Bristol-Myers Squibb, and Merck; he receives research support from GlaxoSmithKline, Merck, and the National Institute of Mental Health. All other authors declare no conflicts of interest. 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Affect. Disord. PD MAY 15 PY 2013 VL 148 IS 1 BP 112 EP 117 DI 10.1016/j.jad.2012.08.016 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 139DY UT WOS:000318563000016 PM 23123133 ER PT J AU Plon, M AF Plon, Michel TI GET THE BETTER OF AUTISM Parents, these truths which they hide from you SO QUINZAINE LITTERAIRE LA French DT Book Review CR REYFLAUD H, SORTIR AUTISME PAREN NR 1 TC 0 Z9 0 PU QUINZAINE LITTERAIRE PI PARIS PA 135 RUE SAINT-MARTIN, 75194 PARIS, FRANCE SN 0048-6493 J9 QUINZAINE LITTERAIRE JI Quinz. Litt. PD MAY 15 PY 2013 IS 1083 BP 22 EP 23 PG 2 WC Literature SC Literature GA V37HE UT WOS:000209266100024 ER PT J AU Fonville, L Lao-Kaim, NP Giampietro, V Van den Eynde, F Davies, H Lounes, N Andrew, C Dalton, J Simmons, A Williams, SCR Baron-Cohen, S Tchanturia, K AF Fonville, Leon Lao-Kaim, Nick P. Giampietro, Vincent Van den Eynde, Frederique Davies, Helen Lounes, Naima Andrew, Christopher Dalton, Jeffrey Simmons, Andrew Williams, Steven C. R. Baron-Cohen, Simon Tchanturia, Kate TI Evaluation of Enhanced Attention to Local Detail in Anorexia Nervosa Using the Embedded Figures Test; an fMRI Study SO PLOS ONE LA English DT Article ID AUTISM SPECTRUM DISORDERS; GENERIC BRAIN ACTIVATION; EATING-DISORDERS; CENTRAL COHERENCE; COGNITIVE REMEDIATION; EXECUTIVE FUNCTIONS; ASPERGER-SYNDROME; TASK-PERFORMANCE; WEAK COHERENCE; ONSET AB The behavioural literature in anorexia nervosa and autism spectrum disorders has indicated an overlap in cognitive profiles. One such domain is the enhancement of local processing over global processing. While functional imaging studies of autism spectrum disorder have revealed differential neural patterns compared to controls in response to tests of local versus global processing, no studies have explored such effects in anorexia nervosa. This study uses functional magnetic resonance imaging in conjunction with the embedded figures test, to explore the neural correlates of this enhanced attention to detail in the largest anorexia nervosa cohort to date. On the embedded figures tests participants are required to indicate which of two complex figures contains a simple geometrical shape. The findings indicate that whilst healthy controls showed greater accuracy on the task than people with anorexia nervosa, different brain regions were recruited. Healthy controls showed greater activation in the precuneus whilst people with anorexia nervosa showed greater activation in the fusiform gyrus. This suggests that different cognitive strategies were used to perform the task, i.e. healthy controls demonstrated greater emphasis on visuospatial searching and people with anorexia nervosa employed a more object recognition-based approach. This is in accordance with previous findings in autism spectrum disorder using a similar methodology and has implications for therapies addressing the appropriate adjustment of cognitive strategies in anorexia nervosa. C1 [Fonville, Leon; Lao-Kaim, Nick P.; Van den Eynde, Frederique; Davies, Helen; Lounes, Naima; Tchanturia, Kate] Kings Coll London, Inst Psychiat, Dept Psychol Med, London WC2R 2LS, England. [Giampietro, Vincent; Andrew, Christopher; Dalton, Jeffrey; Simmons, Andrew; Williams, Steven C. R.] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London WC2R 2LS, England. [Simmons, Andrew; Williams, Steven C. R.] South London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, London WC2R 2LS, England. [Simmons, Andrew; Williams, Steven C. R.] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England. [Van den Eynde, Frederique] McGill Univ, Dept Psychiat, Douglas Univ Inst, Eating Disorders Program, Montreal, PQ, Canada. RP Tchanturia, K (reprint author), Kings Coll London, Inst Psychiat, Dept Psychol Med, London WC2R 2LS, England. EM kate.tchanturia@kcl.ac.uk RI Giampietro, Vincent/D-1279-2011; Williams, Steve/D-6979-2011; Simmons, Andrew/B-8848-2008 OI Giampietro, Vincent/0000-0002-9381-8201; Simmons, Andrew/0000-0003-2306-5811 FU Swiss Anorexia Foundation; Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London FX This work was supported by the Swiss Anorexia Foundation and the Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Rubin, Robert A. Natowicz, Marvin R. TI Patterning of Regional Gene Expression in Autism: New Complexity SO SCIENTIFIC REPORTS LA English DT Article ID LISTS AB Autism is a common and often severe neurodevelopmental disorder for which diverse pathophysiological processes have been proposed. Recent gene expression data comparing autistic and control brains suggest that the normal differential gene expression between frontal and temporal cortex is attenuated in autistic brains. It is unknown if regional de-differentiation occurs elsewhere in autistic brain. Using high resolution, genome-wide RNA expression microarrays and brain specimens meeting stringent selection criteria we evaluated gene expression data of two other regions: Brodmann area 19 (occipital cortex) and cerebellar cortex. In contrast to frontal/temporal cortical data, our data do not indicate an attenuation of regional specialization between occipital and cerebellar cortical regions in autistic brains. 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Jones, Nicola Hanley, Mary TI Spontaneous and cued gaze-following in autism and Williams syndrome SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Williams syndrome; Autism; Gaze behavior; Social attention; Social cognition ID TRACKING EYE-MOVEMENTS; SPECTRUM DISORDERS; YOUNG-CHILDREN; ATTENTION; INDIVIDUALS; FACES; PERCEPTION; COMPETENCE; PREVALENCE; DIRECTION AB Background: From a young age the typical development of social functioning relies upon the allocation of attention to socially relevant information, which in turn allows experience at processing such information and thus enhances social cognition. As such, research has attempted to identify the developmental processes that are derailed in some neuro-developmental disorders that impact upon social functioning. Williams syndrome (WS) and autism are disorders of development that are characterized by atypical yet divergent social phenotypes and atypicalities of attention to people. Methods: We used eye tracking to explore how individuals with WS and autism attended to, and subsequently interpreted, an actor's eye gaze cue within a social scene. Images were presented for 3 seconds, initially with an instruction simply to look at the picture. The images were then shown again, with the participant asked to identify the object being looked at. Allocation of eye gaze in each condition was analyzed by analysis of variance and accuracy of identification was compared with t tests. Results: Participants with WS allocated more gaze time to face and eyes than their matched controls, both with and without being asked to identify the item being looked at; while participants with autism spent less time on face and eyes in both conditions. When cued to follow gaze, participants with WS increased gaze to the correct targets; those with autism looked more at the face and eyes but did not increase gaze to the correct targets, while continuing to look much more than their controls at implausible targets. Both groups identified fewer objects than their controls. Conclusions: The atypicalities found are likely to be entwined with the deficits shown in interpreting social cognitive cues from the images. WS and autism are characterized by atypicalities of social attention that impact upon socio-cognitive expertise, but, importantly, the type of atypicality is syndrome specific. C1 [Riby, Deborah M.] Newcastle Univ, Sch Psychol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Hancock, Peter J. B.] Univ Stirling, Sch Nat Sci, Stirling FK9 4LA, Scotland. [Jones, Nicola] Northumbria Univ, Dept Psychol, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England. [Hanley, Mary] Queens Univ Belfast, Sch Psychol, Belfast BT7 1NN, Antrim, North Ireland. RP Hancock, PJB (reprint author), Univ Stirling, Sch Nat Sci, Stirling FK9 4LA, Scotland. EM pjbh1@stir.ac.uk RI Hancock, Peter/A-4633-2009 OI Hancock, Peter/0000-0001-6025-7068 FU Economic & Social Research Council [R000222030]; Nuffield Foundation FX This work was supported by a funding from the Economic & Social Research Council (R000222030) to PJBH and DMR and from the Nuffield Foundation to DMR. 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TI Convergent dysregulation of frontal cortical cognitive and reward systems in eating disorders SO MEDICAL SCIENCE MONITOR LA English DT Review DE cognition; reward systems; eating disorders; frontal cortex; binge eating; bulimia; anorexia; dopamine; morphine ID BODY-IMAGE DISTORTION; DEFICIT HYPERACTIVITY DISORDER; MU-OPIOID RECEPTOR; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; PREFRONTAL CORTEX; ENDOGENOUS MORPHINE; FUNCTIONAL NEUROANATOMY; BEHAVIORAL FLEXIBILITY; SCHIZOPHRENIA AB A substantive literature has drawn a compelling case for the functional involvement of mesolimbic/prefrontal cortical neural reward systems in normative control of eating and in the etiology and persistence of severe eating disorders that affect diverse human populations. Presently, we provide a short review that develops an equally compelling case for the importance of dysregulated frontal cortical cognitive neural networks acting in concert with regional reward systems in the regulation of complex eating behaviors and in the presentation of complex pathophysiological symptoms associated with major eating disorders. Our goal is to highlight working models of major eating disorders that incorporate complementary approaches to elucidate functionally interactive neural circuits defined by their regulatory neurochemical phenotypes. Importantly, we also review evidence-based linkages between widely studied psychiatric and neurodegenerative syndromes (e.g., autism spectrum disorders and Parkinson's disease) and co-morbid eating disorders to elucidate basic mechanisms involving dopaminergic transmission and its regulation by endogenously expressed morphine in these same cortical regions. C1 [Stefano, George B.; Ptacek, Radek; Kuzelova, Hana; Raboch, Jiri; Papezova, Hana; Kream, Richard M.] Charles Univ Prague, Fac Med 1, Ctr Mol & Cognit Neurosci, Prague, Czech Republic. [Stefano, George B.; Mantione, Kirk J.; Kream, Richard M.] SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. [Kuzelova, Hana] Charles Univ Prague, Fac Med 2, Dept Biol & Med Genet, Prague, Czech Republic. RP Stefano, GB (reprint author), Charles Univ Prague, Fac Med 1, Ctr Mol & Cognit Neurosci, Prague, Czech Republic. 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Sci. Monitor PD MAY 10 PY 2013 VL 19 BP 353 EP 358 DI 10.12659/MSM.889133 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 159QE UT WOS:000320059700001 PM 23660852 ER PT J AU Shi, F Wang, L Peng, ZW Wee, CY Shen, DG AF Shi, Feng Wang, Li Peng, Ziwen Wee, Chong-Yaw Shen, Dinggang TI Altered Modular Organization of Structural Cortical Networks in Children with Autism SO PLOS ONE LA English DT Article ID GRAPH-THEORETICAL ANALYSIS; HIGH-FUNCTIONING AUTISM; HUMAN CEREBRAL-CORTEX; SPECTRUM DISORDERS; BRAIN-DEVELOPMENT; ASPERGER-SYNDROME; MRI; THICKNESS; VOLUME; MATTER AB Autism is a complex developmental disability that characterized by deficits in social interaction, language skills, repetitive stereotyped behaviors and restricted interests. Although great heterogeneity exists, previous findings suggest that autism has atypical brain connectivity patterns and disrupted small-world network properties. However, the organizational alterations in the autistic brain network are still poorly understood. We explored possible organizational alterations of 49 autistic children and 51 typically developing controls, by investigating their brain network metrics that are constructed upon cortical thickness correlations. Three modules were identified in controls, including cortical regions associated with brain functions of executive strategic, spatial/auditory/visual, and self-reference/episodic memory. There are also three modules found in autistic children with similar patterns. Compared with controls, autism demonstrates significantly reduced gross network modularity, and a larger number of inter-module connections. However, the autistic brain network demonstrates increased intra-and inter-module connectivity in brain regions including middle frontal gyrus, inferior parietal gyrus, and cingulate, suggesting one underlying compensatory mechanism associated with brain functions of self-reference and episodic memory. Results also show that there is increased correlation strength between regions inside frontal lobe, as well as impaired correlation strength between frontotemporal and frontoparietal regions. This alteration of correlation strength may contribute to the organization alteration of network structures in autistic brains. C1 [Shi, Feng; Wang, Li; Peng, Ziwen; Wee, Chong-Yaw; Shen, Dinggang] Univ N Carolina, Dept Radiol, Chapel Hill, NC 27515 USA. [Shi, Feng; Wang, Li; Peng, Ziwen; Wee, Chong-Yaw; Shen, Dinggang] Univ N Carolina, BRIC, Chapel Hill, NC USA. [Peng, Ziwen] S China Normal Univ, Dept Psychol, Guangzhou, Guangdong, Peoples R China. [Shen, Dinggang] Korea Univ, Dept Brain & Cognit Engn, Seoul, South Korea. RP Shen, DG (reprint author), Univ N Carolina, Dept Radiol, Chapel Hill, NC 27515 USA. EM dgshen@med.unc.edu FU National Institutes of Health (NIH) [EB006733, EB008374, EB009634, AG041721]; National Natural Science Foundation of China [81201049]; University of North Carolina at Chapel Hill's Libraries FX This work was supported in part by National Institutes of Health (NIH) grants EB006733, EB008374, EB009634, AG041721, and National Natural Science Foundation of China (81201049). The University of North Carolina at Chapel Hill's Libraries provided support for open access publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Darling, Ryan D. Alzghoul, Loai Paul, Ian A. Simpson, Kimberly L. Lin, Rick C. S. TI Neonatal citalopram exposure decreases serotonergic fiber density in the olfactory bulb of male but not female adult rats SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE serotonin transporter; olfactory bulb; selective serotonin reuptake inhibitors; sexual dimorphism; autism spectrum disorders ID HIGH-FUNCTIONING AUTISM; BRAIN-SEROTONIN; SPECTRUM DISORDERS; ANTIDEPRESSANT EXPOSURE; NITRIC-OXIDE; CHILDREN; TRANSPORTER; ALTERS; INPUTS; IDENTIFICATION AB Manipulation of serotonin (5HT) during early development has been shown to induce long-lasting morphological changes within the raphe nuclear complex and serotonergic circuitry throughout the brain. Recent studies have demonstrated altered raphe-derived 5HT transporter (SERT) immunoreactive axonal expression in several cortical target sites after brief perinatal exposure to selective 5HT reuptake inhibitors such as citalopram (CTM). Since the serotonergic raphe nuclear complex projects to the olfactory bulb (OB) and perinatal 5HT disruption has been shown to disrupt olfactory behaviors, the goal of this study was to further investigate such developmental effects in the OB of CTM exposed animals. Male and female rat pups were exposed to CTM from postnatal day 8-21. After animals reach adulthood (>90 days), OB tissue sections were processed immunohistochemically for SERT antiserum. Our data revealed that the density of the SERT immunoreactive fibers decreased similar to 40% in the OB of CTM exposed male rats, but not female rats. Our findings support a broad and long-lasting change throughout most of the 5HT system, including the OB, after early manipulation of 5HT. Because dysfunction of the early 5HT system has been implicated in the etiology of neurodevelopmental disorders such as autism spectrum disorders (ASDs), these new findings may offer insight into the abnormal olfactory perception often noted in patients with ASD. C1 [Zhang, Junlin; Darling, Ryan D.; Simpson, Kimberly L.; Lin, Rick C. S.] Univ Mississippi, Med Ctr, Dept Neurobiol & Anat Sci, Jackson, MS 39216 USA. [Dennis, Katie A.] Millsaps Coll, Jackson, MS 39210 USA. [Alzghoul, Loai] Univ Mississippi, Med Ctr, Program Neurosci, Jackson, MS 39216 USA. [Paul, Ian A.; Simpson, Kimberly L.; Lin, Rick C. S.] Univ Mississippi, Med Ctr, Dept Psychiat & Hlth Behav, Jackson, MS 39216 USA. RP Lin, RCS (reprint author), Univ Mississippi, Med Ctr, Dept Neurobiol & Anat Sci, 2500 North State St, Jackson, MS 39216 USA. EM rlin@umc.edu FU National Institutes of Health [EUREKA MH084194] FX This work was supported by the National Institutes of Health under grant number: EUREKA MH084194. 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Cell. Neurosci. PD MAY 10 PY 2013 VL 7 AR 67 DI 10.3389/fncel.2013.00067 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 143CK UT WOS:000318843700001 PM 23675318 ER PT J AU Bauer, AZ Kriebel, D AF Bauer, Ann Z. Kriebel, David TI Prenatal and perinatal analgesic exposure and autism: an ecological link SO ENVIRONMENTAL HEALTH LA English DT Article DE Paracetamol; Acetaminophen; Autism spectrum disorder; Sulfation; Glucuronidation; Pro-inflammatory cytokines ID PERVASIVE DEVELOPMENTAL DISORDERS; MATERNAL INFLUENZA INFECTION; SPECTRUM DISORDERS; INFANTILE-AUTISM; CHILDHOOD AUTISM; UNITED-STATES; RISK-FACTORS; EPIDEMIOLOGIC FINDINGS; NEONATAL CIRCUMCISION; PARACETAMOL EXPOSURE AB Background: Autism and Autism Spectrum Disorder (ASD) are complex neurodevelopmental disorders. Susceptibility is believed to be the interaction of genetic heritability and environmental factors. The synchronous rises in autism/ASD prevalence and paracetamol (acetaminophen) use, as well as biologic plausibility have led to the hypothesis that paracetamol exposure may increase autism/ASD risk. Methods: To explore the relationship of antenatal paracetamol exposure to ASD, population weighted average autism prevalence rates and paracetamol usage rates were compared. To explore the relationship of early neonatal paracetamol exposure to autism/ASD, population weighted average male autism prevalence rates for all available countries and U.S. states were compared to male circumcision rates - a procedure for which paracetamol has been widely prescribed since the mid-1990s. Prevalence studies were extracted from the U.S. Centers for Disease Control and Prevention Summary of Autism/ASD Prevalence Studies database. Maternal paracetamol usage and circumcision rates were identified by searches on Pub Med. Results: Using all available country-level data (n = 8) for the period 1984 to 2005, prenatal use of paracetamol was correlated with autism/ASD prevalence (r = 0.80). For studies including boys born after 1995, there was a strong correlation between country-level (n = 9) autism/ASD prevalence in males and a country's circumcision rate (r = 0.98). A very similar pattern was seen among U.S. states and when comparing the 3 main racial/ethnic groups in the U.S. The country-level correlation between autism/ASD prevalence in males and paracetamol was considerably weaker before 1995 when the drug became widely used during circumcision. Conclusions: This ecological analysis identified country-level correlations between indicators of prenatal and perinatal paracetamol exposure and autism/ASD. State level correlation was also identified for the indicator of perinatal paracetamol exposure and autism/ASD. Like all ecological analyses, these data cannot provide strong evidence of causality. However, biologic plausibility is provided by a growing body of experimental and clinical evidence linking paracetamol metabolism to pathways shown to be important in autism and related developmental abnormalities. Taken together, these ecological findings and mechanistic evidence suggest the need for formal study of the role of paracetamol in autism. C1 [Bauer, Ann Z.; Kriebel, David] Univ Massachusetts, Sch Hlth & Environm, Dept Work Environm, Lowell, MA 01854 USA. RP Bauer, AZ (reprint author), Univ Massachusetts, Sch Hlth & Environm, Dept Work Environm, 1 Univ Ave, Lowell, MA 01854 USA. 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Health PD MAY 9 PY 2013 VL 12 AR 41 DI 10.1186/1476-069X-12-41 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 157NS UT WOS:000319905400001 PM 23656698 ER PT J AU Castelhano, ASS Cassane, GDT Scorza, FA Cysneiros, RM AF Santos Castelhano, Adelisandra Silva Teada Cassane, Gustavo dos Santos Scorza, Fulvio Alexandre Cysneiros, Roberta Monterazzo TI Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE neonatal status epilepticus; pilocarpine; social anxiety; general anxiety; social behavior ID LONG-TERM CONSEQUENCES; STATUS EPILEPTICUS; NEONATAL SEIZURES; DEVELOPING BRAIN; AUTISM; IMPAIRMENT; DEFICITS; MEMORY; MICE; NEUROBIOLOGY AB Neonatal seizures are the most common manifestation of neurological dysfunction in the neonate. The prognosis of neonatal seizures is highly variable, and the controversy remains whether the severity, duration, or frequency of seizures may contribute to brain damage independently of its etiology. Animal data indicates that seizures during development are associated with a high probability of long-term adverse effects such as learning and memory impairment, behavioral changes and even epilepsy, which is strongly age dependent, as well as the severity, duration, and frequency of seizures. In preliminary studies, we demonstrated that adolescent male rats exposed to one-single neonatal status epilepticus (SE) episode showed social behavior impairment, and we proposed the model as relevant for studies of developmental disorders. Based on these facts, the goal of this study was to verify the existence of a persistent deficit and if the anxiety-related behavior could be associated with that impairment. To do so, male Wistar rats at 9 days postnatal were submitted to a single episode of SE by pilocarpine injection (380 mg/kg, i.p.) and control animals received saline (0.9%, 0.1 mL/10 g). It was possible to demonstrate that in adulthood, animals exposed to neonatal Se displayed low preference for social novelty, anxiety-related behavior, and increased stereotyped behavior in anxiogenic environment with no locomotor activity changes. On the balance, these data suggests that neonatal Se in rodents leads to altered anxiety-related and abnormal social behaviors. C1 [Santos Castelhano, Adelisandra Silva; Teada Cassane, Gustavo dos Santos; Cysneiros, Roberta Monterazzo] Presbyterian Mackenzie Univ, Neurobiol Lab, Dev Disabil Grad Program, BR-01302907 Sao Paulo, Brazil. [Scorza, Fulvio Alexandre] Univ Fed Sao Paulo, Escola Paulista Med, Dept Neurol & Neurosurg, Sao Paulo, Brazil. RP Cysneiros, RM (reprint author), Presbyterian Mackenzie Univ, Neurobiol Lab, Dev Disabil Grad Program, Rua Consolacao 930,Predio 28, BR-01302907 Sao Paulo, Brazil. EM roberta.cysneiros@mackenzie.br RI Scorza, Fulvio/C-7048-2013; Cysneiros, Roberta/H-6224-2012 OI Scorza, Fulvio/0000-0002-0694-8674; Cysneiros, Roberta/0000-0002-3191-9146 FU MACKPESQUISA; CInAPCe (Cooperacao Interinstitucional de Apoio a Pesquisa sobre o Cerebro)-FAPESP; CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico); FAPESP/CNPq/MCT (Instituto Nacional de Neurociencia Translacional) FX This work was sponsored by grants from MACKPESQUISA, CInAPCe (Cooperacao Interinstitucional de Apoio a Pesquisa sobre o Cerebro)-FAPESP; CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico); and FAPESP/CNPq/MCT (Instituto Nacional de Neurociencia Translacional). 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Behav. Neurosci. PD MAY 9 PY 2013 VL 7 AR 36 DI 10.3389/fnbeh.2013.00036 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 139NN UT WOS:000318589700001 PM 23675329 ER PT J AU Foss-Feig, JH Tadin, D Schauder, KB Cascio, CJ AF Foss-Feig, Jennifer H. Tadin, Duje Schauder, Kimberly B. Cascio, Carissa J. TI A Substantial and Unexpected Enhancement of Motion Perception in Autism SO JOURNAL OF NEUROSCIENCE LA English DT Article ID DIAGNOSTIC OBSERVATION SCHEDULE; CENTER-SURROUND INTERACTIONS; CONTRAST GAIN-CONTROL; VISUAL-MOTION; PERCEIVED POSITION; CHILDREN; SPECTRUM; SEARCH; CORTEX; EXCITATION/INHIBITION AB Atypical perceptual processing in autism spectrum disorder (ASD) is well documented. In addition, growing evidence supports the hypothesis that an excitatory/inhibitory neurochemical imbalance might underlie ASD. Here we investigated putative behavioral consequences of the excitatory/inhibitory imbalance in the context of visual motion perception. As stimulus size increases, typical observers exhibit marked impairments in perceiving motion of high-contrast stimuli. This result, termed "spatial suppression," is believed to reflect inhibitory motion-processing mechanisms. Motion processing is also affected by gain control, an inhibitory mechanism that underlies saturation of neural responses at high contrast. Motivated by these behavioral correlates of inhibitory function, we investigated motion perception in human children with ASD (n = 20) and typical development (n = 26). At high contrast, both groups exhibited similar impairments in motion perception with increasing stimulus size, revealing no apparent differences in spatial suppression. However, there was a substantial enhancement of motion perception in ASD: children with ASD exhibited a consistent twofold improvement in perceiving motion. Hypothesizing that this enhancement might indicate abnormal weakening of response gain control, we repeated our measurements at low contrast, where the effects of gain control should be negligible. At low contrast, we indeed found no group differences in motion discrimination thresholds. These low-contrast results, however, revealed weaker spatial suppression in ASD, suggesting the possibility that gain control abnormalities in ASD might have masked spatial suppression differences at high contrast. Overall, we report a pattern of motion perception abnormalities in ASD that includes substantial enhancements at high contrast and is consistent with an underlying excitatory/inhibitory imbalance. C1 [Foss-Feig, Jennifer H.] Vanderbilt Univ, Dept Psychol & Human Dev, Nashville, TN 37203 USA. [Tadin, Duje; Cascio, Carissa J.] Vanderbilt Univ, Vanderbilt Kennedy Ctr, Nashville, TN 37203 USA. [Schauder, Kimberly B.] Univ Rochester, Ctr Visual Sci, Dept Brain & Cognit Sci, Rochester, NY 14627 USA. [Schauder, Kimberly B.] Univ Rochester, Dept Ophthalmol, Rochester, NY 14627 USA. [Cascio, Carissa J.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37212 USA. RP Foss-Feig, JH (reprint author), 1601 23rd Ave South,PMB 552, Nashville, TN 37212 USA. EM jennifer.h.foss-feig@vanderbilt.edu FU National Eye Institute-National Institutes of Health [P30 EY001319, P30 EY08126, R01 EY019295, K01-MH090232]; National Center for Research Resources-National Institutes of Health [1 UL1 RR024975]; Autism Speaks Dennis Weatherstone Predoctoral Fellowship FX This work was supported by the National Eye Institute-National Institutes of Health (Core Grants P30 EY001319 and P30 EY08126, Grant R01 EY019295 to D.T., and Grant K01-MH090232 to C.J.C.) and the National Center for Research Resources-National Institutes of Health (Grant 1 UL1 RR024975). J.H.F.-F. was supported by an Autism Speaks Dennis Weatherstone Predoctoral Fellowship. 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RP Krueger, DD (reprint author), Max Planck Inst Expt Med, Dept Mol Neurobiol, Hermann Rein Str 3, D-37075 Gottingen, Germany. 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Suedhof, Thomas C. TI Autism-Associated Neuroligin-3 Mutations Commonly Disrupt Tonic Endocannabinoid Signaling SO NEURON LA English DT Article ID INHIBITORY SYNAPTIC-TRANSMISSION; HIPPOCAMPAL GABAERGIC SYNAPSES; PERISOMATIC INHIBITION; RECEPTOR ACTIVATION; FAST-SPIKING; RELEASE; CANNABINOIDS; MODULATION; NEUREXINS; GABA AB Neuroligins are postsynaptic cell-adhesion molecules that interact with presynaptic neurexins. Rare mutations in neuroligins and neurexins predispose to autism, including a neuroligin-3 amino acid substitution (R451C) and a neuroligin-3 deletion. Previous analyses showed that neuroligin-3 R451C-knockin mice exhibit robust synaptic phenotypes but failed to uncover major changes in neuroligin-3 knockout mice, questioning the notion that a common synaptic mechanism mediates autism pathogenesis in patients with these mutations. Here, we used paired recordings in mice carrying these mutations to measure synaptic transmission at GABAergic synapses formed by hippocampal parvalbumin- and cholecystokinin-expressing basket cells onto pyramidal neurons. We demonstrate that in addition to unique gain-of-function effects produced by the neuroligin-3 R451C-knockin but not the neuroligin-3 knockout mutation, both mutations dramatically impaired tonic but not phasic endocannabinoid signaling. Our data thus suggest that neuroligin-3 is specifically required for tonic endocannabinoid signaling, raising the possibility that alterations in endocannabinoid signaling may contribute to autism pathophysiology. C1 [Foeldy, Csaba; Suedhof, Thomas C.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. [Foeldy, Csaba; Malenka, Robert C.] Stanford Univ, Sch Med, Nancy Pritzker Lab, Stanford, CA 94305 USA. [Malenka, Robert C.; Suedhof, Thomas C.] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. [Suedhof, Thomas C.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. RP Foldy, C (reprint author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. EM foldy@stanford.edu; tcs1@stanford.edu FU Simons Foundation [177850]; NIMH [P50 MH086403]; NIDA [K99DA034029]; NINDS [NS069375] FX We would like to thank Nathan Huang, Scarlett Fang, Ayeh Darvishzadeh, and Shaon Ghosh for technical assistance, and Dr. Jason Aoto for advice. This study was supported by grants from the Simons Foundation (177850 to T.C.S.), the NIMH (P50 MH086403 to R.C.M. and T.C.S.), the NIDA (K99DA034029 to C.F.), and the NINDS (NS069375 to the Stanford Neuroscience Microscopy Service). 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Johnson, Caroline A. Denefrio, Cassandra L. Saulnier, Jessica L. Kornacker, Karl Sabatini, Bernardo L. TI Excitatory/Inhibitory Synaptic Imbalance Leads to Hippocampal Hyperexcitability in Mouse Models of Tuberous Sclerosis SO NEURON LA English DT Article ID NEURODEVELOPMENTAL DISORDERS; AMPA RECEPTORS; AUTISM; EPILEPSY; NEURONS; COMPLEX; TSC1; INHIBITION; TRANSLATION; SUPPRESSION AB Neural circuits are regulated by activity-dependent feedback systems that tightly control network excitability and which are thought to be crucial for proper brain development. Defects in the ability to establish and maintain network homeostasis may be central to the pathogenesis of neurodevelopmental disorders. Here, we examine the function of the tuberous sclerosis complex (TSC)-mTOR signaling pathway, a common target of mutations associated with epilepsy and autism spectrum disorder, in regulating activity-dependent processes in the mouse hippocampus. We find that the TSC-mTOR pathway is a central component of a positive feedback loop that promotes network activity by repressing inhibitory synapses onto excitatory neurons. In Tsc1 KO neurons, weakened inhibition caused by deregulated mTOR alters the balance of excitatory and inhibitory synaptic transmission, leading to hippocampal hyperexcitability. These findings identify the TSC-mTOR pathway as a regulator of neural network activity and have implications for the neurological dysfunction in disorders exhibiting deregulated mTOR signaling. C1 [Bateup, Helen S.; Johnson, Caroline A.; Denefrio, Cassandra L.; Saulnier, Jessica L.; Sabatini, Bernardo L.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02115 USA. [Kornacker, Karl] Ohio State Univ, Div Sensory Biophys, Columbus, OH 43210 USA. RP Sabatini, BL (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02115 USA. EM bsabatini@hms.harvard.edu FU NINDS grant [NS052707]; Nancy Lurie Marks postdoctoral fellowship FX We thank members of the Sabatini lab for helpful comments and critically reading our manuscript. This work was supported by an NINDS grant (NS052707) (to B.L.S.) and a Nancy Lurie Marks postdoctoral fellowship (to H.S.B.). 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Rennert, Owen M. TI Sex-biased gene expression in the developing brain: implications for autism spectrum disorders SO MOLECULAR AUTISM LA English DT Letter DE Autistic disorder; Gene expression; Sex differences ID DE-NOVO MUTATIONS; TRANSCRIPTOME AB Autism spectrum disorders affect significantly more males than females. Understanding sex differences in normal human brain development may provide insight into the mechanism(s) underlying this disparity; however, studies of sex differences in brain development at the genomic level are lacking. Here, we report a re-analysis of sex-specific gene expression from a recent large transcriptomic study of normal human brain development, to determine whether sex-biased genes relate to specific mechanistic processes. We discovered that male-biased genes are enriched for the processes of extracellular matrix formation/glycoproteins, immune response, chromatin, and cell cytoskeleton. We highlight that these pathways have been repeatedly implicated in autism and demonstrate that autism candidate genes are also enriched for these pathways. We propose that the overlap of these male-specific brain transcriptional modules with the same pathways in autism spectrum disorders may partially explain the increased incidence of autism in males. C1 [Ziats, Mark N.; Rennert, Owen M.] NICHHD, NIH, Bethesda, MD 20814 USA. [Ziats, Mark N.] Robinson Coll, NIH Univ Cambridge Biomed Scholars Program, Cambridge CB3 9AN, England. [Ziats, Mark N.] Baylor Coll Med MSTP, Houston, TX 77030 USA. RP Ziats, MN (reprint author), NICHHD, NIH, 49 Convent Dr,Bldg 49,Room 2C08, Bethesda, MD 20814 USA. 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Autism PD MAY 7 PY 2013 VL 4 AR 10 DI 10.1186/2040-2392-4-10 PG 3 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 254VA UT WOS:000327195300001 PM 23651621 ER PT J AU Lloyd-Fox, S Blasi, A Elwell, CE Charman, T Murphy, D Johnson, MH AF Lloyd-Fox, S. Blasi, A. Elwell, C. E. Charman, T. Murphy, D. Johnson, M. H. TI Reduced neural sensitivity to social stimuli in infants at risk for autism SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE functional near infrared spectroscopy; social; infancy; development; autism spectrum disorder; voice processing ID NEAR-INFRARED SPECTROSCOPY; FUNCTIONAL BRAIN-DEVELOPMENT; AGE 2 YEARS; EYE GAZE; ATYPICAL DEVELOPMENT; SPECTRUM DISORDERS; TEMPORAL CORTEX; VOICE; FACE; PERCEPTION AB In the hope of discovering early markers of autism, attention has recently turned to the study of infants at risk owing to being the younger siblings of children with autism. Because the condition is highly heritable, later-born siblings of diagnosed children are at substantially higher risk for developing autism or the broader autism phenotype than the general population. Currently, there are no strong predictors of autism in early infancy and diagnosis is not reliable until around 3 years of age. Because indicators of brain functioning may be sensitive predictors, and atypical social interactions are characteristic of the syndrome, we examined whether temporal lobe specialization for processing visual and auditory social stimuli during infancy differs in infants at risk. In a functional near-infrared spectroscopy study, infants aged 4-6 months at risk for autism showed less selective neural responses to social stimuli (auditory and visual) than low-risk controls. These group differences could not be attributed to overall levels of attention, developmental stage or chronological age. Our results provide the first demonstration of specific differences in localizable brain function within the first 6 months of life in a group of infants at risk for autism. Further, these differences closely resemble known patterns of neural atypicality in children and adults with autism. Future work will determine whether these differences in infant neural responses to social stimuli predict either later autism or the broader autism phenotype frequently seen in unaffected family members. C1 [Lloyd-Fox, S.; Blasi, A.; Johnson, M. H.] Univ London, Ctr Brain & Cognit Dev, London WC1E 7HX, England. [Elwell, C. E.] UCL, Dept Med Phys & Bioengn, London, England. [Charman, T.] Kings Coll London, Inst Psychiat, Dept Psychol, London WC2R 2LS, England. [Murphy, D.] Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, London WC2R 2LS, England. RP Lloyd-Fox, S (reprint author), Univ London, Ctr Brain & Cognit Dev, Malet St, London WC1E 7HX, England. EM s.fox@bbk.ac.uk RI Charman, Tony/A-2085-2014 OI Charman, Tony/0000-0003-1993-6549 FU BASIS; Simon's Foundation [SFARI201287]; BASIS by Autistica FX Recruitment, ethical approval (UK National Health Service National Research Ethics Service London REC 08/H0718/76 and 06/MRE02/73) and informed consent, as well as background data on participating families with high-risk infants, were made available for the current study through BASIS. Data and research materials supporting the results in the article are stored in the BASIS Network Data Repository. BASIS provides support for scientific projects and access to published datasets once these projects become affiliated with the network (for further details see http://www.basisnetwork.org).We are very grateful for the enormous contributions the BASIS families have made towards this study. The UK Medical Research Council (G0701484), a grant from The Simon's Foundation (no. SFARI201287 to M.H.J.) and the BASIS funding consortium led by Autistica (www.basisnetwork.org) supports the research of M.H.J. 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R. Soc. B-Biol. Sci. PD MAY 7 PY 2013 VL 280 IS 1758 AR 20123026 DI 10.1098/rspb.2012.3026 PG 9 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA 110AJ UT WOS:000316413700005 PM 23486434 ER PT J AU Frenkel-Toledo, S Bentin, S Perry, A Liebermann, DG Soroker, N AF Frenkel-Toledo, Silvi Bentin, Shlomo Perry, Anat Liebermann, Dario G. Soroker, Nachum TI Dynamics of the EEG power in the frequency and spatial domains during observation and execution of manual movements SO BRAIN RESEARCH LA English DT Article DE EEG; Mu-rhythm; Alpha-rhythm; Mirror-neuron; Perception-action cycle ID MIRROR-NEURON SYSTEM; EVENT-RELATED DESYNCHRONIZATION; AUTISM SPECTRUM DISORDERS; HIGH-RESOLUTION EEG; PRIMARY MOTOR CORTEX; MU-RHYTHM; FUNCTIONAL-SIGNIFICANCE; CORTICAL ACTIVATION; VOLUNTARY MOVEMENT; THETA OSCILLATIONS AB Mu suppression is the attenuation of EEG power in the alpha frequency range (8-12 Hz) while executing or observing a motor action. Whereas typically observed at central scalp sites, there are diverging reports about the extent of the attenuation over the cortical mantle, its exact frequency range and the specificity of this phenomenon. We investigated the modulation of EEG oscillations in frequency-bands between 4 to 12 Hz at frontal, central, parietal and occipital sites during the execution of manual movements and during observation of similar actions from allocentric (i.e., facing the actor) and egocentric (i.e., seeing the actor from behind) viewpoints. Suppression was determined relative to observation of a non-biological movement. Action observation elicited greater suppression in the lower (8-10 Hz) compared to the higher mu range (10-12 Hz), and greater suppression in the entire range (4-12 Hz) at frontal and central sites compared to parietal and occipital sites. In addition, suppression tended to be greater during observation of a motor action from allocentric compared to egocentric viewpoints. During execution of movement, suppression of the EEG occurred primarily in the higher alpha range and was absent at occipital sites. In the theta range (4-8 Hz), the EEG amplitude was suppressed during action observation and execution. The results suggest a functional distinction between modulation of mu and alpha rhythms, and between the higher and lower ranges of the mu rhythms. The activity of the presumed human mirror-neuron system seems primarily evident in the lower mu range and in the theta range. (C) 2013 Elsevier B.V. All rights reserved. C1 [Frenkel-Toledo, Silvi; Soroker, Nachum] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel. [Frenkel-Toledo, Silvi; Soroker, Nachum] Loewenstein Hosp & Rehabil Ctr, Dept Neurol Rehabil, Raanana, Israel. [Bentin, Shlomo; Perry, Anat] Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel. [Bentin, Shlomo] Hebrew Univ Jerusalem, Interdisciplinary Ctr Neural Computat, Jerusalem, Israel. [Liebermann, Dario G.] Tel Aviv Univ, Sackler Fac Med, Phys Therapy Dept, Tel Aviv, Israel. [Frenkel-Toledo, Silvi] Tel Aviv Univ, Fac Med, PT Dept, Stanley Steyer Sch Hlth Profess, Tel Aviv, Israel. RP Frenkel-Toledo, S (reprint author), Loewenstein Hosp & Rehabil Ctr, 278 Ahuza, IL-43100 Raanana, Israel. EM silvi197@bezeqint.net FU Legacy Foundation through the Loewenstein Rehabilitation Hospital; Steyer Family Endowment through the Stanley Steyer School of Health Professions of the Sadder Faculty of Medicine - Tel Aviv University; Israeli Ministry of Health [3-00000-7772] FX This research project was carried out by the first author in partial fulfillment of the requirements for the PhD degree at the Sackler Faculty of Medicine - Tel Aviv University, under the supervision of Shlomo Bentin, Dario G. Liebermann and Nachum Soroker. We dedicate the paper in memory of Professor Shlomo Bentin, who recently passed away in a tragic accident. We wish to thank the participants for their cooperation in the experiment. This research was partially funded by the Legacy Foundation granted through the Loewenstein Rehabilitation Hospital, the Steyer Family Endowment through the Stanley Steyer School of Health Professions of the Sadder Faculty of Medicine - Tel Aviv University and the Israeli Ministry of Health no. 3-00000-7772. 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PD MAY 6 PY 2013 VL 1509 BP 43 EP 57 DI 10.1016/j.brainres.2013.03.004 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 146LU UT WOS:000319093400005 PM 23500633 ER PT J AU Esposito, G Yoshida, S Ohnishi, R Tsuneoka, Y Rostagno, MD Yokota, S Okabe, S Kamiya, K Hoshino, M Shimizu, M Venuti, P Kikusui, T Kato, T Kuroda, KO AF Esposito, Gianluca Yoshida, Sachine Ohnishi, Ryuko Tsuneoka, Yousuke Rostagno, Maria del Carmen Yokota, Susumu Okabe, Shota Kamiya, Kazusaku Hoshino, Mikio Shimizu, Masaki Venuti, Paola Kikusui, Takefumi Kato, Tadafumi Kuroda, Kumi O. TI Infant Calming Responses during Maternal Carrying in Humans and Mice SO CURRENT BIOLOGY LA English DT Article ID TRANSPORT; RAT; ATTACHMENT; CONTACT; ROCKING; AUTISM; ABUSE; GENE AB Background: Mother-infant bonding is the earliest and most critical social relationship of mammalian infants. To promote this bond, infants have innate behaviors to seek maternal proximity and protest upon separation via communication with the mother vocally and through body movement. However, the physiological mechanisms regulating these infant behaviors remain largely undefined. Results: Here we show a novel set of infant cooperative responses during maternal carrying. Infants under 6 months of age carried by a walking mother immediately stopped voluntary movement and crying and exhibited a rapid heart rate decrease, compared with holding by a sitting mother. Furthermore, we identified strikingly similar responses in mouse pups as defined by immobility and diminished ultrasonic vocalizations and heart rate. Using pharmacologic and genetic interventions in mouse pups, we identified the upstream and downstream neural systems regulating the calming response. Somatosensory and proprioceptive input signaling are required for induction, and parasympathetic and cerebellar functions mediate cardiac and motor output, respectively. The loss of the calming response hindered maternal rescue of the pups, suggesting a functional significance for the identified calming response. Conclusions: Our study has demonstrated for the first time that the infant calming response to maternal carrying is a coordinated set of central, motor, and cardiac regulations and is a conserved component of mammalian mother-infant interactions. Our findings provide evidence for and have the potential to impact current parenting theory and practice, since unsoothable crying is the major risk factor for child abuse. C1 [Esposito, Gianluca; Yoshida, Sachine; Ohnishi, Ryuko; Tsuneoka, Yousuke; Kuroda, Kumi O.] RIKEN Brain Sci Inst, Unit Affiliat Social Behav, Wako, Saitama 3510198, Japan. [Kato, Tadafumi] RIKEN Brain Sci Inst, Lab Mol Dynam Mental Disorders, Wako, Saitama 3510198, Japan. [Rostagno, Maria del Carmen; Venuti, Paola] Univ Trent, Dept Psychol & Cognit Sci, I-38068 Rovereto, Trento, Italy. [Yokota, Susumu] Saitama Childrens Med Ctr, Dept Clin Lab, Saitama 3398551, Japan. [Shimizu, Masaki] Saitama Childrens Med Ctr, Div Neonatol, Saitama 3398551, Japan. [Okabe, Shota; Kikusui, Takefumi] Azabu Univ, Sch Vet Med, Sagamihara, Kanagawa 2525201, Japan. [Kamiya, Kazusaku] Juntentdo Univ, Sch Med, Dept Otorhinolaryngol, Bunkyo Ku, Tokyo 1138421, Japan. [Hoshino, Mikio] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Biochem & Cellular Biol, Kodaira, Tokyo 1878551, Japan. RP Kuroda, KO (reprint author), RIKEN Brain Sci Inst, Unit Affiliat Social Behav, Wako, Saitama 3510198, Japan. EM oyako@brain.riken.jp RI Esposito, Gianluca/B-1374-2012; Esposito, Gianluca/K-9353-2013; Kato, Tadafumi/J-3583-2014 OI Esposito, Gianluca/0000-0002-9442-0254; Esposito, Gianluca/0000-0002-9442-0254; Kato, Tadafumi/0000-0001-7856-3952 FU RIKEN; JSPS FX We thank M. Ogawa for the reeler strain; S. Sato, Y. Tanaka, H. Gateau, A. Terashima, and C. Yokoyama for insightful discussion and comments; P. Rigo and F. Riccardi for the drawing of Figure 1A; and T. Fillman, A. Ozaki, our lab members, and RIKEN staff for assistance. This work was supported by RIKEN and JSPS grants-in-aid (K.O.K, 2007-2008; S.Y., 2010-2012; G.E., 2010 and 2012-2013). 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Studer, Lorenz TI Directed Differentiation and Functional Maturation of Cortical Interneurons from Human Embryonic Stem Cells SO CELL STEM CELL LA English DT Article ID MEDIAL GANGLIONIC EMINENCE; HUMAN CEREBRAL-CORTEX; NEURAL DEVELOPMENT; BASAL FOREBRAIN; HUMAN NEOCORTEX; FLOOR PLATE; MOUSE-BRAIN; HUMAN ES; NEURONS; EXPRESSION AB Human pluripotent stem cells are a powerful tool for modeling brain development and disease. The human cortex is composed of two major neuronal populations: projection neurons and local interneurons. Cortical interneurons comprise a diverse class of cell types expressing the neurotransmitter GABA. Dysfunction of cortical interneurons has been implicated in neuropsychiatric diseases, including schizophrenia, autism, and epilepsy. Here, we demonstrate the highly efficient derivation of human cortical interneurons in an NKX2.1::GFP human embryonic stem cell reporter line. Manipulating the timing of SHH activation yields three distinct GFP+ populations with specific transcriptional profiles, neurotransmitter phenotypes, and migratory behaviors. Further differentiation in a murine cortical environment yields parvalbumin- and somatostatin-expressing neurons that exhibit synaptic inputs and electrophysiological properties of cortical interneurons. Our study defines the signals sufficient for modeling human ventral forebrain development in vitro and lays the foundation for studying cortical interneuron involvement in human disease pathology. C1 [Maroof, Asif M.; Ganat, Yosif M.; Liu, Becky; Studer, Lorenz] Sloan Kettering Inst Canc Res, Ctr Stem Cell Biol, New York, NY 10065 USA. [Maroof, Asif M.; Ganat, Yosif M.; Liu, Becky; Studer, Lorenz] Sloan Kettering Inst Canc Res, Dev Biol Program, New York, NY 10065 USA. [Tyson, Jennifer A.; Goulburn, Adam; Anderson, Stewart A.] Weill Cornell Med Coll, Dept Psychiat, New York, NY 10021 USA. [Keros, Sotirios; Ying, Shui-Wang; Goldstein, Peter A.] Weill Cornell Med Coll, Dept Anesthesiol, New York, NY 10021 USA. [Keros, Sotirios] Weill Cornell Med Coll, Div Pediat Neurol, Dept Pediat, New York, NY 10021 USA. [Stanley, Edouard G.; Elefanty, Andrew G.] Monash Univ, Monash Immunol & Stem Cell Labs, Clayton, Vic 3800, Australia. [Widmer, Hans Ruedi] Univ Bern, Dept Neurosurg, Inselspital, CH-3010 Bern, Switzerland. [Maroof, Asif M.; Merkle, Florian T.; Eggan, Kevin] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Anderson, Stewart A.] Childrens Hosp Philadelphia, Dept Psychiat, Philadelphia, PA 19104 USA. [Anderson, Stewart A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Stanley, Edouard G.; Elefanty, Andrew G.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. RP Anderson, SA (reprint author), Sloan Kettering Inst Canc Res, Ctr Stem Cell Biol, New York, NY 10065 USA. EM andersons3@email.chop.edu; studerl@mskcc.org RI Elefanty, Andrew/A-6066-2008; Stanley, Ed/A-2985-2013 OI Stanley, Ed/0000-0002-6389-3665 FU NIMH [2RO1 MH066912, 1RC1MH089690]; Swiss National Science Foundation [31003A_135565] FX We would like to thank J. Hendrikx (Sloan-Kettering Institute [SKI] Flow Cytometry Core), A. Viale (SKI Genomics Core laboratory), M. Leversha (Molecular Cytogenetics Core), and E. Tu and M. Tomishima (SKI Stem Cell Facility) for excellent technical support. We further thank the Department of Gynecology (directors: M. Mueller and D. Surbek), University of Bern, Switzerland for providing us with the human fetal tissue. Studies using the NKX2.1::GFP hESC line were supported by grants from NYSTEM (S.A.), the European Commission project NeuroStemcell (L.S.), and the C.V. Starr Foundation (S.A. and L.S.). Experiments using hESC line WA-09 or iPSC lines were supported by NIMH grants 2RO1 MH066912 (S.A.) and 1RC1MH089690 (S.A. and L.S.) and by the Swiss National Science Foundation grant no. 31003A_135565 (H.R.W.). 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Lam, Kristen S. L. Parlier, Morgan Daniels, Julie L. Piven, Joseph TI Autism and the broad autism phenotype: familial patterns and intergenerational transmission SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Broad autism phenotype; Endophenotype; Assessment; Genetics; Personality ID MULTIPLE-INCIDENCE; SPECTRUM DISORDERS; TWIN PAIRS; DE-NOVO; PARENTS; INDIVIDUALS; QUESTIONNAIRE; PERSONALITY; POPULATION; GENETICS AB Background: Features of the Broad Autism Phenotype (BAP) are disproportionately prevalent in parents of a child with autism, highlighting familial patterns indicative of heritability. It is unclear, however, whether the presence of BAP features in both parents confers an increased liability for autism. The current study explores whether the presence of BAP features in two biological parents occurs more frequently in parents of a child with autism relative to comparison parents, whether parental pairs of a child with autism more commonly consist of one or two parents with BAP features, and whether these features are associated with severity of autism behaviors in probands. Method: Seven hundred eleven parents of a child with an autism spectrum disorder and 981 comparison parents completed the Broad Autism Phenotype Questionnaire. Parents of a child with autism also completed the Social Communication Questionnaire. Results: Although parental pairs of a child with autism were more likely than comparison parental pairs to have both parents characterized by the presence of the BAP, they more commonly consisted of a single parent with BAP features. The presence of the BAP in parents was associated with the severity of autism behaviors in probands, with the lowest severity occurring for children of parental pairs in which neither parent exhibited a BAP feature. Severity did not differ between children of two affected parents and those of just one. Conclusions: Collectively, these findings indicate that parental pairs of children with autism frequently consist of a single parent with BAP characteristics and suggest that future studies searching for implicated genes may benefit from a more narrow focus that identifies the transmitting parent. The evidence of intergenerational transmission reported here also provides further confirmation of the high heritability of autism that is unaccounted for by the contribution of de novo mutations currently emphasized in the field of autism genetics. C1 [Sasson, Noah J.] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75080 USA. [Lam, Kristen S. L.; Parlier, Morgan; Daniels, Julie L.; Piven, Joseph] Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, Chapel Hill, NC USA. [Daniels, Julie L.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Sasson, NJ (reprint author), Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75080 USA. EM nsasson@utdallas.edu; joe_piven@med.unc.edu FU Research Registry Core of the Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center (IDDRC) at UNC-Chapel Hill [HD003110]; Centers for Disease Control and Prevention [U10 DD000184-06, U50/CCU422345] FX We greatly appreciate the help of Renee Clark and the Research Registry Core of the Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center (IDDRC) at UNC-Chapel Hill (grant no. HD003110) and conversations with Veronica Vieland, PhD, about ideas in this paper. This work was further supported by the Centers for Disease Control and Prevention (grant nos. U10 DD000184-06, U50/CCU422345). 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Neurodev. Disord. PD MAY 2 PY 2013 VL 5 AR 11 DI 10.1186/1866-1955-5-11 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 143XE UT WOS:000318901700001 PM 23639131 ER PT J AU Wolff, JJ Hazlett, HC Lightbody, AA Reiss, AL Piven, J AF Wolff, Jason J. Hazlett, Heather C. Lightbody, Amy A. Reiss, Allan L. Piven, Joseph TI Repetitive and self-injurious behaviors: associations with caudate volume in autism and fragile X syndrome SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Caudate; Fragile X syndrome; Repetitive behavior; Self-injurious behavior ID NEURODEVELOPMENTAL DISORDERS; MENTAL-RETARDATION; STRIATAL VOLUME; YOUNG-CHILDREN; RISK-FACTORS; BOYS; DOPAMINE; BRAIN; ADULTS; ADOLESCENTS AB Background: Following from previous work suggesting that neurobehavioral features distinguish fragile X and idiopathic variants of autism, we investigated the relationships between four forms of repetitive behavior (stereotypy, self-injury, compulsivity, ritual behavior) and caudate nuclei volume in two groups: boys with fragile X syndrome, a subset of whom met criteria for autism, and a comparison group of boys with idiopathic autism. Methods: Bilateral caudate nuclei volumes were measured in boys aged 3 to 6 years with fragile X syndrome (n = 41), the subset of boys with fragile X syndrome and autism (n = 16), and boys with idiopathic autism (n = 30). Repetitive behaviors were measured using the Repetitive Behavior Scales-Revised. Results: For boys with idiopathic autism, left caudate volume was modestly associated with self-injury, while both compulsive and ritual behaviors showed significant positive correlations with bilateral caudate nuclei volumes, replicating previous results. For boys with fragile X syndrome, there was no such association between caudate volume and compulsive behaviors. However, we did identify significant positive correlations between self-injury total scores and number of self-injury topographies with bilateral caudate nuclei volumes. Conclusions: These findings suggest a specific role for the caudate nucleus in the early pathogenesis of self-injurious behavior associated with both idiopathic autism and fragile X syndrome. Results further indicate that the caudate may be differentially associated with compulsive behavior, highlighting the utility of isolating discrete brain-behavior associations within and between subtypes of autism spectrum disorder. C1 [Wolff, Jason J.; Hazlett, Heather C.; Piven, Joseph] Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. [Hazlett, Heather C.; Piven, Joseph] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. [Lightbody, Amy A.; Reiss, Allan L.] Stanford Univ, Ctr Interdisciplinary Brain Sci Res, Stanford, CA 94305 USA. [Lightbody, Amy A.; Reiss, Allan L.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Wolff, JJ (reprint author), Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, CB 3367, Chapel Hill, NC 27599 USA. EM jason.wolff@cidd.unc.edu FU NIH [MH64708-05, MH61696, MH050047, P30 HD03110] FX Sincere thanks to our participating children and their families. Thanks also to Michael Graves, Martin Styner, Ph.D., and Jim Bodfish, Ph.D. Research was supported by NIH grants MH64708-05 (Piven, Reiss), MH61696 (Piven), MH050047 (Reiss), and P30 HD03110 (Piven). 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Discussion: A comprehensive review of the literature indicates that, with regard to the four phenotypes of (1) restricted interests and repetitive behavior, (2) short-range and long-range structural and functional brain connectivity, (3) global and local visual perception and processing, and (4) the presence of absolute pitch, the differences between autistic individuals and typically developing individuals closely parallel the differences between younger and older children. Summary: The results of this study are concordant with a model of 'developmental heterochrony', and suggest that evolutionary extension of child development along the human lineage has potentiated and structured genetic risk for autism and the expression of autistic perception, cognition and behavior. C1 Simon Fraser Univ, Dept Biol Sci, Burnaby, BC V5A 1S6, Canada. RP Crespi, B (reprint author), Simon Fraser Univ, Dept Biol Sci, 8888 Univ Dr, Burnaby, BC V5A 1S6, Canada. 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PD MAY 1 PY 2013 VL 309 IS 17 BP 1765 EP 1765 DI 10.1001/jama.2013.4802 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 134SU UT WOS:000318235600007 ER PT J AU Goldman, GS AF Goldman, G. S. TI Comparison of VAERS fetal-loss reports during three consecutive influenza seasons: Was there a synergistic fetal toxicity associated with the two-vaccine 2009/2010 season? SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article DE Human toxicology; immunization; influenza vaccine; spontaneous abortion; stillbirth; Thimerosal ID CAPTURE-RECAPTURE METHODS; AUTISM SPECTRUM DISORDERS; VACCINATION COVERAGE; MERCURY EXPOSURE; PREGNANT-WOMEN; UNITED-STATES; ASCERTAINMENT; CHILDREN; PORPHYRINURIA; PREVALENCE AB The aim of this study was to compare the number of inactivated-influenza vaccine-related spontaneous abortion and stillbirth (SB) reports in the Vaccine Adverse Event Reporting System (VAERS) database during three consecutive flu seasons beginning 2008/2009 and assess the relative fetal death reports associated with the two-vaccine 2009/2010 season. The VAERS database was searched for reports of fetal demise following administration of the influenza vaccine/vaccines to pregnant women. Utilization of an independent surveillance survey and VAERS, two-source capture-recapture analysis estimated the reporting completeness in the 2009/2010 flu season. Capture-recapture demonstrated that the VAERS database captured about 13.2% of the total 1321 (95% confidence interval (CI): 815-2795) estimated reports, yielding an ascertainment-corrected rate of 590 fetal-loss reports per million pregnant women vaccinated (or 1 per 1695). The unadjusted fetal-loss report rates for the three consecutive influenza seasons beginning 2008/2009 were 6.8 (95% CI: 0.1-13.1), 77.8 (95% CI: 66.3-89.4), and 12.6 (95% CI: 7.2-18.0) cases per million pregnant women vaccinated, respectively. The observed reporting bias was too low to explain the magnitude increase in fetal-demise reporting rates in the VAERS database relative to the reported annual trends. Thus, a synergistic fetal toxicity likely resulted from the administration of both the pandemic (A-H1N1) and seasonal influenza vaccines during the 2009/2010 season. EM gsgoldman@roadrunner.com FU National Coalition of Organized Women (NCOW) FX This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The open access fee was contributed by the National Coalition of Organized Women (NCOW). CR Adams JB, 2009, J TOXICOL, DOI DOI 10.1155/2009/532640 [Anonymous], 22967926 US EPA INT [Anonymous], 2006, INFL VACC COV LEV 20 Austin DW, 2008, J TOXICOL ENV HEAL A, V71, P1349, DOI 10.1080/15287390802271723 Ahluwalia I. 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PD MAY PY 2013 VL 32 IS 5 BP 464 EP 475 DI 10.1177/0960327112455067 PG 12 WC Toxicology SC Toxicology GA 148DM UT WOS:000319223100002 PM 23023030 ER PT J AU Yoo, JY Kim, JN Shin, KJ Kim, SH Choi, HG Jeon, HS Koh, KS Song, WC AF Yoo, Ja-Young Kim, Jeong-Nam Shin, Kang-Jae Kim, Soon-Heum Choi, Hyun-Gon Jeon, Hyun-Soo Koh, Ki-Seok Song, Wu-Chul TI Centralization or Decentralization of Facial Structures in Korean Young Adults SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Centralization; face; width; height ID ATTRACTIVENESS; AVERAGENESS; ASYMMETRY; AUTISM; BEAUTY; FACE; EYE AB It is well known that facial beauty is dictated by facial type, and harmony between the eyes, nose, and mouth. Furthermore, facial impression is judged according to the overall facial contour and the relationship between the facial structures. The aims of the present study were to determine the optimal criteria for the assessment of gathering or separation of the facial structures and to define standardized ratios for centralization or decentralization of the facial structures. Four different lengths were measured, and 2 indexes were calculated from standardized photographs of 551 volunteers. Centralization and decentralization were assessed using the width index (interpupillary distance / facial width) and height index (eyes-mouth distance / facial height). The mean ranges of the width index and height index were 42.0 to 45.0 and 36.0 to 39.0, respectively. The width index did not differ with sex, but males had more decentralized faces, and females had more centralized faces, vertically. The incidence rate of decentralized faces among the men was 30.3%, and that of centralized faces among the women was 25.2%. The mean ranges in width and height indexes have been determined in a Korean population. Faces with width and height index scores under and over the median ranges are determined to be "centralized" and "decentralized," respectively. C1 [Yoo, Ja-Young; Kim, Jeong-Nam; Shin, Kang-Jae; Koh, Ki-Seok; Song, Wu-Chul] Konkuk Univ, Sch Med, Dept Anat, Res Inst Med Sci, Seoul 143701, South Korea. [Kim, Soon-Heum; Choi, Hyun-Gon] Konkuk Univ, Sch Med, Dept Plast & Reconstruct Surg, Res Inst Med Sci, Seoul 143701, South Korea. [Jeon, Hyun-Soo] Konkuk Univ, Sch Med, Dept Gynecol, Res Inst Med Sci, Seoul 143701, South Korea. RP Song, WC (reprint author), Konkuk Univ, Sch Med, Dept Anat, 1 Hwayang Dong, Seoul 143701, South Korea. EM anatomy@kku.ac.kr FU Konkuk University FX This work was supported by Konkuk University in 2012. 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PD MAY PY 2013 VL 24 IS 3 BP 1007 EP 1010 DI 10.1097/SCS.0b013e318275ecfc PG 4 WC Surgery SC Surgery GA 294WI UT WOS:000330078200113 PM 23714934 ER PT J AU Parsons, S Kasari, C AF Parsons, Sarah Kasari, Connie TI Schools at the centre of educational research in autism: Possibilities, practices and promises SO AUTISM LA English DT Editorial Material CR Kasari C, 2006, J CHILD PSYCHOL PSYC, V47, P611, DOI 10.1111/j.1469-7610.2005.01567.x Parsons S., 2011, EUROPEAN J SPECIAL N, V26, P47, DOI 10.1080/08856257.2011.543532 Reichow B, 2008, J AUTISM DEV DISORD, V38, P1311, DOI 10.1007/s10803-007-0517-7 NR 3 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD MAY PY 2013 VL 17 IS 3 SI SI BP 251 EP 253 DI 10.1177/1362361313483624 PG 3 WC Psychology, Developmental SC Psychology GA 298EQ UT WOS:000330307300001 PM 23802324 ER PT J AU Kasari, C Smith, T AF Kasari, Connie Smith, Tristram TI Interventions in schools for children with autism spectrum disorder: Methods and recommendations SO AUTISM LA English DT Article DE autism; implementation science; intervention; school-based intervention; treatment effectiveness evaluation ID RANDOMIZED CONTROLLED-TRIAL; JOINT ATTENTION; YOUNG-CHILDREN; SOCIAL-SKILLS; FLEXIBILITY; ATTITUDES; PROGRAMS; BEHAVIOR; SCIENCE; ANXIETY AB Although researchers have identified many promising teaching strategies and intervention programs for children with autism spectrum disorder, research on implementation of these interventions in school settings has lagged. Barriers to implementation include incompletely developed interventions, limited evidence of their utility in promoting long-term and meaningful change, and poor fit with school environments. To overcome these barriers, interventions need to be detailed in manuals that identify key components yet allow for flexibility, and studies need to evaluate long-term, real-life outcomes. Innovative research strategies also may be important, particularly carrying out research on new interventions in school settings from the outset, conducting partial effectiveness trials in which study personnel administer interventions in school settings, using community-partnered participatory research approaches, and redesigning interventions in a modular format. C1 [Kasari, Connie] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Smith, Tristram] Univ Rochester, Rochester, NY 14627 USA. RP Kasari, C (reprint author), Univ Calif Los Angeles, 760 Westwood Blvd,405 Hilgard Ave, Los Angeles, CA 90095 USA. 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L., 2003, FOCUS AUTISM OTHER D, V18, P166, DOI DOI 10.1177/10883576030180030401 Smith T, 2007, J AUTISM DEV DISORD, V37, P354, DOI 10.1007/s10803-006-0173-3 Stahmer AC, 2009, PSYCHOL SERV, V6, P223, DOI 10.1037/a0010738 Strain PS, 2011, TOP EARLY CHILD SPEC, V31, P133, DOI 10.1177/0271121411408740 United States Government Accounting Office, 2005, US GOV ACC OFF PUBL Weisz JR, 2012, ARCH GEN PSYCHIAT, V69, P274, DOI 10.1001/archgenpsychiatry.2011.147 Weisz JR, 2000, ARCH GEN PSYCHIAT, V57, P837, DOI 10.1001/archpsyc.57.9.837 Wells K, 2009, JAMA-J AM MED ASSOC, V302, P320, DOI 10.1001/jama.2009.1033 NR 46 TC 9 Z9 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD MAY PY 2013 VL 17 IS 3 SI SI BP 254 EP 267 DI 10.1177/1362361312470496 PG 14 WC Psychology, Developmental SC Psychology GA 298EQ UT WOS:000330307300002 PM 23592848 ER PT J AU Parsons, S Charman, T Faulkner, R Ragan, J Wallace, S Wittemeyer, K AF Parsons, Sarah Charman, Tony Faulkner, Rachel Ragan, Jude Wallace, Simon Wittemeyer, Kerstin TI Commentary - bridging the research and practice gap in autism: The importance of creating research partnerships with schools SO AUTISM LA English DT Article DE collaboration; evidence-based practice; partnership; research-practice gap; schools ID SPECTRUM DISORDERS; SPECIAL-EDUCATION; CHILDREN; INTERVENTION; CONSULTATION; TEACHERS AB While the last 10 years have seen a significant increase in research published on early intervention and autism, there is a persistent disconnect between educational research and practice. Governments have invested significant funds in autism education, and a range of approaches have been implemented in schools, but there is limited research exploring whether these educational strategies are effective and a lack of involvement of teaching professionals in the research. Given that the majority of children and young people with autism spend most of their time in school and not in early or specialised intervention programmes, there is a compelling need to conduct better educational research and implement educational interventions in schools. We argue that building collaborative partnerships between researchers and school practitioners is central to achieving improved understanding of, and outcomes for, pupils on the autism spectrum. 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TI The role of treatment fidelity on outcomes during a randomized field trial of an autism intervention SO AUTISM LA English DT Article DE autism; fidelity; implementation science; randomized trials; school-based intervention ID INTENSIVE BEHAVIORAL INTERVENTION; COMMUNICATION-SYSTEM PECS; MENTAL-HEALTH-SERVICES; SPECTRUM DISORDERS; YOUNG-CHILDREN; COMPREHENSIVE TREATMENTS; PIVOTAL RESPONSE; IMPLEMENTATION; DISSEMINATION; CHALLENGES AB This randomized field trial comparing Strategies for Teaching based on Autism Research and Structured Teaching enrolled educators in 33 kindergarten-through-second-grade autism support classrooms and 119 students, aged 5-8 years in the School District of Philadelphia. Students were assessed at the beginning and end of the academic year using the Differential Ability Scales. Program fidelity was measured through video coding and use of a checklist. Outcomes were assessed using linear regression with random effects for classroom and student. Average fidelity was 57% in Strategies for Teaching based on Autism Research classrooms and 48% in Structured Teaching classrooms. There was a 9.2-point (standard deviation = 9.6) increase in Differential Ability Scales score over the 8-month study period, but no main effect of program. There was a significant interaction between fidelity and group. In classrooms with either low or high program fidelity, students in Strategies for Teaching based on Autism Research experienced a greater gain in Differential Ability Scales score than students in Structured Teaching (11.2 vs 5.5 points and 11.3 vs 8.9 points, respectively). In classrooms with moderate fidelity, students in Structured Teaching experienced a greater gain than students in Strategies for Teaching based on Autism Research (10.1 vs 4.4 points). 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Using a unique combination of quantitative, qualitative and social network methods, we investigated the extent and nature of autistic children's friendships from their perspective and from those of their mothers, teachers and classroom peers. Consistent with previous research, children with autism (n = 12), aged between 9 and 11 years, rated their friendships to be of poorer quality than their non-autistic classroom peers (n = 11). There was, however, much variability in autistic children's ratings, which, unexpectedly, was related to neither children's cognitive ability nor their theory of mind ability. Encouragingly, the children generally reported satisfaction with their friendships, and although no child was socially isolated, the degree of inclusion in friendship networks varied widely. Furthermore, autistic children's social motivation emerged as a key factor in parents' and teachers' reports in determining both the nature and extent of their friendships. Adults played an active role in supporting children's friendships, but this sometimes conflicted with what the children wanted. These findings highlight the need to ascertain the perspectives of young people with autism on their friendships and to consider the social and ethical implications of when and how to intervene. C1 [Calder, Lynsey; Hill, Vivian; Pellicano, Elizabeth] Univ London, Inst Educ, London WC1H 0AA, England. [Calder, Lynsey] Haringey Educ Psychol Serv, London, England. RP Pellicano, E (reprint author), Univ London, Inst Educ, Dept Psychol & Human Dev, Ctr Res Autism & Educ CRAE, 25 Woburn Sq, London WC1H 0AA, England. 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Gal, Eynat TI Increasing social engagement in children with high-functioning autism spectrum disorder using collaborative technologies in the school environment SO AUTISM LA English DT Article DE children with high-functioning autism spectrum disorder; cognitive behavioral therapy; social engagement; technology ID ASPERGER-SYNDROME; TRAINING-PROGRAM; PEER INTERACTION; INTERVENTION; ADOLESCENTS; SKILLS; ADULTS; MIND; IMPAIRMENT; PERCEPTION AB This study examined the effectiveness of a school-based, collaborative technology intervention combined with cognitive behavioral therapy to teach the concepts of social collaboration and social conversation to children with high-functioning autism spectrum disorders (n = 22) as well as to enhance their actual social engagement behaviors (collaboration and social conversation) with peers. Two computer programs were included in the intervention: "Join-In" to teach collaboration and "No-Problem" to teach conversation. Assessment in the socio-cognitive area included concept perception measures, problem solving, Theory of Mind, and a dyadic drawing collaborative task to examine change in children's social engagement. Results demonstrated improvement in the socio-cognitive area with children providing more active social solutions to social problems and revealing more appropriate understanding of collaboration and social conversation after intervention, with some improvement in Theory of Mind. Improvement in actual social engagement was more scattered. C1 [Bauminger-Zviely, Nirit; Eden, Sigal] Bar Ilan Univ, IL-52900 Ramat Gan, Israel. [Zancanaro, Massimo] FBK, Trento, Italy. [Weiss, Patrice L.; Gal, Eynat] Univ Haifa, IL-31999 Haifa, Israel. RP Bauminger-Zviely, N (reprint author), Bar Ilan Univ, Sch Educ, IL-52900 Ramat Gan, Israel. 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TI A play and joint attention intervention for teachers of young children with autism: A randomized controlled pilot study SO AUTISM LA English DT Article DE autism; intervention; joint attention; joint engagement; play; preschool; teachers ID SYMBOLIC PLAY; SPECTRUM-DISORDER; LANGUAGE; COMMUNICATION; PRESCHOOLERS; ENGAGEMENT; TODDLERS AB The aim of this study was to pilot test a classroom-based intervention focused on facilitating play and joint attention for young children with autism in self-contained special education classrooms. Thirty-three children with autism between the ages of 3 and 6 years participated in the study with their classroom teachers (n = 14). The 14 preschool special education teachers were randomly assigned to one of three groups: (1) symbolic play then joint attention intervention, (2) joint attention then symbolic intervention, and (3) wait-list control period then further randomized to either group 1 or group 2. In the intervention, teachers participated in eight weekly individualized 1-h sessions with a researcher that emphasized embedding strategies targeting symbolic play and joint attention into their everyday classroom routines and activities. The main child outcome variables of interest were collected through direct classroom observations. Findings indicate that teachers can implement an intervention to significantly improve joint engagement of young children with autism in their classrooms. Furthermore, multilevel analyses showed significant increases in joint attention and symbolic play skills. Thus, these pilot data emphasize the need for further research and implementation of classroom-based interventions targeting play and joint attention skills for young children with autism. C1 [Wong, Connie S.] Univ N Carolina, Chapel Hill, NC 27599 USA. RP Wong, CS (reprint author), Univ N Carolina, Frank Porter Graham Child Dev Inst, Sheryl Mar South CB 8040, Chapel Hill, NC 27599 USA. 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TI Adapted shared reading at school for minimally verbal students with autism SO AUTISM LA English DT Article DE autism; engagement; literacy; school-based intervention; shared reading; single-case research design ID SPECTRUM DISORDER; JOINT ATTENTION; CHILDREN; DISABILITIES; COMPREHENSION; INSTRUCTION; PATTERNS; STORIES AB Almost nothing is known about the capacity of minimally verbal students with autism to develop literacy skills. Shared reading is a regular practice in early education settings and is widely thought to encourage language and literacy development. There is some evidence that children with severe disabilities can be engaged in adapted shared reading activities. The current study examines the impact of teacher-led adapted shared reading activities on engagement and story comprehension in minimally verbal 5-6-year-old children with autism using a multiple baseline/alternating treatment design. Four students and three teachers participated. Teachers conducted adapted shared reading activities with modified books (visual supports, three-dimensional objects, simplified text) and used specific strategies for increasing student engagement. Student performance during adapted activities was compared to performance during standard shared reading sessions. Results: All four students showed increased story comprehension and engagement during adapted shared reading. Average percentage of session engaged was 87%-100% during adapted sessions, compared with 41%-52% during baseline. Average number of correct responses to story comprehension questions was 4.2-4.8 out of 6 during adapted sessions compared with 1.2-2 during baseline. Visual supports, tactile objects, and specific teaching strategies offer ways for minimally verbal students to meaningfully participate in literacy activities. Future research should investigate adapted shared reading activities implemented classroomwide as well as joint engagement, language, and literacy outcomes after using such activities over time. C1 [Mucchetti, Charlotte A.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Mucchetti, CA (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,Rm 68-217, Los Angeles, CA 90024 USA. EM cmucchetti@gmail.com CR Anderson DK, 2007, J CONSULT CLIN PSYCH, V75, P594, DOI 10.1037/0022-006X.75.4.594 Biemiller A., 2003, READING PSYCHOL, V24, P323, DOI DOI 10.1080/02702710390227297 Browder D, 2009, REM SPEC EDUC, V30, P269, DOI 10.1177/0741932508315054 Browder DM, 2008, RES PRACT PERS SEV D, V33, P3 Browder DM, 2006, EXCEPT CHILDREN, V72, P392 Bruinsma Y, 2004, MENT RETARD DEV D R, V10, P169, DOI 10.1002/mrdd.20036 Coyne M., 2004, EXCEPTIONALITY, V12, P145, DOI DOI 10.1207/S15327035EX1203_3 Davie J, 2002, ED PSYCHOL, V22, P445, DOI 10.1080/0144341022000003123 Fisher D, 2008, READ TEACH, V61, P548, DOI 10.1598/RT.61.7.4 Gormley S, 2005, READ WRIT Q, V21, P307, DOI 10.1080/10573560591007353 Holdaway D., 1982, THEOR PRACT, V21, P293, DOI 10.1080/00405848209543021 Justice LM, 2002, TEACHING EXCEPTIONAL, V34, P8 Kasari C, 2010, J AUTISM DEV DISORD, V40, P1045, DOI 10.1007/s10803-010-0955-5 Katims DS, 2000, EDUC TRAIN MENT RET, V35, P3 Kazdin A. 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S., 2007, INT J SPECIAL ED, V22, P54 NR 31 TC 1 Z9 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD MAY PY 2013 VL 17 IS 3 SI SI BP 358 EP 372 DI 10.1177/1362361312470495 PG 15 WC Psychology, Developmental SC Psychology GA 298EQ UT WOS:000330307300008 PM 23592847 ER PT J AU Fitzmaurice, CS Corbier, JR Wikstrom, EA Sherry, L Cordova, ML Howden, R AF Fitzmaurice, Christopher S. Corbier, Jean-Ronel Wikstrom, Erik A. Sherry, Lee Cordova, Mitchell L. Howden, Reuben TI Effects Of Resistance Training On Social Behavior, Self-esteem, And Physical Fitness In Children With Autism SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [Fitzmaurice, Christopher S.; Wikstrom, Erik A.; Sherry, Lee; Howden, Reuben] UNC Charlotte, Charlotte, NC USA. [Corbier, Jean-Ronel] Carolinas Med Ctr North East, Concord, NC USA. [Cordova, Mitchell L.] Florida Gulf Coast Univ, Ft Myers, FL USA. NR 0 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 2033 BP 472 EP 472 PG 1 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469703364 ER PT J AU Schenkelberg, MA Rosenkranz, RR Milliken, GA Dzewaltowski, DA AF Schenkelberg, Michaela A. Rosenkranz, Richard R. Milliken, George A. Dzewaltowski, David A. TI Social Environmental Variables Associated with Physical Activity Behaviors of Children with Autism Spectrum Disorders SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-College-of-Sports-Medicine CY MAY 28-JUN 01, 2013 CL Indianapolis, IN SP Amer Coll Sports Med C1 [Schenkelberg, Michaela A.; Rosenkranz, Richard R.; Milliken, George A.; Dzewaltowski, David A.] Kansas State Univ, Manhattan, KS 66506 USA. NR 0 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2013 VL 45 IS 5 SU 1 MA 2080 BP 486 EP 486 PG 1 WC Sport Sciences SC Sport Sciences GA 300ND UT WOS:000330469704025 ER PT J AU Roxburgh, CA Carbone, VJ AF Roxburgh, Carole A. Carbone, Vincent J. TI The Effect of Varying Teacher Presentation Rates on Responding During Discrete Trial Training for Two Children With Autism SO BEHAVIOR MODIFICATION LA English DT Article DE antecedent manipulations; autism; instructional demands; presentation rate; problem behavior ID BEHAVIORAL TREATMENT; INTERVAL DURATION; SELF-STIMULATION; ESCAPE AB Recent research has emphasized the importance of manipulating antecedent variables to reduce interfering behaviors when teaching persons with autism. Few studies have focused on the effects of the rate of teacher-presented instructional demands as an independent variable. In this study, an alternating treatment design was used to evaluate the effects of varied rates of teacher-presented demands (1 s, 5 s, 10 s) on the occurrence of problem behavior, opportunities to respond, responses emitted, accuracy of responding, and magnitude and rate of reinforcement for two children with autism. Results indicated that fast presentation rate (1 s) resulted in lower rates of problem behavior, higher frequencies of instructional demands, higher frequencies of participant responding, and greater magnitudes and rates of reinforcement. Differential effects on accuracy of responding across conditions were not observed. Implications for manipulating the rate of teacher-presented instructional demands as an antecedent variable to reduce problem behavior are discussed. C1 [Roxburgh, Carole A.; Carbone, Vincent J.] Carbone Clin, Valley Cottage, NY 10989 USA. RP Carbone, VJ (reprint author), Carbone Clin, 614 Corp Way,Suite 1, Valley Cottage, NY 10989 USA. EM drvjc@aol.com CR BARLOW DH, 1979, J APPL BEHAV ANAL, V12, P199, DOI 10.1901/jaba.1979.12-199 Carbone V. 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F., 2008, EFFECTIVE PRACTICES, P181 Tincani M., 2005, J DIRECT INSTRUCTION, V5, P97 Tincani M., 2012, J DEV PHYS DISABILIT Tincani M., 2008, J BEHAV ED, V17, P79, DOI DOI 10.1007/S10864-008-9063-4 VALCANTE G, 1989, J APPL BEHAV ANAL, V22, P43, DOI 10.1901/jaba.1989.22-43 Wilder D. A., 1998, BEHAV INTERVENT, V13, P43, DOI [10.1002/(SICI)1099-078X(199802)13:1<43::AID-BIN3>3.0.CO;2-1, DOI 10.1002/(SICI)1099-078X(199802)] NR 39 TC 3 Z9 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 EI 1552-4167 J9 BEHAV MODIF JI Behav. Modificat. PD MAY PY 2013 VL 37 IS 3 BP 298 EP 323 DI 10.1177/0145445512463046 PG 26 WC Psychology, Clinical SC Psychology GA 297YK UT WOS:000330290800002 PM 23144174 ER PT J AU Falkai, P Reich-Erkelenz, D Malchow, B Schmitt, A Majtenyi, K AF Falkai, P. Reich-Erkelenz, D. Malchow, B. Schmitt, A. Majtenyi, K. TI Brain Development before Onset of the First Psychotic Episode and during Outcome of Schizophrenia SO FORTSCHRITTE DER NEUROLOGIE PSYCHIATRIE LA German DT Review DE brain development; first-episode schizophrenia; schizoprenic disorder ID LIMBIC SYSTEM; BASAL GANGLIA; HIPPOCAMPAL; VOLUMES; NEUREGULIN-1; METAANALYSIS; 1ST-EPISODE; POSTMORTEM; PLASTICITY; PATHOLOGY AB A circumscribed association between copy number variations and the diagnosis of schizophrenia or autism but not bipolar disorder supports the notion of schizophrenia and autism principally representing a disturbed brain development. Data of multiply affected families show certain brain structural (e.g. hippocampal) changes to also be present in their first-grade relatives with: out leading to psychopathological abnormalities. It thus can be concluded that there exist regional fronto-temporal changes in schizophrenia due to genetically early determined primary vulnerability. The transition of this vulnerability into a prodrome to the point of the fully developed disease is triggered by relevant environmental factors. Hippocampal brain structural changes do not base on neuronal loss, for which reason the underlying mechanism might be a reduction of neuropil and thus a disturbance of synaptic processes or even regenerative mechanisms. Thus, disturbed regenerative mechanisms might be linked to the course of schizophrenic psychosis: the more pronounced the negative symptoms, the more evident the impaired synaptic or neuronal plasticity. Based on initial data we speculate the disturbed synaptic/plastic processes to result from an impaired epigenetic regulation. This could explain how relevant environmental factors (pregnancy and birth complications, early childhood abuse or cannabis abuse) via risk genes might lead to a destabilized neuronal network which in the end could trigger schizophrenia symptoms on the behavioral level. C1 [Falkai, P.; Reich-Erkelenz, D.; Malchow, B.; Schmitt, A.] Univ Munich, Klin Psychiat & Psychotherapie, D-80336 Munich, Germany. [Majtenyi, K.] Semmelweis Univ Budapest, Neuropathol & Prion Dis Reference Ctr, Budapest, Hungary. RP Falkai, P (reprint author), Univ Munich, Klin Psychiat & Psychotherapie, Nussbaumstr 7, D-80336 Munich, Germany. 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Psychiatr. PD MAY PY 2013 VL 81 IS 5 BP 260 EP 264 DI 10.1055/s-0033-1335548 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 161VK UT WOS:000320221200021 PM 23695790 ER PT J AU d'Abrera, C Franklin, C O'Brien, G Trollor, J AF d'Abrera, Carlos Franklin, Catherine O'Brien, Gregory Trollor, Julian TI PSYCHIATRIC ILLNESS AND BEHAVIOURAL DISORDERS IN ADULTS WITH AUTISM: ESSENTIAL MANAGEMENT SKILLS FOR THE PSYCHIATRIST SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract ID MENTAL ILL-HEALTH; INTELLECTUAL DISABILITIES; PREVALENCE C1 [Franklin, Catherine; O'Brien, Gregory] Univ Queensland, St Lucia, Qld, Australia. [Trollor, Julian] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. CR Cooper SA, 2007, BRIT J PSYCHIAT, V190, P27, DOI 10.1192/bjp.bp.106.022483 Melville CA, 2008, J AUTISM DEV DISORD, V38, P1676, DOI 10.1007/s10803-008-0549-7 NR 2 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2013 VL 47 IS S1 SU 1 BP 6 EP 7 PG 2 WC Psychiatry SC Psychiatry GA 287LI UT WOS:000329542900015 ER PT J AU Eapen, V Fulton, E Crncec, R Walter, A AF Eapen, Valsamma Fulton, Elizabeth Crncec, Rudi Walter, Amelia TI EARLY START DENVER MODEL: AN EARLY INTERVENTION PROGRAM FOR PRESCHOOL CHILDREN W ITH AUTISM SPECTRUM DISORDER (ASD) SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 [Eapen, Valsamma; Crncec, Rudi; Walter, Amelia] Univ New S Wales, Sydney, NSW, Australia. [Fulton, Elizabeth] KU Childrens Serv, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2013 VL 47 IS S1 SU 1 BP 19 EP 19 PG 1 WC Psychiatry SC Psychiatry GA 287LI UT WOS:000329542900045 ER PT J AU Cecinati, V Principi, N Brescia, L Giordano, P Esposito, S AF Cecinati, Valerio Principi, Nicola Brescia, Letizia Giordano, Paola Esposito, Susanna TI Vaccine administration and the development of immune thrombocytopenic purpura in children SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Review DE adverse events; immune thrombocytopenic purpura; MMR; platelets; vaccine safety; vaccine ID MUMPS-RUBELLA IMMUNIZATION; HEPATITIS-B-VACCINE; INFLUENZA VACCINATION; UNITED-STATES; MMR VACCINE; MEASLES; RISK; ADULTS AB The most important reasons cited by the opponents of vaccines are concerns about vaccine safety. Unlike issues such as autism for which no indisputable documentation of direct relationship with vaccine use is available, immune thrombocytopenic purpura (ITP) is an adverse event that can really follow vaccine administration, and may limit vaccine use because little is known about which vaccines it may follow, its real incidence and severity, the risk of chronic disease, or the possibility of recurrences after new doses of the same vaccine. The main aim of this review is to clarify the real importance of thrombocytopenia as an adverse event and discuss how it may interfere with recommended vaccination schedules. The available data clearly indicate that ITP is very rare and the only vaccine for which there is a demonstrated cause-effect relationship is the measles, mumps and rubella (MMR) vaccine that can occur in 1 to 3 children every 100,000 vaccine doses. However, also in this case, the incidence of ITP is significantly lower than that observed during the natural diseases that the vaccine prevents. Consequently, ITP cannot be considered a problem limiting vaccine use except in the case of children suffering from chronic ITP who have to receive MMR vaccine. In these subjects, the risk-benefit ratio of the vaccine should be weighed against the risk of measles in the community. C1 [Cecinati, Valerio] Santo Spirito Hosp, Dept Hematol, Div Pediat Hematol & Oncol, Pescara, Italy. [Principi, Nicola; Esposito, Susanna] Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Pathophysiol & Transplantat, Pediat Clin 1, Milan, Italy. [Brescia, Letizia] IRCCS Bambino Gesu Hosp, Hematol Oncol Unit, Rome, Italy. [Giordano, Paola] Univ Bari, Dept Dev Age Biomed, Bari, Italy. RP Esposito, S (reprint author), Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Pathophysiol & Transplantat, Pediat Clin 1, Milan, Italy. EM susanna.esposito@unimi.it FU Italian Ministry of Health (Bando Giovani Ricercatori) FX The authors have no conflict of interest to declare. This study was supported in part by a grant from the Italian Ministry of Health (Bando Giovani Ricercatori 2007). 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PD MAY 1 PY 2013 VL 9 IS 5 BP 1158 EP 1162 DI 10.4161/hv.23601 PG 5 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 259SD UT WOS:000327545700031 PM 23324619 ER PT J AU Gabriels, RL Agnew, JA Pan, ZX Holt, KD Reynolds, A Laudenslager, ML AF Gabriels, Robin L. Agnew, John A. Pan, Zhaoxing Holt, Katherine D. Reynolds, Ann Laudenslager, Mark L. TI Elevated repetitive behaviors are associated with lower diurnal salivary cortisol levels in autism spectrum disorder SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Adjunctive behavior; Autism spectrum disorder; Cortisol; Rhythms; Coping; Cortisol awakening response; Individual variability; Hypothalamic-pituitary-adrenal axis; Repetitive behaviors; Stereotypies; Sleep ID PITUITARY-ADRENAL ACTIVITY; STEREOTYPED BEHAVIORS; MENTAL-RETARDATION; CIRCADIAN-RHYTHMS; YOUNG-CHILDREN; CHRONIC STRESS; ADULTS; DETERMINANTS; SENSITIVITY; PREVALENCE AB Previously, we reported a subgroup of children with autism spectrum disorders (ASD) had consistently high rates of repetitive behaviors (RBs) with abnormal sensory sensitivity. Given evidence of lower cortisol levels in response to stress and associated sensory sensitivity in the ASD population, this pilot study evaluates whether the presence of RBs reflects an underlying pathophysiology related to cortisol regulation. Diurnal salivary cortisol from 21 children with ASD and high versus low occurrence RBs were collected at four time points over three consecutive days. Although a typical decline in salivary cortisol was observed, participants in the high RB group showed 36% lower diurnal salivary cortisol than the low RB group. Age, IQ, RB type, and sleep quality were unrelated to observed differences. These findings suggest that RBs may serve to mitigate distress or that the glucocorticoid system has been down regulated in association with prolonged distress in this sample population. Published by Elsevier B.V. C1 [Gabriels, Robin L.; Agnew, John A.; Pan, Zhaoxing; Holt, Katherine D.; Reynolds, Ann] Childrens Hosp Colorado, Aurora, CO 80045 USA. [Gabriels, Robin L.; Agnew, John A.; Pan, Zhaoxing; Laudenslager, Mark L.] Univ Colorado Denver, Aurora, CO 80045 USA. RP Gabriels, RL (reprint author), Childrens Hosp Colorado, 13123 E 16th Ave, Aurora, CO 80045 USA. EM Robin.gabriels@childrenscolorado.org; John.agnew@colorado.edu; Zhaoxing.pan@childrenscolorado.org; katherineduncanholt@gmail.com; Ann.Reynolds@childrenscolorado.org; Mark.Laudenslager@ucdenver.edu FU NIH [NR012736-01]; Colorado CTSI [UL1 RR025780]; Developmental Psychobiology Endowment Fund; University of Colorado Denver Anschutz Medical Campus; Department of Psychiatry; Autism Speaks [7498] FX The present study was supported in part by an NIH Grant, NR012736-01 (RLG), and Colorado CTSI Grant Number UL1 RR025780, a grant from the Developmental Psychobiology Endowment Fund, University of Colorado Denver Anschutz Medical Campus, Department of Psychiatry, and Award # 7498 (MLL) from Autism Speaks. The authors are grateful to Briar DeChant, Mark Goldstein, Crystal Natvig, and Kendra Sherwood for their valuable contributions to this study. 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PD MAY PY 2013 VL 93 IS 2 BP 262 EP 268 DI 10.1016/j.biopsycho.2013.02.017 PG 7 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 245LK UT WOS:000326465000002 PM 23466586 ER PT J AU Vanzo, RJ Martin, MM Sdano, MR South, ST AF Vanzo, Rena J. Martin, Megan M. Sdano, Mallory R. South, Sarah T. TI Familial KANK1 deletion that does not follow expected imprinting pattern SO EUROPEAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE 9p24.3; Autism spectrum disorders; Cerebral palsy; Imprinting; KANK1; Monoallelic expression ID COPY-NUMBER VARIANTS; MATERNAL ISODISOMY; UNIPARENTAL DISOMY; CHROMOSOME-9; GENE AB Deletion of the KANK1 gene (also called ANKRD15), located at chromosome position 9p24.3, has been associated with neurodevelopmental disease including congenital cerebral palsy, hypotonia, quadriplegia, and intellectual disability in a four-generation family. The inheritance pattern in this family was suggested to be maternal imprinting, as all affected individuals inherited the deletion from their fathers and monoallelic protein expression was observed. We present a family in which the proband's phenotype, including autism spectrum disorder, motor delay, and intellectual disability, is consistent with this previous report of KANK1 deletions. However, a paternally inherited deletion in the proband's unaffected sibling did not support maternal imprinting. This family raises consideration of further complexity of the KANK1 locus, including variable expressivity, incomplete penetrance, and the additive effects of additional genomic variants or the potential benign nature of inherited copy number variations (CNVs). However, when considered with the previous publication, our case also suggests that KANK1 may be subject to random monoallelic expression as a possible mode of inheritance. It is also important to consider that KANK1 has two alternately spliced transcripts, A and B. These have differential tissue expression and thus potentially differential clinical significance. Based upon cases in the literature, the present case, and information in the Database of Genomic Variants, it is possible that only aberrations of variant A contribute to neurodevelopmental disease. The familial deletion in this present case does not support maternal imprinting as an inheritance pattern. We suggest that other inheritance patterns and caveats should be considered when evaluating KANK1 deletions, which may become increasingly recognized through whole genome microarray testing, whole genome sequencing, and whole exome sequencing techniques. (C) 2013 Elsevier Masson SAS. All rights reserved. C1 [Vanzo, Rena J.; Martin, Megan M.; Sdano, Mallory R.] Lineagen Inc, Salt Lake City, UT 84108 USA. [South, Sarah T.] ARUP Labs, Salt Lake City, UT USA. 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TI Nitric Oxide Mediated Colonic Motility Is Altered in the Neuroligin-3 R451c Mouse Model of Autism SO GASTROENTEROLOGY LA English DT Meeting Abstract CT Digestive Disease Week CY MAY 18-21, 2013 CL Orlando, FL NR 0 TC 0 Z9 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2013 VL 144 IS 5 SU 1 BP S543 EP S543 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 199LY UT WOS:000322997203161 ER PT J AU Theoharides, T Zhang, BD Asadi, S Weng, ZY AF Theoharides, Theoharis Zhang, Bodi Asadi, Shahrzad Weng, Zuyi TI Human mast cells secrete mitochondrial DNA that has inflammatory actions, is increased in the serum of children with autism, and is inhibited by luteolin SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Theoharides, Theoharis; Zhang, Bodi; Asadi, Shahrzad; Weng, Zuyi] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Theoharides, Theoharis; Asadi, Shahrzad] Tufts Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P3155 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987103081 ER PT J AU [Anonymous] AF [Anonymous] TI Autism research priorities SO PSYCHOLOGIST LA English DT Letter NR 0 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 2013 VL 26 IS 5 BP 323 EP 323 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 204KH UT WOS:000323363700020 ER PT J AU Hopkins, WD Taglialatela, JP AF Hopkins, William D. Taglialatela, Jared P. TI Initiation of Joint Attention is Associated with Morphometric Variation in the Anterior Cingulate Cortex of Chimpanzees (Pan troglodytes) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE anterior cingulate cortex; communication; joint attention ID AUTISM SPECTRUM DISORDER; GORILLAS GORILLA-GORILLA; WHOLE-BRAIN ANALYSIS; VON ECONOMO NEURONS; NEUROCOGNITIVE FUNCTION; GESTURAL COMMUNICATION; FUTURE-DIRECTIONS; SOCIAL COGNITION; STRUCTURAL MRI; YOUNG-CHILDREN AB In developing human children, joint attention (JA) is an important preverbal skill fundamental to the development of language. Poor JA skills have been described as a behavioral risk factor for some neurodevelopmental disorders, such as autism spectrum disorder. It has been hypothesized that the anterior cingulate cortex (ACC) plays an important role in the development of JA in human children. Here, we tested whether the morphometry and lateralization of the ACC differed between chimpanzees that were classified as either consistently or inconsistently engaging in JA with a human experimenter. Results showed that chimpanzees that performed poorly on the JA task had larger gray matter (GM) volumes in the ACC compared to apes that performed well on the task. In addition, both population-level asymmetries and sex differences in the volume of GM were found within the ACC. Specifically, females had relatively larger GM volumes in two of the three subregions of the ACC compared to males, and significant leftward asymmetries were found for two of the subregions whereas a rightward bias was observed in the third. Based on these findings, we suggest that the ACC plays an important role in mediating JA, not just in humans, but also chimpanzees. We further suggest that the differences found between groups may reflect inherent differences in the amount of white matter within the ACC, thereby suggesting reduced connectivity between the ACC and other cortical regions in chimpanzees with poor JA skills. Am. J. Primatol. 75:441-449, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Hopkins, William D.; Taglialatela, Jared P.] Yerkes Natl Primate Res Ctr, Div Dev & Cognit Neurosci, Atlanta, GA USA. [Hopkins, William D.] Georgia State Univ, Inst Neurosci, Atlanta, GA 30303 USA. [Hopkins, William D.] Georgia State Univ, Language Res Ctr, Atlanta, GA 30303 USA. [Taglialatela, Jared P.] Kennesaw State Univ, Dept Biol & Phys, Kennesaw, GA USA. RP Hopkins, WD (reprint author), POB 5030, Atlanta, GA 30302 USA. EM whopkins4@gsu.edu FU NIH [MH-92923, NS-42867, HD-56232, HD-60563] FX Contract grant sponsor: NIH; contract grant numbers: MH-92923; NS-42867; HD-56232; HD-60563. 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J. Primatol. PD MAY PY 2013 VL 75 IS 5 SI SI BP 441 EP 449 DI 10.1002/ajp.22120 PG 9 WC Zoology SC Zoology GA 115LY UT WOS:000316814900006 PM 23300067 ER PT J AU Roberts, AL Lyall, K Rich-Edwards, JW Ascherio, A Weisskopf, MG AF Roberts, Andrea L. Lyall, Kristen Rich-Edwards, Janet W. Ascherio, Alberto Weisskopf, Marc G. TI Association of Maternal Exposure to Childhood Abuse With Elevated Risk for Autism in Offspring SO JAMA PSYCHIATRY LA English DT Article ID RECEPTOR-ALPHA EXPRESSION; PITUITARY-ADRENAL AXIS; MEDIAL PREOPTIC AREA; SPECTRUM DISORDERS; SEXUAL-ABUSE; ADULT WOMEN; HOUSEHOLD DYSFUNCTION; PSYCHIATRIC-DISORDERS; DIAGNOSTIC INTERVIEW; PRENATAL INFECTION AB Importance: Adverse perinatal circumstances have been associated with increased risk for autism in offspring. Women exposed to childhood abuse experience more adverse perinatal circumstances than women unexposed, but whether maternal abuse is associated with autism in offspring is unknown. Objectives: To determine whether maternal exposure to childhood abuse is associated with risk for autism in offspring and whether possible increased risk is accounted for by a higher prevalence of adverse perinatal circumstances among abused women, including toxemia, low birth weight, gestational diabetes, previous induced abortion, intimate partner abuse, pregnancy length shorter than 37 weeks, selective serotonin reuptake inhibitor use, and alcohol use and smoking during pregnancy. Design and Setting: Nurses' Health Study II, a population-based longitudinal cohort of 116 430 women. Participants: Nurses with data on maternal childhood abuse and child's autism status (97.0% were of white race/ethnicity). Controls were randomly selected from among children of women who did not report autism in offspring (participants included 451 mothers of children with autism and 52 498 mothers of children without autism). Main Outcome Measures: Autism spectrum disorder in offspring, assessed by maternal report and validated with the Autism Diagnostic Interview-Revised in a subsample. Results: Exposure to abuse was associated with increased risk for autism in children in a monotonically increasing fashion. The highest level of abuse was associated with the greatest prevalence of autism (1.8% vs 0.7% among women not abused, P=.005) and with the greatest risk for autism adjusted for demographic factors (risk ratio, 3.7; 95% CI, 2.3-5.8). All adverse perinatal circumstances except low birth weight were more prevalent among women abused in childhood. Adjusted for perinatal factors, the association of maternal childhood abuse with autism in offspring was slightly attenuated (risk ratio for highest level of abuse, 3.0; 95% CI, 1.9-4.8). Conclusions and Relevance: We identify an intergenerational association between maternal exposure to childhood abuse and risk for autism in the subsequent generation. Adverse perinatal circumstances accounted for only a small portion of this increased risk. C1 [Roberts, Andrea L.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Roberts, Andrea L.; Lyall, Kristen; Ascherio, Alberto; Weisskopf, Marc G.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Rich-Edwards, Janet W.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Lyall, Kristen] Univ Calif Davis, Med Invest Neurodev Disorders MIND Inst, Sacramento, CA 95817 USA. RP Roberts, AL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Kresge Bldg,677 Huntington Ave, Boston, MA 02115 USA. EM aroberts@hsph.harvard.edu FU Department of Defense [W81XWH-08-1-0499]; US Army Medical Research and Materiel Command [A-14917]; National Institutes of Health [5-T32MH073124-08, CA50385] FX This study was funded by grant W81XWH-08-1-0499 from the Department of Defense, by grant A-14917 from the US Army Medical Research and Materiel Command (Drs Ascherio and Weisskopf), and by grant 5-T32MH073124-08 from the National Institutes of Health (Dr Lyall). The Nurses' Health Study II is funded in part by grant CA50385 from the National Institutes of Health. 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Sandin, Sven Reichenberg, Abraham Langstrom, Niklas Lichtenstein, Paul McGrath, John J. Hultman, Christina M. TI Autism Risk Across Generations A Population-Based Study of Advancing Grandpaternal and Paternal Age SO JAMA PSYCHIATRY LA English DT Article ID DE-NOVO MUTATIONS; PERVASIVE DEVELOPMENTAL DISORDERS; COPY-NUMBER VARIATION; SPECTRUM DISORDERS; PARENTAL AGE; SCHIZOPHRENIA; SPERM; EPIDEMIOLOGY; PATTERNS; DISEASE AB Importance: Advancing paternal age has been linked to autism. Objective: To further expand knowledge about the association between paternal age and autism by studying the effect of grandfathers' age on childhood autism. Design: Population-based, multigenerational, case-control study. Setting: Nationwide multigeneration and patient registers in Sweden. Participants: We conducted a study of individuals born in Sweden since 1932. Parental age at birth was obtained for more than 90% of the cohort. Grandparental age at the time of birth of the parent was obtained for a smaller subset (5936 cases and 30 923 controls). Main Outcome and Measure: International Classification of Diseases diagnosis of childhood autism in the patient registry. Results: A statistically significant monotonic association was found between advancing grandpaternal age at the time of birth of the parent and risk of autism in grandchildren. Men who had fathered a daughter when they were 50 years or older were 1.79 times (95% CI, 1.35-2.37; P<.001) more likely to have a grandchild with autism, and men who had fathered a son when they were 50 years or older were 1.67 times (95% CI, 1.35-2.37; P<.001) more likely to have a grandchild with autism, compared with men who had fathered children when they were 20 to 24 years old, after controlling for birth year and sex of the child, age of the spouse, family history of psychiatric disorders, highest family educational level, and residential county. A statistically significant monotonic association was also found between advancing paternal age and risk of autism in the offspring. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on grandparental age. Conclusions and Relevance: Advanced grandparental age was associated with increased risk of autism, suggesting that risk of autism could develop over generations. The results are consistent with mutations and/or epigenetic alterations associated with advancing paternal age. C1 [Frans, Emma M.; Sandin, Sven; Langstrom, Niklas; Lichtenstein, Paul; Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Langstrom, Niklas] Karolinska Inst, Ctr Violence Prevent, SE-17177 Stockholm, Sweden. [Sandin, Sven; Reichenberg, Abraham] Kings Coll London, Kings Hlth Partners, Inst Psychiat, Dept Psychosis Studies, London WC2R 2LS, England. 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However, this does not preclude the effect of various environmental factors on functional brain lateralization. A strong association of non-right-handedness (left- and mixed-handedness) with various neurodevelopmental conditions (e.g. schizophrenia, autism, Rett syndrome) implies that in some cases, non-right-handedness may be acquired rather than inherited (i.e., pathologically determined). Objective The aim of the study was: (a) re-investigation of several known risk factors for left-handedness (age of mother and/or father, twin pregnancies, and birth order), and (b) examination of hitherto un-investigated factors (type of birth, Apgar score, maternal smoking during pregnancy). Methods Putative, causative environmental agents for this shift in manual distributions are explored in a sample of 1031 high school students (404 males and 627 females) from Belgrade. Both pre-existing (age of parents, twin pregnancy, and birth order) and new (Apgar score, maternal smoking, type of birth) putative agents are examined. Results We found that maternal smoking and low Apgar score (2-6) can significantly increase risk for left-handedness (p=0.046 and p=0.042, respectively).The remaining factors showed no significant association with left-handedness in adolescents. Conclusion Our study clearly demonstrates that left-handedness may be related to maternal smoking during pregnancy and a low Apgar score on birth. C1 [Dragovic, Milan] Graylands Hosp, North Metropolitan Area Hlth Serv Mental Hlth, Clin Res Ctr, Perth, WA, Australia. [Dragovic, Milan] Univ Western Australia, Sch Psychiat & Clin Neurosci, Ctr Clin Res Neuropsychiat, Perth, WA 6009, Australia. [Milenkovic, Sanja] Univ Belgrade, Sch Med, Inst Hyg & Med Ecol, Belgrade, Serbia. [Kocijancic, Dusica] Clin Ctr Serbia, Clin Gynecol & Obstet, Belgrade, Serbia. 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TI Social-Communication Subtypes in Higher Functioning Autism Spectrum Disorders: An Examination Using Factor Analysis SO CLINICAL NEUROPSYCHOLOGIST LA English DT Meeting Abstract NR 0 TC 0 Z9 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD MAY 1 PY 2013 VL 27 IS 4 BP 637 EP 637 PG 1 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 163TZ UT WOS:000320361100213 ER PT J AU Stevens, SJ Van Hecke, A Ryan, M Audrey, C Jeffrey, K Kirsten, S Bridget, D AF Stevens, S. J. Van Hecke, A. Ryan, M. Audrey, C. Jeffrey, K. Kirsten, S. Bridget, D. TI Condition-Dependent Neural Responses in Adolescents With Autism Spectrum Disorders Suggest Modified Continuous EEG Protocols in Autism Experiments Investigating Social Behavior SO CLINICAL NEUROPSYCHOLOGIST LA English DT Meeting Abstract NR 0 TC 0 Z9 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD MAY 1 PY 2013 VL 27 IS 4 BP 641 EP 641 PG 1 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 163TZ UT WOS:000320361100222 ER PT J AU Suh, J Eigsti, I Naigles, L Barton, M Kelley, E Fein, DA AF Suh, J. Eigsti, I Naigles, L. Barton, M. Kelley, E. Fein, D. A. TI Narrative Competence and Pragmatic Language Abilities of Optimal Outcome Children With a History of Autism Spectrum Disorders as Evaluated by Peer Ratings SO CLINICAL NEUROPSYCHOLOGIST LA English DT Meeting Abstract NR 0 TC 0 Z9 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD MAY 1 PY 2013 VL 27 IS 4 BP 642 EP 642 PG 1 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 163TZ UT WOS:000320361100224 ER PT J AU Georgi, B Voight, BF Bucan, M AF Georgi, Benjamin Voight, Benjamin F. Bucan, Maja TI From Mouse to Human: Evolutionary Genomics Analysis of Human Orthologs of Essential Genes SO PLOS GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; DE-NOVO MUTATIONS; VARIANTS; TRANSCRIPTOMES; PATTERNS; SELECTION; DATABASE; RATES AB Understanding the core set of genes that are necessary for basic developmental functions is one of the central goals in biology. Studies in model organisms identified a significant fraction of essential genes through the analysis of null-mutations that lead to lethality. Recent large-scale next-generation sequencing efforts have provided unprecedented data on genetic variation in human. However, evolutionary and genomic characteristics of human essential genes have never been directly studied on a genome-wide scale. Here we use detailed phenotypic resources available for the mouse and deep genomics sequencing data from human populations to characterize patterns of genetic variation and mutational burden in a set of 2,472 human orthologs of known essential genes in the mouse. Consistent with the action of strong, purifying selection, these genes exhibit comparatively reduced levels of sequence variation, skew in allele frequency towards more rare, and exhibit increased conservation across the primate and rodent lineages relative to the remainder of genes in the genome. In individual genomes we observed similar to 12 rare mutations within essential genes predicted to be damaging. Consistent with the hypothesis that mutations in essential genes are risk factors for neurodevelopmental disease, we show that de novo variants in patients with Autism Spectrum Disorder are more likely to occur in this collection of genes. While incomplete, our set of human orthologs shows characteristics fully consistent with essential function in human and thus provides a resource to inform and facilitate interpretation of sequence data in studies of human disease. C1 [Georgi, Benjamin; Voight, Benjamin F.; Bucan, Maja] Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA. [Voight, Benjamin F.] Univ Penn, Dept Pharmacol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Georgi, B (reprint author), Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA. EM bvoight@upenn.edu; bucan@mail.med.upenn.edu FU CHOP/Upenn Autsim Center of Excellence, Pennsylvania Commonwealth grant (PI Schultz); NIH/NIMH R01 grant [R01MH093415]; German Research Foundation (DFG); Alfred P. Sloan Foundation FX This work was supported by the CHOP/Upenn Autsim Center of Excellence, Pennsylvania Commonwealth grant (PI Schultz), and NIH/NIMH R01 grant R01MH093415 (to MB and Steven M. Paul, multiple PIs). BG was supported by a fellowship from the German Research Foundation (DFG). BFV was supported by a fellowship from the Alfred P. Sloan Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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We take stock of the evidence from these studies to explore potentials and limitations of pharmacotherapeutic applications. In healthy participants, intranasally administered OT leads to better emotion recognition and more trust in conspecifics, but the effects appear to be moderated by context (perceived threat of the 'out-group'), personality and childhood experiences. In individuals with untoward childhood experiences, positive behavioral or neurobiological effects seem lowered or absent. In 19 clinical trials, covering autism, social anxiety, postnatal depression, obsessive-compulsive problems, schizophrenia, borderline personality disorder and post-traumatic stress, the effects of OT administration were tested, with doses ranging from 15 IU to more than 7000 IU. The combined effect size was d=0.32 (N=304; 95% confidence interval (CI): 0.18-0.47; P<0.01). However, of all disorders, only studies on autism spectrum disorder showed a significant combined effect size (d=0.57; N=68; 95% CI: 0.15-0.99; P<0.01). We hypothesize that for some of the other disorders, etiological factors rooted in negative childhood experiences may also have a role in the diminished effectiveness of treatment with OT. C1 [Bakermans-Kranenburg, M. J.; van IJzendoorn, M. H.] Leiden Univ, Ctr Child & Family Studies, Rommert Casimir Inst Dev Psychopathol, NL-2300 RB Leiden, Netherlands. RP Bakermans-Kranenburg, MJ (reprint author), Leiden Univ, Ctr Child & Family Studies, Rommert Casimir Inst Dev Psychopathol, POB 9555, NL-2300 RB Leiden, Netherlands. EM bakermans@fsw.leidenuniv.nl; vanijzen@fsw.leidenuniv.nl FU Netherlands Organization for Scientific Research (NWO) FX We were supported by awards from the Netherlands Organization for Scientific Research (NWO) (MJBK: VICI Grant; MHvIJ: SPINOZA prize). 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TI Haplotype structure enables prioritization of common markers and candidate genes in autism spectrum disorder SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE AGRE; autism genetics; autism spectrum disorders; bibliome mining ID DE-NOVO MUTATIONS; GENOME-WIDE; SUSCEPTIBILITY GENE; CHROMOSOME 7Q; COMPULSIVE BEHAVIORS; LINKAGE; ASSOCIATION; LOCUS; RISK; REVEALS AB Autism spectrum disorder (ASD) is a neurodevelopmental condition that results in behavioral, social and communication impairments. ASD has a substantial genetic component, with 88-95% trait concordance among monozygotic twins. Efforts to elucidate the causes of ASD have uncovered hundreds of susceptibility loci and candidate genes. However, owing to its polygenic nature and clinical heterogeneity, only a few of these markers represent clear targets for further analyses. In the present study, we used the linkage structure associated with published genetic markers of ASD to simultaneously improve candidate gene detection while providing a means of prioritizing markers of common genetic variation in ASD. We first mined the literature for linkage and association studies of single-nucleotide polymorphisms, copy-number variations and multi-allelic markers in Autism Genetic Resource Exchange (AGRE) families. From markers that reached genome-wide significance, we calculated male-specific genetic distances, in light of the observed strong male bias in ASD. Four of 67 autism-implicated regions, 3p26.1, 3p26.3, 3q25-27 and 5p15, were enriched with differentially expressed genes in blood and brain from individuals with ASD. Of 30 genes differentially expressed across multiple expression data sets, 21 were within 10 cM of an autism-implicated locus. Among them, CNTN4, CADPS2, SUMF1, SLC9A9, NTRK3 have been previously implicated in autism, whereas others have been implicated in neurological disorders comorbid with ASD. This work leverages the rich multimodal genomic information collected on AGRE families to present an efficient integrative strategy for prioritizing autism candidates and improving our understanding of the relationships among the vast collection of past genetic studies. C1 [Vardarajan, B. N.; Jung, J-Y; Wall, D. P.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02116 USA. [Vardarajan, B. N.] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. [Eran, A.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. [Eran, A.; Kunkel, L. M.] Boston Childrens Hosp, Div Genet, Program Genom, Boston, MA USA. RP Wall, DP (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, 10 Shattuck St, Boston, MA 02116 USA. EM dpwall@hms.harvard.edu FU National Institute of Health [1R01MH085143-01, 1R01MH090611-01A1] FX We would like to thank Autism Speaks, AGRE, and participating families for making the data for this research available. We thank Wall lab members and Professors Isaac Kohane, Marco Ramoni and Peter Tonellato for engaging discussions related to the project. This work was supported by the National Institute of Health Grants 1R01MH085143-01 and 1R01MH090611-01A1 awared to DPW. 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Psychiatr. PD MAY PY 2013 VL 3 AR e262 DI 10.1038/tp.2013.38 PG 9 WC Psychiatry SC Psychiatry GA 174VJ UT WOS:000321184400008 PM 23715297 ER PT J AU Sung, M Ooi, YP Law, GC Goh, TJ Weng, SJ Sriram, B AF Sung, Min Ooi, Yoon Phaik Law, Gloria C. Goh, Tze Jui Weng, Shih Jen Sriram, Bhavani TI Features of Autism in a Singaporean Child with Down Syndrome SO ANNALS ACADEMY OF MEDICINE SINGAPORE LA English DT Letter ID SPECTRUM DISORDERS C1 [Sung, Min; Ooi, Yoon Phaik; Goh, Tze Jui; Weng, Shih Jen] Inst Mental Hlth, Dept Child & Adolescent Psychiat, Buangkok, Singapore. [Sung, Min; Ooi, Yoon Phaik; Weng, Shih Jen] Duke NUS Grad Med Sch Singapore, Singapore, Singapore. [Ooi, Yoon Phaik] Univ Basel, Dept Psychol, CH-4003 Basel, Switzerland. [Law, Gloria C.] Nanyang Technol Univ, Natl Inst Educ, Singapore, Singapore. [Sriram, Bhavani] KK Womens & Childrens Hosp, Singapore, Singapore. 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EM Min_Sung@imh.com.sg RI Ooi, Yoon Phaik/D-3944-2015 CR Aman M., 1986, ABERRANT BEHAV CHECK Capone GT, 2005, AM J MED GENET A, V134A, P373, DOI 10.1002/ajmg.a.30622 Carter JC, 2007, AM J MED GENET B, V144B, P87, DOI 10.1002/ajmg.b.30407 Castillo H, 2008, J DEV BEHAV PEDIATR, V33, P89 Frost LA, 1999, PECS TRAINING MANUAL Goldberg WA, 2003, J AUTISM DEV DISORD, V33, P607, DOI 10.1023/B:JADD.0000005998.47370.ef Kraijer D, 2005, J AUTISM DEV DISORD, V35, P499, DOI 10.1007/s10803-005-5040-0 Lord C., 2002, AUTISM DIAGNOSTIC OB Molloy CA, 2009, J INTELL DISABIL RES, V53, P143, DOI 10.1111/j.1365-2788.2008.01138.x Rutter M., 2003, ADI R AUTISM DIAGNOS Sparrow SS, 2005, VINELAND ADAPTIVE BE Starr EM, 2005, J AUTISM DEV DISORD, V35, P665, DOI 10.1007/s10803-005-0010-0 NR 12 TC 0 Z9 0 PU ACAD MEDICINE SINGAPORE PI REPUBLIC SINGAPORE PA 142 NEIL RD, REPUBLIC SINGAPORE 088871, SINGAPORE SN 0304-4602 J9 ANN ACAD MED SINGAP JI Ann. Acad. Med. Singap. PD MAY PY 2013 VL 42 IS 5 BP 251 EP 252 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 165JZ UT WOS:000320481500008 PM 23771114 ER PT J AU Sweatt, JD AF Sweatt, J. David TI Pitt-Hopkins Syndrome: intellectual disability due to loss of TCF4-regulated gene transcription SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Review DE autism; epigenetics; learning; language cognition; memory; Pitt-Hopkins Syndrome; TCF4 ID LOOP-HELIX PROTEINS; MENTAL-RETARDATION; RETT-SYNDROME; TCF4 GENE; BREATHING ABNORMALITIES; LYMPHOCYTE DEVELOPMENT; SYNAPTIC PLASTICITY; MISSENSE MUTATIONS; CLINICAL SCORE; GENOME-WIDE AB TCF4 (transcription factor 4; E2-2, ITF2) is a transcription factor that when haplo-insufficient causes Pitt-Hopkins Syndrome (PTHS), an autism-spectrum disorder that is associated with pervasive developmental delay and severe intellectual disability. The TCF4 gene is also a risk factor with highly significant linkage to schizophrenia, presumably via overexpression of the TCF4 gene product in the central nervous system. This review will present an overview of the clinical manifestations of PTHS and relate those clinical attributes to the underlying molecular genetics of TCF4. In order to provide a molecular biological context for the loss of function of TCF4 in PTHS, the review will also present a brief overview of the basic biochemistry of TCF4-mediated regulation of cellular and neuronal gene expression. In the final section of this review, I will discuss and speculate upon possible roles for the TCF4 transcription factor in neuronal function and comment upon how understanding these roles may give new insights into the molecular neurobiology of human cognition. C1 [Sweatt, J. David] Univ Alabama Birmingham, Dept Neurobiol, Civitan Int Res Ctr, Birmingham, AL 35294 USA. [Sweatt, J. David] Univ Alabama Birmingham, Evelyn F McKnight Brain Inst, Civitan Int Res Ctr, Birmingham, AL 35294 USA. RP Sweatt, JD (reprint author), Univ Alabama Birmingham, Dept Neurobiol, Civitan Int Res Ctr, 1825 Univ Blvd,SHEL 1010, Birmingham, AL 35294 USA. EM dsweatt@uab.edu FU PTHS Foundation; Simons Foundation; NIMH Grant [MH 57014]; Civitan International; Evelyn F. McKnight Brain Research Foundation FX I thank Andrew Kennedy, Audrey Davidow, Theresa Pauca, Sue Routledge and the entire PTHS support group for innumerable helpful discussions. The work in the author's lab is supported by the PTHS Foundation, the Simons Foundation, NIMH Grant MH 57014, Civitan International and Evelyn F. McKnight Brain Research Foundation. 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Mol. Med. PD MAY PY 2013 VL 45 AR e21 DI 10.1038/emm.2013.32 PG 15 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 174VR UT WOS:000321185200001 PM 23640545 ER PT J AU Stodgell, CJ Bennetto, L Hyman, SL AF Stodgell, Christopher J. Bennetto, L. Hyman, S. L. TI Teratology of autism: From animal models to endophenotypes SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Neurobehavioral-Teratology-Society Held in Conjunction with the 53rd Annual Meeting of the Teratology-Society / 26th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 22-26, 2013 CL Tucson, AZ SP Neurobehavioral Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Stodgell, Christopher J.] Univ Rochester, Sch Med, OB GYN, Rochester, NY USA. [Bennetto, L.] Univ Rochester, Rochester, NY USA. [Hyman, S. L.] Univ Rochester, Sch Med, Rochester, NY USA. NR 0 TC 0 Z9 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2013 VL 37 BP 78 EP 79 DI 10.1016/j.ntt.2013.03.021 PG 2 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 164SD UT WOS:000320428900027 ER PT J AU Miller, MT Ventura, L Stomland, K AF Miller, Marilyn T. Ventura, Liana Stomland, Kerstin TI Thalidomide, Moebius Sequence and misoprostol: Pieces of the autism puzzle SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Neurobehavioral-Teratology-Society Held in Conjunction with the 53rd Annual Meeting of the Teratology-Society / 26th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 22-26, 2013 CL Tucson, AZ SP Neurobehavioral Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Miller, Marilyn T.] U Illinois Eye & Ear Infirm, Chicago, IL USA. [Ventura, Liana] Altino Ventura Fdn, Recife, PE, Brazil. [Stomland, Kerstin] Gothenburg Univ, Inst Neurosci & Physiol, Gothenburg, Sweden. NR 0 TC 0 Z9 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2013 VL 37 BP 79 EP 79 DI 10.1016/j.ntt.2013.03.022 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 164SD UT WOS:000320428900028 ER PT J AU Wenger, TL Kao, C Deardorff, MA McDonald-McGinn, D Zackai, EH Emanuel, BS Schultz, RT Hakonarson, H AF Wenger, Tara L. Kao, C. Deardorff, M. A. McDonald-McGinn, D. Zackai, E. H. Emanuel, B. S. Schultz, R. T. Hakonarson, H. TI Syndromes and the study of autism SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Neurobehavioral-Teratology-Society Held in Conjunction with the 53rd Annual Meeting of the Teratology-Society / 26th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 22-26, 2013 CL Tucson, AZ SP Neurobehavioral Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Wenger, Tara L.; Deardorff, M. A.; McDonald-McGinn, D.; Zackai, E. H.; Emanuel, B. S.] Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA. [Kao, C.; Hakonarson, H.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Wenger, Tara L.; Schultz, R. T.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2013 VL 37 BP 79 EP 79 DI 10.1016/j.ntt.2013.03.023 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 164SD UT WOS:000320428900029 ER PT J AU Stodgell, CJ Bennetto, L Hyman, SL AF Stodgell, C. J. Bennetto, L. Hyman, S. L. TI Teratology of Autism: From Animal Models to Endophenotypes SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Stodgell, C. J.] Univ Rochester, Sch Med, Dept Obstet & Gynecol, Rochester, NY USA. [Bennetto, L.] Univ Rochester, Rochester, NY USA. [Hyman, S. L.] Univ Rochester, Sch Med, Dept Pediat, Rochester, NY 14642 USA. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 283 EP 283 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100027 ER PT J AU Miller, MT Ventura, L Stomland, K AF Miller, M. T. Ventura, L. Stomland, K. TI Thalidomide, Moebius Sequence, and Misoprostol: Pieces of the Autism Puzzle SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Miller, M. T.] Univ Illinois, Eye & Ear Infirm, Chicago, IL 60612 USA. [Ventura, L.] Altino Ventura Fdn, Recife, PE, Brazil. [Stomland, K.] Gothenburg Univ, Inst Neurosci & Physiol, Gothenburg, Sweden. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 284 EP 284 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100028 ER PT J AU Wenger, TL Kao, C Deardorff, MA Mcdonald-Mcgin, D Zackai, EH Emanuel, BS Schultz, RT Hakonarson, H AF Wenger, T. L. Kao, C. Deardorff, M. A. Mcdonald-Mcgin, D. Zackai, E. H. Emanuel, B. S. Schultz, R. T. Hakonarson, H. TI Syndromes and the Study of Autism SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Wenger, T. L.; Deardorff, M. A.; Mcdonald-Mcgin, D.; Zackai, E. H.; Emanuel, B. S.] Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA. [Kao, C.; Hakonarson, H.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Wenger, T. L.; Schultz, R. T.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 284 EP 284 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100029 ER PT J AU Grant, KS Stone, W Ibanez, L Vredevoogd, M Burbacher, TM Faustman, EM Newschaffer, C Lampron, Z Abdullah, M Burkhom, D Clarke, N Durkin, M Ferrell, C Golden, A Kuo, A Lakes, K Lambert, B Landa, R Landrigan, PJ Messinger, D Paterson, S Wang, AT Warren, Z AF Grant, K. S. Stone, W. Ibanez, L. Vredevoogd, M. Burbacher, T. M. Faustman, E. M. Newschaffer, C. Lampron, Z. Abdullah, M. Burkhom, D. Clarke, N. Durkin, M. Ferrell, C. Golden, A. Kuo, A. Lakes, K. Lambert, B. Landa, R. Landrigan, P. J. Messinger, D. Paterson, S. Wang, A. T. Warren, Z. TI Advancing Early Diagnosis of Autism Spectrum Disorder for the National Children's Study SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Grant, K. S.; Vredevoogd, M.; Burbacher, T. M.; Faustman, E. M.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Stone, W.; Ibanez, L.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Newschaffer, C.; Lampron, Z.] Drexel Univ, AJ Drexel Autism Inst, Philadelphia, PA 19104 USA. [Abdullah, M.; Lakes, K.] Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA. [Burkhom, D.; Clarke, N.] Battelle Mem Inst, Ctr Analyt & Publ Hlth, Baltimore, MD USA. [Durkin, M.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. [Durkin, M.] Univ Wisconsin, Dept Pediat, Madison, WI USA. [Ferrell, C.; Landrigan, P. J.] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY USA. [Golden, A.; Landrigan, P. J.] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY USA. [Wang, A. T.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Wang, A. T.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY USA. [Kuo, A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Kuo, A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Lambert, B.; Messinger, D.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Messinger, D.] Univ Miami, Dept Pediat, Coral Gables, FL 33124 USA. [Landa, R.] Kennedy Krieger Inst, Ctr Autism & Related Disorders, Baltimore, MD USA. [Paterson, S.] Univ Penn, Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. [Paterson, S.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Warren, Z.] Vanderbilt Univ, Dept Pediat, Nashville, TN USA. [Warren, Z.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37235 USA. RI Durkin, Maureen/B-7834-2015 NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 332 EP 333 PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100116 ER PT J AU Salafia, CM Dalton, JL Misra, D Stodgell, CJ Katzman, PJ Ruffolo, LI Culhane, J Wadlinger, S Torres, C Landrigan, P Littman, L Sheffield, P Leuthner, S Szabo, S Thiex, N Specker, B Swanson, J Dole, N Thorp, J Eucker, B Clark, EB Varner, MW Taggart, E Durkin, MS Sandoval, MN Moye, J Miller, RK AF Salafia, C. M. Dalton, J. L. Misra, D. Stodgell, C. J. Katzman, P. J. Ruffolo, L., I Culhane, J. Wadlinger, S. Torres, C. Landrigan, P. Littman, L. Sheffield, P. Leuthner, S. Szabo, S. Thiex, N. Specker, B. Swanson, J. Dole, N. Thorp, J. Eucker, B. Clark, E. B. Varner, M. W. Taggart, E. Durkin, M. S. Sandoval, M-N Moye, J. Miller, R. K. CA Natl Children's Study Placental Re TI The Chorionic Surface Vascular Network in Human Placenta: Quantifying Structure to Estimate Gestational Stressors and Life Course Risks, Autism Spectrum Disorder (ASD) As a Model for Future Analyses: National Children's Study and EARLI SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Salafia, C. M.; Dalton, J. L.; Misra, D.; Stodgell, C. J.; Katzman, P. J.; Ruffolo, L., I; Culhane, J.; Wadlinger, S.; Torres, C.; Landrigan, P.; Littman, L.; Sheffield, P.; Leuthner, S.; Szabo, S.; Thiex, N.; Specker, B.; Swanson, J.; Dole, N.; Thorp, J.; Eucker, B.; Clark, E. B.; Varner, M. W.; Taggart, E.; Durkin, M. S.; Sandoval, M-N; Moye, J.; Miller, R. K.; Natl Children's Study Placental Re] Natl Childrens Study Placenta Consortium, Bethesda, MD USA. [Salafia, C. M.; Dalton, J. L.; Misra, D.] Placental Analyt Inc, Larchmont, NY USA. [Stodgell, C. J.; Katzman, P. J.; Ruffolo, L., I; Miller, R. K.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Culhane, J.; Wadlinger, S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Torres, C.] Columbia Univ, New York, NY USA. [Landrigan, P.; Littman, L.; Sheffield, P.] Icahn Sch Med Mt Sinai, New York, NY USA. [Leuthner, S.; Szabo, S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Thiex, N.; Specker, B.] S Dakota State Univ, Brookings, SD 57007 USA. [Swanson, J.] Univ Calif Irvine, Irvine, CA USA. [Dole, N.; Thorp, J.; Eucker, B.] Univ N Carolina, Chapel Hill, NC USA. [Clark, E. B.; Varner, M. W.; Taggart, E.] Univ Utah, Salt Lake City, UT USA. [Durkin, M. S.; Sandoval, M-N] Univ Wisconsin, Madison, WI USA. [Moye, J.] NIH, Natl Childrens Study, Bethesda, MD 20892 USA. RI Durkin, Maureen/B-7834-2015 NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 333 EP 333 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100117 ER PT J AU Jordan, B AF Jordan, Bertrand TI Non-random randomness SO M S-MEDECINE SCIENCES LA French DT Article ID MUTATION; AUTISM AB Whole-genome sequencing of monozygotic twin pairs and of their parents brings new and surprising insights into the rate and distribution of de nova mutations. C1 CoReBio PACA, F-13288 Marseille 9, France. RP Jordan, B (reprint author), CoReBio PACA, Case 901,Parc Sci Luminy, F-13288 Marseille 9, France. EM bertrand.jordan@univ-amu.fr CR Emery AEH, 1983, PRINCIPLES PRACTICE Jordan B., 2012, AUTISME GENE INTROUV Michaelson JJ, 2012, CELL, V151, P1431, DOI 10.1016/j.cell.2012.11.019 Rosenberg SM, 2001, NAT REV GENET, V2, P504, DOI 10.1038/35080556 Sanders SJ, 2011, NEURON, V70, P863, DOI 10.1016/j.neuron.2011.05.002 NR 5 TC 0 Z9 0 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD MAY PY 2013 VL 29 IS 5 BP 545 EP 547 DI 10.1051/medsci/2013295020 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 163NW UT WOS:000320345200020 PM 23732106 ER PT J AU Hoffmann, A Martens, MA Fox, R Rabidoux, P Andridge, R AF Hoffmann, Anne Martens, Marilee A. Fox, Robert Rabidoux, Paula Andridge, Rebecca TI Pragmatic Language Assessment in Williams Syndrome: A Comparison of the Test of Pragmatic Language-2 and the Children's Communication Checklist-2 SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE pragmatics; assessment; Williams syndrome; developmental disabilities ID AUTISM SPECTRUM DISORDERS; IMPAIRMENT; ABILITIES; DEFICITS AB Purpose: Individuals with Williams syndrome (WS) are recognized as having a strong desire for social relationships, yet many of them have difficulty forming and maintaining peer relationships. One cause may be impairments in pragmatic language. The current study compared the assessment of pragmatic language skills in individuals with WS using the Test of Pragmatic Language-Second Edition (TOPL-2; Phelps-Terasaki & Phelps-Gunn, 2007) and the Children's Communication Checklist-Second Edition (CCC-2; Bishop, 2003). Method: Twenty children and adolescents diagnosed with WS were given the TOPL-2, and their parents completed the CCC-2. Results: The TOPL-2 identified 8 of the 14 older children (ages 8-16 years) as having pragmatic language impairment and all of the 6 younger children (ages 6-7 years) as having such. In comparison, the CCC-2 identified 6 of the 14 older children and 2 of the 6 younger children as having pragmatic language impairment. The older group also had a higher composite score than the younger group on the CCC-2. Conclusion: The TOPL-2 identified significantly more participants as having pragmatic language impairment than did the CCC-2. The TOPL-2 may be more useful in assessing pragmatic language in older children than younger children. The results offer important preliminary clinical implications of language measures that may be beneficial in the assessment of individuals with WS. C1 [Hoffmann, Anne; Martens, Marilee A.; Fox, Robert; Rabidoux, Paula; Andridge, Rebecca] Ohio State Univ, Columbus, OH 43210 USA. RP Hoffmann, A (reprint author), Ohio State Univ, Columbus, OH 43210 USA. EM hoffmann.255@osu.edu RI Andridge, Rebecca/C-8457-2012 OI Andridge, Rebecca/0000-0001-9991-9647 CR Adams C, 2001, INT J LANG COMM DIS, V36, P289, DOI 10.1080/13682820119881 Berko-Gleason J, 2009, DEV LANGUAGE Bishop D. V., 2006, CHILDRENS COMMUNICAT Bishop D. V. M., 2003, CHILDRENS COMMUNICAT Bishop DVM, 2009, INT J LANG COMM DIS, V44, P600, DOI 10.1080/13682820802259662 Bishop DVM, 1998, J CHILD PSYCHOL PSYC, V39, P879, DOI 10.1017/S0021963098002832 Brock J, 2007, CLIN LINGUIST PHONET, V21, P673, DOI 10.1080/02699200701541433 Carrow-Woolfolk E, 1999, COMPREHENSIVE ASSESS Grant J, 2002, J CHILD LANG, V29, P403, DOI 10.1017/S030500090200510X Impara J. 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J., 1998, STRONG NARRATIVE ASS Sullivan K, 2003, DEV NEUROPSYCHOL, V23, P85, DOI 10.1207/S15326942DN231&2_5 Tager-Flusberg H, 2000, COGNITION, V76, P59, DOI 10.1016/S0010-0277(00)00069-X Volden J, 2010, AM J SPEECH-LANG PAT, V19, P204, DOI 10.1044/1058-0360(2010/09-0011) Williams K. T., 1997, EXPRESSIVE VOCABULAR Young EC, 2005, LANG SPEECH HEAR SER, V36, P62, DOI 10.1044/0161-1461(2005/006) NR 43 TC 0 Z9 0 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD MAY 1 PY 2013 VL 22 IS 2 BP 198 EP 204 DI 10.1044/1058-0360(2012/11-0131) PG 7 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 156LD UT WOS:000319822600021 PM 23184135 ER PT J AU van Kamp, I Davies, H AF van Kamp, Irene Davies, Hugh TI Noise and health in vulnerable groups: A review SO NOISE & HEALTH LA English DT Review DE Adverse effects; health; noise; vulnerable groups ID ROAD-TRAFFIC NOISE; INTENSIVE-CARE-UNIT; QUALITY-OF-LIFE; ENVIRONMENTAL NOISE; AIRCRAFT NOISE; BLOOD-PRESSURE; CLASSROOM NOISE; SCHOOL-CHILDREN; COMMUNITY NOISE; CORONARY-HEART AB Vulnerable or susceptible groups are mentioned in most reviews and documents regarding noise and health. But only a few studies address this issue in a concrete and focused way. Groups at risk most often mentioned in the literature are children, the elderly, the chronically ill and people with a hearing impairment. The other categories encountered are those of sensitive persons, shiftworkers, people with mental illness (e.g., schizophrenia or autism), people suffering from tinnitus, and fetuses and neonates. The mechanism for this vulnerability has not been clearly described and relevant research has seldom focused on the health effects of noise in these groups in an integrated manner. This paper summarizes the outcomes and major conclusions of a systematic, qualitative review of studies over the past 5 years. This review was prepared for the 10 (th) Conference on Noise as a Public Health Problem (ICBEN, 2011). Evidence is reviewed describing effects, groups assumed to be at risk, and mechanisms pertaining to noise sensitivity and learned helplessness. C1 [Davies, Hugh] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. RP van Kamp, I (reprint author), POB 1,Postvak 10, NL-3720 BA Bilthoven, Netherlands. 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MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1463-1741 J9 NOISE HEALTH JI Noise Health PD MAY-JUN PY 2013 VL 15 IS 64 BP 153 EP 159 DI 10.4103/1463-1741.112361 PG 7 WC Audiology & Speech-Language Pathology; Public, Environmental & Occupational Health SC Audiology & Speech-Language Pathology; Public, Environmental & Occupational Health GA 159RH UT WOS:000320063000001 PM 23689296 ER PT J AU Bateman, C AF Bateman, Chris TI Autism - mitigating a global epidemic SO SAMJ SOUTH AFRICAN MEDICAL JOURNAL LA English DT News Item EM chrisb@hmpg.co.za CR Jepson B, 2007, CHANGING COURSE AUTI McCandless J, 2009, CHILDREN STARVING BR The Centre for Disease Control's National Center for Health Statistics, 2013, CHANG PREV PAR REP A, P65 NR 3 TC 1 Z9 2 PU SA MEDICAL ASSOC PI PRETORIA PA BLOCK F CASTLE WALK CORPORATE PARK, NOSSOB STREET, ERASMUSKLOOF EXT3, PRETORIA, 0002, SOUTH AFRICA SN 0256-9574 J9 SAMJ S AFR MED J JI SAMJ S. Afr. Med. J. PD MAY PY 2013 VL 103 IS 5 BP 276 EP + DI 10.7196/SAMJ.6915 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 155CB UT WOS:000319721900009 PM 23971108 ER PT J AU Ketterer, T West, DW Sanders, VP Hossain, J Kondo, MA Sharif, I AF Ketterer, Tara West, David W. Sanders, Victoria P. Hossain, Jobayer Kondo, Michelle A. Sharif, Iman TI Correlates of Patient Portal Enrollment and Activation in Primary Care Pediatrics SO ACADEMIC PEDIATRICS LA English DT Article DE digital divide; disparities; electronic health records; Medicaid; patient portal ID HEALTH INFORMATION; DIGITAL DIVIDE; INTERNET USE; DISPARITIES; PREFERENCES; SERVICES; CHILDREN; PARENTS AB OBJECTIVE: To identify the demographic, practice site, and clinical predictors of patient portal enrollment and activation among a pediatric primary care population. METHODS: We conducted a cross-sectional analysis of the primary care database of an academic children's hospital that introduced a patient portal in December 2007. RESULTS: We analyzed data for 84,015 children. Over a 4-year period, 38% enrolled in the portal; of these, 26% activated the account. The adjusted odds of portal enrollment was lower for adolescents, Medicaid recipients, low-income families, Asian or other race, and Hispanic ethnicity, and higher for patients with more office encounters, and presence of autism on the problem list. Once enrolled, the odds of portal activation [adjusted odds ratio (95% confidence interval)] was decreased for: Medicaid [0.55 (0.50-0.61)1 and uninsured [0.79 (0.64-0.97)] (vs private insurance), black [0.53 (0.49-0.57)] and other [0.80 (0.71-0.91)] (vs white race), Hispanic ethnicity [0.77 (0.62-0.97)], and increased for: infant age [1.26 (1.15-1.37)] (vs school age), attendance at a resident continuity practice site [1.91 (1.23-2.97)], living further away from the practice (vs under 2 miles)[4.5-8.8 miles: 1.14 (1.02-1.29); more than 8.8 miles: 1.19 (1.07-1.33)], having more office encounters (vs 1-3) [4-7 encounters: 1.40 (1.24-1.59); 8-12 encounters: 1.58 (1.38-1.81); 13+ encounters: 2.09 (1.72-2.55)], and having 3 or more items on the problem list (vs 0) [1.19 (1.07-1.33)]. CONCLUSIONS: Sociodemographic disparities exist in patient portal enrollment/activation in primary care pediatrics. Attendance at a resident continuity practice site, living farther away from the practice, having more office encounters, and having more problem list items increased the odds of portal activation. C1 [Ketterer, Tara; Hossain, Jobayer] Nemours Biomed Res, Wilmington, DE USA. [West, David W.] Nemours Hlth Informat, Wilmington, DE USA. [Sanders, Victoria P.] Nemours Childrens Clin Orlando, NHI Business & Ancillary Support, Orlando, FL USA. [Kondo, Michelle A.] US Forest Serv, USDA, Philadelphia Field Stn, Philadelphia, PA USA. [Kondo, Michelle A.] Univ Penn, Philadelphia, PA 19104 USA. [Sharif, Iman] Alfred I DuPont Hosp Children, Dept Gen Pediat, Wilmington, DE 19803 USA. [Sharif, Iman] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, Philadelphia, PA 19107 USA. RP Sharif, I (reprint author), Alfred I DuPont Hosp Children, Div Gen Pediat, 1600 Rockland Rd, Wilmington, DE 19803 USA. 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Pediatr. PD MAY-JUN PY 2013 VL 13 IS 3 BP 264 EP 271 PG 8 WC Pediatrics SC Pediatrics GA 148MW UT WOS:000319249700013 PM 23680344 ER PT J AU Dahdouh-Guermouche, A Taleb, M Courtet, P Semaoune, B Malafosse, A AF Dahdouh-Guermouche, Aicha Taleb, Mohammed Courtet, Philippe Semaoune, Boualem Malafosse, Alain TI Consanguinity, schizophrenia and bipolar disorder SO ANNALES MEDICO-PSYCHOLOGIQUES LA French DT Article DE Bipolar disorder; Consanguinity; Genetic; Inbreeding; Psychosis; Schizophrenia ID HUMAN-POPULATIONS; COUSIN MARRIAGE; HOMOZYGOSITY; DISEASES; RISK; GENOME; RUNS; IDENTIFICATION; EXPERIENCE; EVOLUTION AB Consanguinity is a relationship between two people who share a common ancestor. It is usually defined as resulting from sexual reproduction between two related individuals. In other words, consanguineous marriages refer to unions which are contracted between two biologically linked individuals. These unions remain frequent and are widely practiced in certain areas of the globe. The most frequently concerned regions extend from the southern shore of the Mediterranean Sea, across the Middle East, Mesopotamia, the Persian Gulf and sub continental India extending into Southeast Asia. Based on available data, it appears that couples who are second-degree relations or closer and their offspring represent 10.4% of the world's current population. The consequences on the rates of genetically determined diseases are significant, especially in autosomal recessive diseases. Twin and adoption studies as well as risk estimations for the occurrence of mental disorders in families of patients who suffer from mental disorders have confirmed the existence of a genetic component in the vulnerability to numerous psychiatric diseases. Recent techniques examining the entire genome or pan-genomic association studies (Genome-Wide Association Studies or GWAS), have enabled us to identify increasing numbers of genes that are implicated in major mental disorders such as schizophrenia, autism and bipolar disorders. Epidemiological genetic studies in consanguineous populations and/or within geographic isolates have shown an increased rate in infant mortality and morbidity, monogenetic recessive diseases and common multifactorial diseases such as psychotic disorders. These confirm the existence of a significant link between consanguinity, mental disorders and increased risk within the offspring of consanguineous couples. Studies concerning the links between consanguinity and psychotic disorders are few. Rare available data seem to plead in favour of an increased frequency of schizophrenia and bipolar disorder in the offspring of consanguineous parents. The recent discovery of rare genetic variants and their implications in psychotic disorders represents an argument in favour of the "common disease-rare variants" hypothesis. Within this framework, the study of consanguineous families could contribute to testing the links between these rare variants and certain phenotypes and to establish descriptive genotype-phenotype associations. The development of new techniques in molecular genetics should facilitate such studies. All of these aspects show the importance of studying consanguineous populations in order to better understand the role of genetic determinants in psychiatric pathologies and to highlight the interest of genetic counselling in communities with increased risks of mental disorders. This may also enable governments to enact prevention policies and to launch awareness campaigns concerning the risks of consanguineous marriages. (C) 2013 Elsevier Masson SAS. All rights reserved. RP Taleb, M (reprint author), Pavillon Calmette,5,Rue Dr Burnet, F-27200 Vernon, France. 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Med.-Psychol. PD MAY PY 2013 VL 171 IS 4 BP 246 EP 250 DI 10.1016/j.amp.2013.01.036 PG 5 WC Pharmacology & Pharmacy; Psychiatry; Psychology; Psychology, Multidisciplinary SC Pharmacology & Pharmacy; Psychiatry; Psychology GA 152QK UT WOS:000319546000006 ER PT J AU Buie, T AF Buie, Timothy TI The Relationship of Autism and Gluten SO CLINICAL THERAPEUTICS LA English DT Review DE autism; autism spectrum disorders; diet; gluten; treatment ID CELIAC-DISEASE; FOOD ALLERGY; FREE DIET; SENSITIVITY; DISORDERS; PERMEABILITY; ASSOCIATION; HYPOTHESIS; DIAGNOSIS; CHILDREN AB Background: Autism is now a common condition with a prevalence of 1 in 88 children. There is no known etiology. Speculation about possible treatments for autism or autism spectrum disorders (ASD) has included the use of various dietary interventions, including a gluten-free diet. Objective: The goal of this article was to review the literature available evaluating the use of gluten-free diets in patients with autism to determine if diet should be instituted as a treatment. Methods: A literature review was performed, identifying previously published studies in which a gluten-free diet was instituted as an autism treatment. These studies were not limited to randomized controlled trials because only 1 article was available that used a double-blind crossover design. Most publish reports were unblinded, observational studies. Results: In the only double-blind, crossover study, no benefit of a gluten-free diet was identified. Several other studies did report benefit from gluten-free diet. Controlling for observer bias and what may have represented unrelated progress over time in these studies is not possible. There are many barriers to evaluating treatment benefits for patients with autism. Gluten sensitivity may present in a variety of ways, including gastrointestinal and neurologic symptoms. Although making a diagnosis of celiac disease is easier with new serology and genetic testing, a large number of gluten-sensitive patients do not have celiac disease. Testing to confirm non celiac gluten sensitivity is not available. Conclusions: A variety of symptoms may be present with gluten sensitivity. Currently, there is insufficient evidence to support instituting a gluten-free diet as a treatment for autism. There may be a subgroup of patients who might benefit from a gluten-free diet, but the symptom or testing profile of these candidates remains unclear. (c) 2013 Elsevier HS Journals, Inc. All rights reserved. C1 [Buie, Timothy] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Boston, MA 02114 USA. RP Buie, T (reprint author), Harvard Univ, Sch Med, 175 Cambridge St, Boston, MA 02114 USA. 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Ther. PD MAY PY 2013 VL 35 IS 5 BP 578 EP 583 DI 10.1016/j.clinthera.2013.04.011 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 153YA UT WOS:000319637500006 PM 23688532 ER PT J AU Theoharides, TC AF Theoharides, Theoharis C. TI Is a Subtype of Autism an Allergy of the Brain? SO CLINICAL THERAPEUTICS LA English DT Review DE allergy; autism; brain; inflammation; mast cells; mitochondria ID CORTICOTROPIN-RELEASING HORMONE; HUMAN MAST-CELLS; SPECTRUM DISORDERS; MITOCHONDRIAL-DNA; NEUROTENSIN RECEPTOR; HISTAMINE-SECRETION; MEDIATOR RELEASE; LUTEOLIN; ACTIVATION; MASTOCYTOSIS AB Background: Autism spectrum disorders (ASDs) are characterized by deficits in social communication and language and the presence of repetitive behaviors that affect as many as 1 in 50 US children. Perinatal stress and environmental factors appear to play a significant role in increasing the risk for ASDs. There is no definitive pathogenesis, which therefore significantly hinders the development of a cure. Objective: We aimed to identify publications using basic or clinical data that suggest a possible association between atopic symptoms and ASDs, as well as evidence of how such an association could lead to brain disease, that may explain the pathogenesis of ASD. Methods: PubMed was searched for articles published since 1995 that reported any association between autism and/or ASDs and any one of the following terms: allergy, atopy, brain, corticotropin-releasing hormone, cytokines, eczema, food allergy, food intolerance, gene mutation, inflammation, mast cells, mitochondria, neurotensin, phenotype, stress, subtype, or treatment. Results: Children with ASD respond disproportionally to stress and also present with food and skin allergies that involve mast cells. Brain mast cells are found primarily in the hypothalamus, which participates in the regulation of behavior and language. Corticotropin-releasing hormone is secreted from the hypothalamus under stress and, together with neurotensin, stimulates brain mast cells that could result in focal brain allergy and neurotoxicity. Neurotensin is significantly increased in serum of children with ASD and stimulates mast cell secretion of mitochondrial adenosine triphosphate and DNA, which is increased in these children; these mitochondrial components are misconstrued as innate pathogens, triggerng an autoallergic response in the brain. Gene mutations associated with higher risk of ASD have been linked to reduction of the phosphatase and tensin homolog, which inhibits the mammalian target of rapamycin (mTOR). These same mutations also lead to mast cell activation and proliferation. Corticotropin-releasing hormone, neurotensin, and environmental toxins could further trigger the already activated mTOR, leading to superstimulation of brain mast cells in those areas responsible for ASD symptoms. Preliminary evidence indicates that the flavonoid luteolin is a stronger inhibitor of mTOR than rapamycin and is a potent mast cell blocker. Conclusion: Activation of brain mast cells by allergic, environmental, immune, neurohormonal, stress, and toxic triggers, especially in those areas associated with behavior and language, lead to focal brain allergies and subsequent focal encephalitis. This possibility is more likely in the subgroup of patients with ASD susceptibility genes that also involve mast cell activation. (c) 2013 Elsevier HS Journals, Inc. All rights reserved. C1 [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Dept Mol Physiol & Pharmacol, Mol Immunopharmacol & Drug Discovery Lab, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Dept Internal Med, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Med Ctr, Boston, MA USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Dept Psychiat, Boston, MA 02111 USA. RP Theoharides, TC (reprint author), Tufts Univ, Sch Med, Dept Mol Physiol & Pharmacol, Mol Immunopharmacol & Drug Discovery Lab, 136 Harrison Ave, Boston, MA 02111 USA. EM theoharis.theoharides@tufts.edu FU National Institutes of Health [NS38326, AR47652]; Autism Collaborative; Autism Research Institute; National Autism Association; Safe Minds; Theta Biomedical Consulting and Development Co, Inc (Brookline, Massachusetts) FX Aspects of our work were funded by National Institutes of Health grants NS38326 and AR47652, as well as the Autism Collaborative, the Autism Research Institute, National Autism Association, Safe Minds, and Theta Biomedical Consulting and Development Co, Inc (Brookline, Massachusetts). Many thanks are due to Smaro Panagiotidou for her excellent word processing skills. Dr. Theoharides was the sole author responsible for the literature search, data interpretation, figure creation, and writing of the manuscript. 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Ther. PD MAY PY 2013 VL 35 IS 5 BP 584 EP 591 DI 10.1016/j.clinthera.2013.04.009 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 153YA UT WOS:000319637500007 PM 23688533 ER PT J AU Taliou, A Zintzaras, E Lykouras, L Francis, K AF Taliou, Anilia Zintzaras, Elias Lykouras, Lefteris Francis, Kostantinos TI An Open-Label Pilot Study of a Formulation Containing the Anti-Inflammatory Flavonoid Luteolin and Its Effects on Behavior in Children With Autism Spectrum Disorders SO CLINICAL THERAPEUTICS LA English DT Article DE ASD; luteolin; flavonoids; inflammation; brain ID GLOBAL IMPRESSION SCALE; ADAPTIVE-BEHAVIOR; CLINICAL-TRIALS; INFLAMMATION; ADOLESCENTS; RISPERIDONE; CHECKLIST; PROGRESS; DISEASE; SCORES AB Background: Accumulating evidence suggests an association between autism spectrum disorders (ASD) and inflammation in brain regions related to cognitive function. The natural flavonoid luteolin has antioxidant, anti-inflammatory, mast cell blocking, and neuroprotective effects. It was shown to improve cognitive performance in a mouse model of ASD, but its effect in humans has not been adequately studied. Objectives: The goal of this study was to assess the effectiveness and tolerability in white children with ASD of a dietary supplement containing 2 flavonoids (>95% pure), luteolin (100 mg/capsule, from chamomile) and quercetin (70 mg/capsule), and the quercetin glycoside rutin (30 mg/capsule) from the Sophora japonica leaf, formulated in olive kernel oil to increase oral absorption. Methods: Fifty children (4-10 years old; 42 boys and 8 girls) with ASD were enrolled in a 26-week, prospective, open-label trial at the 2nd University Department of Psychiatry at "Attikon" General Hospital, Athens, Greece. Children were referred for the study by their respective physicians or came from the practice of the senior author. ASD diagnosis by clinical assessment was based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, symptom list and corroborated by using the Autism Diagnostic Observation Schedule. The dose of the study formulation used was 1 capsule per 10 kg weight per day with food. The primary outcome measures were the age-equivalent scores in the Vineland Adaptive Behavior Scales domains. Secondary outcomes included the Aberrant Behavior Checklist, the Autism Treatment Evaluation Checklist, and the Clinical Global Impression Improvement score. Data were measured at baseline, week 18, and week 26. Parents were interviewed for any possible improvements they noticed and instructed to report any unusual adverse events. Results: A total of 40 children completed the protocol. There was a significant improvement in adaptive functioning as measured by using the VABS age-equivalent scores (8.43 months in the communication domain, 7.17 months in daily living skills, and 8 months in the social domain; P < 0.005), as well as in overall behavior as indicated by the reduction (26.6%-34.8%) in Aberrant Behavior Checklist subscale scores. Age, sex, and history of allergies had no effect on the results, whereas the initial level of functioning or difficulty did predict the final outcome in most of the measures used. There was a transient (1-8 weeks) increased irritability in 27 of the 50 participants. Conclusions: These results are encouraging in that the combination of the flavonoids luteolin and quercetin seemed to be effective in reducing ASD symptoms, with no major adverse effects. (c) 2013 Elsevier HS Journals, Inc. All rights reserved. C1 [Taliou, Anilia; Lykouras, Lefteris; Francis, Kostantinos] Univ Athens, Sch Med, Dept Psychiat 2, Attikon Gen Hosp, Athens 12462, Greece. [Zintzaras, Elias] Univ Larissa, Dept Math & Bioinformat, Larisa, Greece. RP Francis, K (reprint author), Univ Athens, Sch Med, Dept Psychiat 2, Attikon Gen Hosp, 1 Rimini St, Athens 12462, Greece. EM cfrancis@otenet.gr FU Algonot, LLC FX This study was funded by Algonot, LLC, the maker of the study formulation. This support consisted of free formulation to the patients for the duration of the study and a small honorarium to Drs. Taliou, Lykouras, and Francis for the time required to perform the diagnoses, the administration of the outcome instruments, and the tabulation and writing of the results. The biostatistician (Dr. Zintzaras) performed the analysis blinded and pro bono. Study sponsors had no involvement in the study design; in the collection, analysis, and interpretation of data; the writing of the manuscript; or in the decision to submit the manuscript for publication. 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TI Empathizing, Systemizing, and Autistic Traits: Latent Structure in Individuals With Autism, Their Parents, and General Population Controls SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE autism; factor analysis; genetics; broader autism phenotype; family studies ID SPECTRUM QUOTIENT AQ; HIGH-FUNCTIONING AUTISM; WEAK CENTRAL COHERENCE; NORMAL SEX-DIFFERENCES; MALE BRAIN THEORY; ASPERGER-SYNDROME; COGNITIVE PHENOTYPE; FAMILY-HISTORY; FIT INDEXES; DE-NOVO AB The search for genes involved in autism spectrum conditions (ASC) may have been hindered by the assumption that the different symptoms that define the condition can be attributed to the same causal mechanism. Instead the social and nonsocial aspects of ASC may have distinct causes at genetic, cognitive, and neural levels. It has been posited that the core features of ASC can be explained by a deficit in empathizing alongside intact or superior systemizing; the drive to understand and derive rules about a system. 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Cunnington, Ross TI Cognitive empathy and motor activity during observed actions SO NEUROPSYCHOLOGIA LA English DT Article DE Mu; Beta; EEG; Empathy; Perspective taking; Mirror neuron system ID INFERIOR FRONTAL GYRUS; MIRROR NEURON SYSTEM; SOCIAL COGNITION; AUTISM; PAIN; PERCEPTION; MODULATION; HUMANS; MU; OSCILLATIONS AB Whether empathy depends on activation of the mirror neuron system is controversial. This study tested the relationship between cognitive empathy and motor activation during action observation through the sensorimotor system. EEG activity was recorded over the motor area while participants observed and then performed a task demonstrated by a model. Analyses revealed significant suppression in mu/alpha (8-12 Hz) and beta (18-22 Hz) EEG bands, indicative of sensorimotor activity, during both observed and executed actions. Crucially, participants rating higher in perspective taking as a measure of trait cognitive empathy showed significantly less beta suppression when observing actions. The direction of this relationship, contrary to studies involving induced emotional empathy, may reflect individual differences in mentalizing and mirroring mechanisms to understand others' actions. Implications of these findings for the hypothesised empathy-mirror neuron system link are discussed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Milston, Sashenka I.; Vanman, Eric J.; Cunnington, Ross] Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. [Cunnington, Ross] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. RP Cunnington, R (reprint author), Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. 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Freeth, Megan Rosas-Martinez, Luisa TI Visual search performance is predicted by the degree to which selective attention to features modulates the ERP between 350 and 600 ms SO NEUROPSYCHOLOGIA LA English DT Article DE Visual search; Autistic traits; P3B; Selection negativity; ERPs; Induced gamma-band power ID AUTISM SPECTRUM DISORDER; INDEPENDENT COMPONENT ANALYSIS; EVENT-RELATED POTENTIALS; FUNCTIONING AUTISM; RESPONSES; CORTEX; EEG; PERCEPTION; SUPERIOR; TRAITS AB Efficient visual search necessitates perception of items in the visual array, rapid classification of items as either targets or distractors, and the selection of target items. Individuals vary in the speed with which they perform these operations and can detect targets within cluttered arrays, as shown in visual search tasks. Individuals with autism spectrum disorders (ASD) show particular strengths in visual search. The aim of the current study was to develop an understanding the origin of individual variability in visual search by delineating the processes involved in feature-based target detection, and establishing which, if any, of these processes predict search efficiency. EEG was recorded while participants performed a feature-based selective attention task from which the following EEG variables were computed: P1 amplitude; P1 latency; selection negativity; induced gamma-band power and P3b amplitude. These variables are considered to reflect stimulus encoding, feedback amplification of attended features, cognitive utilization and resource allocation during event classification respectively. Participants also completed a separate visual search task. Regression analyses revealed that only the ERP component associated with resource allocation during event classification (P3b) significantly predicted search efficiency. These data suggest that individual variability in visual search is related to a reduction in modulation of attention allocation to visual features. Implications for the understanding of superior visual search in individuals with ASD are discussed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Milne, Elizabeth; Dunn, Stephanie A.; Freeth, Megan; Rosas-Martinez, Luisa] Univ Sheffield, Sheffield Autism Res Lab, Dept Psychol, Sheffield S10 2TN, S Yorkshire, England. RP Milne, E (reprint author), Univ Sheffield, Sheffield Autism Res Lab, Dept Psychol, Sheffield S10 2TN, S Yorkshire, England. EM E.Milne@sheffield.ac.uk FU Experimental Psychology Society FX This work was supported, in part, by an award from the Experimental Psychology Society. We would like to thank Abby Dickenson for her help with EEG pre-processing. 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Folkes, O. M. Harrison, F. E. TI Behavioral and serotonergic response changes in the Dhcr7-HET mouse model of Smith-Lemli-Opitz syndrome SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Cholesterol; Behavior; Serotonin; Smith-Lemli-Opitz syndrome; Autism; Pharmacological testing ID AUTISM SPECTRUM DISORDERS; SEROTONIN(1A) RECEPTOR; REDUCTASE GENE; CHOLESTEROL; ABNORMALITIES; MUTATIONS; MICE; PATHOGENESIS; PHENOTYPE; RELEVANT AB Smith-Lemli-Opitz syndrome (SLOS) is a developmental disorder resulting from mutations to the Dhcr7 gene, which is required for cholesterol synthesis. Patients with SLOS typically exhibit a number of severe behavioral deficits and many are diagnosed with autistic spectrum disorder. Although the molecular pathophysiology underlying behavioral changes in SLOS and autism spectrum disorders is poorly understood, there is evidence for the involvement of the serotonergic system in SLOS and autism in general. Behavioral testing was undertaken to ascertain the basal behavioral differences between Dhcr7-heterozygous (HET) and wildtype control mice and explore the utility of a Dhcr7-HET mouse line in the development of new treatments for this disorder. Dhcr7-HET mice did not differ from wild-type control mice on basic measures of locomotor activity, anxiety and neuromuscular ability. However, female Dhcr7-HET mice at 6 months of age or older were significantly more likely to win on the social dominance tube test against an unfamiliar mouse. Pharmacological testing, using the 5-HT2A agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), showed increased head-twitch response in Dhcr7-HET mice, which was apparent from 6 months of age. No differences were found between the genotypes in testing for 5-HT1A agonist 8-OH-DPAT-induced hypothermia. These data indicate an underlying dysfunction of the 5-HT2A receptors in Dhcr7-HET mice that warrants further investigation to establish how this may relate to behavioral disturbances in human patients carrying Dhcr7 mutations. (C) 2013 Elsevier Inc. All rights reserved. C1 [Folkes, O. M.; Harrison, F. E.] Vanderbilt Univ, Med Ctr, Div Diabet Endocrinol & Metab, Nashville, TN USA. [Korade, Z.] Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN USA. [Korade, Z.; Harrison, F. E.] Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN USA. RP Harrison, FE (reprint author), 7465 MRB 4,2213 Garland Ave, Nashville, TN 37232 USA. EM Fiona.Harrison@Vanderbilt.edu FU Vanderbilt Kennedy Center; Division of Diabetes, Endocrinology and Metabolism, of Vanderbilt University; NICHD [P30 HD15052] FX The authors are grateful for funding from the Vanderbilt Kennedy Center and the Division of Diabetes, Endocrinology and Metabolism, of Vanderbilt University, and NICHD grant P30 HD15052 to the Vanderbilt Kennedy Center for Research on Human Development. We are grateful to Dr. Jeremy Veenstra-VanderWeele for advice about pharmacological testing. We wish to thank Refayat Ahsen for help with pharmacological testing. 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SO PLOS ONE LA English DT Article ID CHILD-DIRECTED SPEECH; SPECTRUM DISORDERS; PHYSIOLOGICAL PRECURSORS; DOUBLE VIDEO; COMMUNICATION; SYNCHRONY; MOTHERESE; RESPONSES; RECOGNITION; PREFERENCES AB Background: Whether development of autism impacts the interactive process between an infant and his/her parents remains an unexplored issue. Methodology and Principal Findings: Using computational analysis taking into account synchronic behaviors and emotional prosody (parentese), we assessed the course of infants' responses to parents' type of speech in home movies from typically developing (TD) infants and infants who will subsequently develop autism aged less than 18 months. Our findings indicate: that parentese was significantly associated with infant responses to parental vocalizations involving orientation towards other people and with infant receptive behaviours; that parents of infants developing autism displayed more intense solicitations that were rich in parentese; that fathers of infants developing autism spoke to their infants more than fathers of TD infants; and that fathers' vocalizations were significantly associated with intersubjective responses and active behaviours in infants who subsequently developed autism. Conclusion: The parents of infants who will later develop autism change their interactive pattern of behaviour by both increasing parentese and father's involvement in interacting with infants; both are significantly associated with infant's social responses. We stress the possible therapeutic implications of these findings and its implication for Dean Falk's theory regarding pre-linguistic evolution in early hominins. C1 [Cohen, David; Cassel, Raquel S.; Saint-Georges, Catherine] Univ Paris 06, Grp Hosp Pitie Salpetriere, AP HP, Dept Child & Adolescent Psychiat, Paris, France. [Cohen, David; Cassel, Raquel S.; Saint-Georges, Catherine; Mahdhaoui, Ammar; Chetouani, Mohamed] Univ Paris 06, Ctr Natl Rech Sci UMR 7222, Inst Syst Intelligents & Robot, Paris, France. [Laznik, Marie-Christine] Assoc Sante Mentale 13Eme, Dept Child & Adolescent Psychiat, Paris, France. [Apicella, Fabio; Muratori, Pietro; Maestro, Sandra; Muratori, Filippo] Univ Pisa, Stella Maris Sci Inst, Div Child Neurol & Psychiat, Calambrone, Italy. RP Cohen, D (reprint author), Univ Paris 06, Grp Hosp Pitie Salpetriere, AP HP, Dept Child & Adolescent Psychiat, Paris, France. EM david.cohen@psl.aphp.fr FU Italian Ministry of Instruction, University, and Research; Fondation de France [2008005170]; Universite Pierre et Marie Curie; European Commission [288241]; fund "Entreprendre pour aider" FX The Pisa "home video in autism" project was supported by grants PRIN 2003-2005 and PRIN 2005-2007 from the Italian Ministry of Instruction, University, and Research. The current study was supported by a grant (no2008005170) from the Fondation de France given to MC and DC, by the Universite Pierre et Marie Curie (Projet Emergence 2010) the European Commission (FP7: Michelangelo under grant agreement no 288241), and the fund "Entreprendre pour aider". The funding agencies and the University were not involved in the study design, collection, analysis and interpretation of data, writing of the paper, or the decision to submit for publication. 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TI Is Superior Local Processing in the Visuospatial Domain a Function of Drawing Talent Rather Than Autism Spectrum Disorder? SO PSYCHOLOGY OF AESTHETICS CREATIVITY AND THE ARTS LA English DT Article DE autism; local processing; giftedness; drawing ID WEAK CENTRAL COHERENCE; DISEMBEDDING PERFORMANCE; ASPERGER-SYNDROME; CHILDREN; ADOLESCENTS; ABILITY; INTACT; IQ AB This study challenges the prevailing assumption that superior local processing is specific to autism spectrum diagnosis and suggests instead that such processing skill is a function of realistic drawing talent. Fifteen children with autism spectrum disorder (ASD) and 15 without ASD made an observational drawing scored for level of drawing realism and completed 2 tasks that allowed for the assessment of a local processing bias: the Block Design Task in unsegmented and segmented form at three levels of perceptual cohesiveness (minimal, intermediate, and maximal), and the Group Embedded Figures Test. Drawing realism score, not ASD diagnosis, predicted performance on the unsegmented version of the Block Design Task and on the most difficult items-the unsegmented maximally cohesive items. Accuracy on the Group Embedded Figures Test was also more strongly associated with level of drawing realism than ASD diagnosis. Thus, the superior local processing seen in ASD may be due to the drawing talent so often present in those with ASD. C1 [Drake, Jennifer E.] Boston Coll, Chestnut Hill, MA 02467 USA. RP Drake, JE (reprint author), Boston Coll, Dept Psychol, 140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM drakejc@bc.edu CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Caron MJ, 2006, BRAIN, V129, P1789, DOI 10.1093/brain/awl072 Charman T, 2011, PSYCHOL MED, V41, P619, DOI 10.1017/S0033291710000991 Chen F, 2008, RES AUTISM SPECT DIS, V2, P739, DOI 10.1016/j.rasd.2008.03.003 Daniels AM, 2011, J AUTISM DEV DISORD, V41, P110, DOI 10.1007/s10803-010-1031-x de Jonge M, 2009, EUR CHILD ADOLES PSY, V18, P197, DOI 10.1007/s00787-008-0708-6 Drake J. E., 2012, GIFTED ED INT, DOI [10.1177/0261429412447708, DOI 10.1177/0261429412447708] Drake JE, 2010, J AUTISM DEV DISORD, V40, P762, DOI 10.1007/s10803-009-0923-0 Edgin JO, 2005, J AUTISM DEV DISORD, V35, P729, DOI 10.1007/s10803-005-0020-y Hoy JA, 2004, AUTISM, V8, P267, DOI 10.1177/1362361304045218 Jolliffe T, 1997, J CHILD PSYCHOL PSYC, V38, P527, DOI 10.1111/j.1469-7610.1997.tb01539.x Kaland N, 2007, AUTISM, V11, P81, DOI 10.1177/1362361307070988 Kaufman A. 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Aesthet. Creat. Arts. PD MAY PY 2013 VL 7 IS 2 BP 203 EP 209 DI 10.1037/a0030636 PG 7 WC Humanities, Multidisciplinary; Psychology, Experimental SC Arts & Humanities - Other Topics; Psychology GA 146FZ UT WOS:000319076600011 ER PT J AU Iwanaga, R Tanaka, G Nakane, H Honda, S Imamura, A Ozawa, H AF Iwanaga, Ryoichiro Tanaka, Goro Nakane, Hideyuki Honda, Sumihisa Imamura, Akira Ozawa, Hiroki TI Usefulness of near-infrared spectroscopy to detect brain dysfunction in children with autism spectrum disorder when inferring the mental state of others SO PSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article DE autism spectrum disorders; child; near-infrared spectroscopy; prefrontal cortex; theory of mind ID ASPERGER-SYNDROME; MIND; TASKS; ATTRIBUTION; ACTIVATION; CORTEX; SYSTEM; ADULTS AB Aims The purpose of this study was to examine the usefulness of near-infrared spectroscopy (NIRS) for identifying abnormalities in prefrontal brain activity in children with autism spectrum disorders (ASD) as they inferred the mental states of others. Methods The subjects were 16 children with ASD aged between 8 and 14 years and 16 age-matched healthy control children. Oxygenated hemoglobin concentration was measured in the subject's prefrontal brain region on NIRS during tasks expressing a person's mental state (MS task) and expressing an object's characteristics (OC task). Results There was a significant main effect of group (ASD vs control), with the control group having more activity than the ASD group. But there was no significant main effect of task (MS task vs OC task) or hemisphere (right vs left). Significant interactions of task and group were found, with the control group showing more activity than the ASD group during the MS task relative to the OC task. Conclusions NIRS showed that there was lower activity in the prefrontal brain area when children with ASD performed MS tasks. Therefore, clinicians might be able to use NIRS and these tasks for conveniently detecting brain dysfunction in children with ASD related to inferring mental states, in the clinical setting. C1 [Iwanaga, Ryoichiro; Tanaka, Goro; Nakane, Hideyuki; Honda, Sumihisa] Nagasaki Univ, Dept Hlth Sci, Grad Sch Biomed Sci, Div Phys & Occupat Therapy, Nagasaki 8528520, Japan. [Imamura, Akira; Ozawa, Hiroki] Nagasaki Univ, Dept Translat Med Sci, Grad Sch Biomed Sci, Div Neuropsychiat, Nagasaki 8528520, Japan. RP Iwanaga, R (reprint author), Nagasaki Univ, Dept Hlth Sci, Grad Sch Biomed Sci, 1-7-1 Sakamoto, Nagasaki 8528520, Japan. EM iwanagar@nagasaki-u.ac.jp FU Japan Society for the Promotion of Science [17790712] FX This study was supported by a Grant-in-aid for Young Scientists (B) no. 17790712 from the Japan Society for the Promotion of Science. All authors declare that they have no conflict of interest. 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PD MAY PY 2013 VL 67 IS 4 BP 203 EP 209 DI 10.1111/pcn.12052 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 148DT UT WOS:000319223800002 PM 23683150 ER PT J AU Cook, R Brewer, R Shah, P Bird, G AF Cook, Richard Brewer, Rebecca Shah, Punit Bird, Geoffrey TI Alexithymia, Not Autism, Predicts Poor Recognition of Emotional Facial Expressions SO PSYCHOLOGICAL SCIENCE LA English DT Article DE autism; alexithymia; face perception; identity recognition; emotion recognition; emotions; facial expressions; individual differences ID IMPAIRED RECOGNITION; SPECTRUM DISORDER; PERCEPTION; CHILDREN; VALIDITY; IDENTITY; DEFICITS; AMYGDALA; ADULTS AB Despite considerable research into whether face perception is impaired in autistic individuals, clear answers have proved elusive. In the present study, we sought to determine whether co-occurring alexithymia (characterized by difficulties interpreting emotional states) may be responsible for face-perception deficits previously attributed to autism. Two experiments were conducted using psychophysical procedures to determine the relative contributions of alexithymia and autism to identity and expression recognition. Experiment 1 showed that alexithymia correlates strongly with the precision of expression attributions, whereas autism severity was unrelated to expression-recognition ability. Experiment 2 confirmed that alexithymia is not associated with impaired ability to detect expression variation; instead, results suggested that alexithymia is associated with difficulties interpreting intact sensory descriptions. Neither alexithymia nor autism was associated with biased or imprecise identity attributions. These findings accord with the hypothesis that the emotional symptoms of autism are in fact due to co-occurring alexithymia and that existing diagnostic criteria may need to be revised. C1 [Cook, Richard] City Univ London, Dept Psychol, London EC1R 0JD, England. [Brewer, Rebecca; Bird, Geoffrey] Univ London, Kings Coll, Inst Psychiat, Med Res Council Social Genet & Dev Psychiat Ctr, London WC1E 7HU, England. [Shah, Punit] Univ London, Birkbeck Coll, Dept Psychol Sci, London WC1E 7HU, England. [Bird, Geoffrey] UCL, Inst Cognit Neurosci, London WC1E 6BT, England. RP Cook, R (reprint author), City Univ London, Dept Psychol, Whiskin St, London EC1R 0JD, England. 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Using the same structure as the Attentional Network Test (ANT), we developed a variant of this test to examine attentional effects in response to stimuli with and without social-cognitive content. Fish, drawings or photographs of faces looking to the left or right were used as target stimuli. Results collected from twenty-four university students showed that photographs of faces positively affected attentional orienting and executive control, whereas reduced the efficiency of alerting, as compared to both face drawings and fish. These results support the status of human faces as a special class of visual stimuli for the human attentional systems. (C) 2013 Elsevier B.V. All rights reserved. C1 [Federico, Francesca; Adriani, Tiziana] Univ Roma La Sapienza, Dipartimento Psicol Proc Sviluppo & Socializzaz, Rome, Italy. [Marotta, Andrea; Maccari, Lisa; Casagrande, Maria] Univ Roma La Sapienza, Dipartimento Psicol, Rome, Italy. 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PD MAY PY 2013 VL 143 IS 1 BP 65 EP 70 DI 10.1016/j.actpsy.2013.02.006 PG 6 WC Psychology, Experimental SC Psychology GA 139KW UT WOS:000318582600009 PM 23542806 ER PT J AU Jin, X Cui, NG Zhong, WW Jin, XT Jiang, C AF Jin, Xin Cui, Ningren Zhong, Weiwei Jin, Xiao-Tao Jiang, Chun TI GABAergic synaptic inputs of locus coeruleus neurons in wild-type and Mecp2-null mice SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE Rett syndrome; brainstem; locus coeruleus; noradrenaline; GABAergic ID PRESYNAPTIC GABA(B) RECEPTORS; RETT-SYNDROME; MOUSE MODEL; BRAIN-STEM; NORADRENERGIC NEURONS; CO2 CHEMOSENSITIVITY; INFERIOR COLLICULUS; GLUTAMATE RELEASE; CERULEUS NEURONS; NEONATAL-RAT AB Rett syndrome is an autism spectrum disorder resulting from defects in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Deficiency of the Mecp2 gene causes abnormalities in several systems in the brain, especially the norepinephrinergic and GABAergic systems. The norepinephrinergic neurons in the locus coeruleus (LC) modulate a variety of neurons and play an important role in multiple functions in the central nervous system. In Mecp2(-/Y) mice, defects in the intrinsic membrane properties of LC neurons have been identified, while how their synaptic inputs are affected remains unclear. Therefore, we performed these brain slice studies to demonstrate how LC neurons are regulated by GABAergic inputs and how such synaptic inputs are affected by Mecp2 knockout. In whole cell current clamp, the firing activity of LC neurons was strongly inhibited by the GABA(A) receptor agonist muscimol, accompanied by hyperpolarization and a decrease in input resistance. Such a postsynaptic inhibition was significantly reduced (by similar to 30%) in Mecp2(-/Y) mice. Post-and presynaptic GABA(B)ergic inputs were found in LC neurons, which were likely mediated by the G protein-coupled, Ba2+-sensitive K+ channels. The postsynaptic GABABergic inhibition was deficient by similar to 50% in Mecp2 knockout mice. Although the presynaptic GABA(B)ergic modulation appeared normal, both frequency and amplitude of the GABA(A)ergic mIPSCs were drastically decreased (by 30-40%) in Mecp2-null mice. These results suggest that the Mecp2 disruption causes defects in both post-and presynaptic GABAergic systems in LC neurons, impairing GABA(A)ergic and GABA(B)ergic postsynaptic inhibition and decreasing the GABA release from presynaptic terminals. C1 [Jin, Xin; Cui, Ningren; Zhong, Weiwei; Jin, Xiao-Tao; Jiang, Chun] Georgia State Univ, Dept Biol, Atlanta, GA 30302 USA. RP Jiang, C (reprint author), Georgia State Univ, Dept Biol, 100 Piedmont Ave, Atlanta, GA 30302 USA. EM cjiang@gsu.edu RI Jin, Xin/O-4506-2014; Jin, Xin/E-2746-2010 FU National Institute of Neurological Disorders and Stroke [NS-073875]; International Rett Syndrome Foundation FX This work was supported by the National Institute of Neurological Disorders and Stroke NS-073875 and the International Rett Syndrome Foundation. 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TI An Unbalanced Translocation Involving Loss of 10q26.2 and Gain of 11q25 in a Pedigree with Autism Spectrum Disorder and Cerebellar Juvenile Pilocytic Astrocytoma SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE autism; astrocytoma; NTM; OPCML; t(10;11) C1 [Minhas, Hassan M.; Pescosolido, Matthew F.; Schwede, Matthew; Piasecka, Justyna; Morrow, Eric M.] Brown Univ, Emma Pendleton Bradley Hosp, Warren Alpert Med Sch, Dev Disorders Genet Res Program, Providence, RI 02912 USA. [Minhas, Hassan M.] Brown Univ, Emma Pendleton Bradley Hosp, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Minhas, Hassan M.; Pescosolido, Matthew F.; Gaitanis, John; Morrow, Eric M.] Brown Univ, RI CART, Warren Alpert Med Sch, Providence, RI 02912 USA. [Schwede, Matthew; Morrow, Eric M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. [Schwede, Matthew; Morrow, Eric M.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Gaitanis, John] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Providence, RI 02903 USA. [Tantravahi, Umadevi] Brown Univ, Dept Pathol, Woman & Infants Hosp, Div Genet,Warren Alpert Med Sch, Providence, RI 02912 USA. RI Morrow, Eric/J-2767-2013 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 2013 VL 73 IS 9 SU S MA 210 BP 68S EP 68S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800211 ER PT J AU Alaerts, K Di Martino, A Swinnen, SP Wenderoth, N AF Alaerts, Kaat Di Martino, Adriana Swinnen, Stephan P. Wenderoth, Nicole TI Underconnectivity of STS Predicts Socio-Cognitive Deficits in Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Autism Spectrum Disorders; Functional Magnetic Resonance Imaging; Functional Connectivity; Superior Temporal Sulcus; Point Light Displays C1 [Alaerts, Kaat; Di Martino, Adriana] NYU, Ctr Child Study, New York, NY USA. [Swinnen, Stephan P.] Katholieke Univ Leuven, Movement Control & Neuroplast Res Grp, Louvain, Belgium. [Wenderoth, Nicole] ETH, Dept Hlth Sci & Technol, Zurich, Switzerland. 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 2013 VL 73 IS 9 SU S MA 267 BP 87S EP 87S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800267 ER PT J AU Schaer, M Eliez, S Scariati, E Glaser, B AF Schaer, Marie Eliez, Stephan Scariati, Elisa Glaser, Bronwyn TI Decreased Frontal Gyrification Associated with Altered Connectivity in Children with Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE autism; neuroimaging; gyrification; connectivity; tractography C1 [Schaer, Marie; Eliez, Stephan; Scariati, Elisa; Glaser, Bronwyn] Off Medicopedag, Dept Psychiat, Geneva, Switzerland. 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 2013 VL 73 IS 9 SU S MA 268 BP 87S EP 88S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800268 ER PT J AU Hardan, AY Hallmayer, J Lazzeroni, L Berquist, S Raman, MR Patnaik, S Phillips, J Reiss, AL Cleveland, S AF Hardan, Antonio Y. Hallmayer, Joachim Lazzeroni, Laura Berquist, Sean Raman, Mira R. Patnaik, Sweta Phillips, Jennifer Reiss, Allan L. Cleveland, Susan TI Structural MRI Investigations in Twins with Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Autism; MRI; Structural; Youth C1 [Hardan, Antonio Y.; Hallmayer, Joachim; Lazzeroni, Laura; Berquist, Sean; Raman, Mira R.; Patnaik, Sweta; Phillips, Jennifer; Reiss, Allan L.; Cleveland, Susan] Stanford Univ, Stanford, CA 94305 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 2013 VL 73 IS 9 SU S MA 269 BP 88S EP 88S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800269 ER PT J AU Schreiner, MJ Karlsgodt, KH Chow, C Jonas, RK Montojo, C Jalbrzikowski, M Bearden, CE AF Schreiner, Matthew J. Karlsgodt, Katherine H. Chow, Carolyn Jonas, Rachel K. Montojo, Caroline Jalbrzikowski, Maria Bearden, Carrie E. TI 22Q11.2 Deletion Syndrome and the Resting State: An Investigation of Functional Connectivity in the Default Mode Network and its Association with Social Behavior SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Velocardiofacial syndrome; Autism Spectrum disorder; Schizophrenia; Reciprocal social behavior; Default Mode Network C1 [Schreiner, Matthew J.; Jonas, Rachel K.] Univ Calif Los Angeles, Neurosci Interdept Program, Los Angeles, CA USA. [Schreiner, Matthew J.; Chow, Carolyn; Jonas, Rachel K.; Montojo, Caroline; Bearden, Carrie E.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Karlsgodt, Katherine H.] Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY USA. [Jalbrzikowski, Maria; Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RI Karlsgodt, Katherine/H-2964-2013 OI Karlsgodt, Katherine/0000-0003-3332-4231 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 2013 VL 73 IS 9 SU S MA 272 BP 88S EP 89S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800271 ER PT J AU Corbett, BA Schupp, CW AF Corbett, Blythe A. Schupp, Clayton W. TI Comprehensive Investigation of the Cortisol Awakening Response in Children with Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE cortisol; autism; diurnal rhythm; HPA axis; children C1 [Corbett, Blythe A.] Vanderbilt Univ, Nashville, TN USA. [Schupp, Clayton W.] Canc Prevent Inst Calif, CPIC, Fremont, CA 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 2013 VL 73 IS 9 SU S MA 298 BP 96S EP 97S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800297 ER PT J AU Hollocks, MJ Papadopoulos, A Howlin, P Simonoff, E AF Hollocks, Matthew J. Papadopoulos, Andrew Howlin, Patricia Simonoff, Emily TI The Physiological Correlates of Anxiety in Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Autism; Anxiety; Stress; Cortisol; Heart Rate C1 [Hollocks, Matthew J.; Papadopoulos, Andrew; Howlin, Patricia; Simonoff, Emily] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. RI Howlin, Patricia/A-7622-2011 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 2013 VL 73 IS 9 SU S MA 296 BP 96S EP 96S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800295 ER PT J AU Teixeira, AL Rodrigues, DH Rocha, NP Sousa, LF Barbosa, IG Kummer, A AF Teixeira, Antonio L. Rodrigues, David H. Rocha, Natalia P. Sousa, Larissa F. Barbosa, Izabela G. Kummer, Arthur TI Changes in Adipokine Levels in Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Autism; Adipokines; Cytokines; Immunology C1 [Teixeira, Antonio L.; Rodrigues, David H.; Rocha, Natalia P.; Sousa, Larissa F.; Barbosa, Izabela G.; Kummer, Arthur] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. 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 2013 VL 73 IS 9 SU S MA 297 BP 96S EP 96S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800296 ER PT J AU Hazlett, HC AF Hazlett, Heather C. TI Early Brain Development in Infants at High Risk for Autism Spectrum Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE neurodevelopment; autism; neuroimaging; sMRI C1 [Hazlett, Heather C.] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 357 BP 115S EP 115S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800353 ER PT J AU Bearden, CE AF Bearden, Carrie E. TI Molecular Profile of 22Q11DS Reveals Unique Biological Pathways Associated with Autism Spectrum and Psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE gene expression; psychosis; autism spectrum disorder; neurodevelopment; 22q11.2 deletion syndrome C1 [Bearden, Carrie E.] Univ Calif Los Angeles, Los Angeles, CA 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 2013 VL 73 IS 9 SU S MA 422 BP 136S EP 136S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800418 ER PT J AU Sikich, L Alderman, C Hazzard, L Bethea, TC Gregory, S Johnson, J AF Sikich, Linmarie Alderman, Cheryl Hazzard, Lindsey Bethea, Terrence C. Gregory, Simon Johnson, Jacqueline TI Pilot Study of Sustained Oxytocin Treatment in Children and Adolescents with Autistic Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Autism; Oxytocin; Clinical Trial; Social deficits; pediatric C1 [Sikich, Linmarie; Alderman, Cheryl; Hazzard, Lindsey; Bethea, Terrence C.; Johnson, Jacqueline] Univ N Carolina, Chapel Hill, NC USA. [Gregory, Simon] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 450 BP 145S EP 145S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800446 ER PT J AU Wiggins, JL Swartz, JR Martin, DM Lord, C Monk, CS AF Wiggins, Jillian Lee Swartz, Johnna R. Martin, Donna M. Lord, Catherine Monk, Christopher S. TI The Impact of Serotonin Transporter Genotype on Amygdala Habituation in Youth with Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE autism; serotonin transporter; face; amygdala; habituation C1 [Wiggins, Jillian Lee; Swartz, Johnna R.; Martin, Donna M.; Monk, Christopher S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Lord, Catherine] Weill Cornell Med Coll, New York, NY USA. [Monk, Christopher S.] Univ Michigan, Ctr Human Growth & Dev, Ann Arbor, MI 48109 USA. RI Monk, Christopher/J-1805-2014 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 2013 VL 73 IS 9 SU S MA 453 BP 146S EP 146S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800449 ER PT J AU Morrow, EM Gamsiz, ED Viscidi, EW Nagpal, S Triche, EW Istrail, S AF Morrow, Eric M. Gamsiz, Ece D. Viscidi, Emma W. Nagpal, Shailender Triche, Elizabeth W. Istrail, Sorin CA Simons Simplex Collection Genetics TI Intellectual Disability is Associated with Increased Runs-of-Homozygosity in Simplex Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE autism; genetics; homozygosity; autosomal recessive; intellectual disability C1 [Morrow, Eric M.; Gamsiz, Ece D.; Viscidi, Emma W.; Nagpal, Shailender] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Triche, Elizabeth W.; Istrail, Sorin] Brown Univ, Providence, RI 02912 USA. RI Morrow, Eric/J-2767-2013 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 2013 VL 73 IS 9 SU S MA 454 BP 147S EP 147S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800450 ER PT J AU Skafidas, E Testa, R Zantomio, D Chana, G Everall, IP Pantelis, C AF Skafidas, Efstratios Testa, Renee Zantomio, Daniela Chana, Gursharan Everall, Ian P. Pantelis, Christos TI Genetic Factors Identifying Risk and Resilience in Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE autistic disorder/diagnosis; childhood development disorders; predictive testing; risk markers; resilience markers C1 [Skafidas, Efstratios] Univ Melbourne, Ctr Neural Engn, Parkville, Vic 3052, Australia. [Testa, Renee; Pantelis, Christos] Univ Melbourne, Dept Psychiat, Melbourne Neuropsychiat Ctr, Parkville, Vic 3052, Australia. [Testa, Renee; Pantelis, Christos] Melbourne Hlth, Parkville, Vic, Australia. [Zantomio, Daniela] Austin Hlth, Dept Haematol, Heidelberg, Vic, Australia. [Chana, Gursharan; Everall, Ian P.] Univ Melbourne, Dept Psychiat, Parkville, Vic 3052, Australia. 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 2013 VL 73 IS 9 SU S MA 455 BP 147S EP 147S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671800451 ER PT J AU Berner, JE AF Berner, Jon E. TI Marijuana Use in Chronic Pain Patients Inversely Correlates with the Density of Comorbid Autistic Traits SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE pain; autism; cannabinoid; GABA; anxiety C1 [Berner, Jon E.] Woodinville Psychiat Associates, Woodinville, WA 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 2013 VL 73 IS 9 SU S MA 1000 BP 320S EP 320S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801308 ER PT J AU Nordahl, CW Braunschweig, D Iosif, AM Lee, A Rogers, S Ashwood, P Amaral, DG Van de Water, J AF Nordahl, Christine Wu Braunschweig, Daniel Iosif, Ana-Maria Lee, Aaron Rogers, Sally Ashwood, Paul Amaral, David G. Van de Water, Judy TI Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Autism spectrum disorder; MRI; Structural neuroimaging; Maternal antibody; Autoantibody ID DIAGNOSTIC OBSERVATION SCHEDULE; MRI; INDIVIDUALS; ANTIBODIES; GROWTH AB Autism spectrum disorder (ASD) is very heterogeneous and multiple subtypes and etiologies likely exist. The maternal immune system has been implicated in the pathogenesis of some forms of ASD. Previous studies have identified the presence of specific maternal IgG autoantibodies with reactivity to fetal brain proteins at 37 and 73 kDa in up to 12% of mothers of children with ASD. The current study evaluates the presence of these autoantibodies in an independent cohort of mothers of 181 preschool-aged male children (131 ASD, 50 typically developing (TD) controls). We also investigated whether ASD children born to mothers with these autism-specific maternal IgG autoantibodies exhibit a distinct neural phenotype by evaluating total brain volume using structural magnetic resonance imaging (MRI). Of the 131 ASD children, 10 (7.6%) were born to mothers with the 37/73 kDa IgG autoantibodies (ASD-IgG). The mothers of the remaining ASD children and all TD controls were negative for these paired autoantibodies. While both ASD groups exhibited abnormal brain enlargement that is commonly observed in this age range, the ASD-IgG group exhibited a more extreme 12.1% abnormal brain enlargement relative to the TD controls. In contrast, the remaining ASD children exhibited a smaller 4.4% abnormal brain enlargement relative to TD controls. Lobar and tissue type analyses revealed that the frontal lobe is selectively enlarged in the ASD-IgG group and that both gray and white matter are similarly affected. These results suggest that maternal autoantibodies associated with autism spectrum disorder may impact brain development leading to abnormal enlargement. (C) 2013 Elsevier Inc. All rights reserved. C1 [Nordahl, Christine Wu; Rogers, Sally; Ashwood, Paul; Amaral, David G.; Van de Water, Judy] Univ Calif Davis, MIND Inst, Sch Med, Sacramento, CA 95817 USA. [Nordahl, Christine Wu; Lee, Aaron; Rogers, Sally; Amaral, David G.] Univ Calif Davis, Sch Med, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. [Braunschweig, Daniel; Ashwood, Paul; Van de Water, Judy] Univ Calif Davis, Sch Med, Dept Internal Med, Davis, CA 95616 USA. [Iosif, Ana-Maria] Univ Calif Davis, Div Biostat, Dept Publ Hlth Sci, Davis, CA 95616 USA. RP Nordahl, CW (reprint author), Univ Calif Davis, MIND Inst, 2805 50th St, Sacramento, CA 95817 USA. EM crswu@ucdavis.edu FU NIMH [R01MH089626, U24MH081810, R00MH085099]; UC Davis M.I.N.D. Institute FX Funding was provided by the NIMH (R01MH089626, U24MH081810, R00MH085099) and the UC Davis M.I.N.D. Institute. The authors would like to acknowledge the Autism Phenome Project staff for helping in the logistics of family visits and data collection. We especially thank all of the families and children who participated in the study. 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Immun. PD MAY PY 2013 VL 30 BP 61 EP 65 DI 10.1016/j.bbi.2013.01.084 PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 142YT UT WOS:000318834200009 PM 23395715 ER PT J AU Tang, B Jia, HQ Kast, RJ Thomas, EA AF Tang, Bin Jia, Haiqun Kast, Ryan J. Thomas, Elizabeth A. TI Epigenetic changes at gene promoters in response to immune activation in utero SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Histone; Gene expression; Schizophrenia; Psychiatric; Glutamate; Immune; Neurodevelopment ID FETAL-BRAIN; PSYCHIATRIC-DISORDERS; HUNTINGTONS-DISEASE; DNA MICROARRAYS; MESSENGER-RNAS; SCHIZOPHRENIA; INTERLEUKIN-6; EXPRESSION; MODELS; CELLS AB Increasing evidence suggests that maternal infection increases the risk of psychiatric disorders, such as schizophrenia and autism in offspring. However, the molecular mechanisms associated with these effects are unclear. Here, we have studied epigenetic gene regulation in mice exposed to non-specific immune activation elicited by polyI:C injection to pregnant dams. Using Western blot analysis, we detected global hypoacetylation of histone H3, at lysine residues 9 and 14, and histone H4, at lysine residue 8, in the cortex from juvenile (similar to 24 days of age) offspring exposed to polyI:C in utero, but not from adult (3 months of age) offspring, which exhibit significant behavioral abnormalities. Accordingly, we detected robust deficits in the expression of genes associated with neuronal development, synaptic transmission and immune signaling in the cortex of polyI:C-exposed juvenile mice. In particular, we found that several genes in the glutamate receptor signaling pathway, including Gria1 and Slc17a7, showed decreases in promoter-specific histone acetylation, and corresponding gene expression deficits, in polyI:C-exposed offspring at both juvenile and adult ages. In contrast, the expression of these same genes, in addition to Disci and Ntrk3, was elevated in the hippocampus of juvenile mice, in concordance with elevated levels of promoter-specific histone acetylation. We suggest that these early epigenetic changes contribute to the delayed behavioral abnormalities that are observed in adult animals after exposure to polyI:C, and which resemble symptoms seen in schizophrenia and related disorders. (C) 2013 Elsevier Inc. All rights reserved. C1 [Tang, Bin; Jia, Haiqun; Kast, Ryan J.; Thomas, Elizabeth A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. RP Thomas, EA (reprint author), Scripps Res Inst, Dept Mol Biol, SP-2030,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. 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Immun. PD MAY PY 2013 VL 30 BP 168 EP 175 DI 10.1016/j.bbi.2013.01.086 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 142YT UT WOS:000318834200022 PM 23402795 ER PT J AU Goodwin, H AF Goodwin, Hayley TI Working with parents of newly diagnosed child with an autism spectrum disorder: a guide for professionals SO BRITISH JOURNAL OF OCCUPATIONAL THERAPY LA English DT Book Review CR Keen D, 2012, WORKING PARENTS NEWL NR 1 TC 0 Z9 0 PU COLL OCCUPATIONAL THERAPISTS LTD PI SOUTHWARK PA 106-114 BOROUGH HIGH ST, SOUTHWARK, LONDON SE1 1LB, ENGLAND SN 0308-0226 J9 BRIT J OCCUP THER JI Br. J. Occup. Ther. PD MAY PY 2013 VL 76 IS 5 BP 249 EP 249 PG 1 WC Rehabilitation SC Rehabilitation GA 146JF UT WOS:000319086700009 ER PT J AU Berry-Kravis, E Doll, E Sterling, A Kover, ST Schroeder, SM Mathur, S Abbeduto, L AF Berry-Kravis, Elizabeth Doll, Emily Sterling, Audra Kover, Sara T. Schroeder, Susen M. Mathur, Shaguna Abbeduto, Leonard TI Development of an Expressive Language Sampling Procedure in Fragile X Syndrome: A Pilot Study SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE fragile X syndrome; FMR1; expressive language; outcome measure; autistic disorder ID DOWN-SYNDROME; CHILDREN; ADOLESCENTS; PROFILES; AUTISM; LENGTH; TRIAL; GENE AB Objective: There is a great need for valid outcome measures of functional improvement for impending clinical trials of targeted interventions for fragile X syndrome (FXS). Families often report conversational language improvement during clinical treatment, but no validated measures exist to quantify this outcome. This small-scale study sought to determine the feasibility, reproducibility, and clinical validity of highly structured expressive language sampling as an outcome measure reflecting language ability. Methods: Narrative and conversation tasks were administered to 36 verbal participants (25 males and 11 females) with FXS (aged 5-36 years, mean, 18 +/- 7 years). Alternate versions were used with randomized task order at 2- to 3-week intervals (mean, 19.6 +/- 6.4 days). Audio recordings of sessions were transcribed and analyzed. Dependent measures reflected talkativeness (total number of utterances), utterance planning (proportion of communication [C] units with mazes), articulation (proportion of unintelligible/partly unintelligible C-units), vocabulary (number of different word roots), and syntactic ability (mean length of utterance [MLU] in words). Reproducibility of measures was evaluated with intraclass correlation coefficients (ICC). Results: All participants could complete the tasks. Coded data were highly reproducible with Pearson's correlations at p < .01 for all measures and ICC values of .911 to .966 (conversation) and .728 to .940 (narration). Some measures including MLU and different word roots were correlated with expressive language subscale scores from the Vineland Adaptive Behavior Scale. Conclusions: These expressive language sampling tasks appear to be feasible, reproducible, and clinically valid and should be further validated in a larger cohort, as a promising means of assessing functional expressive language outcomes during clinical trials in FXS. C1 [Berry-Kravis, Elizabeth] Rush Univ, Med Ctr, Dept Pediat Neurol Sci & Biochem, Chicago, IL 60612 USA. [Doll, Emily] Rush Univ, Med Ctr, Sch Med, Chicago, IL 60612 USA. [Sterling, Audra; Schroeder, Susen M.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. [Sterling, Audra; Kover, Sara T.] Univ Wisconsin, Dept Commun Sci & Disorders, Madison, WI USA. [Mathur, Shaguna] Rush Univ, Med Ctr, Dept Pediat, Chicago, IL 60612 USA. [Abbeduto, Leonard] Univ Calif Davis, Sch Med, MIND Inst, Sacramento, CA 95817 USA. RP Berry-Kravis, E (reprint author), Rush Univ, Med Ctr, 1725 West Harrison,Suite 718, Chicago, IL 60612 USA. EM elizabeth_m_berry-kravis@rush.edu FU National Fragile X Foundation; FRAXA Research Foundation, a Rush University Summer Student Deans Fellowship; National Institutes of Health [R01HD024356] FX This work was supported in part by summer student funding from the National Fragile X Foundation and the FRAXA Research Foundation, a Rush University Summer Student Deans Fellowship to E. Doll, and by National Institutes of Health grant R01HD024356 awarded to L. Abbeduto. For the remaining authors, no conflicts of interest or sources of funding were declared. CR Abbeduto L, 2010, HANDBOOK OF MEDICAL NEUROPSYCHOLOGY: APPLICATIONS OF COGNITIVE NEUROSCIENCE, P193, DOI 10.1007/978-1-4419-1364-7_11 Abbeduto L, 2012, J DEV BEHAV IN PRESS Abbeduto L, 2007, MENT RETARD DEV D R, V13, P36, DOI 10.1002/mrdd.20142 Berry-Kravis E, 2009, J MED GENET, V46, P266, DOI 10.1136/jmg.2008.063701 Berry-Kravis E, 2011, J NEURODEV DISORD, V3, P193, DOI 10.1007/s11689-011-9074-7 Berry-Kravis E, 2008, J DEV BEHAV PEDIATR, V29, P293, DOI 10.1097/DBP.0b013e31817dc447 Berry-Kravis E, 2006, J CHILD ADOL PSYCHOP, V16, P525, DOI 10.1089/cap.2006.16.525 Berry-Kravis EM, 2012, SCI TRANSL MED, V4, DOI 10.1126/scitranslmed.3004214 Condouris K, 2003, AM J SPEECH-LANG PAT, V12, P349, DOI 10.1044/1058-0360(2003/080) ContiRamsden G, 1997, J SPEECH LANG HEAR R, V40, P765 Craig HK, 2000, J SPEECH LANG HEAR R, V43, P366 De Rubeis S, 2012, ADV EXP MED BIOL, V970, P517, DOI 10.1007/978-3-7091-0932-8_23 D'Hulst C, 2009, J MED GENET, V46, P577, DOI 10.1136/jmg.2008.064667 Dunn L. M., 2007, PEABODY PICTURE VOCA Finestack LH, 2010, J SPEECH LANG HEAR R, V53, P1334, DOI 10.1044/1092-4388(2010/09-0125) Gross C, 2011, NEUROPSYCHOPHARMACOL, V37, P178 Heilmann J, 2010, LANG SPEECH HEAR SER, V41, P393, DOI 10.1044/0161-1461(2009/09-0023) Hoff E, 2012, HDB CHILD LANGUAGE R, P330 Jacquemont S., 2011, SCI TRANSL MED, V3, P1, DOI DOI 10.1126/SCITRANSLMED.3001708 Kover ST, 2012, J SPEECH LANG HEAR R, V55, P1022, DOI 10.1044/1092-4388(2011/11-0075) Kover ST, 2010, J INTELL DISABIL RES, V54, P246, DOI 10.1111/j.1365-2788.2010.01255.x Mayer M, 1973, FROG HIS OWN Mayer M., 1974, FROG GOES DINNER Mervis CB, 2005, APPL PSYCHOLINGUIST, V26, P41, DOI 10.1017/S0142716405050058 Miller J., 2008, SYSTEMATIC ANAL LANG Oostra BA, 2009, BBA-GEN SUBJECTS, V1790, P467, DOI 10.1016/j.bbagen.2009.02.007 Rice ML, 2006, J SPEECH LANG HEAR R, V49, P793, DOI 10.1044/1092-4388(2006/056) Semel E., 2003, CLIN EVALUATION LANG, V4th Turner G, 1996, AM J MED GENET, V64, P196, DOI 10.1002/(SICI)1096-8628(19960712)64:1<196::AID-AJMG35>3.0.CO;2-G Yoder PJ, 2011, J SPEECH LANG HEAR R, V54, P1170, DOI 10.1044/1092-4388(2010/09-0246) NR 30 TC 0 Z9 0 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 2013 VL 34 IS 4 BP 245 EP 251 DI 10.1097/DBP.0b013e31828742fc PG 7 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 146BZ UT WOS:000319065100004 PM 23669871 ER PT J AU Berube, M Hubbard, C Mallory, L Larsen, E Morrison, P Augustyn, M AF Berube, Megan Hubbard, Carol Mallory, Leah Larsen, Eric Morrison, Peter Augustyn, Marilyn TI Historic Condition in a Modern Child with Autism SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material DE autism; developmental pediatrics; mental retardation/intellectual disability; neurology; behavior; nutrition ID SPECTRUM DISORDERS; FOOD SELECTIVITY AB CASE: Haven is an 11-year-old primary care patient who you have followed since her birth. She was the 9 lb 6 oz product of a 38-week gestation complicated by maternal hypertension and seizure disorder treated with tegretol. Her delivery and neonatal course were uneventful. She was diagnosed with austistic disorder at age 2 years, at which time she used no functional language or gestures, had repetitive motor mannerisms, and limited eye contact. She had strong tactile sensory aversions. Her diet was very restricted including only banana yogurt and drinking milk and apple juice for the first several years of life. She was followed by a developmental-behavioral pediatrician approximately annually through age 8 years and then more frequently. She was healthy other than lead exposure (maximum serum level 18 at age 3 years) and multiple febrile seizures with other possible absence episodes. Her development remained very delayed with use of single words and short phrases. She developed multiple repetitive, anxious, obsessive behaviors (picking up lint, organizing, cleaning, and freezing in certain postures) that were treated with a selective serotonin reuptake inhibitors fluvoxamine. Sensory issues were ongoing, with restrictive eating (primarily peanut butter and jelly sandwiches, cereal bars, milk, and a kiwi-strawberry drink). She took a liquid multivitamin until age 8. At age 11 years, 3 weeks prior to admission, Haven developed acute loss of ambulation over the course of 1 day, initially dragging her right leg, and then refusing to walk and her parents brought her in to see you. She had fever, vomiting, and general weakness. She developed extensive bruising over her legs, especially in the popliteal fossae. She was also noted to have friability and dark discoloration of her gums. Initially, you suspected a post-viral syndrome and close monitoring. She was seen twice in the next 2 weeks in a local emergency room where her erythrocyte sedimentation rate was reported to be elevated and juvenile rheumatoid arthritis or a reaction to fluvoxamine were suspected. Antibiotics were also prescribed for gingivitis. She was seen by an orthopedist who felt it was not an orthopedic issue and leg films were unremarkable. With her second emergency room visit, she was transferred to a tertiary medical center and admitted for further evaluation. Where would you go from here? C1 [Berube, Megan; Hubbard, Carol; Mallory, Leah; Larsen, Eric; Morrison, Peter] Maine Med Ctr, Dept Pediat, Portland, ME 04102 USA. [Augustyn, Marilyn] Boston Univ, Sch Med, Dept Pediat, Div Dev & Behav Pediat, Boston, MA 02215 USA. RP Berube, M (reprint author), Maine Med Ctr, Dept Pediat, Portland, ME 04102 USA. CR Bandini LG, 2010, J PEDIATR-US, V157, P259, DOI 10.1016/j.jpeds.2010.02.013 Cermak SA, 2010, J AM DIET ASSOC, V110, P238, DOI 10.1016/j.jada.2009.10.032 Hyman Susan L, 2012, Pediatrics, V130 Suppl 2, pS145, DOI 10.1542/peds.2012-0900L NR 3 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD MAY PY 2013 VL 34 IS 4 BP 288 EP 290 DI 10.1097/DBP.0b013e31829094bb PG 3 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 146BZ UT WOS:000319065100010 PM 23669873 ER PT J AU Maffie, JK Dvoretskova, E Bougis, PE Martin-Eauclaire, MF Rudy, B AF Maffie, Jon K. Dvoretskova, Elena Bougis, Pierre Edouard Martin-Eauclaire, Marie-France Rudy, Bernardo TI Dipeptidyl-peptidase-like-proteins confer high sensitivity to the scorpion toxin AmmTX3 to Kv4-mediated A-type K+ channels SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CEREBELLAR GRANULE CELLS; KV4.2 POTASSIUM CHANNELS; PYRAMIDAL NEURONS; BETA-SUBUNIT; CURRENTS; EXCITABILITY; MODULATION; BRAIN; PLASTICITY; DENDRITES AB Key points center dot AmmTX3, a member of the -KTX15 family of scorpion toxins, efficiently and specifically blocks the subthreshold-operating A-type K+ current in cerebellar granule neurons from wild-type mice but not in neurons from mice lacking the Kv4 channel-associated protein DPP6. center dot In heterologous cells high-affinity blockade of Kv4.2 and Kv4.3 channels by AmmTX3 requires the presence of the associated proteins DPP6 and DPP10. center dot These results validate AmmTX3 as a specific blocker of Kv4 channels in CNS neurons and explain the discrepancy between previous observations in neurons and heterologous cells. center dot They contribute a powerful tool to investigate the physiological role of A-type K+ currents, believed to be important in dendritic integration and plasticity and to be involved in a number of diseases. center dot Our results demonstrate that, in addition to changing the kinetics and voltage dependence of Kv4 channel complexes, DDP-like Kv4-associated proteins also affect their pharmacological profile. Abstract K+ channels containing Kv4.2 and Kv4.3 pore-forming subunits mediate most of the subthreshold-operating somatodendritic A-type K+ current in CNS neurons. These channels are believed to be important in regulating the frequency of repetitive firing, the backpropagation of action potential into dendrites, and dendritic integration and plasticity. Moreover, they have been implicated in several diseases from pain to epilepsy and autism spectrum disorders. The lack of toxins that specifically and efficiently block these channels has hampered studies aimed at confirming their functional role and their involvement in disease. AmmTX3 and other related members of the -KTX15 family of scorpion toxins have been shown to block the A-type K+ current in cultured neurons, but their specificity has been questioned because the toxins do not efficiently block the currents mediated by Kv4.2 or Kv4.3 subunits expressed in heterologous cells. Here we show that the high-affinity blockade of Kv4.2 and Kv4.3 channels by AmmTX3 depends on the presence of the auxiliary subunits DPP6 and DPP10. These proteins are thought to be components of the Kv4 channel complex in neurons and to be important for channel expression in dendrites. These studies validate the use of AmmTX3 as a blocker of the Kv4-mediated A-type K+ current in neurons. C1 [Maffie, Jon K.; Dvoretskova, Elena; Rudy, Bernardo] NYU Sch Med, Smilow Neurosci Program, Dept Physiol & Neurosci, NYU Neurosci Inst, New York, NY 10016 USA. [Bougis, Pierre Edouard; Martin-Eauclaire, Marie-France] Aix Marseille Univ, Fac Med Nord, CNRS UMR 7286, CRN2M, F-13344 Marseille 15, France. RP Rudy, B (reprint author), NYU Sch Med, Smilow Neurosci Program, 522 1st Ave, New York, NY 10016 USA. EM pierre-edouard.bougis@univ-amu.fr; rudyb01@med.nyu.edu FU NINDS [NS04517, F30 NS071660] FX `We thank Dr Chiung-Yin Chung and Dr Brigitte Ceard for their skilful technical assistance. We thank the reviewers of this paper for their constructive suggestions. This work was supported by NINDS grants NS04517 to BR, F30 NS071660 to J.M. The authors declare no competing financial interests. 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TI MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways SO NEUROGENETICS LA English DT Article DE MEF2C haploinsufficiency; Intellectual disability; Autism; Infant-onset myoclonic epilepsy; Infantile spasms; Hyperkinesis; Deletion 5q14.3 ID SEVERE MENTAL-RETARDATION; TRANSCRIPTION FACTOR MEF2C; MICRODELETION SYNDROME; INFANTILE SPASMS; GENE-EXPRESSION; RETT-SYNDROME; PHENOTYPE; DELETION; ARX; IDENTIFICATION AB MEF2C haploinsufficiency syndrome is an emerging neurodevelopmental disorder associated with intellectual disability, autistic features, epilepsy, and abnormal movements. We report 16 new patients with MEF2C haploinsufficiency, including the oldest reported patient with MEF2C deletion at 5q14.3. We detail the neurobehavioral phenotype, epilepsy, and abnormal movements, and compare our subjects with those previously reported in the literature. We also investigate Mef2c expression in the developing mouse forebrain. A spectrum of neurofunctional deficits emerges, with hyperkinesis a consistent finding. Epilepsy varied from absent to severe, and included intractable myoclonic seizures and infantile spasms. Subjects with partial MEF2C deletion were statistically less likely to have epilepsy. Finally, we confirm that Mef2c is present both in dorsal primary neuroblasts and ventral gamma-aminobutyric acid(GABA)ergic interneurons in the forebrain of the developing mouse. Given interactions with several key neurodevelopmental genes such as ARX, FMR1, MECP2, and TBR1, it appears that MEF2C plays a role in several developmental stages of both dorsal and ventral neuronal cell types. C1 [Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Dept Neurol, Ctr Neural Dev & Dis, Rochester, NY 14642 USA. [Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Dept Pediat, Ctr Neural Dev & Dis, Rochester, NY 14642 USA. [Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Dept Biomed Genet, Ctr Neural Dev & Dis, Rochester, NY 14642 USA. [Traylor, Ryan N.; Rosenfeld, Jill A.; Schultz, Roger A.; Shaffer, Lisa G.; Ballif, Blake C.] PerkinElmer Inc, Signature Genom Labs, Spokane, WA USA. [Hoover, Jacqueline M.] Childrens Hosp Pittsburgh, Dept Med Genet, Pittsburgh, PA 15213 USA. [Harris, Catharine J.] Univ Missouri, Dept Child Hlth, Div Med Genet, Columbia, MO 65201 USA. [Winter, Susan] Childrens Hosp Cent Calif, Dept Med Genet Metab, Madera, CA USA. [Lacassie, Yves] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA USA. [Lacassie, Yves] Childrens Hosp, New Orleans, LA USA. [Bialer, Martin] North Shore Long Isl Jewish Hlth Syst, Div Med Genet, New Hyde Pk, NY USA. [Lamb, Allen N.] Univ Utah, ARUP Labs, Salt Lake City, UT USA. [Berry-Kravis, Elizabeth] Rush Univ, Dept Pediat, Med Ctr, Chicago, IL 60612 USA. [Berry-Kravis, Elizabeth] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA. [Berry-Kravis, Elizabeth] Rush Univ, Dept Biochem, Med Ctr, Chicago, IL 60612 USA. [Porter, Brenda E.] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA. [Falk, Marni] Childrens Hosp Philadelphia, Dept Med Genet, Philadelphia, PA 19104 USA. [Venkat, Anu; Marsh, Eric D.] Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA. [Vanzo, Rena J.] Lineagen Inc, Salt Lake City, UT USA. [Cohen, Julie S.; Fatemi, Ali] Johns Hopkins Med Inst, Kennedy Krieger Inst, Div Neurogenet, Baltibmore, MD USA. [Dobyns, William B.] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA. [Dobyns, William B.] Seattle Childrens Res Inst, Seattle, WA USA. RP Paciorkowski, AR (reprint author), Univ Rochester, Med Ctr, Dept Neurol, Ctr Neural Dev & Dis, 601 Elmwood Ave, Rochester, NY 14642 USA. EM Alex_Paciorkowski@urmc.rochester.edu FU NINDS [R01 NS058721] FX WBD is funded by NINDS R01 NS058721; JAR and RAS are employees of Signature Genomic Laboratories, PerkinElmer; ANL is an employee of ARUP Laboratories; and RJV is an employee of Lineagen, Inc. The other authors have no disclosures. 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W. Shimizu-Motohashi, Y. Campbell, M. G. Lee, I. H. Collins, C. D. Brewster, S. J. Holm, I. A. Rappaport, L. Kohane, I. S. Kunkel, L. M. TI Peripheral blood gene expression signature differentiates children with autism from unaffected siblings SO NEUROGENETICS LA English DT Article DE Autism spectrum disorders; Unaffected sibling; Simplex family; Gene expression ID PERVASIVE DEVELOPMENTAL DISORDERS; LYMPHOBLASTOID CELL-LINES; COPY-NUMBER VARIATION; RARE DE-NOVO; SPECTRUM DISORDERS; FUNCTIONAL IMPACT; RECURRENCE RISK; DYSFUNCTION; PATHWAYS; REVEALS AB Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders with high heritability, yet a majority of genetic contribution to pathophysiology is not known. Siblings of individuals with ASD are at increased risk for ASD and autistic traits, but the genetic contribution for simplex families is estimated to be less when compared to multiplex families. To explore the genomic (dis-) similarity between proband and unaffected sibling in simplex families, we used genome-wide gene expression profiles of blood from 20 proband-unaffected sibling pairs and 18 unrelated control individuals. The global gene expression profiles of unaffected siblings were more similar to those from probands as they shared genetic and environmental background. A total of 189 genes were significantly differentially expressed between proband-sib pairs (nominal p < 0.01) after controlling for age, sex, and family effects. Probands and siblings were distinguished into two groups by cluster analysis with these genes. Overall, unaffected siblings were equally distant from the centroid of probands and from that of unrelated controls with the differentially expressed genes. Interestingly, five of 20 siblings had gene expression profiles that were more similar to unrelated controls than to their matched probands. In summary, we found a set of genes that distinguished probands from the unaffected siblings, and a subgroup of unaffected siblings who were more similar to probands. The pathways that characterized probands compared to siblings using peripheral blood gene expression profiles were the up-regulation of ribosomal, spliceosomal, and mitochondrial pathways, and the down-regulation of neuroreceptor-ligand, immune response and calcium signaling pathways. Further integrative study with structural genetic variations such as de novo mutations, rare variants, and copy number variations would clarify whether these transcriptomic changes are structural or environmental in origin. C1 [Kong, S. W.; Campbell, M. G.; Lee, I. H.; Kohane, I. S.] Boston Childrens Hosp, Harvard Mit Div Hlth Sci & Technol, Informat Program, Boston, MA 02115 USA. [Shimizu-Motohashi, Y.; Collins, C. D.; Brewster, S. J.; Holm, I. A.; Kunkel, L. M.] Boston Childrens Hosp, Div Genet, Program Genom, Boston, MA 02115 USA. [Rappaport, L.] Boston Childrens Hosp, Div Dev Med, Boston, MA 02115 USA. [Kohane, I. S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. RP Kunkel, LM (reprint author), Boston Childrens Hosp, Div Genet, Program Genom, Boston, MA 02115 USA. EM kunkel@enders.tch.harvard.edu FU Simons Foundation [SFARI 95117]; NIH [5RO1MH085143] FX This work was supported by a grant from the Simons Foundation (SFARI 95117 to L. M. K. and I. S. K.), and NIH 5RO1MH085143 to L. M. K. We gratefully acknowledge all the participating families and their contributions. We are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. 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Med. PD MAY PY 2013 VL 10 IS 3 BP 229 EP 229 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 141LW UT WOS:000318727700006 ER PT J AU Auyeung, B Lombardo, MV Baron-Cohen, S AF Auyeung, Bonnie Lombardo, Michael V. Baron-Cohen, Simon TI Prenatal and postnatal hormone effects on the human brain and cognition SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Review DE Prenatal testosterone; Postnatal testosterone; Testosterone administration; Oxytocin; Sex differences; Amniotic fluid; Amniocentesis; Puberty ID CONGENITAL ADRENAL-HYPERPLASIA; HUMAN SEXUAL DEVELOPMENT; AUTISM SPECTRUM QUOTIENT; CAST CHILDHOOD ASPERGER; CENTRAL NERVOUS-SYSTEM; FETAL TESTOSTERONE; NEURAL CIRCUITRY; AMNIOTIC-FLUID; SYSTEMATIZING QUOTIENT; EXOGENOUS TESTOSTERONE AB This review examines the role of hormones in the development of social and nonsocial cognition and the brain. Research findings from human studies designed to elucidate the effects of both prenatal and postnatal exposure to hormones in children and young adults are summarized. Effects are found to be both time and dose dependent, with exposure to abnormal hormone levels having a limited impact outside the "critical window" in development. Particular attention is given to the role of prenatal hormone exposure, which appears to be vital for early organization of the brain. In later life, measurements of circulating hormone levels and the administration of testosterone and oxytocin are found to predict behavior, but the effect is thought to be one of "activation" or "fine-tuning" of the early organization of the brain. Possible directions for valuable future research are discussed. C1 [Auyeung, Bonnie; Lombardo, Michael V.; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. RP Auyeung, B (reprint author), Univ Cambridge, Dept Psychiat, Autism Res Ctr, Douglas House,18B Trumpington Rd, Cambridge CB2 8AH, England. EM ba251@cam.ac.uk FU Nancy Lurie Marks Family Foundation; Shirley Foundation; MRC; Wellcome Trust FX BA, MVL, and SBC were supported by grants from the Nancy Lurie Marks Family Foundation, the Shirley Foundation, the MRC, and the Wellcome Trust during the period of this work. We are grateful to our colleagues and the families who have taken part in the research over the years. Parts of this review have been updated from Baron-Cohen, S., Tager-Flusberg, H., Lombardo, MV. (eds) Understanding Other Minds (Oxford University Press). 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[Madhavan, S.; Sambamoorthi, U.] W Virginia Univ, Sch Pharm, Morgantown, WV 26506 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2013 VL 16 IS 3 BP A67 EP A68 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 144CE UT WOS:000318916400348 PM 23694491 ER PT J AU [Anonymous] AF [Anonymous] TI Neurophysiology Treatment corrects autism in mice SO BIOFUTUR LA French DT News Item NR 0 TC 0 Z9 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0294-3506 J9 BIOFUTUR JI Biofutur PD MAY PY 2013 IS 343 BP 13 EP 13 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 141WF UT WOS:000318756500024 ER PT J AU Devine, RT Hughes, C AF Devine, Rory T. Hughes, Claire TI Silent Films and Strange Stories: Theory of Mind, Gender, and Social Experiences in Middle Childhood SO CHILD DEVELOPMENT LA English DT Article ID HIGH-FUNCTIONING AUTISM; FAMILY AFFLUENCE SCALE; FALSE-BELIEF; INDIVIDUAL-DIFFERENCES; ASPERGER-SYNDROME; PEER RELATIONS; CHILDREN; LONELINESS; ADULTS; DISSATISFACTION AB In this study of two hundred and thirty 8- to 13-year-olds, a new Silent Films task is introduced, designed to address the dearth of research on theory of mind in older children by providing a film-based analogue of F. G. E. Happe's (1994) Strange Stories task. Confirmatory factor analysis showed that all items from both tasks loaded onto a single theory-of-mind latent factor. With effects of verbal ability and family affluence controlled, theory-of-mind latent factor scores increased significantly with age, indicating that mentalizing skills continue to develop through middle childhood. 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PD MAY PY 2013 VL 13 IS 4 BP 322 EP 322 PG 1 WC Pathology SC Pathology GA 139YJ UT WOS:000318620900005 ER PT J AU Kuntoro, IA Saraswati, L Peterson, C Slaughter, V AF Kuntoro, Ike Anggraika Saraswati, Liliek Peterson, Candida Slaughter, Virginia TI Micro-cultural influences on theory of mind development: A comparative study of middle-class and pemulung children in Jakarta, Indonesia SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article DE cultural differences; false belief; Indonesia; socio-economic status; theory of mind ID FALSE-BELIEF; AUTISM; METAANALYSIS; LANGUAGE; SIBLINGS; DEAFNESS; EMOTION; MOTHERS; STEPS AB We investigated cultural influences on young children's acquisition of social-cognitive concepts. A theory of mind (ToM) scale (Wellman & Liu, 2004) was given to 129 children (71 boys, 58 girls) ranging in age from 3 years 0 months to 7 years 10 months. The children were from three distinct cultural groups: (a) trash pickers (pemulung) living a subsistence lifestyle in Jakarta, Indonesia; (b) middle-class Jakartans living and attending preschools within 5 km of the pemulung group; and (c) middle-class Australians. All children were individually tested in their native language. Cross-group comparisons revealed no significant differences among the three groups in mastery of false belief (the traditional ToM indicator), despite their widely different socio-economic circumstances. However, the pemulung children were slower than the two middle-class groups in mastering two other ToM concepts, namely knowledge access and emotion concealment. These findings shed new light on patterns of cross-cultural consistency in false-belief mastery, as well as revealing cross-cultural variation in other ToM concepts that plausibly reflect variation in children's everyday life circumstances. 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J. Behav. Dev. PD MAY PY 2013 VL 37 IS 3 BP 266 EP 273 DI 10.1177/0165025413478258 PG 8 WC Psychology, Developmental SC Psychology GA 140IJ UT WOS:000318647400010 ER PT J AU Lu, YH Wang, N Jin, F AF Lu, Yue-hong Wang, Ning Jin, Fan TI Long-term follow-up of children conceived through assisted reproductive technology SO JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B LA English DT Review DE Assisted reproductive technologies (ART); Children; Follow-up ID IN-VITRO FERTILIZATION; INTRACYTOPLASMIC SPERM INJECTION; IMPRINTING CONTROL REGIONS; AUTISM SPECTRUM DISORDERS; POPULATION-BASED COHORT; DOUBLE EMBRYO-TRANSFER; LOW-BIRTH-WEIGHT; DNA METHYLATION; CEREBRAL-PALSY; ICSI CHILDREN AB Children conceived via assisted reproductive technologies (ART) are nowadays a substantial proportion of the population. It is important to follow up these children and evaluate whether they have elevated health risks compared to naturally conceived (NC) children. In recent years there has been a lot of work in this field. This review will summarize what is known about the health of ART-conceived children, encompassing neonatal outcomes, birth defects, growth and gonadal developments, physical health, neurological and neurodevelopmental outcomes, psychosocial developments, risk for cancer, and epigenetic abnormalities. Most of the children conceived after ART are normal. However, there is increasing evidence that ART-conceived children are at higher risk of poor perinatal outcome, birth defects, and epigenetic disorders, and the mechanism(s) leading to these changes have not been elucidated. Continuous follow-up of children after ART is of great importance as they progress through adolescence into adulthood, and new ART techniques are constantly being introduced. C1 [Lu, Yue-hong; Wang, Ning; Jin, Fan] Zhejiang Univ, Key Lab Reprod Genet Zhejiang, Minist Educ, Hangzhou 310006, Zhejiang, Peoples R China. 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Zhejiang Univ.-SCI. B PD MAY PY 2013 VL 14 IS 5 BP 359 EP 371 DI 10.1631/jzus.B1200348 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 139BY UT WOS:000318557700001 PM 23645173 ER PT J AU Sheridan, C AF Sheridan, Cormac TI Drugmakers plow more resources into autism SO NATURE BIOTECHNOLOGY LA English DT News Item CR 2008, CELL, V135, P401 2007, P NATL ACAD SCI, V104, P11489 2009, P NATL ACAD USA, V106, P2029 2011, SCI TRANSL MED, V3 2012, SCI TRANSL MED, V4, P152 2012, SCI TRANSL MED, V4 2012, BRAIN BEHAV IMMUN, V26, P383 NR 7 TC 0 Z9 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2013 VL 31 IS 5 BP 367 EP 369 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 139NM UT WOS:000318589600003 PM 23657371 ER PT J AU Kujala, T Lepisto, T Naatanen, R AF Kujala, T. Lepisto, T. Naatanen, R. TI The neural basis of aberrant speech and audition in autism spectrum disorders SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Autism spectrum; Asperger syndrome; Mismatch negativity (MMN); P3a; Speech; Central auditory processing; Event-related potentials ID EVENT-RELATED POTENTIALS; LANGUAGE-ASSOCIATION CORTEX; HIGH-FUNCTIONING AUTISM; CEREBRAL-BLOOD-FLOW; ASPERGER-SYNDROME; MISMATCH NEGATIVITY; CHILDHOOD AUTISM; INFANTILE-AUTISM; INVOLUNTARY ATTENTION; COGNITIVE DECLINE AB Autism spectrum disorders (ASD) are characterized by deficits in communication and social behavior and by narrow interests. Individuals belonging to this spectrum have abnormalities in various aspects of language, ranging from semantic-pragmatic deficits to the absence of speech. They also have aberrant perception, especially in the auditory domain, with both hypo- and hypersensitive features. Neurophysiological approaches with high temporal resolution have given novel insight into the processes underlying perception and language in ASD. Neurophysiological recordings, which are feasible for investigating infants and individuals with no speech, have shown that the representation of and attention to language has an abnormal developmental path in ASD. Even the basic mechanisms for fluent speech perception are degraded at a low level of neural speech analysis. Furthermore, neural correlates of perception and some traits typical of subgroups of individuals on this spectrum have helped in understanding the diversity on this spectrum. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Kujala, T.] Univ Helsinki, Cicero Learning, FI-00014 Helsinki, Finland. [Kujala, T.; Lepisto, T.; Naatanen, R.] Univ Helsinki, Cognit Brain Res Unit, Inst Behav Sci, FI-00014 Helsinki, Finland. [Lepisto, T.] Univ Helsinki, Dept Child Neurol, Hosp Children & Adolescents, Helsinki 00250, Finland. [Naatanen, R.] Univ Tartu, Inst Psychol, EE-50090 Tartu, Estonia. [Naatanen, R.] Univ Aarhus, Ctr Integrat Neurosci CFIN, Aarhus, Denmark. RP Kujala, T (reprint author), Univ Helsinki, Cicero Learning, POB 9, FI-00014 Helsinki, Finland. EM teija.m.kujala@helsinki.fi FU Academy of Finland [128840, 122745]; University of Helsinki FX This study was supported by the Academy of Finland (grant numbers 128840 and 122745) and the University of Helsinki. We thank Ms. Julie Uusinarkaus for revising the language of the manuscript. 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Biobehav. Rev. PD MAY PY 2013 VL 37 IS 4 BP 697 EP 704 DI 10.1016/j.neubiorev.2013.01.006 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 139JX UT WOS:000318580100011 PM 23313648 ER PT J AU Guastella, AJ Hickie, IB McGuinness, MM Otis, M Woods, EA Disinger, HM Chan, HK Chen, TF Banati, RB AF Guastella, Adam J. Hickie, Ian B. McGuinness, Margaret M. Otis, Melissa Woods, Elizabeth A. Disinger, Hannah M. Chan, Hak-Kim Chen, Timothy F. Banati, Richard B. TI Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research SO PSYCHONEUROENDOCRINOLOGY LA English DT Review DE Social cognition; Nasal spray; Bioavailability; Hormone; Peptide; Human; Blood brain barrier; Absorption; Clinical trials; Methods ID COMPUTATIONAL FLUID-DYNAMICS; CENTRAL-NERVOUS-SYSTEM; DRUG-DELIVERY; MUCOCILIARY CLEARANCE; INTRANASAL DELIVERY; PARTICLE DEPOSITION; IN-VITRO; SPRAY; BRAIN; TRANSPORT AB A series of studies have reported on the salubrious effects of oxytocin nasal spray on social cognition and behavior in humans, across physiology (e.g., eye gaze, heart rate variability), social cognition (e.g., attention, memory, and appraisal), and behavior (e.g., trust, generosity). Findings suggest the potential of oxytocin nasal spray as a treatment for various psychopathologies, including autism and schizophrenia. There are, however, increasing reports of variability of response to oxytocin nasal spray between experiments and individuals. In this review, we provide a summary of factors that influence transmucosat nasal drug delivery, deposition, and their impact on bioavailability. These include variations in anatomy and resultant airflow dynamic, vascularisation, status of blood vessels, mode of spray application, gallenic formulation (including presence of uptake enhancers, control release formulation), and amount and method of administration. These key variables are generally poorly described and controlled in scientific reports, in spite of their potential to alter the course of treatment outcome studies. Based on this review, it should be of no surprise that differences emerge across individuals and experiments when nasal drug delivery methods are employed. We present recommendations for researchers to use when developing and administering the spray, and guidelines for reporting on peptide nasal spray studies in humans. We hope that these recommendations assist in establishing a scientific standard that can improve the rigor and subsequent reliability of reported effects of oxytocin nasal spray in humans. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved. C1 [Guastella, Adam J.; Hickie, Ian B.; McGuinness, Margaret M.; Otis, Melissa; Woods, Elizabeth A.; Disinger, Hannah M.; Banati, Richard B.] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2006, Australia. [McGuinness, Margaret M.; Otis, Melissa] Boston Univ, Fac Arts & Sci, Boston, MA 02215 USA. [Disinger, Hannah M.] Univ Minnesota, Crookston, MN 55455 USA. [Woods, Elizabeth A.] Univ Kentucky, Coll Pharm, Lexington, KY 40506 USA. [Chan, Hak-Kim; Chen, Timothy F.] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia. [Banati, Richard B.] Univ Sydney, Fac Hlth Sci, Lidcombe, NSW 2141, Australia. [Banati, Richard B.] Australian Nucl Sci & Technol Org, Kirrawee, NSW 2232, Australia. RP Guastella, AJ (reprint author), Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2006, Australia. EM adam.guastella@sydney.edu.au FU NHMRC [623624, 623625, 1043664]; ARC Linkage grant [LP110100513]; BUPA health foundation [2012-00004]; NHMRC Australian Fellowship [511921] FX We would like to thank Daniel Wermeling (University of Kentucky), Anita Van Zwieten, and Lisa Whittle for comments on this manuscript, and Nigel Chen for assistance with manuscript preparation. This research was supported by NHMRC grants (No. 623624, No. 623625, No. 1043664), ARC Linkage grant (No. LP110100513), and a BUPA health foundation grant (No. 2012-00004) to Guastella. We also acknowledge a NHMRC Australian Fellowship (No. 511921) to Hickie. 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El-Sayed, Eman M. TI Proposed remedies for some developmental disorders SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE Developmental disorders; vitamins; minerals; herbs; amino acids; fatty acids ID GINKGO-BILOBA EXTRACT; NEURAL-TUBE DEFECTS; AUTISTIC SPECTRUM DISORDERS; ABNORMAL FOLATE METABOLISM; MATERNAL IRON-DEFICIENCY; ESSENTIAL FATTY-ACIDS; EGB 761 PROTECTS; DOWN-SYNDROME; OXIDATIVE STRESS; DOUBLE-BLIND AB Developmental disorders (DDs) are important leading cause of disability in developed countries and also in the United States. DDs are a group of individual conditions that result from abnormal nervous system development and cause altered function. They can begin at any time from prenatal to 22 years of age and the disability usually presents itself throughout a person's life time. Down syndrome, autism, neural tube defects, schizophrenia, cretinism, and attention-deficit hyperactivity disorder are among the most common DDs that currently plague numerous countries and have varying incidence rates. Their occurrence may be partially attributable to the lack of certain dietary nutrients. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population of America and developed countries and are exceptionally deficient in patients suffering from mental disorders. Typically, most of these disorders are treated with prescription drugs, but many of these drugs cause unwanted side effects. Therefore, psychiatrists recommend alternative or complementary nutritional remedies to overcome the adverse effects of those drugs. Studies have shown that daily supplements of vital nutrients, such as that contain amino acids, often effectively reduce symptoms of the patients, because they are converted into neurotransmitters that alleviate depression and other mental disorders. The aim of this article is to discuss the role of dietary imbalances in the incidence of DD and to emphasize which dietary supplements can aid in the treatment of the above-mentioned DD. C1 [Ibrahim, Khadiga S.] Natl Res Ctr, Dept Environm & Occupat Med, Cairo, Egypt. [El-Sayed, Eman M.] Natl Res Ctr, Dept Food Sci & Nutr, Cairo, Egypt. RP Ibrahim, KS (reprint author), Natl Res Ctr, Dept Environm & Occupat Med, Giza 11141, Egypt. 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Ind. Health PD MAY PY 2013 VL 29 IS 4 BP 367 EP 384 DI 10.1177/0748233711433937 PG 18 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 141TP UT WOS:000318749700008 PM 22301819 ER PT J AU Yang, K Cao, FJ Sheikh, AM Malik, M Wen, G Wei, HG Brown, WT Li, XH AF Yang, Kun Cao, Fujiang Sheikh, Ashfaq M. Malik, Mazhar Wen, Guang Wei, Hongen Brown, W. Ted Li, Xiaohong TI Up-regulation of Ras/Raf/ERK1/2 signaling impairs cultured neuronal cell migration, neurogenesis, synapse formation, and dendritic spine development SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Ras/Raf/ERK1/2 signaling pathway; Autism; Apoptosis; Neural development; Dendritic spines ID AUTISM SPECTRUM DISORDERS; FRAGILE-X-SYNDROME; AMPA RECEPTOR TRAFFICKING; LONG-TERM POTENTIATION; DENTATE GYRUS; KINASE; ERK; PLASTICITY; PROTEIN; ACTIVATION AB The Ras/Raf/ERK1/2 signaling pathway controls many cellular responses such as cell proliferation, migration, differentiation, and death. In the nervous system, emerging evidence also points to a death-promoting role for ERK1/2 in both in vitro and in vivo models of neuronal death. Recent studies have suggested that abnormal apoptosis in the central nervous system may be involved in the pathogenesis of autism. Two studies reported that both a microdeletion and microduplication on chromosome 16, which includes the MAPK3 gene that encodes ERK1, are associated with autism. In addition, our recent work showed that Ras/Raf/ERK1/2 signaling activities were significantly up-regulated in the frontal cortex of autistic individuals and in the BTBR murine model of autism. To further investigate how Ras/Raf/ERK1/2 up-regulation may lead to the development of autism, we developed a cellular model of Raf/ERK up-regulation by over-expressing c-Raf in cultured cortical neurons (CNs) and cerebellar granule cells (CGCs). We found that Raf/ERK up-regulation stimulates the migration of both CNs and CGCs, and impairs the formation of excitatory synapses in CNs. In addition, we found that Raf/ERK up-regulation inhibits the development of mature dendritic spines in CNs. Investigating the possible mechanisms through which Raf/ERK up-regulation affects excitatory synapse formation and dendritic spine development, we discovered that Raf/ERK up-regulation suppresses the development and maturation of CNs. Together, these results suggest that the up-regulation of the Raf/ERK signaling pathway may contribute to the pathogenesis of autism through both its impairment of cortical neuron development and causing neural circuit imbalances. C1 [Yang, Kun; Cao, Fujiang; Sheikh, Ashfaq M.; Malik, Mazhar; Wei, Hongen; Brown, W. Ted; Li, Xiaohong] NY State Inst Basic Res Dev Disabil, Dept Neurochem, New York, NY 10314 USA. [Yang, Kun] Qingdao Univ, Coll Med, Affiliated Hosp, Dept Mol Biol, Qingdao 266003, Peoples R China. [Wen, Guang] NY State Inst Basic Res Dev Disabil, Dept Dev Neurobiol, New York, NY 10314 USA. RP Li, XH (reprint author), NY State Inst Basic Res Dev Disabil, Dept Neurochem, 1050 Forest Hill Rd, New York, NY 10314 USA. EM Xiaohongli99@gmail.com FU NYS Office for People with Developmental Disabilities; Rural India Charitable Trust; Northfield Bank Foundation FX This work was supported by the NYS Office for People with Developmental Disabilities, the Rural India Charitable Trust and Northfield Bank Foundation. 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Funct. PD MAY PY 2013 VL 218 IS 3 BP 669 EP 682 DI 10.1007/s00429-012-0420-7 PG 14 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 135TE UT WOS:000318310600004 PM 22555958 ER PT J AU Fiebelkorn, IC Foxe, JJ McCourt, ME Dumas, KN Molholm, S AF Fiebelkorn, Ian C. Foxe, John J. McCourt, Mark E. Dumas, Kristina N. Molholm, Sophie TI Atypical category processing and hemispheric asymmetries in high-functioning children with autism: Revealed through high-density EEG mapping SO CORTEX LA English DT Article DE Autism spectrum disorders; Category processing; Hemispheric asymmetries; Attention; Electroencephalography ID CORPUS-CALLOSUM; OBJECT-RECOGNITION; SELECTIVE ATTENTION; VISUAL-PERCEPTION; CLOSURE PROCESSES; FACE RECOGNITION; INDIVIDUALS; CONNECTIVITY; ACTIVATION; SHAPE AB Behavioral evidence for an impaired ability to group objects based on similar physical or semantic properties in autism spectrum disorders (ASD) has been mixed. Here, we recorded brain activity from high-functioning children with ASD as they completed a visual-target detection task. We then assessed the extent to which object-based selective attention automatically generalized from targets to non-target exemplars from the same well-known object class (e.g., dogs). Our results provide clear electrophysiological evidence that children with ASD (N = 17, aged 8-13 years) process the similarity between targets (e.g., a specific dog) and same-category non-targets (SCNT) (e.g., another dog) to a lesser extent than do their typically developing (TD) peers (N = 21). A closer examination of the data revealed striking hemispheric asymmetries that were specific to the ASD group. These findings align with mounting evidence in the autism literature of anatomic underconnectivity between the cerebral hemispheres. Years of research in individuals with TD have demonstrated that the left hemisphere (LH) is specialized toward processing local (or featural) stimulus properties and the right hemisphere (RH) toward processing global (or configural) stimulus properties. We therefore propose a model where a lack of communication between the hemispheres in ASD, combined with typical hemispheric specialization, is a root cause for impaired categorization and the oft-observed bias to process local over global stimulus properties. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Fiebelkorn, Ian C.; Foxe, John J.; Dumas, Kristina N.; Molholm, Sophie] Albert Einstein Coll Med, Sheryl & Daniel R Tishman Cognit Neurophysiol Lab, CERC, Dept Pediat, Bronx, NY 10467 USA. [Fiebelkorn, Ian C.; Foxe, John J.; Dumas, Kristina N.; Molholm, Sophie] Albert Einstein Coll Med, Sheryl & Daniel R Tishman Cognit Neurophysiol Lab, CERC, Dept Neurosci, Bronx, NY 10467 USA. [Fiebelkorn, Ian C.; McCourt, Mark E.] N Dakota State Univ, Dept Psychol, Ctr Visual & Cognit Neurosci, Fargo, ND 58105 USA. RP Molholm, S (reprint author), Albert Einstein Coll Med, Sheryl & Daniel R Tishman Cognit Neurophysiol Lab, CERC, Dept Pediat, Van Etten Bldg 1C, Bronx, NY 10467 USA. EM sophie.molholm@einstein.yu.edu RI McCourt, Mark/C-5143-2012 OI McCourt, Mark/0000-0001-8675-8231 FU National Institute of Mental Health [MH-085322]; National Science Foundation [BCS0642584]; National Center for Research Resources (NCRR); National Institute for General Medicine (NIGMS) of the National Institutes of Health (NIH) [P20 RR020151, P20 GM103505]; P30 center grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD071593] FX This work was supported by a National Institute of Mental HealthMH-085322 to SM and JJF, and a National Science FoundationBCS0642584 to JJF. ICF and MEM received support from the National Center for Research Resources (NCRR) and the National Institute for General Medicine (NIGMS) of the National Institutes of Health (NIH) through Grants P20 RR020151 and P20 GM103505. The contents of this report are solely the responsibility of the authors and do not necessarily reflect the official views of the NIH, NCRR or NIGMS. We would like to thank Dr. Natalie Russo and Sarah Ruberman for their help at various stages of the project. We would also like to acknowledge the contributions of the staff at the Human Clinical Phenotyping Core (HCP) of the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (IDDRC) during the recruitment and clinical classification of a portion of the participants who served in this study. This core is supported through a P30 center grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD071593). 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Twenty-four children with autism underwent on average two years of IBI and completed (interrupted language, daily living skills, cognitive, and motor assessments (Early Learning Accomplishment time-series with Profile and the Learning Accomplishment Profile-Diagnostic, 3rd edition) every six months. We one group) used multilevel analysis to identify potential longitudinal predictors including gender, age, intervention intensity, intervention duration, total intervention time, and pre-intervention functioning. Results indicated that total intervention time, pre-intervention functioning, and age caused the greatest increase in goodness-of-fit of the longitudinal multilevel models. Longitudinal analysis is a promising analytical strategy to identify reliable predictors of the clinical outcome of IBI. (C) 2012 Asociacion Espanola de Psicologia Conductual. Published by Elsevier Espana, S.L. All rights reserved. C1 [Virues-Ortega, Javier; Yu, C. T.] Univ Manitoba, Winnipeg, MB, Canada. 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PD MAY PY 2013 VL 13 IS 2 BP 91 EP 100 PG 10 WC Psychology, Clinical SC Psychology GA 139KR UT WOS:000318582100002 ER PT J AU Durrleman, S Pennec, X Trouve, A Braga, J Gerig, G Ayache, N AF Durrleman, Stanley Pennec, Xavier Trouve, Alain Braga, Jose Gerig, Guido Ayache, Nicholas TI Toward a Comprehensive Framework for the Spatiotemporal Statistical Analysis of Longitudinal Shape Data SO INTERNATIONAL JOURNAL OF COMPUTER VISION LA English DT Article DE Longitudinal data; Statistics; Growth; Shape regression; Spatiotemporal registration; Time warp ID AGE 2 YEARS; BRAIN GROWTH; REGISTRATION; DIFFEOMORPHISMS; DEFORMATION; PATTERN; MORPHOMETRY; SEQUENCES; AUTISM; MOTION AB This paper proposes an original approach for the statistical analysis of longitudinal shape data. The proposed method allows the characterization of typical growth patterns and subject-specific shape changes in repeated time-series observations of several subjects. This can be seen as the extension of usual longitudinal statistics of scalar measurements to high-dimensional shape or image data. The method is based on the estimation of continuous subject-specific growth trajectories and the comparison of such temporal shape changes across subjects. Differences between growth trajectories are decomposed into morphological deformations, which account for shape changes independent of the time, and time warps, which account for different rates of shape changes over time. Given a longitudinal shape data set, we estimate a mean growth scenario representative of the population, and the variations of this scenario both in terms of shape changes and in terms of change in growth speed. Then, intrinsic statistics are derived in the space of spatiotemporal deformations, which characterize the typical variations in shape and in growth speed within the studied population. They can be used to detect systematic developmental delays across subjects. In the context of neuroscience, we apply this method to analyze the differences in the growth of the hippocampus in children diagnosed with autism, developmental delays and in controls. Result suggest that group differences may be better characterized by a different speed of maturation rather than shape differences at a given age. In the context of anthropology, we assess the differences in the typical growth of the endocranium between chimpanzees and bonobos. We take advantage of this study to show the robustness of the method with respect to change of parameters and perturbation of the age estimates. C1 [Durrleman, Stanley; Gerig, Guido] Sci Comp & Imaging SCI Inst, Salt Lake City, UT 84112 USA. [Durrleman, Stanley; Pennec, Xavier; Ayache, Nicholas] INRIA Sophia Antipolis, Asclepios Team Project, F-06902 Sophia Antipolis, France. [Durrleman, Stanley; Trouve, Alain] CNRS ENS Cachan, CMLA, F-94235 Cachan, France. [Braga, Jose] Univ Toulouse 3, CNRS, Lab Paleoanthropol Assistee Ordinateur, F-37073 Toulouse, France. RP Durrleman, S (reprint author), Sci Comp & Imaging SCI Inst, 72 S Cent Dr, Salt Lake City, UT 84112 USA. EM stanley.durrleman@gmail.com RI Pennec, Xavier/L-2537-2013; Braga, Jose/A-4025-2010 OI Pennec, Xavier/0000-0002-6617-7664; Braga, Jose/0000-0002-8483-076X FU INRIA ARC 3D-Morphine (PI: Sylvain Prima); European IP Project Health-e-child [IST-2004-027749]; Microsoft Research FX We would like to thank B. Combes (IRISA, France) for preprocessing the endocast data, J. Piven, director of Carolina Institute for Developmental Disabilities at UNC Chapel Hill, for providing imaging data related to autism research, and M. Styner (Psychiatry UNC Chapel Hill) for processing the subcortical structures. We thank W. Van Neer and E. Gilissen the previous and current curator of the "Musee de l'Afrique Centrale" at Tervuren (Belgium). We are indebted to Chems Touati for his help for creating figures and movies and James Fishbaugh for his kind proofreading of the manuscript, both at the Scientific Computing and Imaging Institute, University of Utah. This work has been funded in part by the INRIA ARC 3D-Morphine (PI: Sylvain Prima), the European IP Project Health-e-child (IST-2004-027749) and Microsoft Research. CR Aljabar P, 2008, NEUROIMAGE, V39, P348, DOI 10.1016/j.neuroimage.2007.07.067 Allassonniere S, ESAIM PROBA IN PRESS Chandrashekara R, 2003, LECT NOTES COMPUT SC, V2732, P599 Courchesne E, 2011, BRAIN RES, V1380, P138, DOI 10.1016/j.brainres.2010.09.101 Davis B. 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Swank, Paul TI Social Interaction in Young Children with Inflicted and Accidental Traumatic Brain Injury: Relations with Family Resources and Social Outcomes SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Joint attention; Gaze; Developmental outcome; Social cognition; High risk; Child abuse; Communication; Adaptive behavior; Cognition; Infants ID INFANT JOINT ATTENTION; SHAKEN-BABY SYNDROME; PRESCHOOL-CHILDREN; EXECUTIVE PROCESSES; VISUAL-ATTENTION; HEAD-INJURY; COGNITION; COMPETENCE; AUTISM; SKILLS AB Core social interaction behaviors were examined in young children 0-36 months of age who were hospitalized for accidental (n = 61) or inflicted (n = 64) traumatic brain injury (TBI) in comparison to typically developing children (n = 60). Responding to and initiating gaze and joint attention (JA) were evaluated during a semi-structured sequence of social interactions between the child and an examiner at 2 and 12 months after injury. The accidental TBI group established gaze less often and had an initial deficit initiating JA that resolved by the follow-up. Contrary to expectation, children with inflicted TBI did not have lower rates of social engagement than other groups. Responding to JA was more strongly related than initiating JA to measures of injury severity and to later cognitive and social outcomes. Compared to complicated-mild/moderate TBI, severe TBI in young children was associated with less responsiveness in social interactions and less favorable caregiver ratings of communication and social behavior. JA response, family resources, and group interacted to predict outcomes. Children with inflicted TBI who were less socially responsive and had lower levels of family resources had the least favorable outcomes. Low social responsiveness after TBI may be an early marker for later cognitive and adaptive behavior difficulties. C1 [Ewing-Cobbs, Linda; Prasad, Mary R.; Barnes, Marcia A.; Swank, Paul] Univ Texas Hlth Sci Ctr Houston, Dept Pediat, Houston, TX USA. [Ewing-Cobbs, Linda; Prasad, Mary R.; Barnes, Marcia A.; Swank, Paul] Univ Texas Hlth Sci Ctr Houston, Childrens Learning Inst, Houston, TX USA. [Ewing-Cobbs, Linda] Univ Texas Hlth Sci Ctr Houston, Dept Psychiat & Behav Sci, Houston, TX USA. [Mendez, Donna] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. RP Ewing-Cobbs, L (reprint author), Childrens Learning Inst, Dept Pediat, 7000 Fannin,Suite 2401, Houston, TX 77030 USA. EM linda.ewing-cobbs@uth.tmc.edu FU National Institute of Neurological Disorders and Stroke [R01 NS029462] FX This publication was supported by Grant Number R01 NS029462 from the National Institute of Neurological Disorders and Stroke. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. The participation of the children and families, as well as the assistance of the Texas Department of Protective and Regulatory Services, is gratefully acknowledged. The authors report no financial or other conflict of interest. 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TI Assessing Social Cognition and Pragmatic Language in Adolescents with Traumatic Brain Injuries SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Emotion; Theory of mind; Pragmatics; Sarcasm; Brain injury; Adolescence ID HIGH-FUNCTIONING AUTISM; HEAD-INJURY; FRONTOTEMPORAL DEMENTIA; EMOTION RECOGNITION; ASPERGER-SYNDROME; RIGHT-HEMISPHERE; CHILDREN; MIND; SARCASM; COMMUNICATION AB Traumatic brain injuries (TBI) in children and adolescents can impair social cognition and communication skills but there are few assessment tools suitable for adolescents. The Awareness of Social Inference Test (TASIT) uses professionally enacted audiovisual vignettes of everyday conversational exchanges and is a valid measure of social perception disorders in adults. This study examined its utility for assessing impairments in social cognition in a group of 16 adolescents with TBI, compared to a group of 16 typically developing (TD) adolescents. Adolescents with TBI were, on average, no different to their TD peers on TASIT 1 (emotion recognition) and TASIT 3 (recognizing lies and sarcasm when provided with additional cues) but performed more poorly on TASIT 2 which required them to interpret sarcastic and sincere conversational exchanges with few cues other than the demeanor of the speakers. Within the TBI group, poor performance on TASIT correlated to both relative and self-reported communication difficulties at home. It also correlated with IQ, face recognition and severity of injury as indexed by duration of post-traumatic amnesia. Overall, this study suggests TASIT is a valid measure for adolescents although it raised questions as to how effective normative data is for comparing performance in social cognition during childhood and adolescence. C1 [McDonald, Skye; English, Therese; Randall, Rebekah; Longman, Thea; Togher, Leanne; Tate, Robyn L.] Univ New S Wales, Sch Psychol, Sydney, NSW 2052, Australia. RP McDonald, S (reprint author), Univ New S Wales, Sch Psychol, Sydney, NSW 2052, Australia. EM s.mcdonald@unsw.edu.au RI McDonald, Skye/G-4118-2014 OI McDonald, Skye/0000-0003-0723-6094 FU National Health and Medical Research Council of Australia FX This research was funded by the National Health and Medical Research Council of Australia. We are grateful to the Prince of Wales Children's Hospital, Brain Injury Unit and the John Hunter Pediatric Brain Injury Service for their assistance with recruitment. We are especially indebted to the young people and their families who participated in this research. The Awareness of Social Inference Test (TASIT) is sold commercially by Pearson Assessment and the first author receives royalties for this. Other than this there are no conflicts of interest. 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TI The Developmental Brain Gene NPAS3 Contains the Largest Number of Accelerated Regulatory Sequences in the Human Genome SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE NPAS3; brain; evolution; humans; schizophrenia ID TRANSCRIPTION FACTOR; MOLECULAR EVOLUTION; MAXIMUM-LIKELIHOOD; POSITIVE SELECTION; ADAPTIVE EVOLUTION; CANDIDATE-GENE; ZEBRAFISH; AUTISM; SCHIZOPHRENIA; EXPRESSION AB To identify the evolutionary genetic novelties that contributed to shape human-specific traits such as the use of a complex language, long-term planning and exceptional learning abilities is one of the ultimate frontiers of modern biology. Evolutionary signatures of functional shifts could be detected by comparing noncoding regions that are highly conserved across mammals or primates and rapidly accumulated nucleotide substitutions only in the lineage leading to humans. As gene loci densely populated with human-accelerated elements (HAEs) are more likely to have contributed to human-specific novelties, we sought to identify the transcriptional units and genomic 1 Mb intervals of the entire human genome carrying the highest number of HAEs. To this end, we took advantage of four available data sets of human genomic accelerated regions obtained through different comparisons and algorithms and performed a meta-analysis of the combined data. We found that the brain developmental transcription factor neuronal PAS domain-containing protein 3 (NPAS3) contains the largest cluster of noncoding-accelerated regions in the human genome with up to 14 elements that are highly conserved in mammals, including primates, but carry human-specific nucleotide substitutions. We then tested the ability of the 14 HAEs identified at the NPAS3 locus to act as transcriptional regulatory sequences in a reporter expression assay performed in transgenic zebrafish. We found that 11 out of the 14 HAEs present in NPAS3 act as transcriptional enhancers during development, particularly within the nervous system. As NPAS3 is known to play a crucial role during mammalian brain development, our results indicate that the high density of HAEs present in the human NPAS3 locus could have modified the spatiotemporal expression pattern of NPAS3 in the developing human brain and, therefore, contributed to human brain evolution. C1 [Kamm, Gretel B.; Pisciottano, Francisco; Kliger, Rafi; Franchini, Lucia F.] Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol INGEBI, RA-1033 Buenos Aires, DF, Argentina. RP Franchini, LF (reprint author), Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol INGEBI, RA-1033 Buenos Aires, DF, Argentina. EM franchini@dna.uba.ar FU Agencia Nacional de Promocion Cientifica y Tecnologica [PICT 1071]; Consejo Nacional de Investigaciones Cientificas y Tecnicas grant CONICET-Argentina [PIP 0299]; CONICET FX The authors thank Drs. Sabina Domene and Nora Calcaterra for excellent technical advice in transgenic zebrafish production and handling. They thank Adrian Sestelo for chimpanzee samples. They express their gratitude to Marcelo Rubinstein for permanent support and valuable suggestions on experimental design, data interpretation, and critical comments on the manuscript. This work was supported by the Agencia Nacional de Promocion Cientifica y Tecnologica grant PICT 1071, the Consejo Nacional de Investigaciones Cientificas y Tecnicas grant CONICET-Argentina PIP 0299 to L. F. F., and doctoral fellowships from the CONICET to F. P. and G.B.K. 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The Fmr1 knockout model recapitulates the main traits of the disease(4). Uncontrolled activity of metabotropic glutamate receptor 5 (mGluR5)(5,6) and mammalian target of rapamycin (mTOR) signaling(7-9) seem crucial in the pathophysiology of this disease. The endocannabinoid system (ECS) is a key modulator of synaptic plasticity, cognitive performance, anxiety, nociception and seizure susceptibility(10), all of which are affected in FXS. The ECS receptors, CB1 (CB1R) and CB2 (CB2R), are activated by phospholipid-derived endocannabinoids. Synaptic activation of mGluR5 initiates the synthesis of endocannabinoids(10,11) and promotes CB1R-driven long-term depression of synaptic strength(10). Notably, mGluR5 activation is altered in several brain areas of Fmr1 knockout mice(12-14). We found that CB1R blockade in male Fmr1 knockout (Fmr1-(/y)) mice through pharmacological and genetic approaches normalized cognitive impairment, nociceptive desensitization, susceptibility to audiogenic seizures, overactivated mTOR signaling and altered spine morphology, whereas pharmacological blockade of CB2R normalized anxiolytic-like behavior. Some of these traits were also reversed by pharmacological inhibition of mTOR or mGluR5. Thus, blockade of ECS is a potential therapeutic approach to normalize specific alterations in FXS. C1 [Busquets-Garcia, Arnau; Gomis-Gonzalez, Maria; Guegan, Thomas; de la Torre, Rafael; Maldonado, Rafael; Ozaita, Andres] UPF, Dept Ciencies Experimentals Salut DCEXS, Barcelona, Spain. [Agustin-Pavon, Carmen; Dierssen, Mara] Ctr Genom Regulat CRG, Barcelona, Spain. [Agustin-Pavon, Carmen; Dierssen, Mara] UPF, Barcelona, Spain. [Pastor, Antoni; de la Torre, Rafael] Inst Hosp Mar Investigac Med IMIM, Grup Recerca Clin Farmacol Humana Neurociencies, Barcelona, Spain. [Pastor, Antoni] Univ Autonoma Barcelona, Fac Med, E-08193 Barcelona, Spain. [Mato, Susana; Perez-Samartin, Alberto; Matute, Carlos] Univ Basque Country, Dept Neurociencias, Neurobiol Lab, Leioa, Spain. [Mato, Susana; Perez-Samartin, Alberto; Matute, Carlos] Achucarro Basque Ctr Neurosci, Zamudio, Spain. [Mato, Susana; Perez-Samartin, Alberto; Matute, Carlos] Inst Salud Carlos III, Ctr Investigac Biomed Red Enfermedades Neurodegen, Leioa, Spain. [de la Torre, Rafael] Univ Santiago de Compostela, Hosp Clin, CIBER Fisiopatol Obesidad & Nutr CB06 03 CIBEROBN, Santiago De Compostela, Spain. [Dierssen, Mara] CIBER Enfermedades Raras CIBERER, Barcelona, Spain. RP Ozaita, A (reprint author), UPF, Dept Ciencies Experimentals Salut DCEXS, Barcelona, Spain. EM andres.ozaita@upf.edu RI Maldonado, Rafael/F-5657-2014; SGIKER, Cienciometria/A-5759-2012 OI Maldonado, Rafael/0000-0002-4359-8773; FU Ministerio de Ciencia e Innovacion [SAF2009-07309, BFU2012-33500, SAF2011-29864, SAF2010-21547]; CureFXS E-Rare EU/FIS [PS09102673]; Instituto de Salud Carlos III [RD06/0001/0001]; PLAN E (Plan Espanol para el Estimulo de la Economia y el Empleo); Generalitat de Catalunya [SGR-2009-00731, SGR-2009-00718]; ICREA (Institucio Catalana de Recerca i Estudis Avancats) Academia; Ministerio de Educacion y Cultura; Fundacio La Marato de TV3 [090910] FX We thank C. Fernandez-Aviles, D. Real, M. Linares and H. Gomez for expert technical assistance and O.J. Manzoni for helpful comments. Fmr1 knockout mice in the C57BL/6J background were kindly provided by D. Nelson at Baylor College of Medicine. A.B.-G. is the recipient of a predoctoral fellowship (Ministerio de Educacion y Cultura). S.M. is the recipient of a Ramon y Cajal contract (Ministerio de Educacion y Cultura). This study was supported by grants from Fundacio La Marato de TV3 (090910 to A.O.), Grants from the Ministerio de Ciencia e Innovacion (SAF2009-07309 and BFU2012-33500 to A.O., SAF2011-29864 to R.M. and SAF2010-21547 to C.M.), CureFXS E-Rare EU/FIS PS09102673 to M.D., Instituto de Salud Carlos III (RD06/0001/0001 to R.M.), PLAN E (Plan Espanol para el Estimulo de la Economia y el Empleo), Generalitat de Catalunya (SGR-2009-00731 to R.M. and SGR-2009-00718 to R.d.I.T.) and ICREA (Institucio Catalana de Recerca i Estudis Avancats) Academia to R.M. 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Revising theories of social cognition on the basis of schizophrenia and high functioning autism-spectrum disorders SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Social cognition; Schizophrenia; Autism; Phenomenology; Cognitive science; Psychopathology; Theory of mind ID INTELLECTUAL DISABILITY; 1ST-PERSON PERSPECTIVE; PSYCHIATRIC-DISORDERS; DIRECT PERCEPTION; MIND; ADULTS; BRAIN; CONSCIOUSNESS; PHENOMENOLOGY; SIMULATION AB Schizophrenia and high functioning autism-spectrum disorders (ASD) are neurodevelopmental conditions that mainly impair social competence, while general intelligence (IQ) is spared. Both disorders have a strong ancillary role in theoretical research on social cognition. Recently the debate has started to be inflected by embodied and phenomenological approaches, which claim that the standard portrayal of all social understanding as so-called 'mindreading', i.e. the attribution of mental states to others in the service of explaining and predicting their behavior, is misguided. Instead it is emphasized that we normally perceive others directly as conscious and goal-directed persons, without requiring any theorizing and/or simulation. This paper evaluates some of the implications of abnormal experiences reported by people with schizophrenia and ASD for the current debate in cognitive science. For these people the practice of explicit mindreading seems to be a compensatory strategy that ultimately fails to compensate for - and may even exacerbate - their impairment of intuitive and interactive social understanding. Phenomenological psychopathology thereby supports the emerging view that 'mindreading' is not the principal form of normal social understanding. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Froese, Tom] Univ Nacl Autonoma Mexico, IIMAS, Mexico City 01000, DF, Mexico. [Stanghellini, Giovanni] Univ G DAnnunzio, DISPUTer, Chieti, Italy. [Stanghellini, Giovanni] Univ Diego Portales, Santiago, Chile. [Bertelli, Marco O.] CREA AMG Res & Evolut Ctr, Florence, Italy. RP Froese, T (reprint author), Univ Nacl Autonoma Mexico, Dept Ciencias Comp, Inst Invest Matemat Aplicadas & Sistemas, Ciudad Univ,AP 20-726, Mexico City 01000, DF, Mexico. 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PD MAY PY 2013 VL 34 IS 5 BP 1376 EP 1387 DI 10.1016/j.ridd.2013.01.005 PG 12 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 129WZ UT WOS:000317876000002 PM 23474990 ER PT J AU Sajedi, F Ahmadlou, M Vameghi, R Gharib, M Hemmati, S AF Sajedi, Firoozeh Ahmadlou, Mehran Vameghi, Roshanak Gharib, Masoud Hemmati, Sahel TI Linear and nonlinear analysis of brain dynamics in children with cerebral palsy SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Cerebral palsy; Complexity; Electroencephalography; Gross motor function; Power spectrum analysis ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; GROSS MOTOR FUNCTION; FUZZY SYNCHRONIZATION LIKELIHOOD; LISSENCEPHALY AGYRIA-PACHYGYRIA; AUTISM SPECTRUM DISORDER; VISIBILITY GRAPH; NEURAL-NETWORK; EEG-ANALYSIS; SERIAL EEG; ADOLESCENTS AB This study was carried out to determine linear and nonlinear changes of brain dynamics and their relationships with the motor dysfunctions in CP children. For this purpose power of EEG frequency bands (as a linear analysis) and EEG fractality (as a nonlinear analysis) were computed in eyes-closed resting state and statistically compared between 26 CP and 26 normal children. Based on these characteristics accuracy of the classification between the two groups was obtained by enhanced probabilistic neural network (EPNN). Severity of gross motor and manual disabilities was determined by standard systems and the relation between the deficient brain dynamics and severity of the motor dysfunctions was obtained by Pearson's correlation coefficient. A definitely higher delta and lower theta and alpha powers, and higher EEG complexity in CP patients. As such a high accuracy of 94.8% in distinguishing the two groups was obtained. Moreover significant positive correlations were found between beta power and severity of manual disabilities and gross motor dysfunctions in the boys with CP. It is concluded that the obtained brain dynamics' characteristics are useful in diagnosis of CP. Furthermore severity of the motor dysfunctions in boys with CP could be evaluated by the beta activity. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Sajedi, Firoozeh; Vameghi, Roshanak; Gharib, Masoud; Hemmati, Sahel] Univ Social Welf & Rehabil Sci, Pediat Neurorehabil Res Ctr, Tehran, Iran. [Sajedi, Firoozeh; Ahmadlou, Mehran] Dynam Brain Res Inst, Tehran, Iran. [Ahmadlou, Mehran] Netherlands Inst Neurosci, Amsterdam, Netherlands. RP Ahmadlou, M (reprint author), Netherlands Inst Neurosci, Meibergdreef 47, Amsterdam, Netherlands. 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Dev. Disabil. PD MAY PY 2013 VL 34 IS 5 BP 1388 EP 1396 DI 10.1016/j.ridd.2013.01.016 PG 9 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 129WZ UT WOS:000317876000003 PM 23474991 ER PT J AU Hill-Chapman, CR Herzog, TK Maduro, RS AF Hill-Chapman, Crystal R. Herzog, Teresa K. Maduro, Ralitsa S. TI Aligning over the child: Parenting alliance mediates the association of autism spectrum disorder atypicality with parenting stress SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism spectrum disorder; Child atypicality; Parenting alliance; Parenting stress ID BEHAVIOR PROBLEMS; MENTAL-HEALTH; DEVELOPMENTAL DELAY; PERCEPTIONS; MARRIAGE; TODDLERS; FATHERS; MOTHERS AB Children's symptoms of autism are robustly linked to diminished parent well-being and relationship distress, however they are less clearly linked to other aspects of family development. We focused on child atypical symptoms (i.e., behavioral stereotypies) and investigated relations to parental stress and the parenting alliance. We verified that relations between atypicality and parenting stress were partially mediated by a child-focused aspect of the parenting alliance. These results suggested that parents of highly atypical children reported less stress than parents of children with low levels of these behaviors, an effect that acted through an assessment of the parenting partner as highly involved with the child. However, parents with highly atypical children did not report a similarly better self-focused parenting alliance, indicating that direct emotional support from the partner did not differ between the groups. We discuss the possibility that, among parents who stay together in the face of severe child disability, enhanced perceptions of parenting are not uncommon. (C) 2013 Elsevier Ltd. All rights reserved. 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PD MAY PY 2013 VL 34 IS 5 BP 1498 EP 1504 DI 10.1016/j.ridd.2013.01.004 PG 7 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 129WZ UT WOS:000317876000014 PM 23475000 ER PT J AU Collin, L Bindra, J Raju, M Gillberg, C Minnis, H AF Collin, Lisa Bindra, Jasmeet Raju, Monika Gillberg, Christopher Minnis, Helen TI Facial emotion recognition in child psychiatry: A systematic review SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Review DE Facial emotion recognition; Child psychiatry; Systematic review ID PEDIATRIC BIPOLAR DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; GENERALIZED ANXIETY DISORDER; DEFICIT HYPERACTIVITY DISORDER; ONSET CONDUCT DISORDER; AMYGDALA ACTIVATION; ANOREXIA-NERVOSA; EXPRESSION RECOGNITION; LABELING DEFICITS; SOCIAL COGNITION AB This review focuses on facial affect (emotion) recognition in children and adolescents with psychiatric disorders other than autism. A systematic search, using PRISMA guidelines, was conducted to identify original articles published prior to October 2011 pertaining to face recognition tasks in case-control studies. Used in the qualitative synthesis were: 2 studies on schizophrenia, 18 on mood disorders, 16 on anxiety disorders, 4 on eating disorders, 14 on ADHD and 9 on conduct disorder. Our review suggests that there are abnormalities in facial emotion recognition in a wide range of child psychiatric disorders and that these are likely to have a negative effect on both family and peer relationships. Scope for further research has been identified. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Collin, Lisa; Bindra, Jasmeet; Raju, Monika] NHS Greater Glasgow & Clyde, Glasgow, Lanark, Scotland. [Gillberg, Christopher; Minnis, Helen] Univ Glasgow, Inst Hlth & Wellbeing, Glasgow G12 8QQ, Lanark, Scotland. RP Minnis, H (reprint author), Univ Glasgow, Inst Hlth & Wellbeing, Glasgow G12 8QQ, Lanark, Scotland. 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Dev. Disabil. PD MAY PY 2013 VL 34 IS 5 BP 1505 EP 1520 DI 10.1016/j.ridd.2013.01.008 PG 16 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 129WZ UT WOS:000317876000015 PM 23475001 ER PT J AU Ashworth, A Hill, CM Karmiloff-Smith, A Dimitriou, D AF Ashworth, Anna Hill, Catherine M. Karmiloff-Smith, Annette Dimitriou, Dagmara TI Cross syndrome comparison of sleep problems in children with Down syndrome and Williams syndrome SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Sleep problems; Williams syndrome; Down syndrome; Actigraphy; Developmental disorders ID SCHOOL-AGED CHILDREN; PRADER-WILLI; DISORDERS; ADOLESCENTS; ACTIGRAPHY; PATTERNS; APNEA; DISTURBANCE; HABITS; AUTISM AB Based on previous findings of frequent sleep problems in children with Down syndrome (DS) and Williams syndrome (WS), the present study aimed to expand our knowledge by using parent report and actigraphy to define sleep problems more precisely in these groups. Twenty-two school-aged children with DS, 24 with WS and 52 typically developing (TD) children took part in the study. Each child wore an actiwatch for a minimum of four nights and parents completed the Children's Sleep Habits Questionnaire (CSHQ). Sleep problems were common in both developmental disorders. Children with DS had the greatest sleep disruption, with frequent and longer night wakings as well as restlessness. Parents reported symptoms of sleep-disordered breathing and a range of other problems including grinding teeth, bedtime resistance and sleep anxiety. Children with WS had problems initiating sleep and parents also reported bed-wetting and body pain. Despite these problems, the mean actual sleep time, as measured by actigraphy, did not differ between the three groups. CSHQ reports were in agreement with actigraphy for children's sleep duration, but this was not the case for sleep latency, restlessness and the night wakings variables. Sleep problems in DS and WS are common and appear to be syndrome-specific. Due to the inaccuracy of parent report, it is recommended that children at risk undergo objective measures of sleep assessment. (C) 2013 Elsevier Ltd. All rights reserved. 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Dev. Disabil. PD MAY PY 2013 VL 34 IS 5 BP 1572 EP 1580 DI 10.1016/j.ridd.2013.01.031 PG 9 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 129WZ UT WOS:000317876000021 PM 23475007 ER PT J AU Sappok, T Diefenbacher, A Budczies, J Schade, C Grubich, C Bergmann, T Bolte, S Dziobek, I AF Sappok, Tanja Diefenbacher, Albert Budczies, Jan Schade, Christoph Grubich, Claudia Bergmann, Thomas Bolte, Sven Dziobek, Isabel TI Diagnosing autism in a clinical sample of adults with intellectual disabilities: How useful are the ADOS and the ADI-R? SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism; Intellectual disability; Diagnostics; ADOS; ADI-R; Adults ID PERVASIVE DEVELOPMENTAL DISORDERS; OBSERVATION-SCHEDULE ADOS; SPECTRUM DISORDERS; MENTAL-RETARDATION; REPETITIVE BEHAVIORS; REVISED ALGORITHMS; PRESCHOOL-CHILDREN; DISABLED ADULTS; YOUNG-CHILDREN; ASD-DA AB Intellectual disability (ID) and autism spectrum disorder (ASD) are frequently co-occurring conditions. Carefully diagnosing ASD in individuals with ID would allow for more tailored clinical interventions that would improve mental health and quality of life. In this study, we evaluated the psychometric properties of the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) in a clinical sample of 79 adults with ID who were suspected of also having ASD. In the testable cases (68%), the ADOS was over-inclusive (specificity 45%) but highly sensitive (100%) of ASD. In the ADI-R, the feasibility was 37%, with a sensitivity of 88% and a specificity of 80%. Previously proposed adaptations of the ADOS algorithm were evaluated, and new items and tasks were suggested. The ADOS and the ADI-R were found to be valuable diagnostic tools for adults with ID. Adjustments of the setting and the tasks may further improve their feasibility and specificity. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Sappok, Tanja; Diefenbacher, Albert; Schade, Christoph; Grubich, Claudia; Bergmann, Thomas] Ev Krankenhaus Konigin Elisabeth Herzberge, Berlin, Germany. [Budczies, Jan] Charite, Berlin, Germany. [Bolte, Sven] Karolinska Inst KIND, Ctr Neurodev Disorders, Stockholm, Sweden. [Dziobek, Isabel] Free Univ Berlin, Berlin, Germany. RP Sappok, T (reprint author), Ev Krankenhaus Konigin Elisabeth Herzberge, Berlin, Germany. 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Dev. Disabil. PD MAY PY 2013 VL 34 IS 5 BP 1642 EP 1655 DI 10.1016/j.ridd.2013.01.028 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 129WZ UT WOS:000317876000028 PM 23475013 ER PT J AU Heald, M Allen, D Villa, D Oliver, C AF Heald, M. Allen, D. Villa, D. Oliver, C. TI Discrimination training reduces high rate social approach behaviors in Angelman syndrome: Proof of principle SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Behavioral phenotype; Aggression; Intervention; Discrimination learning; Errorless learning; Angelman syndrome; Extinction ID HAPPY PUPPET SYNDROME; DEVELOPMENTAL-DISABILITIES; FUNCTIONAL COMMUNICATION; DOWN-SYNDROME; CHILDREN; AUTISM; INTERVENTION; PRESCHOOLERS; INDIVIDUALS; PREVALENCE AB This proof of principle study was designed to evaluate whether excessively high rates of social approach behaviors in children with Angelman syndrome (AS) can be modified using a multiple schedule design. Four children with AS were exposed to a multiple schedule arrangement, in which social reinforcement and extinction, cued using a novel stimulus, were alternated. Twenty-five to 35 discrimination training sessions were conducted and levels of approach behaviors were measured before and after the discrimination training for two children. All four participants evidenced discrimination between conditions of reinforcement and extinction after 16-20 teaching sessions as. indicated by lower rates of social approach behaviors in the presence of the S-Delta for extinction. Reversal effects for the two children for whom this design was implemented were evident. The results demonstrate that after repeated training, the use of a novel stimulus can serve as a cue for children with AS to discriminate adult availability. This is a potentially effective component of a broader intervention strategy but highlights the need for sustained teaching procedures within this population. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Heald, M.; Allen, D.; Villa, D.; Oliver, C.] Univ Birmingham, Sch Psychol, Cerebra Ctr Neurodev Disorders, Edgbaston B15 2TT, W Midlands, England. RP Heald, M (reprint author), Univ Birmingham, Sch Psychol, Cerebra Ctr Neurodev Disorders, Edgbaston B15 2TT, W Midlands, England. 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Dev. Disabil. PD MAY PY 2013 VL 34 IS 5 BP 1794 EP 1803 DI 10.1016/j.ridd.2013.02.012 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 129WZ UT WOS:000317876000043 PM 23518390 ER PT J AU Rojahn, J Schroeder, SR Mayo-Ortega, L Oyama-Ganiko, R LeBlanc, J Marquis, J Berke, E AF Rojahn, Johannes Schroeder, Stephen R. Mayo-Ortega, Liliana Oyama-Ganiko, Rosao LeBlanc, Judith Marquis, Janet Berke, Elizabeth TI Validity and reliability of the Behavior Problems Inventory, the Aberrant Behavior Checklist, and the Repetitive Behavior Scale - Revised among infants and toddlers at risk for intellectual or developmental disabilities.: A multi-method assessment approach SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Aberrant Behavior Checklist; Behavior Problems Inventory; Repetitive Behavior Scale - Revised; Psychometric properties; Reliability, Validity; Multitrait-multimethod; Neurodevelopmental disorders; At risk; Infants; Toddlers; Children ID MENTAL-RETARDATION; SHORT FORM; INDIVIDUALS; AUTISM; VALIDATION AB Reliable and valid assessment of aberrant behaviors is essential in empirically verifying prevention and intervention for individuals with intellectual or developmental disabilities (IDD). Few instruments exist which assess behavior problems in infants. The current longitudinal study examined the performance of three behavior-rating scales for individuals with IDD that have been proven psychometrically sound in older populations: the Aberrant Behavior Checklist (ABC), the Behavior Problems Inventory (BPI-01), and the Repetitive Behavior Scale - Revised (RBS-R). Data were analyzed for 180 between six and 36 months old children at risk for IDD. Internal consistency (Cronbach's alpha) across the subscales of the three instruments was variable. Test-retest reliability of the three BPI-01 subscales ranged from .68 to .77 for frequency ratings and from .65 to .80 for severity ratings (intraclass correlation coefficients). Using a multitrait-multimethod matrix approach high levels of convergent and discriminant validity across the three instruments was found. As anticipated, there was considerable overlap in the information produced by the three instruments; however, each behavior-rating instrument also contributed unique information. Our findings support using all three scales in conjunction if possible. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Rojahn, Johannes; Berke, Elizabeth] George Mason Univ, Fairfax, VA 22033 USA. [Schroeder, Stephen R.; Mayo-Ortega, Liliana; LeBlanc, Judith; Marquis, Janet] Univ Kansas, Lawrence, KS 66045 USA. RP Rojahn, J (reprint author), George Mason Univ, Dept Psychol, 10340 Democracy Lane,Suite 202, Fairfax, VA 22033 USA. EM jrojahn@gmu.edu CR Aman M., 1986, ABERRANT BEHAV CHECK Aman M. 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Dev. Disabil. PD MAY PY 2013 VL 34 IS 5 BP 1804 EP 1814 DI 10.1016/j.ridd.2013.02.024 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 129WZ UT WOS:000317876000044 PM 23511345 ER PT J AU Hill, DA Kearley, R AF Hill, Doris Adams Kearley, Regina TI Autism litigation: Outcomes for 2010, trends in decision making and changes in diagnostic criteria SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Review DE Autism; Legislation; Case law; LexisNexis AB The diagnosis of autism spectrum disorder has systematically risen since Manner's description in 1943 and Asperger's definition in 1944. An increase in numbers has met with an increase in litigation regarding autism spectrum disorder (ASD) and the Individuals with Disabilities Education Improvement Act (IDEIA). Outcomes that first favored parents (2002-2004) have moved to outcomes favoring school districts. The authors update the reader on case outcomes for 2010 and discuss how pending changes in legislation and diagnostic criteria may impact navigation through the education system as individuals seek a free appropriate public education (FAPE) and placement in the least restrictive environment (LRE). (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hill, Doris Adams; Kearley, Regina] Auburn Univ, Auburn, AL 36849 USA. RP Hill, DA (reprint author), Auburn Univ, Auburn, AL 36849 USA. EM hilldol@auburn.edu CR American Psychiatric and Association, 2012, DIAGN STAT MAN MENT American Psychiatric Association, 2000, DIAGN STAT MAN MENT [Anonymous], 2012, CBS NEWS Autism Society of America, 2011, AB AUT Boutot E. A., 2011, AUTISM SPECTRUM DISO Centers for Disease Control and Prevention, 2012, SURVEILLANCE SUMMARI, V61, P1 Centers for Medicare & Medicaid Services, 2012, ICD 10 TRANS INTR Conroy T., 2010, FOCUS EXCEPTIONAL CH, V43, P2 Grossman L., 2007, AUTISM ADVOCATE, P9 Hartley SL, 2009, J AUTISM DEV DISORD, V39, P1715, DOI 10.1007/s10803-009-0810-8 Heward W., 2013, EXCEPTIONAL CHILDREN, V10th Hill D., 2011, PREVENTING SCH FAILU, V55, P214 Hill D., 2012, PREVENTING SCH FAILU, V56, P157 Hulett K., 2009, LEGAL ASPECTS SPECIA Kaland N, 2011, RES AUTISM SPECT DIS, V5, P984, DOI 10.1016/j.rasd.2011.01.011 LexisNexis, 2011, AB LEXISNEXIS Resnick M., 2010, AM SCH BOARD J, V197, P6 Strauss V., 2012, WASHINGTON POST U.S. Department of Education, 2012, ESEA FLEX Yell M. L., 2006, LAW SPECIAL ED NR 20 TC 0 Z9 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-4222 J9 RES DEV DISABIL JI Res. Dev. Disabil. PD MAY PY 2013 VL 34 IS 5 BP 1843 EP 1848 DI 10.1016/j.ridd.2013.02.018 PG 6 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 129WZ UT WOS:000317876000048 PM 23528441 ER PT J AU Mester, J Eng, C AF Mester, Jessica Eng, Charis TI When Overgrowth Bumps Into Cancer: The PTEN-Opathies SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE PTEN; Cowden syndrome; AKT; PIK3CA; PI3K; mTOR ID RILEY-RUVALCABA-SYNDROME; TUMOR-SUPPRESSOR GENE; AUTISM SPECTRUM DISORDERS; TUBEROUS SCLEROSIS COMPLEX; LHERMITTE-DUCLOS DISEASE; BANNAYAN-ZONANA-SYNDROME; ATP-BINDING MOTIFS; PROTEUS-SYNDROME; COWDEN-SYNDROME; MAMMALIAN TARGET AB PTEN is a dual-specificity phosphatase and well-known tumor suppressor gene. When functioning properly, it works in its canonical pathway to inhibit AKT/mTOR and MAPK signaling, leading to cell death and growth regulation. PTEN mutations cause dysregulation of these pathways, resulting in cellular proliferation and overgrowth. When germline mutations are present as in patients with PTEN Hamartoma Tumor Syndrome (PHTS), benign and malignant neoplasias occur as well as cerebral overgrowth and neurodevelopmental abnormalities. This review article will summarize recent laboratory and clinical investigations relating to PTEN, highlighting the overgrowth aspects of this syndrome and the molecular drivers behind these key phenotypes. Finally, therapies developed targeted the PI3K/AKT/mTOR pathway for other tumor predisposition syndromes will be discussed. (c) 2013 Wiley Periodicals, Inc. C1 [Mester, Jessica; Eng, Charis] Cleveland Clin, PTEN Cowden Multidisciplinary Clin, Cleveland, OH USA. RP Eng, C (reprint author), FACP, 9500 Euclid Ave NE50, Cleveland, OH 44195 USA. EM engc@ccf.org FU National Cancer Institute; American Cancer Society; Breast Cancer Research Foundation; Doris Duke Distinguished Clinical Scientist Award; Department of Defense Breast Cancer Research Program; William Randolph Hearst Foundations; Susan G. Komen for the Cure FX Grant sponsor: National Cancer Institute; Grant sponsor: American Cancer Society; Grant sponsor: Breast Cancer Research Foundation; Grant sponsor: Doris Duke Distinguished Clinical Scientist Award; Grant sponsor: Department of Defense Breast Cancer Research Program; Grant sponsor: William Randolph Hearst Foundations; Grant sponsor: Susan G. Komen for the Cure. 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J. Med. Genet. C PD MAY PY 2013 VL 163C IS 2 SI SI BP 114 EP 121 DI 10.1002/ajmg.c.31364 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 133VR UT WOS:000318169400006 PM 23613428 ER PT J AU Kverka, M Tlaskalova-Hogenova, H AF Kverka, Miloslav Tlaskalova-Hogenova, Helena TI Two faces of microbiota in inflammatory and autoimmune diseases: triggers and drugs SO APMIS LA English DT Review DE Inflammation; autoimmunity; probiotics; microbiota; intestinal barrier; inflammatory bowel disease; rheumatic diseases; celiac disease; diabetes; allergy; autism ID PLACEBO-CONTROLLED TRIAL; SEGMENTED FILAMENTOUS BACTERIA; INTESTINAL EPITHELIAL-CELLS; DEPENDENT DIABETES-MELLITUS; PROBIOTIC ESCHERICHIA-COLI; IRRITABLE-BOWEL-SYNDROME; GERM-FREE MICE; CROHNS-DISEASE; GUT MICROBIOTA; DOUBLE-BLIND AB The prevalence of chronic autoimmune and inflammatory diseases, such as inflammatory bowel disease, allergies, or rheumatic diseases, is steadily increasing in developed countries. This increase is probably accelerated by environmental factors, such as decrease in infectious burden or changes in food processing. These lifestyle changes then strongly influence the strongest stimulus for the immune system commensal microbiota. Despite the differences in the affected organ, the immune-mediated diseases have one or more factors in common microbe either as a trigger or as a protector, mucosal barrier dysfunction, and dysregulation of the immune system. The core questions, which microbes are involved and how these diseases can be cured or even prevented still remain unsolved. Powered by the recent progress in technology, by new insights into the function of immune system, by advances in microbiome research, and extended use of gnotobiological techniques, these mechanisms are now being unravelled and new therapeutic possibilities are emerging. To secure their niche, the microbes devised many ingenious ways, how to dampen the inflammation. Nonpathogenic microorganisms or microbial components isolated from probiotic, commensal or even pathogenic microbes could be, therefore, used to interfere with the pathogenetic mechanisms of immune-mediated diseases. C1 [Kverka, Miloslav; Tlaskalova-Hogenova, Helena] Acad Sci Czech Republic, Inst Microbiol, Dept Immunol & Gnotobiol, Prague, Czech Republic. RP Kverka, M (reprint author), Inst Microbiol AS CR, Videnska 1083, Prague 14220 4, Krc, Czech Republic. EM kverka@biomed.cas.cz RI Kverka, Miloslav/H-2507-2014; Tlaskalova-Hogenova, Helena/J-8008-2014 OI Kverka, Miloslav/0000-0002-1335-5252; FU Czech Science Foundation [P303/12/0535, P304/11/1252]; Ministry of Health of the Czech Republic [NT13483-4/2012]; Institutional Research Concept of Institute of Microbiology AS CR [RVO: 61388971] FX Authors are supported by research grants from the Czech Science Foundation (P303/12/0535 and P304/11/1252), The Ministry of Health of the Czech Republic (NT13483-4/2012), and by Institutional Research Concept of Institute of Microbiology AS CR (RVO: 61388971). 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Wright, Margaret J. Hansell, Narelle K. Montgomery, Grant W. Martin, Nicholas G. TI No Association Between General Cognitive Ability and Rare Copy Number Variation SO BEHAVIOR GENETICS LA English DT Article DE Intelligence; Copy-number variation; Genetic burden; Association ID LINKED MENTAL-RETARDATION; GENOME-WIDE ASSOCIATION; HUMAN INTELLIGENCE; BIPOLAR DISORDER; INCREASE RISK; SCHIZOPHRENIA; DELETIONS; VARIANTS; AUTISM; CNVS AB There is increasing evidence for the role of rare copy-number variation (CNV) in the development of neuropsychiatric disorders. It is likely that such variants also have an effect on the variation of cognition in what is considered the "normal" phenotypic range. The role of rare CNV (> 20 KB in length; frequency < 5 %) on general cognitive ability is investigated in a sample of 800 individuals (mean age = 16.5, SD = 1.2) using copy-number variants called from the Illumina 610K SNP genotyping array with the software QuantiSNP. We assessed three measures of CNV burden-total CNV length, number of CNV and average CNV length-for both deletions and duplications in combination and separately. No correlation was found between any of the measures of CNV burden and IQ, or when comparing the top and bottom 10 % of the sample for IQ, both on a genome-wide scale and at individual positions across the genome. C1 [McRae, Allan F.] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia. [McRae, Allan F.; Wright, Margaret J.; Hansell, Narelle K.; Montgomery, Grant W.; Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. RP McRae, AF (reprint author), Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia. EM a.mcrae@uq.edu.au RI McRae, Allan/J-2644-2014 OI McRae, Allan/0000-0001-5286-5485 FU Australian Research Council [ARC: A7960034, A79906588, A79801419, DP0212016, DP0343921, DP0664638, DP1093900, FT0991360]; Australian National Health and Medical Research Council (NHMRC: Medical Bioinformatics Genomics Proteomics Program) [389891]; NHMRC [339446, 619667] FX We thank our twin sample for their participation; Marlene Grace and Ann Eldridge for sample collection; Anjali Henders, Megan Campbell, Lisa Bowdler, Steven Crooks, and staff of the QIMR Molecular Epidemiology Laboratory for DNA sample processing and preparation; Kerrie McAloney for study co-ordination; and Harry Beeby, Daniel Park, and David Smyth for IT support. This work was supported by grants from the Australian Research Council (ARC: A7960034, A79906588, A79801419, DP0212016, DP0343921, DP0664638, DP1093900, FT0991360) and the Australian National Health and Medical Research Council (NHMRC: Medical Bioinformatics Genomics Proteomics Program, 389891). G. W. M. is supported by the NHMRC Fellowship Scheme (339446, 619667). 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Method Population-based studies in childhood epilepsy which have focused on global measures of psychopathology and rates of specific behavioural and psychiatric disorders were reviewed with respect to prevalence of disorders and possible correlates of difficulties. Clinic-based studies and meta-analyses were reviewed where they added to an understanding of the correlates or treatment of psychopathology in childhood epilepsy. The systematic review methodology was based on a search of PubMed from January 1980 to June 2011. Results Children with epilepsy are at significantly higher risk for a range of behavioural and psychiatric disorders including attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), depressive and anxiety disorders. Available evidence suggests that these difficulties are under-recognised and there have been few studies focussing on interventions to treat these behavioural and psychiatric issues in childhood epilepsy. 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This study explored parents' experiences of a specialist autism spectrum psychological intervention service located within a broader Neurodevelopmental and Social Communication Disorders Team. Method Forty-nine parents completed a telephone based survey designed to assess experiences of a specialist intervention service. Results High levels of satisfaction were reported. Parents reported aspects of the service that they found most useful. Conclusion Most parents reported satisfaction with the service and suggested improvements were used to guide service development. C1 [Kingston, Cara] Kings Coll London, Inst Psychiat, London SE 8AF, England. [Hibberd, Charlotte] Univ Surrey, Guildford GU2 5XH, Surrey, England. [Ozsivadjian, Ann] Guys Hosp, Newcomen Ctr, London SE1 9RT, England. RP Kingston, C (reprint author), Kings Coll London, Inst Psychiat, De Crespigny Pk, London SE 8AF, England. 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Health PD MAY PY 2013 VL 18 IS 2 BP 109 EP 115 DI 10.1111/j.1475-3588.2012.00667.x PG 7 WC Psychology, Clinical; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 126GN UT WOS:000317601300007 ER PT J AU Conn, C AF Conn, Carmel TI Play-Based Interventions for Children and Adolescents with Autism Spectrum Disorders SO CHILD AND ADOLESCENT MENTAL HEALTH LA English DT Book Review C1 [Conn, Carmel] Univ Bristol, Grad Sch Educ, Bristol BS8 1TH, Avon, England. RP Conn, C (reprint author), Univ Bristol, Grad Sch Educ, Bristol BS8 1TH, Avon, England. CR Rubin L. C., 2012, PLAY BASED INTERVENT NR 1 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1475-357X J9 CHILD ADOL MENT H-UK JI Child Adolesc. Ment. Health PD MAY PY 2013 VL 18 IS 2 BP 125 EP 126 DI 10.1111/camh.12031_6 PG 2 WC Psychology, Clinical; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 126GN UT WOS:000317601300015 ER PT J AU Thompson, E AF Thompson, Emily TI Sleep Difficulties and Autism Spectrum Disorders: A Guide for Parents and Professionals SO CHILD AND ADOLESCENT MENTAL HEALTH LA English DT Book Review C1 [Thompson, Emily] Northumberland Tyne & Wear NHS Trust, Northumberland, England. RP Thompson, E (reprint author), Northumberland Tyne & Wear NHS Trust, Northumberland, England. CR AITKEN KJ, 2012, SLEEP DIFFICULTIES A NR 1 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1475-357X J9 CHILD ADOL MENT H-UK JI Child Adolesc. Ment. Health PD MAY PY 2013 VL 18 IS 2 BP 127 EP 127 DI 10.1111/camh.12031_10 PG 1 WC Psychology, Clinical; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 126GN UT WOS:000317601300019 ER PT J AU Carter, MT Scherer, SW AF Carter, M. T. Scherer, S. W. TI Autism spectrum disorder in the genetics clinic: a review SO CLINICAL GENETICS LA English DT Review DE autism spectrum disorder copy; number variant; diagnosis genetic; testing; microarray; synapse ID FRAGILE-X-SYNDROME; DE-NOVO MUTATIONS; UTAH EPIDEMIOLOGIC SURVEY; 22Q13 DELETION SYNDROME; COPY NUMBER VARIATION; RECURRENCE RISK; DEVELOPMENTAL DISORDERS; CODING SEQUENCE; MECP2 MUTATIONS; SYNDROME REGION AB Carter MT, Scherer SW. Autism spectrum disorder in the genetics clinic: a review. Clin Genet 2013: 83: 399-407. (C) John Wiley & Sons A/S. Published by Blackwell Publishing Ltd, 2013 Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders affecting social communication, language and behavior. The underlying cause(s) in a given individual is often elusive, with the exception of clinically recognizable genetic syndromes with readily available molecular diagnosis, such as fragile X syndrome. Clinical geneticists approach patients with ASDs by ruling out known genetic and genomic syndromes, leaving more than 80% of families without a definitive diagnosis and an uncertain risk of recurrence. Advances in microarray technology and next-generation sequencing are revealing rare variants in genes with important roles in synapse formation, function and maintenance. This review will focus on the clinical approach to ASDs, given the current state of knowledge about their complex genetic architecture. C1 [Carter, M. T.] Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. [Scherer, S. W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. [Scherer, S. W.] Hosp Sick Children, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada. [Scherer, S. W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. [Scherer, S. W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. RP Carter, MT (reprint author), Hosp Sick Children, Div Clin & Metab Genet, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM melissa.carter@sickkids.ca RI Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU University of Toronto McLaughlin Centre; NeuroDevNet FX The authors wish to thank Dr Janet Buchanan and Dr Bridget Fernandez for helpful comments on the manuscript. S. W. S. holds the GlaxoSmithKline Pathfinder Chair in Genome Sciences at the University of Toronto and the Hospital for Sick Children. This work was supported by funds from the University of Toronto McLaughlin Centre and NeuroDevNet. 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Psychopathol. PD MAY PY 2013 VL 25 IS 2 BP 307 EP 320 DI 10.1017/S0954579412001071 PG 14 WC Psychology, Developmental SC Psychology GA 136LY UT WOS:000318364600003 PM 23627946 ER PT J AU Cornish, K Cole, V Longhi, E Karmiloff-Smith, A Scerif, G AF Cornish, Kim Cole, Victoria Longhi, Elena Karmiloff-Smith, Annette Scerif, Gaia TI Mapping developmental trajectories of attention and working memory in fragile X syndrome: Developmental freeze or developmental change? SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID DEFICIT/HYPERACTIVITY DISORDER; NEUROPSYCHOLOGICAL PROFILE; WILLIAMS-SYNDROME; YOUNG MALES; CHILDREN; BOYS; HYPERACTIVITY; DEFICITS; AUTISM AB Fragile X syndrome (FXS) has a characteristic cognitive "signature" that by late childhood includes core weaknesses in attention and working memory (WM), but their earlier developmental trajectories remain uncharted. Using a combined cross-sectional and prospective longitudinal design, we tested whether early profiles of attention and WM impairment in FXS indicate developmental freeze or developmental change. In Study 1, 26 young boys with FXS and 55 typically developing (TD) boys completed two experimental paradigms designed to assess cognitive aspects of attention and WM, in addition to behavioral indices of inattention and hyperactivity. Study 2 mapped longitudinal changes in 21 children with FXS and 21 TD children. In Study 1, significant weaknesses emerged for boys with FXS, with no substantial improvement over chronological age. Mapping performance against mental age level revealed delay, but it also yielded a similar attention and WM profile to TD boys. In Study 2, longitudinal improvements for boys with FXS paralleled those in TD children. In conclusion, cognitive attention and WM, although delayed in FXS, reveal developmental change, rather than "arrest." Our findings underscore the need for going beyond cross-sectional group comparisons and gross behavioral indices to map cognitive changes longitudinally in developmental disorders. C1 [Cornish, Kim] Monash Univ, Clayton, Vic 3800, Australia. [Cole, Victoria; Longhi, Elena; Scerif, Gaia] Univ Oxford, Oxford OX1 3UD, England. [Karmiloff-Smith, Annette] Univ London, London WC1E 7HU, England. RP Scerif, G (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England. EM gaia.scerif@psy.ox.ac.uk CR Awh E, 2006, NEUROSCIENCE, V139, P201, DOI 10.1016/j.neuroscience.2005.08.023 Bertone A, 2010, J AUTISM DEV DISORD, V40, P1531, DOI 10.1007/s10803-010-1109-5 Bertone A, 2010, J AUTISM DEV DISORD, V40, P1541, DOI 10.1007/s10803-010-1110-z Burack J. 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Psychopathol. PD MAY PY 2013 VL 25 IS 2 BP 365 EP 376 DI 10.1017/S0954579412001113 PG 12 WC Psychology, Developmental SC Psychology GA 136LY UT WOS:000318364600007 PM 23627950 ER PT J AU Boosani, CS Agrawal, DK AF Boosani, Chandra S. Agrawal, Devendra K. TI PTEN modulators: a patent review SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE cancer; cardiovascular diseases; kinases; modulators; obesity; phosphatase; PTEN; transcription factors ID TUMOR-SUPPRESSOR PTEN; PROSTATE-CANCER CELLS; NF-KAPPA-B; TENSIN-HOMOLOG; BREAST-CANCER; PROTEIN STABILITY; INDUCED APOPTOSIS; ACTIVATES PTEN; INHIBITS PTEN; UP-REGULATION AB Introduction: PTEN (phosphatase and tensin homolog deleted on chromosome 10) plays a pivotal role in controlling intracellular signaling for cell survival and proliferation by inhibiting the PI3K/Akt pathway, and its dysfunction is associated with several neoplastic diseases. PTEN is frequently found mutated in many pathological conditions highlighting its importance in normal physiological function. Unlike several cellular proteins which are activated by phosphorylation, PTEN is inactivated upon phosphorylation by specific kinases which phosphorylate serine and threonine residues in its C-terminal region. Therefore, development of therapeutic agents that specifically target kinases and kinase-domain-containing proteins affecting PTEN would lead to the treatment of PTEN-related diseases. Areas covered: With increasing evidence on the role of PTEN in many human diseases, the present review focuses on the clinical relevance of PTEN with a comprehensive list of currently identified modulators of PTEN, and proposes potentially novel molecular targets which could aid in the development of drug candidates for the treatment of PTEN-related diseases such as cardiovascular diseases, diabetes, obesity, cancer, autism, Parkinson's and Alzheimer's diseases. Expert opinion: This review describes several target sites that could help in the development of novel drug candidates to regulate or restore the normal physiological functions of PTEN and are essential in the treatment of human diseases where PTEN plays a pivotal role. C1 [Boosani, Chandra S.; Agrawal, Devendra K.] Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA. [Agrawal, Devendra K.] Creighton Univ, Sch Med, Dept Internal Med, Omaha, NE 68178 USA. [Agrawal, Devendra K.] Creighton Univ, Sch Med, Dept Med Microbiol & Immunol, Omaha, NE 68178 USA. [Agrawal, Devendra K.] Creighton Univ, Sch Med, Ctr Clin & Translat Sci, Omaha, NE 68178 USA. RP Agrawal, DK (reprint author), Creighton Univ, Sch Med, Dept Biomed Sci, CRISS 2 Room 510,2500 Calif Plaza, Omaha, NE 68178 USA. EM DevendraAgrawal@creighton.edu FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01HL090580, R01HL104516, R01HL112597] FX The authors declare no conflict of interest. Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Numbers R01HL090580, R01HL104516, and R01HL112597. 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Ther. Patents PD MAY PY 2013 VL 23 IS 5 BP 569 EP 580 DI 10.1517/13543776.2013.768985 PG 12 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 130RI UT WOS:000317936300003 PM 23379765 ER PT J AU Hart, R Norman, RJ AF Hart, Roger Norman, Robert J. TI The longer-term health outcomes for children born as a result of IVF treatment. Part IIMental health and development outcomes SO HUMAN REPRODUCTION UPDATE LA English DT Review DE IVF; ICSI; ART; long-term outcome; mental health ID IN-VITRO FERTILIZATION; INTRACYTOPLASMIC SPERM INJECTION; ASSISTED REPRODUCTIVE TECHNOLOGIES; SPONTANEOUSLY CONCEIVED CHILDREN; AUTISM SPECTRUM DISORDERS; FOLLOW-UP; CEREBRAL-PALSY; PSYCHOMOTOR DEVELOPMENT; INFERTILITY TREATMENT; PARENTAL INFERTILITY AB Limited data exist with regard to longer-term mental health and psychological functioning of children born from IVF treatment. With the known adverse perinatal outcome for children born from IVF treatment, it would be expected that there is a negative impact upon their mental development. A search strategy restricted to studies relating to the medical condition of children of at least 1 year of age, born from IVF treatment was performed to include case series, data linkage and prospective studies published from 1 January 2000 to 1 April 2012. Limited long-term follow-up data suggest that there is an increase in the incidence of cerebral palsy and neurodevelopmental delay related to the confounders of prematurity and low birthweight. Previous reports of associations with autism and attention-deficit disorder are believed to be related to maternal and obstetric factors. There exists a potential increase in the prevalence of early adulthood clinical depression and binge drinking in the offspring of IVF, with the reassuring data of no changes with respect to cognitive development, school performance, social functioning and behaviour. Whether these potential associations are related to the IVF treatment, the adverse obstetric outcomes associated with IVF treatment, the genetic or subsequent environmental influences on the children is yet to be determined. In general, the longer-term mental and emotional health outcome for children born from IVF treatment is reassuring, and is very similar to that of naturally conceived children; however, further studies are required to explore any association with depression, and its causality in more detail. C1 [Hart, Roger] Univ Western Australia, Sch Womens & Infants Hlth, King Edward Mem Hosp, Perth, WA 6008, Australia. [Hart, Roger] Fertil Specialists Western Australia, Perth, WA 6010, Australia. [Norman, Robert J.] Univ Adelaide, Robinson Inst, Fertil SA, Adelaide, SA 5006, Australia. RP Hart, R (reprint author), Univ Western Australia, Sch Womens & Infants Hlth, King Edward Mem Hosp, Perth, WA 6008, Australia. 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Reprod. Update PD MAY-JUN PY 2013 VL 19 IS 3 BP 244 EP 250 DI 10.1093/humupd/dmt002 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 133AG UT WOS:000318109200005 PM 23449643 ER PT J AU Gentile, I Bravaccio, C Bonavolta, R Zappulo, E Scarica, S Riccio, MP Settimi, A Portella, G Pascotto, A Borgia, G AF Gentile, Ivan Bravaccio, Carmela Bonavolta, Raffaele Zappulo, Emanuela Scarica, Sabrina Riccio, Maria Pia Settimi, Alessandro Portella, Giuseppe Pascotto, Antonio Borgia, Guglielmo TI Response to Measles-Mumps-Rubella Vaccine in Children with Autism Spectrum Disorders SO IN VIVO LA English DT Article DE Autism spectrum disorders; autistic disorder; MMR vaccine; seropositivity ID PERVASIVE DEVELOPMENTAL DISORDERS; MYELIN BASIC-PROTEIN; CAUSAL ASSOCIATION; SCLEROSING PANENCEPHALITIS; MULTIPLE-SCLEROSIS; MMR VACCINE; NO EVIDENCE; POPULATION; ANTIBODIES; VIRUS AB Background/Aim: The etiology of autism spectrum disorders (ASD) is unknown. The measles-mumps-rubella (MMR) vaccination has been in the past implicated in ASD pathogenesis. The aim of our study was to evaluate the rate of seropositivity and the levels of antibodies against MMR antigens in a cohort of children with ASD compared to control children. Patients and Methods: In a cohort of children with ASD and same-age healthy controls, we measured levels and seropositivity of antibodies against MMR. Results: A total of 60 children, 31 with ASD and 29 controls were enrolled. The seropositivity rate and levels of all the three antibodies were similar in cases and controls. Conclusion: Children with ASD have a similar level and seropositivity rate of antibodies against the MMR vaccine to same-age controls. As persistent infections are typically associated with high antibody levels, our results support the arguments against a role of MMR vaccination as a causal factor or co-factor in development of ASD. C1 [Gentile, Ivan; Zappulo, Emanuela; Scarica, Sabrina; Borgia, Guglielmo] Univ Naples Federico II, Dept Clin Med & Surg, Infect Dis Sect, Naples, Italy. Univ Naples Federico II, Dept Med Translat Sci, I-80131 Naples, Italy. [Bravaccio, Carmela; Bonavolta, Raffaele; Settimi, Alessandro; Portella, Giuseppe] Univ Naples Federico II, Dept Med Translat Sci, Naples, Italy. [Riccio, Maria Pia; Pascotto, Antonio] Univ Naples 2, Dept Mental & Phys Hlth & Prevent Med, Naples, Italy. RP Bravaccio, C (reprint author), Univ Naples Federico II, Dept Med Translat Sci, Via S Pansini 5, I-80131 Naples, Italy. 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TI Recent Legal Developments of Interest to Special Educators SO INTERVENTION IN SCHOOL AND CLINIC LA English DT Article DE law; legal; policy; Section 504; ADA AB An overview is provided of five recent legal developments that merit special attention of special educators: (a) the amended Individuals with Disabilities Education Improvement Act (IDEIA) regulations concerning parental consent, including subsequent agency interpretations concerning their practical application; (b) the IDEIA provisions and resulting state laws and implementation issues for response to intervention; (c) the IDEIA provision for basing the individualized education program statement of special education on peer-reviewed research to the extent practicable and subsequent case law applying this provision; (d) the case law on behalf of students with autism spectrum disorder, including the issues of eligibility and free appropriate public education or least restrictive environment; and (e) the IDEIA revisions concerning discipline, with special attention to suspensions/expulsions, disproportionality, and the corresponding Section 504 requirements. C1 Lehigh Univ, Bethlehem, PA 18015 USA. RP Zirkel, PA (reprint author), Lehigh Univ, 111 Res Dr, Bethlehem, PA 18015 USA. CR [Anonymous], 1996, COMMUNICATION [Anonymous], 2009, COMMUNICATION [Anonymous], 2010, COMMUNICATION Etscheidt S, 2010, EXCEPTIONALITY, V18, P138, DOI 10.1080/09362835.2010.491988 IDEA regulations' commentary, 2008, FED REG, V73 Zirkel P., 2011, CONNECTICUT PUBLIC I, V10, P323 Zirkel P. A., 2011, COMMUNIQUE, V39, P30 Zirkel P. A., 2010, TEACHING EXCEPTIONAL, V43, P60 Zirkel P. A., 2011, W ED LAW REPORTER, V268, P1 Zirkel P. A., 2011, J SPECIAL ED LEADERS, V24, P92 Zirkel P. A., 2012, J SPECIAL ED LEADERS, V25, P99 Zirkel PA, 2010, REM SPEC EDUC, V31, P378, DOI 10.1177/0741932509355993 NR 12 TC 2 Z9 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1053-4512 J9 INTERV SCH CLIN JI Interv. Sch. Clin. PD MAY PY 2013 VL 48 IS 5 BP 319 EP 322 PG 4 WC Education, Special SC Education & Educational Research GA 132LH UT WOS:000318068900008 ER PT J AU Ajamian, M Kosofsky, BE Wormser, GP Rajadhyaksha, AM Alaedini, A AF Ajamian, Mary Kosofsky, Barry E. Wormser, Gary P. Rajadhyaksha, Anjali M. Alaedini, Armin TI Serologic Markers of Lyme Disease in Children With Autism SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Ajamian, Mary; Alaedini, Armin] Columbia Univ, Dept Med, Med Ctr, New York, NY 10027 USA. [Kosofsky, Barry E.; Rajadhyaksha, Anjali M.] Weill Cornell Med Coll, Dept Pediat, New York, NY USA. [Wormser, Gary P.] New York Med Coll, Div Infect Dis, Valhalla, NY 10595 USA. RP Ajamian, M (reprint author), Columbia Univ, Dept Med, Med Ctr, New York, NY 10027 USA. 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PD MAY 1 PY 2013 VL 309 IS 17 BP 1771 EP 1773 DI 10.1001/jama.2013.618 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 134SU UT WOS:000318235600018 PM 23632714 ER PT J AU Anitha, A Thanseem, I Nakamura, K Yamada, K Iwayama, Y Toyota, T Iwata, Y Suzuki, K Sugiyama, T Tsujii, M Yoshikawa, T Mori, N AF Anitha, Ayyappan Thanseem, Ismail Nakamura, Kazuhiko Yamada, Kazuo Iwayama, Yoshimi Toyota, Tomoko Iwata, Yasuhide Suzuki, Katsuaki Sugiyama, Toshiro Tsujii, Masatsugu Yoshikawa, Takeo Mori, Norio TI Protocadherin alpha (PCDHA) as a novel susceptibility gene for autism SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID BRAIN-SEROTONIN; FAMILY; DISORDERS; SPECTRUM; NEURONS; CLUSTER; GENOME AB Background: Synaptic dysfunction has been shown to be involved in the pathogenesis of autism. We hypothesized that the protocadherin alpha gene cluster (PCDHA), which is involved in synaptic specificity and in serotonergic innervation of the brain, could be a suitable candidate gene for autism. Methods: We examined 14 PCDHA single nucleotide polymorphisms (SNPs) for genetic association with autism in DNA samples of 3211 individuals (841 families, including 574 multiplex families) obtained from the Autism Genetic Resource Exchange. Results: Five SNPs (rs251379, rs1119032, rs17119271, rs155806 and rs17119346) showed significant associations with autism. The strongest association (p < 0.001) was observed for rs1119032 (z score of risk allele G = 3.415) in multiplex families; SNP associations withstand multiple testing correction in multiplex families (p = 0.041). Haplotypes involving rs1119032 showed very strong associations with autism, withstanding multiple testing corrections. In quantitative transmission disequilibrium testing of multiplex families, the G allele of rs1119032 showed a significant association (p = 0.033) with scores on the Autism Diagnostic Interview-Revised (ADI-R)_D (early developmental abnormalities). We also found a significant difference in the distribution of ADI-R_A (social interaction) scores between the A/A, A/G and G/G genotypes of rs17119346 (p = 0.002). Limitations: Our results should be replicated in an in dependent population and/or in samples of different racial backgrounds. Conclusion: Our study provides strong genetic evidence of PCDHA as a potential candidate gene for autism. C1 [Anitha, Ayyappan; Suzuki, Katsuaki; Tsujii, Masatsugu; Mori, Norio] Hamamatsu Univ Sch Med, Res Ctr Child Mental Dev, Hamamatsu, Shizuoka 4313192, Japan. [Thanseem, Ismail; Nakamura, Kazuhiko; Iwata, Yasuhide; Mori, Norio] Hamamatsu Univ Sch Med, Dept Psychiat & Neurol, Hamamatsu, Shizuoka 4313192, Japan. 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Psychiatry Neurosci. PD MAY PY 2013 VL 38 IS 3 BP 192 EP 198 DI 10.1503/jpn.120058 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 132AL UT WOS:000318040000007 PM 23031252 ER PT J AU King, BH Veenstra-VanderWeele, J Lord, C AF King, Bryan H. Veenstra-VanderWeele, Jeremy Lord, Catherine TI DSM-5 and Autism: Kicking the Tires and Making the Grade SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID SPECTRUM DISORDERS; DIAGNOSIS; CHILDREN C1 [King, Bryan H.] Univ Washington, Seattle, WA 98105 USA. [King, Bryan H.] Seattle Childrens Autism Ctr, Seattle, WA 98105 USA. [Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Nashville, TN 37235 USA. [Lord, Catherine] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Lord, Catherine] Columbia Univ, Ctr Autism & Developing Brain, New York, NY 10027 USA. 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PD MAY PY 2013 VL 52 IS 5 BP 454 EP 457 DI 10.1016/j.jaac.2013.02.009 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 136WW UT WOS:000318395100002 PM 23622845 ER PT J AU Narayanan, S Georgiou, PG AF Narayanan, Shrikanth Georgiou, Panayiotis G. TI Behavioral Signal Processing: Deriving Human Behavioral Informatics From Speech and Language SO PROCEEDINGS OF THE IEEE LA English DT Article DE Affective computing; behavior; computational psychology; computational social sciences; emotions; health applications; multimodal signal processing; natural language processing; speech understanding ID DIAGNOSTIC OBSERVATION SCHEDULE; HIGH-FUNCTIONING AUTISM; EMOTION RECOGNITION; SPEAKER DIARIZATION; COUPLE THERAPY; CLASSIFICATION; CHILDREN; MODEL; PATTERNS; FEATURES AB The expression and experience of human behavior are complex and multimodal and characterized by individual and contextual heterogeneity and variability. Speech and spoken language communication cues offer an important means for measuring and modeling human behavior. Observational research and practice across a variety of domains from commerce to healthcare rely on speech-and language-based informatics for crucial assessment and diagnostic information and for planning and tracking response to an intervention. In this paper, we describe some of the opportunities as well as emerging methodologies and applications of human behavioral signal processing (BSP) technology and algorithms for quantitatively understanding and modeling typical, atypical, and distressed human behavior with a specific focus on speech-and language-based communicative, affective, and social behavior. We describe the three important BSP components of acquiring behavioral data in an ecologically valid manner across laboratory to real-world settings, extracting and analyzing behavioral cues from measured data, and developing models offering predictive and decision-making support. We highlight both the foundational speech and language processing building blocks as well as the novel processing and modeling opportunities. Using examples drawn from specific real-world applications ranging from literacy assessment and autism diagnostics to psychotherapy for addiction and marital well being, we illustrate behavioral informatics applications of these signal processing techniques that contribute to quantifying higher level, often subjectively described, human behavior in a domain-sensitive fashion. C1 [Narayanan, Shrikanth; Georgiou, Panayiotis G.] Univ So Calif, Ming Hsieh Dept Elect Engn, Los Angeles, CA 90089 USA. RP Narayanan, S (reprint author), Univ So Calif, Ming Hsieh Dept Elect Engn, Los Angeles, CA 90089 USA. EM shri@sipi.usc.edu; georgiou@sipi.usc.edu FU National Science Foundation (NSF); National Institutes of Health (NIH); U.S. Department of Defense (DoD) FX Manuscript received May 28, 2012; revised August 23, 2012 and November 16, 2012; accepted December 6, 2012. Date of publication February 7, 2013; date of current version April 17, 2013. This work was supported by the National Science Foundation (NSF), the National Institutes of Health (NIH), and the U.S. Department of Defense (DoD). This paper is based on the invited lecture material presented by S. Narayanan at the International Conference on Multimedia and Expo (ICME), Barcelona, Spain, July 2011; the ACM Multimedia International Workshop on Social Signal Processing (SSPW), Scottsdale, AZ, November-December 2011; and the Automatic Speech Recognition and Understanding Workshop (ASRU), Honolulu, HI, December 2011. 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IEEE PD MAY PY 2013 VL 101 IS 5 SI SI BP 1203 EP 1233 DI 10.1109/JPROC.2012.2236291 PG 31 WC Engineering, Electrical & Electronic SC Engineering GA 133SK UT WOS:000318159900011 ER PT J AU Wei, X Lenz, KB Blackorby, J AF Wei, Xin Lenz, Keith B. Blackorby, Jose TI Math Growth Trajectories of Students With Disabilities: Disability Category, Gender, Racial, and Socioeconomic Status Differences From Ages 7 to 17 SO REMEDIAL AND SPECIAL EDUCATION LA English DT Article DE math; growth trajectories; hierarchical linear modeling; disability category; gender; race; SES ID LEARNING-DISABILITIES; MATHEMATICS; METAANALYSIS; ACHIEVEMENT; PERFORMANCE; DEFICITS; CHILDREN; GRADES; SCHOOL; GAP AB This study examined math growth trajectories by disability category, gender, race, and socioeconomic status using a nationally representative sample of students ages 7 to 17. The students represented 11 federal disability categories. Compared with the national norming sample, students in all 11 disability categories had lower math achievement levels and slower growth in elementary school. In secondary school, however, the math growth rate slowed down and was similar for all students. Among students with disabilities, those with speech or visual impairments had the highest math achievement, and those with multiple disabilities or intellectual disability had the lowest. Relative to students with learning disabilities on calculation, growth rates for students with autism were significantly slower and those for students with speech impairments decelerated significantly faster. For students with disabilities, gender, White-Black, and socioeconomic status math achievement gaps were significant and stable over time, whereas White-Hispanic math achievement gaps widened over time. C1 [Wei, Xin; Lenz, Keith B.; Blackorby, Jose] SRI Int, Menlo Pk, CA 94025 USA. 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PD MAY-JUN PY 2013 VL 34 IS 3 BP 154 EP 165 DI 10.1177/0741932512448253 PG 12 WC Education, Special SC Education & Educational Research GA 135JQ UT WOS:000318284800003 ER PT J AU Lindenmayer, JP McGurk, SR Khan, A Kaushik, S Thanju, A Hoffman, L Valdez, G Wance, D Herrmann, E AF Lindenmayer, Jean-Pierre McGurk, Susan R. Khan, Anzalee Kaushik, Saurabh Thanju, Amod Hoffman, Lisa Valdez, Gladys Wance, Deborah Herrmann, Edith TI Improving Social Cognition in Schizophrenia: A Pilot Intervention Combining Computerized Social Cognition Training With Cognitive Remediation SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; social cognition; cognitive remediation ID FACIAL AFFECT RECOGNITION; RANDOMIZED CONTROLLED-TRIAL; HIGH-FUNCTIONING AUTISM; ENHANCEMENT THERAPY; EMOTION PERCEPTION; MENTAL-ILLNESS; EFFICACY; NEUROCOGNITION; PERFORMANCE; SCALE AB Background: Social cognition is significantly impaired in schizophrenia and contributes to poor community functioning. This study examined whether cognitive remediation (CR; COGPACK), shown to improve neurocognition, improves an integral component of social cognition, emotion perception, compared with CR combined with a computerized Emotion Perception intervention (Mind Reading: Interactive Guide to Emotions [MRIGE]). Methods: 59 stable schizophrenia or schizoaffective predominantly inpatients were randomized to either CR (N = 27) alone or CR + MRIGE (N = 32) for 12 weeks. Assessments included the Facial Emotion Identification Task (FEIT), Facial Emotion Discrimination Task (FEDT), MCCB-MATRICS, Personal and Social Performance Scale, and the Positive and Negative Syndrome Scale. Results: There was a significant group-by-time effect on FEIT (F = 11.509, P = .004); CR + MRIGE demonstrated significantly greater improvement than CR alone (CR + MRIGE, Z = 1.89, P = .05; CR alone Z = 0.57, P = .13). There was significant group-by-time effect on FEDT (F = 5.663, P = .022); CR + MRIGE demonstrated significantly greater improvement than CR alone (CR + MRIGE, Z = 1.90, P = .05; CR alone Z = 0.67, P = .21). There was also a significant group by time effect for social cognition, measured by the Mayer-Salovey-Caruso Emotional Intelligence Test (F = 5.473, P = .050): CR + MRIGE demonstrated significantly greater improvement than CR alone (CR + MRIGE, Z = 1.98, P = .02; CR alone, Z = 1.00, P =.05). Conclusions: Combined CR with emotion perception remediation produced greater improvements in emotion recognition, emotion discrimination, social functioning, and neurocognition compared with CR alone in chronic schizophrenia. C1 [Lindenmayer, Jean-Pierre; Khan, Anzalee; Kaushik, Saurabh; Thanju, Amod; Hoffman, Lisa; Valdez, Gladys; Wance, Deborah; Herrmann, Edith] Manhattan Psychiat Ctr, New York, NY USA. [Lindenmayer, Jean-Pierre; Kaushik, Saurabh] NYU, Med Ctr, New York, NY 10016 USA. [Lindenmayer, Jean-Pierre; Khan, Anzalee; Kaushik, Saurabh; Thanju, Amod] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [McGurk, Susan R.] Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA. [Khan, Anzalee] ProPhase Training Grp, New York, NY USA. RP Lindenmayer, JP (reprint author), Manhattan Psychiat Ctr, Psychopharmacol Res Dept, 600 E 125 St, Wards Isl, NY 10035 USA. 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Bull. PD MAY PY 2013 VL 39 IS 3 BP 507 EP 517 DI 10.1093/schbul/sbs120 PG 11 WC Psychiatry SC Psychiatry GA 133IN UT WOS:000318132200010 PM 23125396 ER PT J AU Zhang, YB Bolivar, VJ Lawrence, DA AF Zhang, Yubin Bolivar, Valerie J. Lawrence, David A. TI Maternal Exposure to Mercury Chloride During Pregnancy and Lactation Affects the Immunity and Social Behavior of Offspring SO TOXICOLOGICAL SCIENCES LA English DT Article DE mercury; mouse social behavior; IgG antibrain antibodies; maternal influences ID AUTISM SPECTRUM DISORDER; INDUCED AUTOIMMUNITY; NEUROBEHAVIORAL CHANGES; MURINE SUSCEPTIBILITY; AUTOANTIBODY PROFILES; REPETITIVE BEHAVIOR; INBRED STRAINS; T-CELLS; MICE; METHYLMERCURY AB Developmental HgCl2 exposures of F1 offspring (H-2(q/s)) from unsociable SJL/J (H-2(s)) dams with high susceptibility to Hg-induced autoimmunity (SFvF1) and from highly sociable FVB/NJ (FVB; H-2(q)) dams with lower susceptibility to Hg-induced autoimmunity (FvSF1) were investigated. Hg exposure increased the serum IgG levels of all offspring at postnatal day 21 (pnd21) and of SJL/J dams but not of FVB dams. Serum IgG anti-brain antibody (Ab) levels of pnd21 SFvF1 offspring and SJL dams were higher than those of the FvSF1 offspring and FVB dams, but Hg only increased the titers of the FVB dams and their offspring. Hg significantly elevated the presence of IgG in all brain regions of the pnd21 SFvF1 offspring, and the SFvF1 offspring had greater amounts of IgG in the brain than the FvSF1 offspring, which had Hg-induced increases in only two brain regions. Cytokine levels were elevated in the brain regions of Hg-treated pnd21 SFvF1 but not of FvSF1 offspring, and SFvF1 females had more brain regions expressing cytokines than the males. At pnd70, the serum IgG, serum anti-brain Abs, amounts of brain IgG, and brain cytokine levels of all of the Hg-treated offspring were equivalent to those of their appropriate controls, suggesting that developmental Hg exposure did not induce chronic immunological effects. However, the social behaviors of Hg-exposed SFvF1 offspring at pnd70 were significantly impaired, and SFvF1 females displayed greater decline in social behaviors than males, suggesting that the higher neuroinflammation of SFvF1 females earlier in life is associated with the altered behavior. Thus, developmental Hg exposure induces long-lasting effects on social behavior of offspring, which is dependent on sex and genetics and the induction of neuroinflammation. C1 New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY 12201 USA. RP Lawrence, DA (reprint author), Wadsworth Ctr, Immunol Lab, Albany, NY 12201 USA. 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We compared the expression of 84 ETC genes in the post-mortem brains of autism patients and controls. Brain tissues from the anterior cingulate gyrus, motor cortex, and thalamus of autism patients (n=8) and controls (n=10) were obtained from Autism Tissue Program, USA. Quantitative real-time PCR arrays were used to quantify gene expression. We observed reduced expression of several ETC genes in autism brains compared to controls. Eleven genes of Complex I, five genes each of Complex III and Complex IV, and seven genes of Complex V showed brain region-specific reduced expression in autism. ATP5A1 (Complex V), ATP5G3 (Complex V) and NDUFA5 (Complex I) showed consistently reduced expression in all the brain regions of autism patients. Upon silencing ATP5A1, the expression of mitogen-activated protein kinase 13 (MAPK13), a p38 MAPK responsive to stress stimuli, was upregulated in HEK 293 cells. This could have been induced by oxidative stress due to impaired ATP synthesis. We report new candidate genes involved in abnormal brain bioenergetics in autism, supporting the hypothesis that mitochondria, critical for neurodevelopment, may play a role in autism. C1 [Anitha, Ayyappan; Matsuzaki, Hideo; Miyachi, Taishi; Tsujii, Masatsugu; Suzuki, Katsuaki; Mori, Norio] Hamamatsu Univ Sch Med, Res Ctr Child Mental Dev, Hamamatsu, Shizuoka 4313192, Japan. [Nakamura, Kazuhiko; Thanseem, Ismail; Iwata, Yasuhide; Mori, Norio] Hamamatsu Univ Sch Med, Dept Psychiat & Neurol, Hamamatsu, Shizuoka 4313192, Japan. [Sugiyama, Toshiro] Hamamatsu Univ Sch Med, Dept Child & Adolescent Psychiat, Hamamatsu, Shizuoka 4313192, Japan. [Tsujii, Masatsugu] Chukyo Univ, Fac Sociol, Toyota, Japan. RP Nakamura, K (reprint author), Hamamatsu Univ Sch Med, Dept Psychiat & Neurol, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan. EM nakamura@hama-med.ac.jp FU PHS [R 24 MH 068855]; Ministry of Education, Culture, Sports, Science, and Technology of Japan [23591700, 23390288] FX We thank Dr Jane Pickett, Director of Brain Resources and Data, Autism Tissue Program, for facilitating brain tissue collection. Human tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, Maryland. Tissue samples were also provided by the Harvard Brain Tissue Resource Center, which is supported in part by PHS Grant No. R 24 MH 068855. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (23591700 to AA and 23390288 to KN). We thank Tae Takahashi and Mika Oyaizu for technical assistance. 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PD MAY PY 2013 VL 23 IS 3 BP 294 EP 302 DI 10.1111/bpa.12002 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 129TP UT WOS:000317865800007 PM 23088660 ER PT J AU Snow, WM Fry, M Anderson, JE AF Snow, Wanda M. Fry, Mark Anderson, Judy E. TI Increased Density of Dystrophin Protein in the Lateral Versus the Vermal Mouse Cerebellum SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE Purkinje neurons; Dendrites; Quantification; Morphometry; Immunohistochemistry ID DUCHENNE MUSCULAR-DYSTROPHY; CENTRAL-NERVOUS-SYSTEM; AUTISM SPECTRUM DISORDER; DEFICIENT MDX MICE; PURKINJE-CELLS; EXPRESSION; MOTOR; LOCALIZATION; SYNAPSES; MODEL AB Dystrophin, present in muscle, also resides in the brain, including cerebellar Purkinje neurons. The cerebellum, although historically associated with motor abilities, is also implicated in cognition. An absence of brain dystrophin in Duchenne muscular dystrophy (DMD) and in the mdx mouse model results in cognitive impairments. Localization studies of cerebellar dystrophin, however, have focused on the vermal cerebellum, associated with motor function, and have not investigated dystrophin distribution in the lateral cerebellum, considered to mediate cognitive function. The present study examined dystrophin localization in vermal and lateral cerebellar regions and across subcellular areas of Purkinje neurons in the mouse using immunohistochemistry. In both vermal and lateral cerebellum, dystrophin was restricted to puncta on somatic and dendritic membranes of Purkinje neurons. The density of dystrophin puncta was greater in the lateral than the vermal region. Neither the size of puncta nor the area of Purkinje neuron somata differed between regions. Results support the view that cognitive deficits in the DMD and the mdx model may be mediated by the loss of dystrophin, particularly in the lateral cerebellum. Findings have important implications for future studies examining the neurophysiological sequelae of neuronal dystrophin deficiency and the role of the lateral cerebellum in cognition. C1 [Snow, Wanda M.; Fry, Mark; Anderson, Judy E.] Univ Manitoba, Dept Psychol, Winnipeg, MB R3T 2N2, Canada. [Fry, Mark; Anderson, Judy E.] Univ Manitoba, Dept Biol Sci, Fac Sci, Winnipeg, MB R3T 2N2, Canada. RP Anderson, JE (reprint author), Univ Manitoba, Dept Biol Sci, Fac Sci, Biol Sci Bldg,50 Sifton Rd, Winnipeg, MB R3T 2N2, Canada. EM judith.anderson@ad.umanitoba.ca FU Manitoba Institute for Child Health; Natural Sciences and Engineering Research Council FX This research was supported by an operating Grant from Manitoba Institute for Child Health (JEA and MF) and a Postgraduate Scholarship from the Natural Sciences and Engineering Research Council (WMS). The funders did not contribute to the study design, interpretation, or manuscript preparation. The authors wish to thank Ms. R. Upadhaya and Dr. W. Mizunoya (Kyushu University) for advice with cryosectioning and immunostaining and Dr. James Hare for assistance with the statistical analysis. 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Mol. Neurobiol. PD MAY PY 2013 VL 33 IS 4 BP 513 EP 520 DI 10.1007/s10571-013-9917-8 PG 8 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 125GM UT WOS:000317527600006 PM 23436181 ER PT J AU Kanemura, H Sano, F Tando, T Sugita, K Aihara, M AF Kanemura, Hideaki Sano, Fumikazu Tando, Tomoko Sugita, Kanji Aihara, Masao TI Can EEG characteristics predict development of epilepsy in autistic children? SO EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY LA English DT Article DE Autism spectrum disorders (ASD); Electroencephalogram (EEG); Frontal paroxysmal abnormality; Epilepsy ID CHILDHOOD EPILEPSY; ACTIVE EPILEPSY; ABNORMALITIES; DISORDERS; ADOLESCENTS; PATTERNS; SEIZURE; BENIGN; SPIKES AB Background: The high occurrence of epilepsy in children with autism spectrum disorders (ASD) is a clear indication that ASD has a neurobiological basis. The current understanding of the association between epilepsy and ASD is still limited, but from a clinical point of view, this association should not be overlooked. Aims: We investigated the electroencephalogram (EEG) paroxysmal abnormality in children with ASD and the incidence of later development of epilepsy. Methods: Participants were recruited from University of Yamanashi hospital and 5 satellite hospitals between April 1, 2001 and March 31, 2005. EEG recordings and clinical evaluations were performed every 6 months for at least 6 years, focusing on paroxysmal abnormality. We scored the occurrence and the location of spikes and evaluated the relation with later development of epilepsy. Results: The prospective study included 21 patients with ASD (12 males and 9 females) between the ages of 3 and 6 years. EEG paroxysmal abnormalities were present in 11/21 patients (52.4%). In addition, six of 21 patients (28.6%) had epilepsy at some point in their lives. The presence of frontal paroxysms was significantly associated with later development of epilepsy compared with centrotemporal paroxysmus ( p < 0.003). The type of seizure diagnosed was mainly partial; in particular, partial with secondary generalization in 4/6 (66.7%). Conclusion: The presence of frontal paroxysms may indicate a higher risk of epilepsy in ASD. (C) 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. C1 [Kanemura, Hideaki; Sano, Fumikazu; Tando, Tomoko; Sugita, Kanji] Univ Yamanashi, Fac Med, Dept Paediat, Chuo Ku, Kofu, Yamanashi 4093898, Japan. [Aihara, Masao] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Chuo Ku, Kofu, Yamanashi 4093898, Japan. RP Kanemura, H (reprint author), Univ Yamanashi, Fac Med, Dept Paediat, Chuo Ku, Kofu, Yamanashi 4093898, Japan. EM ykimu@yamanashi.ac.jp FU [22591124]; [22591123] FX This work was supported by Grants-in-Aid for Scientific Research (C) (22591124 and 22591123). 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PD MAY PY 2013 VL 17 IS 3 BP 232 EP 237 DI 10.1016/j.ejpn.2012.10.002 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 129UW UT WOS:000317870500003 PM 23122323 ER PT J AU Tsoutsou, E Tzetis, M Giannikou, K Syrmou, A Oikonomakis, V Kosma, K Kanioura, A Kanavakis, E Fryssira, H AF Tsoutsou, Eirini Tzetis, Maria Giannikou, Krinio Syrmou, Areti Oikonomakis, Vasilis Kosma, Konstantina Kanioura, Anastasia Kanavakis, Emmanuel Fryssira, Helen TI Array-CGH revealed one of the smallest 16q21q22.1 microdeletions in a female patient with psychomotor retardation SO EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY LA English DT Article DE Microcephaly; Psychomotor retardation; Autism; 16q2122.1 microdeletion syndrome; Congenital heart defects; Array-CGH ID INTERSTITIAL DELETION; AUTISM AB A 28-month-old girl with dysmorphic craniofacial features, microcephaly, hypotonia, psychomotor retardation, failure to thrive and gastrointestinal problems was referred for clinical evaluation. Array-CGH analysis revealed one of the smallest de novo microdeletions on chromosome 16q21q22.1, 2.03 Mb in size. Advanced molecular analysis contributes to more precise genotype-phenotype correlation and accurate definition of the breakpoints in the deleted/duplicated regions. (C) 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. C1 [Tsoutsou, Eirini; Tzetis, Maria; Giannikou, Krinio; Syrmou, Areti; Oikonomakis, Vasilis; Kosma, Konstantina; Kanavakis, Emmanuel; Fryssira, Helen] Univ Athens, Sch Med, Choremio Res Lab, Dept Med Genet,Aghia Sophia Childrens Hosp, GR-11527 Athens, Greece. [Kanioura, Anastasia] Natl Ctr Sci Res, Inst Radioisotopes & Radiodiagnost Prod, Athens, Greece. RP Fryssira, H (reprint author), Univ Athens, Sch Med, Choremio Res Lab, Dept Med Genet,Aghia Sophia Childrens Hosp, GR-11527 Athens, Greece. EM efrysira@med.uoa.gr FU Alexander S. Onassis Public Benefit Foundation, Athens, Greece FX We thank the family of the patient for their contribution. Krinio Giannikou is supported by a scholarship provided by the Alexander S. Onassis Public Benefit Foundation, Athens, Greece. 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PD MAY PY 2013 VL 17 IS 3 BP 316 EP 320 DI 10.1016/j.ejpn.2012.12.004 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 129UW UT WOS:000317870500017 PM 23352671 ER PT J AU Daprati, E Nico, D Delorme, R Leboyer, M Zalla, T AF Daprati, Elena Nico, Daniele Delorme, Richard Leboyer, Marion Zalla, Tiziana TI Memory for past events: movement and action chains in high-functioning autism spectrum disorders SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Autism; Obsessive-compulsive disorder; Enactment effect; Memory for actions; Action chains; Checking behaviour ID OBSESSIVE-COMPULSIVE DISORDER; SUBJECT-PERFORMED TASKS; DIAGNOSTIC INTERVIEW; SOCIAL COGNITION; CHECKERS; DEFICITS; INFORMATION; SYMPTOMS; CHILDREN; SCALE AB In the present study, we assessed whether individuals with autism spectrum disorders (ASD) show memory impairments for previously performed actions, as previously suggested for people suffering from obsessive-compulsive disorder (OCD) (Ecker and Engelkamp in Behav Cogn Psychother 23:349-371, 1995; Merckelbach and Wessel in J Nerv Ment Dis 188(12):846-848, 2000). To test this possibility, we explored verbal memory for actions in individuals with a diagnosis of ASD, with and without co-morbidity for OCD, and in controls matched for age and gender. Participants observed or observed and enacted a number of actions while listening to the corresponding phrases being spoken. After a suitable delay, they were submitted to an old/new recognition task. Results showed that ASD individuals with OCD were less accurate and slower in responding compared to ASD individuals without OCD and controls, particularly when dealing with phrases describing simple movements. In contrast, ASD participants without OCD were more impaired when phrases described complex actions that involved pantomiming object use or coordinating movements of multiple body parts. These findings are discussed in terms of differential organization of the motor trace for simple versus complex actions in ASD individuals according to the concurrent presence of OCD. C1 [Daprati, Elena] Univ Roma Tor Vergata, Dipartimento Med Sistemi, Rome, Italy. [Daprati, Elena] Univ Roma Tor Vergata, CBMS, Rome, Italy. [Daprati, Elena] IRCCS Fdn Santa Lucia, Dipartimento Fisiol Neuromotoria, Rome, Italy. [Nico, Daniele] Univ Roma La Sapienza, Dipartimento Psicol, Rome, Italy. [Delorme, Richard] Hop Robert Debre, AP HP, F-75019 Paris, France. [Delorme, Richard; Leboyer, Marion] Univ Paris Est Creteil, IMRB, INSERM, U955, Creteil, France. [Leboyer, Marion] Henri Mondor Albert Chenevier Hosp, AP HP, Dept Adult Psychiat, Creteil, France. [Leboyer, Marion] French Natl Sci Fdn, Fdn FondaMental, Creteil, France. [Zalla, Tiziana] Ecole Normale Super, CNRS, Inst Jean Nicod, Paris, France. RP Daprati, E (reprint author), Univ Roma Tor Vergata, Dipartimento Med Sistemi, Rome, Italy. EM elena.daprati@uniroma2.it; tiziana.zalla@ens.fr FU Fondation FondaMental; Fondation Orange; Agence Nationale de la Recherche (Grant Programme "Neurosciences, Neurologie et Psychiatrie") FX We gratefully acknowledge the commitment of all participants and their families to the pursuit of research in autism. This research was supported by Fondation FondaMental and Fondation Orange to TZ and ML and by Agence Nationale de la Recherche (Grant Programme "Neurosciences, Neurologie et Psychiatrie") to TZ. 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PD MAY PY 2013 VL 226 IS 3 BP 325 EP 334 DI 10.1007/s00221-013-3436-1 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 127HP UT WOS:000317689300002 PM 23417648 ER PT J AU Takeuchi, H Taki, Y Sassa, Y Hashizume, H Sekiguchi, A Nagase, T Nouchi, R Fukushima, A Kawashima, R AF Takeuchi, Hikaru Taki, Yasuyuki Sassa, Yuko Hashizume, Hiroshi Sekiguchi, Atsushi Nagase, Tomomi Nouchi, Rui Fukushima, Ai Kawashima, Ryuta TI White matter structures associated with emotional intelligence: Evidence from diffusion tensor imaging SO HUMAN BRAIN MAPPING LA English DT Article DE facial perception; emotional processing; gray matter; intrapersonal factor; interpersonal factor; situation management factor; fractional anisotropy ID VOXEL-BASED MORPHOMETRY; NORMAL PEDIATRIC POPULATION; NERVE-FIBERS; CONDUCTION-VELOCITY; COGNITIVE FUNCTIONS; HEALTHY-ADULTS; NEURAL SYSTEMS; BRAIN; AUTISM; CREATIVITY AB Previous studies of brain lesions, functional activity, and gray matter structures have suggested that emotional intelligence (EI) is associated with regions involved in the network of social cognition (SCN) and in somatic marker circuitry (SMC). Our new study is the first to investigate the association between white matter (WM) integrity and EI. We examined this relationship in the brain of healthy young adult men [n = 74, mean age = 21.5 years, standard deviation (SD) = 1.6] and women (n = 44, mean age = 21.9 years, SD = 1.4). We performed a voxel-based analysis of fractional anisotropy, which is an indicator of WM integrity, using diffusion tensor imaging and used a questionnaire (EI Scale) for measuring EI to identify the correlation of WM integrity with individual EI factor (intrapersonal, interpersonal, and situation management factors). Our results showed that (a) the intrapersonal factor of EI was positively correlated with WM integrity in the right anterior insula, and (b) the interpersonal factor of EI was associated with WM integrity in a part of the right inferior longitudinal fasciculus (ILF). The right anterior insula is one of the important nodes of the SMC, whereas the ILF connects the visual cortex and areas related to SCN, and thus, is a part of the SCN. Our findings further support the notion that the brain regions involved in the SCN and in the SMC are associated with EI. Hum Brain Mapp, 2013. (c) 2011 Wiley Periodicals, Inc. C1 [Takeuchi, Hikaru; Nouchi, Rui; Kawashima, Ryuta] Tohoku Univ, Inst Dev Aging & Canc, Smart Ageing Int Res Ctr, Sendai, Miyagi 9808575, Japan. [Taki, Yasuyuki; Sassa, Yuko; Hashizume, Hiroshi; Kawashima, Ryuta] Tohoku Univ, Inst Dev Aging & Canc, Div Dev Cognit Neurosci, Sendai, Miyagi 9808575, Japan. [Sekiguchi, Atsushi; Fukushima, Ai; Kawashima, Ryuta] Tohoku Univ, Inst Dev Aging & Canc, Dept Funct Brain Imaging, Sendai, Miyagi 9808575, Japan. [Nagase, Tomomi] Tohoku Univ, Fac Med, Sendai, Miyagi 9808575, Japan. 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Brain Mapp. PD MAY PY 2013 VL 34 IS 5 BP 1025 EP 1034 DI 10.1002/hbm.21492 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 122DT UT WOS:000317297500003 PM 22139821 ER PT J AU Sahu, JK Gulati, S Sapra, S Arya, R Chauhan, S Chowdhury, MR Gupta, N Kabra, M Gupta, YK Dwivedi, SN Kalra, V AF Sahu, Jitendra Kumar Gulati, Sheffali Sapra, Savita Arya, Ravindra Chauhan, Sandeepa Chowdhury, Madhumita Roy Gupta, Neerja Kabra, Madhulika Gupta, Y. K. Dwivedi, S. N. Kalra, Veena TI Effectiveness and Safety of Donepezil in Boys With Fragile X Syndrome: A Double-Blind, Randomized, Controlled Pilot Study SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE intellectual function; donepezil; fragile X syndrome; cholinergic ID DOWN-SYNDROME AB The present study was designed as a 12-week, randomized, double-blind, placebo-controlled pilot study to evaluate the effectiveness and safety of donepezil in boys with fragile X syndrome. Twenty boys with fragile X syndrome were randomized to receive 12 weeks of treatment with either placebo or donepezil (2.5 mg daily for initial 4 weeks followed by 5 mg daily for next 8 weeks). The outcome measures included change in intelligence quotient scores on Stanford-Binet Intelligence Scale (Hindi adaptation by Kulshrestha), change in behavioral scores by Conners 3 Parent Rating Scale (Short) and Childhood Autism Rating Scale, safety, and tolerability of donepezil. The study failed to show significant difference in intelligence quotient and behavioral scales with donepezil therapy over 12 weeks. However, donepezil appeared to be safe and well tolerated. C1 [Sahu, Jitendra Kumar] Postgrad Inst Med Educ & Res, Dept Pediat, Chandigarh 160012, India. [Sahu, Jitendra Kumar; Gulati, Sheffali; Sapra, Savita; Arya, Ravindra; Chauhan, Sandeepa; Chowdhury, Madhumita Roy; Gupta, Neerja; Kabra, Madhulika; Kalra, Veena] All India Inst Med Sci, Dept Pediat, New Delhi, India. [Arya, Ravindra] Cincinnati Childrens Hosp Med Ctr, Div Neurol, Comprehens Epilepsy Ctr, Cincinnati, OH USA. [Gupta, Y. K.] All India Inst Med Sci, Dept Pharmacol, New Delhi, India. [Dwivedi, S. N.] All India Inst Med Sci, Dept Biostat, New Delhi, India. RP Gulati, S (reprint author), All India Inst Med Sci, Dept Pediat, Child Neurol Div, New Delhi, India. 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PD MAY PY 2013 VL 162 IS 5 BP 1080 EP 1081 PG 3 WC Pediatrics SC Pediatrics GA 129JW UT WOS:000317836300050 PM 23617979 ER PT J AU Essa, MM Braidy, N Waly, MI Al-Farsi, YM Al-Sharbati, M Subash, S Amanat, A Al-Shaffaee, MA Guillemin, GJ AF Essa, M. M. Braidy, N. Waly, M. I. Al-Farsi, Y. M. Al-Sharbati, M. Subash, S. Amanat, A. Al-Shaffaee, M. A. Guillemin, G. J. TI Impaired antioxidant status and reduced energy metabolism in autistic children SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; ATP; Oxidative stress; NAD(+); Antioxidants ID OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES; NITRIC-OXIDE; CELL-DEATH; MITOCHONDRIAL DYSFUNCTION; NEUROLOGICAL DISEASE; SPECTRUM DISORDERS; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; SCHIZOPHRENIA AB Accumulating evidence suggests that oxidative stress induced mechanisms are believed to be associated with the pathophysiology of autisin. In this study, we recruited 19 Omani autistic children with age-matched controls to analyze their plasma and serum redox status and the levels of ATP, NAD(+) and NADH using well established spectrophotometric assays. A significant decrease was observed in the levels of plasma total antioxidants (TA), reduced glutathione (GSH), superoxide and catalase activity in Omani autistic children as compared to their age-matched controls. In contrary, the level of plasma glutathione peroxidase (GSH-Px) was significantly increased in autistic children. Reduced serum NAD(+) and ATP levels and lower NAnNADH ratio were observedin patients with autism compared to controls. Finally, a significant inverse correlation was observed between plasma GSH, SOD, catalase activity, and serum NAD(+) and ATP levels, and autism severity using Childhood Autism Rating Scale (CARS) scores. The levels of plasma GSH-Px and serum NADH correlated strongly with autism severity whilst no significant correlation was observed for plasma TA. Our data suggests that increased vulnerability to oxidative stress in autism may occur as a consequence of alterations in antioxidant enzymes leading to mitochondrial dysfunction. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved. C1 [Essa, M. M.; Waly, M. I.; Subash, S.; Amanat, A.] Sultan Qaboos Univ, Coll Agr & Marine Sci, Dept Food Sci & Nutr, Muscat, Oman. [Essa, M. M.] Univ New S Wales, Sch Med Sci, Dept Pharmacol, Sydney, NSW, Australia. [Braidy, N.] Univ New S Wales, Fac Med, Ctr Hlth Brain Ageing, Sch Psychiat, Sydney, NSW, Australia. [Al-Farsi, Y. M.; Al-Sharbati, M.; Al-Shaffaee, M. A.] Sultan Qaboos Univ, Coll Med & Hlth Sci, Muscat, Oman. [Guillemin, G. J.] Macquarie Univ, MND & Neurodegenerat Dis Res Ctr, Neuropharmacol Grp, N Ryde, NSW 2109, Australia. RP Guillemin, GJ (reprint author), Macquarie Univ, Australian Sch Adv Med, Neuroinflammat Grp, MND & Neurodegenerat Dis Res Grp, N Ryde, NSW 2109, Australia. 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W., 2002, SCIENCE, P297 NR 63 TC 2 Z9 2 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 MAY PY 2013 VL 7 IS 5 BP 557 EP 565 DI 10.1016/j.rasd.2012.12.006 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 125NE UT WOS:000317545700001 ER PT J AU Manouilenko, I Pagani, M Stone-Elander, S Odh, R Brolin, F Hatherly, R Jacobsson, H Larsson, SA Bejerot, S AF Manouilenko, Irina Pagani, Marco Stone-Elander, Sharon Odh, Richard Brolin, Fredrik Hatherly, Robert Jacobsson, Hans Larsson, Stig A. Bejerot, Susanne TI Autistic traits, ADHD symptoms, neurological soft signs and regional cerebral blood flow in adults with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; ADHD; Neurological soft signs; Temporo-parietal junction; Thalamus; Caudate ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; PERVASIVE DEVELOPMENTAL DISORDERS; ASPERGER-SYNDROME; CHILDHOOD AUTISM; HEALTHY-INDIVIDUALS; GLUCOSE-METABOLISM; FUNCTIONAL-ANATOMY AB The resting regional cerebral blood flow (rCBF) patterns related to co-occurring symptoms such as inattention, hyperactivity, neurological soft signs and motor problems have not yet been disclosed in autism spectrum disorders (ASD). In this study thirteen adults with ASD and ten matched neurotypical controls underwent PET. The scores of rating scales for autistic traits, attention deficit hyperactivity disorder (ADHD) and neurological soft signs were included in a factorial analysis and correlated with rCBF. Factors corresponding to "autistic/ADHD traits", "sensory-motor integration" and "Intelligence/Motor sequencing" were identified. In the ASD group, positive correlations with CBF were found for "autistic/ADHD traits" in caudate bilaterally and the inferior parietal lobule, for "sensory-motor integration" in parieto-occipital cortex and for "Intelligence/Motor sequencing" in the right temporal cortex. Notably, CBF in the left thalamus correlated negatively with all three factors. Autistic traits and ADHD symptoms were associated with shared neural substrates. The correlation between "autistic/ADHD traits" and rCBF in the caudate is possibly associated with the executive impairments and ritualistic/stereotyped behaviors apparent in ASD. Furthermore, sensory-motor deficits were correlated with rCBF in the occipital visual cortex, involved in atypical visual perception in ASD. Various behavioral and neurological symptoms are suggested to converge into the ASD phenotype. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Manouilenko, Irina; Stone-Elander, Sharon; Bejerot, Susanne] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Manouilenko, Irina] Jarva Psychiat Out Patient Clin, Praktikertjanst AB, S-16374 Stockholm, Sweden. [Pagani, Marco; Brolin, Fredrik; Hatherly, Robert; Jacobsson, Hans] Karolinska Univ Hosp, Dept Nucl Med, Stockholm, Sweden. [Pagani, Marco] CNR, Inst Cognit Sci & Technol, Rome, Italy. [Stone-Elander, Sharon] Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden. [Odh, Richard] Swedish Radiat Safety Author, Dept Radiat Protect, Stockholm, Sweden. [Larsson, Stig A.] Karolinska Univ Hosp, Dept Diagnost Phys, Stockholm, Sweden. 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Autism Spectr. Disord. PD MAY PY 2013 VL 7 IS 5 BP 566 EP 578 DI 10.1016/j.rasd.2012.12.008 PG 13 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 125NE UT WOS:000317545700002 ER PT J AU Sun, X Allison, C Auyeung, B Matthews, FE Baron-Cohen, S Brayne, C AF Sun, Xiang Allison, Carrie Auyeung, Bonnie Matthews, Fiona E. Baron-Cohen, Simon Brayne, Carol TI What is available for case identification in autism research in mainland China? SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Screening instrument; Diagnostic instrument; Mainland China ID DIAGNOSTIC OBSERVATION SCHEDULE; PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM SCREENING QUESTIONNAIRE; CHILDHOOD AUTISM; RATING-SCALE; BEHAVIOR CHECKLIST; YOUNG-CHILDREN; ASPERGER-SYNDROME; INSTRUMENTS; INTERVIEW AB Little is known about research on Autism Spectrum Conditions (ASC) in mainland China. The few available studies in mainland China have shown the screening and diagnostic instruments for ASC used in mainland China were different from the West. Literature on screening and diagnostic instruments and criteria were reviewed and current available instruments were identified and evaluated. Eight screening instruments and two diagnostic instruments were identified. The Clancy Autism Behaviour Scale (CABS), the Autism Behaviour Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were the most frequently used instruments in mainland China. They were adopted from the West more than two decades ago for detecting individuals with Childhood Autism but not the whole autism spectrum. Standardised instruments need to be validated and adopted into autism research in mainland China. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Sun, Xiang; Brayne, Carol] Univ Cambridge, Cambridge Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge CB2 0SR, England. 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Carolyn TI Screening accuracy for risk of autism spectrum disorder using the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Developmental screening; BITSEA; M-CHAT ID PERVASIVE DEVELOPMENTAL DISORDERS; MODIFIED-CHECKLIST; YOUNG-CHILDREN; EARLY IDENTIFICATION; FOLLOW-UP; INTERVENTION; DIAGNOSIS; QUESTIONNAIRE; PRESCHOOLERS; VALIDITY AB Early identification of autism spectrum disorders (ASDs) is facilitated by the use of standardized screening scales that assess the social emotional behaviors associated with ASD. Authors examined accuracy of Brief Infant-Toddler Social and Emotional Assessment (BITSEA) subscales in detecting Modified Checklist for Autism in Toddlers (M-CHAT) risk for 456 toddlers. An ASD-specific screener, Total ASD, was developed from BITSEA subscales incorporating both behavioral and social communicative features of ASD. 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PD MAY PY 2013 VL 7 IS 5 BP 591 EP 600 DI 10.1016/j.rasd.2013.01.004 PG 10 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 125NE UT WOS:000317545700004 ER PT J AU Lemonnier, E Grandgeorge, M Jacobzone-Leveque, C Bessaguet, C Peudenier, S Misery, L AF Lemonnier, E. Grandgeorge, M. Jacobzone-Leveque, C. Bessaguet, C. Peudenier, S. Misery, L. TI Red dermographism in autism spectrum disorders: A clinical sign of cholinergic dysfunction? SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; ASD; Dermatology; Red dermographism; Acetylcholine ID BRAIN-DEVELOPMENT; CHILDREN; ABNORMALITIES; URTICARIA; RISK; DISTURBANCES; BIOMARKERS; DIAGNOSIS; CORTEX AB The authors hypothesised that red dermographism - a skin reaction involving the cholinergic system - is more frequent in children with autism spectrum disorders (ASDs) than in children exhibiting typical development. We used a dermatological examination to study red dermographism in this transverse study, which compared forty six children with ASDs with seventy one children exhibiting typical development. Both univariate and stratified statistical analyses were performed. In comparison with the control group, children with ASDs had a greater prevalence of red dermographism, especially the subgroup of children with autism and Asperger syndrome. Our results reflect a probable difference in the functionality of the cholinergic system. Indeed, ASDs are usually considered neurodevelopmental disorders caused by several factors. Cholinergic system abnormalities may be involved in the pathophysiology of ASDs, at least for a subgroup of individuals. The implications for a possible treatment strategy and a potential biomarker for ASDs are discussed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Lemonnier, E.; Grandgeorge, M.; Misery, L.] Univ Bretagne Occidentale, Lab Neurosci Brest, EA 4685, Brest, France. [Lemonnier, E.; Grandgeorge, M.] CHRU Brest, Ctr Ressources Autisme, Child Psychiat Serv, Brest, France. [Jacobzone-Leveque, C.; Misery, L.] CHRU Brest, Dept Dermatol, Brest, France. [Bessaguet, C.] CHRU Brest, Dept Biostat, Brest, France. [Peudenier, S.] CHRU Brest, Dept Paediat, Brest, France. RP Grandgeorge, M (reprint author), Hop Bohars, Ctr Ressources Autisme Bretagne, F-29820 Bohars, France. 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PD MAY PY 2013 VL 7 IS 5 BP 601 EP 605 DI 10.1016/j.rasd.2013.01.005 PG 5 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 125NE UT WOS:000317545700005 ER PT J AU Spek, AA Velderman, E AF Spek, Annelies A. Velderman, E. TI Examining the relationship between Autism spectrum disorders and technical professions in high functioning adults SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Technical skills; Attention to detail; Attention switching; Social skill ID COGNITIVE-STYLE; QUOTIENT AQ; RELIABILITY; INTERVIEW AB A relationship has been hypothesized between Autism and technical professions. This has been attributed to superior folk physics in individuals with Autism. Folk physics can be described as the capability to understand physical causality. Since all the previous studies in this area were focused on family members of individuals with Autism, it was unclear if there is a direct relationship between Autism and technical professions. Therefore, we examined the degree to which the professions of high functioning adults with Autism (N = 29) encompass technical skills and compared the results to adults with Schizophrenia (N = 17) and a neurotypical control group (N = 30). Furthermore, we examined whether the degree of technical skills in the professions of the Autism group was related to their autistic traits. The results showed that the last and longest attained professions of the adults with Autism require more technical skills than those of the Schizophrenia and neurotypical group. Furthermore, the degree of technical skills in the professions of the adults with Autism is related to impairments in social skills, but not to strengths in detailed information processing. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Spek, Annelies A.; Velderman, E.] Mental Hlth Inst GGZ Eindhoven, Adult Autism Ctr, NL-5626 AB Eindhoven, Netherlands. RP Spek, AA (reprint author), Mental Hlth Inst GGZ Eindhoven, Adult Autism Ctr, Boschdijk 771,Postvak 1418, NL-5626 AB Eindhoven, Netherlands. EM aa.spek@ggze.nl CR American Psychiatric Association, 2000, DIAGN STAT MAN MENTT Baron-Cohen S, 2001, J AUTISM DEV DISORD, V31, P5, DOI 10.1023/A:1005653411471 Baron-Cohen S., 1998, AUTISM, V2, P296, DOI 10.1177/1362361398023008 Baron-Cohen S., 1997, NEW DIR CHILD ADOLES, V75, P45 Baron-Cohen S, 1997, AUTISM INT J RES PRA, V1, P153 Calvert P., 2005, LIB MANAGEMENT, V26, P139, DOI 10.1108/01435120510580889 Cath DC, 2008, PSYCHOPATHOLOGY, V41, P101, DOI 10.1159/000111555 De Jonge M., 2007, ADI R AUTISM DIAGNOS First M. 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TI Interceptive skills in children aged 9-11 years, diagnosed with Autism Spectrum Disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Catching; Tau-coupling; Motor Control; Timing; ASD ID HIGH-FUNCTIONING AUTISM; TO-GRASP MOVEMENT; ASPERGERS-DISORDER; MOTOR IMPAIRMENT; PARKINSONS-DISEASE; REACHING MOVEMENTS; KINEMATIC ANALYSIS; PRETERM INFANTS; SENSORY-MOTOR; DEFICIT AB Growing evidence suggests that significant motor problems are associated with a diagnosis of Autism Spectrum Disorders (ASD), particularly in catching tasks. Catching is a complex, dynamic skill that involves the ability to synchronise one's own movement to that of a moving target. To successfully complete the task, the participant must pick up and use perceptual information about the moving target to arrive at the catching place at the right time. This study looks at catching ability in children diagnosed with ASD (mean age 10.16 +/- 0.9 years) and age-matched non-verbal (9.72 +/- 0.79 years) and receptive language (9.51 +/- 0.46) control groups. Participants were asked to "catch" a ball as it rolled down a fixed ramp. Two ramp heights provided two levels of task difficulty, whilst the sensory information (audio and visual) specifying ball arrival time was varied. Results showed children with ASD performed significantly worse than both the receptive language (p =.02) and non-verbal (p =.02) control groups in terms of total number of balls caught. A detailed analysis of the movement kinematics showed that difficulties with picking up and using the sensory information to guide the action may be the source of the problem. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Whyatt, Caroline; Craig, Cathy M.] Queens Univ Belfast, Sch Psychol, Belfast BT9 5BN, Antrim, North Ireland. RP Whyatt, C (reprint author), Queens Univ Belfast, Sch Psychol, 18-30 Malone Rd, Belfast BT9 5BN, Antrim, North Ireland. 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Autism Spectr. Disord. PD MAY PY 2013 VL 7 IS 5 BP 613 EP 623 DI 10.1016/j.rasd.2013.01.003 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 125NE UT WOS:000317545700007 ER PT J AU Garcia-Villamisar, D Dattilo, J Matson, JL AF Garcia-Villamisar, Domingo Dattilo, John Matson, Johnny L. TI Quality of life as a mediator between behavioral challenges and autistic traits for adults with intellectual disabilities SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Intellectual disabilities; Behavioral challenges; Quality of life ID PROFOUND MENTAL-RETARDATION; SELF-INJURIOUS-BEHAVIOR; QUESTIONNAIRE QOL-Q; SPECTRUM DISORDERS; DIAGNOSTIC-ASSESSMENT; DISABLED ADULTS; SOCIAL-SKILLS; DASH-II; ASD-DA; PSYCHOPATHOLOGY AB A multiple mediation model was proposed to integrate core concepts of challenging behaviors with autistic traits to increase understanding of their relationship to quality of life (QoL). It was hypothesized that QoL is a possible mediator between the severity of challenging behaviors and autistic traits in adults with intellectual disability. These constructs are of vital importance because they are essential variables for people with autism, and obviously they influence their psychosocial development. Participants were 70 adults with autism spectrum disorders (ASD) and moderate intellectual disabilities (ID). Results indicated that several dimensions of QoL mediated the relationships between autistic traits and challenging behaviors. The dimensions of QoL, Satisfaction, Competence/Productivity, and Autonomy/Independence are mediators between autistic traits and challenging behaviors. Implications of these data are discussed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Garcia-Villamisar, Domingo] Univ Complutense Madrid, E-28040 Madrid, Spain. [Dattilo, John] Penn State Univ, University Pk, PA 16802 USA. [Matson, Johnny L.] Louisiana State Univ, Baton Rouge, LA 70803 USA. RP Garcia-Villamisar, D (reprint author), Dept Personal & Clin Psychol, Avda Juan 23 Sn, Madrid 28040, Spain. 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Tylki-Szymanska, Anna TI Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder SO ACTA PAEDIATRICA LA English DT Review DE Attention deficit/hyperactivity disorder; Autism spectrum disorder; Developmental disabilities; Mucopolysaccharidosis type III; Speech/language disorders ID BONE-MARROW-TRANSPLANTATION; LYSOSOMAL STORAGE DISORDERS; FLUOROMETRIC ENZYME ASSAY; PREIMPLANTATION GENETIC DIAGNOSIS; SYNDROME TYPE-A; URINARY GLYCOSAMINOGLYCANS; PRENATAL-DIAGNOSIS; FOLLOW-UP; LC-MS/MS; DISEASE AB Mucopolysaccharidosis III is a rare genetic disease characterized by progressive cognitive decline and severe hyperactivity that does not respond to stimulants. Somatic features are relatively mild. Patients are often initially misdiagnosed as having idiopathic developmental delay, attention deficit/hyperactivity disorder and/or autism spectrum disorders, putting them at risk for unnecessary testing and treatments. Conclusion Children with developmental or speech delay, especially those with a characteristic somatic feature or behavioural abnormalities, should be screened for MPS III. C1 [Wijburg, Frits A.] Univ Amsterdam, Acad Med Ctr, Dept Paediat, NL-1105 AZ Amsterdam, Netherlands. [Wegrzyn, Grzegorz] Univ Gdansk, Dept Mol Biol, PL-80952 Gdansk, Poland. [Burton, Barbara K.] Ann & Robert H Lurie Childrens Hosp Chicago, Div Genet Birth Defects & Metab, Chicago, IL USA. [Tylki-Szymanska, Anna] Childrens Mem Hlth Inst, Dept Metab Dis, Warsaw, Poland. RP Wijburg, FA (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Paediat H7 270, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM f.a.wijburg@amc.uva.nl FU Shire Human Genetic Therapies, Inc.; Shire Human Genetic Therapies; Genzyme; BioMarin Pharmaceutical Inc.; Actelion Pharmaceuticals FX Dr. Burton has received honoraria, travel grants or research grants from Shire Human Genetic Therapies. Drs. Tylki-Szymanska and Wczgrzyn have received honoraria and travel grants from Shire Human Genetic Therapies, Inc., Genzyme and BioMarin Pharmaceutical Inc. Dr. Wijburg has received honoraria, travel grants or research grants from Shire Human Genetic Therapies, Inc., Genzyme and Actelion Pharmaceuticals. 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PD MAY PY 2013 VL 102 IS 5 BP 462 EP 470 DI 10.1111/apa.12169 PG 9 WC Pediatrics SC Pediatrics GA 123AW UT WOS:000317361400019 PM 23336697 ER PT J AU Liu, JY Calhoun, VD Chen, JY Claus, ED Hutchison, KE AF Liu, Jingyu Calhoun, Vince D. Chen, Jiayu Claus, Eric D. Hutchison, Kent E. TI Effect of homozygous deletions at 22q13.1 on alcohol dependence severity and cue-elicited BOLD response in the precuneus SO ADDICTION BIOLOGY LA English DT Article DE 22q13.1; alcohol dependence; homozygous deletion; neurobiological phenotype; precuneus ID COPY-NUMBER VARIATION; AUTISM SPECTRUM DISORDERS; HUMAN GENOME; STRUCTURAL VARIATION; DRINKING BEHAVIORS; NEURAL RESPONSE; GENE; SCHIZOPHRENIA; VARIANTS; ASSOCIATION AB Copy number variations (CNVs) can alter the DNA sequence in blocks ranging from kilobases to megabases, involving more total nucleotides than single nucleotide polymorphisms. Yet, its impact in humans is far from fully understood. In this study, we investigate the relationship of genome-wide CNVs with brain function elicited by an alcohol cue in 300 participants with alcohol use disorders. First, we extracted refined neurobiological phenotypes, the brain responses to an alcohol cue versus a juice cue in the precuneus, thalamus and anterior cingulate cortex (ACC). Then, we correlated the CNVs with incidence frequency >1% to the neurobiological phenotypes. One CNV region at 22q13.1 was identified to be associated with alcohol dependence severity and the brain response to alcohol cues. Specifically, the 22k base-pair homozygous deletion at 22q13.1 affects genes APOBEC3a and APOBEC3b. Carriers of this homozygous deletion show a significantly higher score in the alcohol dependence severity (P<0.05) and increased response to alcohol cues in the precuneus (P<1012) than other participants. Tests of a mediation model indicate that the precuneus mediates the association between the homozygous deletions and alcohol dependence severity. Interestingly, the precuneus is not only anatomically and functionally connected to the ACC and thalamus (the main active regions to the alcohol cue), but also has the most predictive power to the alcohol dependence severity. These findings suggest that the homozygous deletion at 22q13.1 may have an important impact on the function of the precuneus with downstream implications for alcohol dependence. C1 [Liu, Jingyu; Calhoun, Vince D.; Chen, Jiayu; Claus, Eric D.; Hutchison, Kent E.] Mind Res Network, Albuquerque, NM 87106 USA. [Liu, Jingyu; Calhoun, Vince D.; Chen, Jiayu] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Hutchison, Kent E.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. RP Liu, JY (reprint author), Mind Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87106 USA. 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Biol. PD MAY PY 2013 VL 18 IS 3 BP 548 EP 558 DI 10.1111/j.1369-1600.2011.00393.x PG 11 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 123ZG UT WOS:000317431500016 PM 21995620 ER PT J AU Whittingham, K Wee, D Sanders, MR Boyd, R AF Whittingham, K. Wee, D. Sanders, M. R. Boyd, R. TI Predictors of psychological adjustment, experienced parenting burden and chronic sorrow symptoms in parents of children with cerebral palsy SO CHILD CARE HEALTH AND DEVELOPMENT LA English DT Article DE cerebral palsy; chronic sorrow; coping; experiential avoidance; parent ID DEVELOPMENTAL-DISABILITIES; DECREASES AGGRESSION; COMMITMENT THERAPY; ACCEPTANCE; STRESS; HEALTH; AUTISM; CAREGIVERS; FAMILIES; BEHAVIOR AB Aim To investigate the role of child behaviour, parental coping and experiential avoidance in predicting the psychological outcomes of: (i) psychological symptoms; (ii) chronic sorrow symptoms; and (iii) experienced parenting burden in parents of children with cerebral palsy (CP). Method This study is a cross-sectional, correlational study. Ninety-four parents of children (aged 212 years) with CP (various levels of motor functioning GMFCS IV) participated. Results Together, the three predictors of child behaviour, parental coping and experiential avoidance explained 36.8% of the variance in psychological symptoms with child behavioural problems and experiential avoidance as significant unique predictors. In addition, 15.8% of the variance in chronic sorrow symptoms was explained by the three predictors with experiential avoidance alone as a significant unique predictor. Lastly, the predictors together explained 24.3% of the variance in experienced parenting burden with child behavioural problems and experiential avoidance as significant unique predictors. Conclusions This study demonstrates a relationship between child behavioural problems and parental psychological symptoms and experienced parenting burden as well as a relationship between experiential avoidance and parental psychological symptoms, experienced parenting burden and chronic sorrow symptoms. C1 [Whittingham, K.; Boyd, R.] Univ Queensland, Fac Hlth Sci, Queensland Cerebral Palsy & Rehabil Res Ctr, Sch Med, Brisbane, Qld 4029, Australia. [Whittingham, K.; Wee, D.] Univ Queensland, Sch Psychol, Fac Social & Behav Sci, Brisbane, Qld 4029, Australia. [Whittingham, K.; Boyd, R.] Univ Queensland, Fac Hlth Sci, Queensland Childrens Med Res Inst, Brisbane, Qld 4029, Australia. [Sanders, M. R.] Univ Queensland, Fac Social & Behav Sci, Sch Psychol, Parenting & Family Support Ctr, Brisbane, Qld 4029, Australia. RP Whittingham, K (reprint author), Univ Queensland, Royal Childrens Hosp, Queensland Cerebral Palsy & Rehabil Res Ctr, Dept Paediat & Child Hlth,Sch Med, Level 3,Fdn Bldg, Brisbane, Qld 4029, Australia. EM koawhittingham@uq.edu.au RI Sanders, Matthew/C-1941-2013; Whittingham, Koa/C-6766-2009; Boyd, Roslyn/A-4498-2011 OI Sanders, Matthew/0000-0003-3479-6337; Whittingham, Koa/0000-0002-5344-9907; Boyd, Roslyn/0000-0002-4919-5975 FU NHMRC [473840, 631712] FX We acknowledge an NHMRC Career Development Award (473840) and a Smart State Fellowship (RB) as well as an NHMRC postdoctoral fellowship (631712) (KW). In addition, we acknowledge the support of the NSW Cerebral Palsy Alliance and the Queensland Cerebral Palsy League who assisted in recruitment. CR Abbeduto L, 2004, AM J MENT RETARD, V109, P237, DOI 10.1352/0895-8017(2004)109<237:PWACIM>2.0.CO;2 Barlow J. 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PD MAY PY 2013 VL 39 IS 3 BP 366 EP 373 DI 10.1111/j.1365-2214.2012.01396.x PG 8 WC Psychology, Developmental; Pediatrics SC Psychology; Pediatrics GA 123WU UT WOS:000317423200006 PM 22676468 ER PT J AU Clarke, JN AF Clarke, Juanne N. TI Surplus suffering: the search for help when a child has mental-health issues SO CHILD & FAMILY SOCIAL WORK LA English DT Article DE children's mental health; intensive mothering; medicalization ID DEPRESSION; PARENTS; ADOLESCENTS; DISORDERS; RITALIN; STIGMA; AUTISM AB Social theorists have demonstrated the growth in dominance of two central discourses for understanding the ways that children's mental-health issues are understood today medicalization and intensive mothering. In this context, this paper reports on a qualitative interview-based study of 16 mothers whose children had received a diagnosis with one or more mental-health or developmental issues such as Tourette's, bipolar, anxiety, depression, autism or attention deficit hyperactivity disorder. It is based on the retrospective accounts of mothers given during interviews, from the time when they noticed what they thought to be unusual behaviours and decided to try to normalize and accommodate to their children's behaviours and then to the various steps they took to seek help. The paper begins with a description of the sorts of problems that mothers noticed. It then moves to the strategies mothers then took to cope, manage and socialize their children. When these failed, mothers sought professional assistance with understanding, remediation and/or a diagnosis for the child(ren). Mothers described uncertainty, confusion and contradictions as they unremittingly sought help. This process may be called surplus suffering. The relevance of the theoretical issues is then reconsidered along with the substantive and practical consequences of the findings. C1 Wilfrid Laurier Univ, Dept Sociol, Waterloo, ON N2L 3C5, Canada. RP Clarke, JN (reprint author), Wilfrid Laurier Univ, Dept Sociol, 75 Univ Ave West, Waterloo, ON N2L 3C5, Canada. EM jclarke@wlu.ca CR Boyle M. 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Slaughter, Virginia Peterson, James Premack, David TI Children with autism can track others' beliefs in a competitive game SO DEVELOPMENTAL SCIENCE LA English DT Article ID MIND DEVELOPMENT; FALSE BELIEF; SPECTRUM; DEAFNESS; TASKS AB Theory of mind (ToM) development, assessed via litmus' false belief tests, is severely delayed in autism, but the standard testing procedure may underestimate these children's genuine understanding. To explore this, we developed a novel test involving competition to win a reward as the motive for tracking other players' beliefs (the Dot-Midge task'). Ninety-six children, including 23 with autism (mean age: 10.36years), 50 typically developing 4-year-olds (mean age: 4.40) and 23 typically developing 3-year-olds (mean age: 3.59) took a standard Sally-Ann' false belief test, the Dot-Midge task (which was closely matched to the Sally-Ann task procedure) and a norm-referenced verbal ability test. Results revealed that, of the children with autism, 74% passed the Dot-Midge task, yet only 13% passed the standard Sally-Ann procedure. A similar pattern of performance was observed in the older, but not the younger, typically developing control groups. This finding demonstrates that many children with autism who fail motivationally barren standard false belief tests can spontaneously use ToM to track their social partners' beliefs in the context of a competitive game. C1 [Peterson, Candida C.; Slaughter, Virginia; Peterson, James] Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. [Premack, David] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. RP Peterson, CC (reprint author), Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. EM candi@psy.uq.edu.au CR (APA) APA, 2000, DIAGN STAT MAN MENT Astingtons J. 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Sci. PD MAY PY 2013 VL 16 IS 3 BP 443 EP 450 DI 10.1111/desc.12040 PG 8 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 129TD UT WOS:000317864500009 PM 23587041 ER PT J AU Donahue, KL Lichtenstein, P Lundstrom, S Anckarsater, H Gumpert, CH Langstrom, N D'Onofrio, BM AF Donahue, Kelly L. Lichtenstein, Paul Lundstrom, Sebastian Anckarsater, Henrik Gumpert, Clara Hellner Langstrom, Niklas D'Onofrio, Brian M. TI Childhood Behavior Problems and Adolescent Sexual Risk Behavior: Familial Confounding in the Child and Adolescent Twin Study in Sweden (CATSS) SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Adolescence; Clustered data analysis; Confounding factors; Mental health; Sex education programs; Sexual behavior ID TELEPHONE INTERVIEW; CAUSAL INFERENCE; VIOLENT CRIME; AUTISM-TICS; A-TAC; INTERCOURSE; AGE; PERSPECTIVE; IMPACT; LEVEL AB Objective: Previous studies have found associations between childhood behavior problems and adolescent sexual risk behavior. Using a quasi-experimental approach, we examined the extent to which this association may be due to between-family differences (i.e., unmeasured familial confounds) not adequately explored in prior research. Methods: We used data from a longitudinal, population-based cohort of young twins in Sweden (first assessment: age 9 or 12 years; second assessment: age 15; n = 2,388). We explored the nature of the association between symptom scores for attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) at age 9 or 12 and the likelihood of having had sexual intercourse and number of sexual partners by age 15. Two-level mixed-effects models were used to estimate the effect of symptom score on each outcome after controlling for potential unmeasured familial confounds. Results: Higher ADHD, ODD, and CD scores were associated with significantly increased likelihood of sexual intercourse by age 15. Higher ADHD and ODD scores were also associated with increased number of sexual partners. After controlling for unmeasured familial confounds, however, behavior problems were no longer significantly associated with either outcome. Conclusion: The association between childhood behavior problems and sexual risk behaviors may be due to characteristics shared within families. Hence, prevention strategies aimed at reducing these behaviors might need to address broader risk factors that contribute to both behavior problems and a greater likelihood of sexual risk behavior. (C) 2013 Society for Adolescent Health and Medicine. All rights reserved. C1 [Donahue, Kelly L.; D'Onofrio, Brian M.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Lichtenstein, Paul; Langstrom, Niklas] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Lundstrom, Sebastian; Anckarsater, Henrik] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden. [Lundstrom, Sebastian; Langstrom, Niklas] Swedish Prison & Probat Serv, Res & Dev, Gothenburg, Sweden. [Gumpert, Clara Hellner] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. RP Donahue, KL (reprint author), Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. EM kldonahu@indiana.edu FU National Institute on Drug Abuse [F31 DA 029376]; National Institute of Child Health and Human Development [R01 HD 061384]; Swedish Council for Working Life and Social Research; Swedish Research Council, Systembolaget; National Board of Forensic Medicine, Riksbanken Tercentenary Foundation; Hedlund Foundation FX This research was supported by award number F31 DA 029376 from the National Institute on Drug Abuse, R01 HD 061384 from the National Institute of Child Health and Human Development, the Swedish Council for Working Life and Social Research, the Swedish Research Council, Systembolaget, the National Board of Forensic Medicine, Riksbanken Tercentenary Foundation, and the Hedlund Foundation. 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TI A Retrospective Study of Amitriptyline in Youth with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Amitriptyline; Autism Spectrum Disorders; Hyperactivity; Impulsivity ID PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT HYPERACTIVITY DISORDER; MENTAL-RETARDATION; DOUBLE-BLIND; BLOOD SEROTONIN; CHILDREN; ADOLESCENTS; PLACEBO; RISPERIDONE; BEHAVIOR AB We performed a retrospective chart review of 50 youths with Autism Spectrum Disorder (ASD), prescribed amitriptyline (AMI) for hyperactivity and impulsivity. Data was systematically extracted from 50 outpatient clinic charts, including AMI treatment duration, dose, trough levels and adverse events. Mean age was 9.4 years (4.6-17.9); 40 were males and 10 females. 30 % had failed atomoxetine and 40 % had failed a parts per thousand yen3 ADHD medications. Mean dose was 1.3 +/- A 0.6 mg/kg/day, mean trough level 114.1 +/- A 50.5 ng/ml, mean duration 3.4 years. Clinical Global Impressions Scale-Improvement (CGI-I) was a parts per thousand currency sign2 in 60 % of patients at the final visit, and in 82 % of patients for at least 50 % of follow-ups. Cautious use of low dose AMI shows promise for treatment-resistant youth with ASD accompanied by hyperactivity, impulsivity, aggression and self injury. C1 [Bhatti, Irfan] Univ Kansas, Med Ctr, Div Child & Adolescent Psychiat, Kansas City, KS 66103 USA. [Thome, Andrew] Univ Missouri, Sch Med M4, Kansas City, MO 64110 USA. [Smith, Patricia Oxler] Univ Kansas, Med Ctr, Sch Nursing, Kansas City, KS 66103 USA. [Yeh, Hung Wen] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA. [Gaffney, Gary R.] Univ Iowa, Med Ctr, Div Child & Adolescent Psychiat, Iowa City, IA USA. [Hellings, Jessica A.] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. RP Hellings, JA (reprint author), Ohio State Univ, Nisonger Ctr, 1581 Dodd Dr, Columbus, OH 43210 USA. 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Autism Dev. Disord. PD MAY PY 2013 VL 43 IS 5 BP 1017 EP 1027 DI 10.1007/s10803-012-1647-0 PG 11 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800002 PM 23135317 ER PT J AU Chiang, CH Wu, CC Hou, YM Chu, CL Liu, JH Soong, WT AF Chiang, Chung-Hsin Wu, Chin-Chin Hou, Yuh-Ming Chu, Ching-Lin Liu, Jiun-Horng Soong, Wei-Tsuen TI Development of T-STAT for Early Autism Screening SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Screening; Young children with Autism; Taiwan ID SPECTRUM DISORDERS; NONVERBAL-COMMUNICATION; MODIFIED CHECKLIST; 2-YEAR-OLDS STAT; YOUNG-CHILDREN; TODDLERS; INFANCY; DIAGNOSIS; IMITATION; SIGNS AB This study's purpose was to modify the Screening Tool for Autism in Two-Year-Olds (STAT) into a Taiwanese version called T-STAT. Study 1 included 15 children with Autism and 15 children with Developmental Delay (DD) or language impairment (LI) aged between 24 and 35 months. Study 2 had 77 young children with Autism, PDD-NOS, or DD/LI as a clinical-based validation sample. In Study 1, the signal detection procedure found that a cutoff score of 2 would yield high sensitivity and specificity in T-STAT. In Study 2, using a score of 2 as a cutoff, the agreement between T-STAT risk and ADOS classification was highly acceptable. Results were promising as a Level 2 screening tool for Autism for ages two to three. C1 [Chiang, Chung-Hsin] Natl Chengchi Univ, Dept Psychol, Taipei 11605, Taiwan. [Chiang, Chung-Hsin] Natl Chengchi Univ, Res Ctr Mind Brain & Learning, Taipei 11605, Taiwan. [Wu, Chin-Chin] Kaohsiung Med Univ, Dept Psychol, Kaohsiung, Taiwan. [Hou, Yuh-Ming; Liu, Jiun-Horng] Chia Yi Christian Hosp, Dept Psychiat, Chiayi, Taiwan. [Chu, Ching-Lin] Natl Chung Cheng Univ, Dept Psychol, Chiayi, Taiwan. [Liu, Jiun-Horng] Chi Mei Med Ctr, Dept Psychiat, Tainan, Taiwan. [Soong, Wei-Tsuen] St Josephs Hosp, Dept Psychiat, Yunlin, Taiwan. 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Autism Dev. Disord. PD MAY PY 2013 VL 43 IS 5 BP 1028 EP 1037 DI 10.1007/s10803-012-1643-4 PG 10 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800003 PM 22976373 ER PT J AU Kim, ES Berkovits, LD Bernier, EP Leyzberg, D Shic, F Paul, R Scassellati, B AF Kim, Elizabeth S. Berkovits, Lauren D. Bernier, Emily P. Leyzberg, Dan Shic, Frederick Paul, Rhea Scassellati, Brian TI Social Robots as Embedded Reinforcers of Social Behavior in Children with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Social robots; Assistive robots; Intervention; Embedded reinforcers ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; ASSISTIVE ROBOTICS; VIRTUAL-REALITY; FIELD TRIAL; COMMUNICATION; THERAPY; INTERVENTIONS; DEFICITS; SKILLS AB In this study we examined the social behaviors of 4- to 12-year-old children with autism spectrum disorders (ASD; N = 24) during three tradic interactions with an adult confederate and an interaction partner, where the interaction partner varied randomly among (1) another adult human, (2) a touchscreen computer game, and (3) a social dinosaur robot. Children spoke more in general, and directed more speech to the adult confederate, when the interaction partner was a robot, as compared to a human or computer game interaction partner. Children spoke as much to the robot as to the adult interaction partner. This study provides the largest demonstration of social human-robot interaction in children with autism to date. Our findings suggest that social robots may be developed into useful tools for social skills and communication therapies, specifically by embedding social interaction into intrinsic reinforcers and motivators. C1 [Kim, Elizabeth S.; Bernier, Emily P.; Leyzberg, Dan; Scassellati, Brian] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. [Kim, Elizabeth S.; Berkovits, Lauren D.; Shic, Frederick; Paul, Rhea] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. [Paul, Rhea] Sacred Heart Univ, Fairfield, CT USA. RP Kim, ES (reprint author), Yale Univ, Sch Med, Ctr Child Study, 40 Temple St Ste 7D, New Haven, CT 06510 USA. 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PD MAY PY 2013 VL 43 IS 5 BP 1038 EP 1049 DI 10.1007/s10803-012-1645-2 PG 12 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800004 PM 23111617 ER PT J AU Goods, KS Ishijima, E Chang, YC Kasari, C AF Goods, Kelly Stickles Ishijima, Eric Chang, Ya-Chih Kasari, Connie TI Preschool Based JASPER Intervention in Minimally Verbal Children with Autism: Pilot RCT SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Minimally verbal; Intervention ID JOINT ATTENTION; SPECTRUM DISORDER; PLAY; LANGUAGE; PREDICTORS; PATTERNS; TRIAL; AGE AB In this pilot study, we tested the effects of a novel intervention (JASPER, Joint Attention Symbolic Play Engagement and Regulation) on 3 to 5 year old, minimally verbal children with autism who were attending a non-public preschool. Participants were randomized to a control group (treatment as usual, 30 h of ABA-based therapy per week) or a treatment group (substitution of 30 min of JASPER treatment, twice weekly during their regular program). A baseline of 12 weeks in which no changes were noted in core deficits was followed by 12 weeks of intervention for children randomized to the JASPER treatment. Participants in the treatment group demonstrated greater play diversity on a standardized assessment. Effects also generalized to the classroom, where participants in the treatment group initiated more gestures and spent less time unengaged. These results provide further support that even brief, targeted interventions on joint attention and play can improve core deficits in minimally verbal children with ASD. C1 [Goods, Kelly Stickles] Univ Calif Los Angeles, Ctr Autism Res & Treatment, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Ishijima, Eric; Chang, Ya-Chih; Kasari, Connie] Univ Calif Los Angeles, Ctr Autism Res & Treatment, Semel Inst Neurosci & Human Behav, Div Psychol Studies Educ, Los Angeles, CA 90024 USA. RP Goods, KS (reprint author), Univ Calif Los Angeles, Ctr Autism Res & Treatment, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,Semel 67-464, Los Angeles, CA 90024 USA. 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Autism Dev. Disord. PD MAY PY 2013 VL 43 IS 5 BP 1050 EP 1056 DI 10.1007/s10803-012-1644-3 PG 7 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800005 PM 22965298 ER PT J AU Wang, L Mandell, DS Lawer, L Cidav, Z Leslie, DL AF Wang, Li Mandell, David S. Lawer, Lindsay Cidav, Zuleyha Leslie, Douglas L. TI Healthcare Service Use and Costs for Autism Spectrum Disorder: A Comparison Between Medicaid and Private Insurance SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Children; Healthcare costs; Service use; Medicaid; Private insurance ID ENROLLED CHILDREN; NATIONAL-SURVEY; NEEDS; EXPENDITURES; ACCESS; LIMITATIONS; DIAGNOSIS; COVERAGE; STATE AB Healthcare costs and service use for autism spectrum disorder (ASD) were compared between Medicaid and private insurance, using 2003 insurance claims data in 24 states. In terms of costs and service use per child with ASD, Medicaid had higher total healthcare costs ($22,653 vs. $5,254), higher ASD-specific costs ($7,438 vs. $928), higher psychotropic medication costs($1,468 vs. $875), more speech therapy visits (13.0 vs. 3.6 visits), more occupational/physical therapy visits (6.4 vs. 0.9 visits), and more behavior modification/social skills visits (3.8 vs. 1.1 visits) than private insurance (all p < 0.0001). In multivariate analysis, being enrolled in Medicaid had the largest effect on costs, after controlling for other variables. The findings emphasize the need for continued efforts to improve private insurance coverage of autism. C1 [Wang, Li; Leslie, Douglas L.] Penn State Univ, Coll Med, Dept Publ Hlth Sci, University Pk, PA 16802 USA. [Wang, Li] Penn State Coll Med Publ Hlth Sci, Hershey, PA 17033 USA. [Mandell, David S.] Univ Penn, Sch Med, Dept Psychiat & Pediat, University Pk, PA USA. [Lawer, Lindsay; Cidav, Zuleyha] Univ Penn, Sch Med, Dept Psychiat, Ctr Mental Hlth Policy & Serv Res, University Pk, PA USA. [Leslie, Douglas L.] Penn State Univ, Coll Med, Dept Psychiat, University Pk, PA 16802 USA. RP Wang, L (reprint author), Penn State Coll Med Publ Hlth Sci, A210 600 Centerview Dr,POB 855, Hershey, PA 17033 USA. 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Autism Dev. Disord. PD MAY PY 2013 VL 43 IS 5 BP 1057 EP 1064 DI 10.1007/s10803-012-1649-y PG 8 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800006 PM 22965299 ER PT J AU Sanderson, C Allen, ML AF Sanderson, Charlotte Allen, Melissa L. TI The Specificity of Inhibitory Impairments in Autism and Their Relation to ADHD-Type Symptoms SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Inhibition; ADHD; Executive function ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SPECTRUM DISORDER; EXECUTIVE FUNCTION; WORKING-MEMORY; INDIVIDUAL-DIFFERENCES; FRONTAL-LOBE; STROOP TASK; DEVELOPMENTAL DISORDERS; RESPONSE-INHIBITION AB Findings on inhibitory control in autism have been inconsistent. This is perhaps a reflection of the different tasks that have been used. Children with autism (CWA) and typically developing controls, matched for verbal and non-verbal mental age, completed three tasks of inhibition, each representing different inhibitory subcomponents: Go/No-Go (delay inhibition), Dog-Pig Stroop (conflict inhibition), and a Flanker task (resistance to distractor inhibition). Behavioural ratings of inattention and hyperactivity/impulsivity were also obtained, as a possible source of heterogeneity in inhibitory ability. CWA were only impaired on the conflict inhibition task, suggesting that inhibitory difficulty is not a core executive deficit in autism. Symptoms of inattention were related to conflict task performance, and thus may be an important predictor of inhibitory heterogeneity. C1 [Sanderson, Charlotte; Allen, Melissa L.] Univ Lancaster, Dept Psychol, Lancaster LA1 4YW, England. RP Sanderson, C (reprint author), UCL, Inst Child Hlth, Behav & Brain Sci Unit, 30 Guilford St, London WC1N 1EH, England. 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TI The Use of the Autism Diagnostic Interview-Revised with a Latino Population of Adolescents and Adults with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE ADI-R; Culture; Latino; Adolescents and adults; Autism ID SPECTRUM DISORDERS; REPETITIVE BEHAVIORS; CHILDREN; MOTHERS; ISSUES; CLASSIFICATION; PERSPECTIVES; SCHEDULE; SERVICES; SPANISH AB Research shows that Latinos are less likely to be diagnosed with autism than their non-Latino counterparts. One factor that may contribute to these differences is that autism diagnostic instruments have not been adapted for the Latino population. The present study compared scores from the Autism Diagnostic Interview-Revised for two groups: 48 Latino adolescents and adults with autism and a matched sample of 96 non-Latino Whites. There were no significant differences between the two groups in total impairments in social reciprocity or communication. 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PD MAY PY 2013 VL 43 IS 5 BP 1098 EP 1105 DI 10.1007/s10803-012-1652-3 PG 8 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800009 PM 22972501 ER PT J AU Lau, YC Hinkley, LBN Bukshpun, P Strominger, ZA Wakahiro, MLJ Baron-Cohen, S Allison, C Auyeung, B Jeremy, RJ Nagarajan, SS Sherr, EH Marco, EJ AF Lau, Yolanda C. Hinkley, Leighton B. N. Bukshpun, Polina Strominger, Zoe A. Wakahiro, Mari L. J. Baron-Cohen, Simon Allison, Carrie Auyeung, Bonnie Jeremy, Rita J. Nagarajan, Srikantan S. Sherr, Elliott H. Marco, Elysa J. TI Autism Traits in Individuals with Agenesis of the Corpus Callosum SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Agenesis of the corpus callosum; Autism spectrum disorders; Autism Spectrum Quotient; Functional connectivity; Magnetoencephalography; Superior temporal gyrus ID PERVASIVE DEVELOPMENTAL DISORDERS; SUPERIOR TEMPORAL GYRUS; WHITE-MATTER COMPROMISE; SPECTRUM QUOTIENT AQ; FRAGILE-X-SYNDROME; FUNCTIONAL CONNECTIVITY; SOCIAL COGNITION; CHILDREN; ADOLESCENTS; PREVALENCE AB Autism spectrum disorders (ASD) have numerous etiologies, including structural brain malformations such as agenesis of the corpus callosum (AgCC). We sought to directly measure the occurrence of autism traits in a cohort of individuals with AgCC and to investigate the neural underpinnings of this association. We screened a large AgCC cohort (n = 106) with the Autism Spectrum Quotient (AQ) and found that 45 % of children, 35 % of adolescents, and 18 % of adults exceeded the predetermined autism-screening cut-off. Interestingly, performance on the AQ's imagination domain was inversely correlated with magnetoencephalography measures of resting-state functional connectivity in the right superior temporal gyrus. Individuals with AgCC should be screened for ASD and disorders of the corpus callosum should be considered in autism diagnostic evaluations as well. C1 [Lau, Yolanda C.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Hinkley, Leighton B. N.; Nagarajan, Srikantan S.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Bukshpun, Polina; Wakahiro, Mari L. J.; Sherr, Elliott H.; Marco, Elysa J.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Strominger, Zoe A.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Baron-Cohen, Simon; Allison, Carrie; Auyeung, Bonnie] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England. [Jeremy, Rita J.] Univ Calif San Francisco, Pediat Clin Res Ctr, Clin & Translat Sci Inst, San Francisco, CA 94143 USA. RP Sherr, EH (reprint author), Univ Calif San Francisco, Dept Neurol, 350 Parnassus Ave,Ste 609,Box 0137, San Francisco, CA 94143 USA. 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The relationships between emotion recognition, visual scan-paths and symptoms of social anxiety, schizotypy and autism were also explored. Results indicated that, compared to both control groups, the FXS group displayed specific emotion recognition deficits for angry and neutral (but not happy or fearful) facial expressions. Despite these evident emotion recognition deficits, the visual scanning of emotional faces was found to be at developmentally appropriate levels in the FXS group. Significant relationships were also observed between visual scan-paths, emotion recognition performance and symptomology in the FXS group. C1 [Shaw, Tracey A.] Macquarie Univ, Dept Cognit Sci, Sydney, NSW 2109, Australia. [Shaw, Tracey A.; Porter, Melanie A.] Macquarie Univ, ARC Ctr Cognit & Its Disorders, Sydney, NSW 2109, Australia. [Porter, Melanie A.] Macquarie Univ, Dept Psychol, Sydney, NSW 2109, Australia. RP Shaw, TA (reprint author), Macquarie Univ, Dept Cognit Sci, Sydney, NSW 2109, Australia. 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Point-lights portrayed actors engaged or not in a social interaction. In study 1, TD children (4-10 years old; n = 36) grasped social intentions from body language, with a notable improvement around 7/8. In study 2, children with ASD (6-12 years old; n = 12) could categorize the point-light displays at above-chance levels, but performed less efficiently, especially for the social interaction displays, than TD children (matched to chronological and non-verbal mental age, 6-12 years old; n = 24). An action representation deficit is discussed in relation to a social representation deficit and it is suggested that these deficits might be linked to altered maturational process of the mirror system in ASD. C1 [Centelles, Laurie; Assaiante, Christine; Schmitz, Christina] Univ Aix Marseille 1, Equipe Dev & Pathol Act, Lab Neurosci Integrat & Adaptat, F-13331 Marseille 03, France. [Centelles, Laurie; Assaiante, Christine; Schmitz, Christina] CNRS, F-13331 Marseille 03, France. 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SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; ADHD; Social skills; Facial and vocal affect recognition; Pragmatic judgment; Parent and teacher report ID DEFICIT HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDER; DIAGNOSTIC OBSERVATION SCHEDULE; HIGH-FUNCTIONING ADULTS; FACIAL EXPRESSIONS; ASPERGERS-SYNDROME; EMOTION RECOGNITION; ADHD; PERCEPTION; COMMUNICATION AB The aim of this study was to compare social cognitive profiles of children and adolescents with Autism Spectrum Disorders (ASD) and ADHD. Participants diagnosed with an ASD (n = 137) were compared to participants with ADHD (n = 436) on tests of facial and vocal affect recognition, social judgment and problem-solving, and parent- and teacher-report of social functioning. Both groups performed significantly worse than the normative sample on all measures. 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PD MAY PY 2013 VL 43 IS 5 BP 1157 EP 1170 DI 10.1007/s10803-012-1657-y PG 14 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800014 PM 23015110 ER PT J AU Major, NE Peacock, G Ruben, W Thomas, J Weitzman, CC AF Major, Nili E. Peacock, Georgina Ruben, Wendy Thomas, Jana Weitzman, Carol C. TI Autism Training in Pediatric Residency: Evaluation of a Case-Based Curriculum SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Medical education; Residency; Curriculum ID SPECTRUM DISORDERS; PRIMARY-CARE; MEDICAL HOMES; CHILDREN; HEALTH AB Despite recent studies indicating the high prevalence of autism spectrum disorders (ASDs), there has been little focus on improving ASD education during pediatric residency training. The objective of this study was to evaluate a new curriculum developed in partnership with the Centers for Disease Control and Prevention and the Maternal and Child Health Bureau about ASDs. "Autism Case Training (ACT): A Developmental-Behavioral Pediatrics Curriculum" consists of 7 case-based teaching modules. Modules were facilitated by faculty at 26 pediatric residency programs and data were obtained on 114 residents. Pre- and post-test data revealed significant short-term improvements in residents' knowledge and self-assessed competence regarding ASDs. Findings suggest that the ACT curriculum is effective in enhancing training about ASDs in pediatric residency programs. C1 [Major, Nili E.; Weitzman, Carol C.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. [Peacock, Georgina] Ctr Dis Control & Prevent, Atlanta, GA USA. [Ruben, Wendy; Thomas, Jana] Porter Novelli, Atlanta, GA USA. RP Major, NE (reprint author), Yale Univ, Sch Med, Dept Pediat, 333 Cedar St,POB 208064, New Haven, CT 06520 USA. EM nili.major@yale.edu; carol.weitzman@yale.edu CR Allen SG, 2010, PEDIATRICS, V126, pS160, DOI 10.1542/peds.2010-1466K Aman MG, 2005, J CLIN PSYCHIAT, V66, P38 American Academy of Pediatrics, 2007, AUT CAR CHILDR AUT S Boreman CD, 2007, CLIN PEDIATR, V46, P135, DOI 10.1177/0009922806290456 Brachlow AE, 2007, ARCH PEDIAT ADOL MED, V161, P399, DOI 10.1001/archpedi.161.4.399 Carbone PS, 2010, J AUTISM DEV DISORD, V40, P317, DOI 10.1007/s10803-009-0874-5 Carbone PS, 2010, AM FAM PHYSICIAN, V81, P453 CDC, 2012, MMWR SURVEILL SUMM, V61, P1 Daniel K L, 2009, Public Health, V123 Suppl 1, pe11, DOI 10.1016/j.puhe.2009.06.002 Davis G, 2003, J EXTENSION, V41 Freed GL, 2009, PEDIATRICS, V123, pS38, DOI 10.1542/peds.2008-1578J Golnik A, 2009, PEDIATRICS, V123, P966, DOI 10.1542/peds.2008-1321 Heidgerken AD, 2005, J AUTISM DEV DISORD, V35, P323, DOI 10.1007/s10803-005-3298-x Johnson CP, 2007, PEDIATRICS, V120, P1183, DOI 10.1542/peds.2007-2361 Kogan MD, 2008, PEDIATRICS, V122, pE1149, DOI 10.1542/peds.2008-1057 Lam TCM, 2003, AM J EVAL, V24, P65, DOI 10.1177/109821400302400106 Liptak Gregory S, 2006, J Pediatr Health Care, V20, P245, DOI 10.1016/j.pedhc.2005.12.008 Myers SM, 2007, PEDIATRICS, V120, P1162, DOI 10.1542/peds.2007-2362 Rhoades Rachel A, 2007, BMC Pediatr, V7, P37, DOI 10.1186/1471-2431-7-37 Swiezy N, 2008, CHILD ADOL PSYCH CL, V17, P907, DOI 10.1016/j.chc.2008.06.001 Warren Z, 2009, J DEV BEHAV PEDIATR, V30, P442, DOI 10.1097/DBP.0b013e3181ba0e4e NR 21 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 MAY PY 2013 VL 43 IS 5 BP 1171 EP 1177 DI 10.1007/s10803-012-1662-1 PG 7 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800015 PM 23008057 ER PT J AU Sonie, S Kassai, B Pirat, E Bain, P Robinson, J Gomot, M Barthelemy, C Charvet, D Rochet, T Tatou, M Assouline, B Cabrol, S Chabane, N Arnaud, V Faure, P Manificat, S AF Sonie, Sandrine Kassai, Behrouz Pirat, Elodie Bain, Paul Robinson, Janine Gomot, Marie Barthelemy, Catherine Charvet, Dorothee Rochet, Thierry Tatou, Mohamed Assouline, Brigitte Cabrol, Stephane Chabane, Nadia Arnaud, Valerie Faure, Patricia Manificat, Sabine TI The French Version of the Autism-Spectrum Quotient in Adolescents: A Cross-Cultural Validation Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Adolescent; Asperger syndrome/diagnosis; Autism spectrum disorders/diagnosis; Cross-cultural comparison; France; Personality assessment ID CHILDRENS VERSION; AQ AB We assessed the accuracy of the French version of the Autism Spectrum Quotient (AQ) in adolescents with Asperger syndrome (AS) and high-functioning autism (HFA) compared to healthy controls and adolescents with psychiatric disorders (PDs). Three groups of adolescents, aged 11-18, were assessed: 116 with AS/HFA (93 with IQ a parts per thousand yen 85 and 20 with 70 a parts per thousand currency sign IQ < 85), 39 with other PDs, and 199 healthy controls. The AS/HFA group scored significantly higher than the healthy control and PD groups. A cut-off score of 26 was used to differentiate the autism group from healthy controls with 0.89 sensitivity and 0.98 specificity. Scores did not vary by age or sex. C1 [Sonie, Sandrine; Pirat, Elodie; Manificat, Sabine] Ctr Hosp Le Vinatier, Ctr Ressource Autisme Rhone Alpes, INSERM U1028, CNRS UMR 5292, F-69677 Bron, France. [Kassai, Behrouz; Pirat, Elodie] INSERM, CIC201, EPICIME, RIPPS, F-69000 Lyon, France. [Kassai, Behrouz; Pirat, Elodie] CHU Lyon, Serv Pharmacol Clin, F-69000 Lyon, France. [Kassai, Behrouz; Pirat, Elodie] Univ Lyon, UMR 5558, F-69000 Lyon, France. [Robinson, Janine] Cambridgeshire & Peterborough NHS Fdn Trust, CLASS, Cambridge, England. [Gomot, Marie; Barthelemy, Catherine] Univ Tours, Ctr Pedopsychiat, CHU Bretonneau, UMR INSERM 930, F-37044 Tours, France. [Charvet, Dorothee] Ctr Hosp St Jean Dieu, Unite Ulysse Adolescents, Lyon, France. [Rochet, Thierry; Tatou, Mohamed] Ctr Hosp Le Vinatier, Serv FLAVIGNY Hosp Adolescents, F-69677 Bron, France. [Assouline, Brigitte] Ctr Hosp Alpes Isere, Ctr Alpin Diagnost Precoce Autisme, St Egreve, France. [Cabrol, Stephane] Ctr Evaluat Savoyard Autisme, Chambery, France. [Chabane, Nadia] Hop Robert Debre, F-75019 Paris, France. [Arnaud, Valerie; Manificat, Sabine] Ctr Hosp St Jean Dieu, Lyon, France. [Faure, Patricia] Ctr Hosp St Jean Dieu, METEORE, Serv Biostat, Grp Francais Epidemiol Psychiat, Lyon, France. RP Sonie, S (reprint author), Ctr Hosp Le Vinatier, Ctr Ressource Autisme Rhone Alpes, INSERM U1028, CNRS UMR 5292, Bat 211,95 Blvd Pinel, F-69677 Bron, France. 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Autism Dev. Disord. PD MAY PY 2013 VL 43 IS 5 BP 1178 EP 1183 DI 10.1007/s10803-012-1663-0 PG 6 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800016 PM 23015111 ER PT J AU Barton, ML Robins, DL Jashar, D Brennan, L Fein, D AF Barton, Marianne L. Robins, Diana L. Jashar, Dasal Brennan, Laura Fein, Deborah TI Sensitivity and Specificity of Proposed DSM-5 Criteria for Autism Spectrum Disorder in Toddlers SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; DSM-5; Toddlers; Diagnosis ID PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC INTERVIEW; YOUNG-CHILDREN; FOLLOW-UP; IV; INDIVIDUALS AB Autism spectrum disorder (ASD) diagnosis is based on behavioral presentation; changes in conceptual models or defining behaviors may significantly impact diagnosis and uptake of ASD-specific interventions. The literature examining impact of DSM-5 criteria is equivocal. Toddlers may be especially vulnerable to the stringent requirements of impairment in all three social-communication symptoms and two restricted/repetitive symptoms. Receiver operating characteristic (ROC) curves identified optimal cutoffs for sums of ADOS and ADI-R criteria mapped to each criterion for 422 toddlers. The optimal modification of DSM-5 criteria (sensitivity = 0.93, specificity = 0.74) required meeting the ROC-determined cutoffs for 2/3 Domain A criteria and 1 point for 1/4 Domain B criteria. This modification will help insure that ASD is identified accurately in young children, facilitating ASD-specific early intervention. C1 [Barton, Marianne L.; Jashar, Dasal; Brennan, Laura; Fein, Deborah] Univ Connecticut, Dept Psychol, Unit 1020, Storrs, CT USA. [Robins, Diana L.] Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. RP Robins, DL (reprint author), Georgia State Univ, Dept Psychol, POB 5010, Atlanta, GA 30302 USA. 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Autism Dev. Disord. PD MAY PY 2013 VL 43 IS 5 BP 1184 EP 1195 DI 10.1007/s10803-013-1817-8 PG 12 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800017 PM 23543293 ER PT J AU Bilder, D Botts, EL Smith, KR Pimentel, R Farley, M Viskochil, J McMahon, WM Block, H Ritvo, E Ritvo, RA Coon, H AF Bilder, Deborah Botts, Elizabeth L. Smith, Ken R. Pimentel, Richard Farley, Megan Viskochil, Joseph McMahon, William M. Block, Heidi Ritvo, Edward Ritvo, Riva-Ariella Coon, Hilary TI Excess Mortality and Causes of Death in Autism Spectrum Disorders: A Follow up of the 1980s Utah/UCLA Autism Epidemiologic Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Mortality; Causes of death; Epilepsy; Intellectual disability ID EPILEPSY; INDIVIDUALS; CHILDREN; SURVEILLANCE; PREVALENCE; UPDATE AB This study's purpose was to investigate mortality among individuals with autism spectrum disorders (ASD) ascertained during a 1980s statewide autism prevalence study (n = 305) in relation to controls. Twenty-nine of these individuals (9.5 %) died by the time of follow up, representing a hazard rate ratio of 9.9 (95 % CI 5.7-17.2) in relation to population controls. Death certificates identified respiratory, cardiac, and epileptic events as the most common causes of death. The elevated mortality risk associated with ASD in the study cohort appeared related to the presence of comorbid medical conditions and intellectual disability rather than ASD itself suggesting the importance of coordinated medical care for this high risk sub-population of individuals with ASD. C1 [Bilder, Deborah; Botts, Elizabeth L.; Farley, Megan; McMahon, William M.; Coon, Hilary] Univ Utah, Dept Psychiat, Salt Lake City, UT 84108 USA. [Bilder, Deborah] Neurobehav HOME Program, Salt Lake City, UT 84108 USA. [Smith, Ken R.; Pimentel, Richard] Univ Utah, Utah Populat Database, Utah Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Viskochil, Joseph] Univ Utah, Dept Educ Psychol, Salt Lake City, UT 84108 USA. [McMahon, William M.; Coon, Hilary] Univ Utah, Inst Brain, Salt Lake City, UT 84108 USA. [Block, Heidi] Univ Utah, Salt Lake City, UT 84108 USA. [Ritvo, Edward] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Ritvo, Riva-Ariella] Yale Univ, Sch Med, Los Angeles, CA 90049 USA. RP Bilder, D (reprint author), Neurobehav HOME Program, 650 Komas Dr,Suite 200, Salt Lake City, UT 84108 USA. 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Autism Dev. Disord. PD MAY PY 2013 VL 43 IS 5 BP 1196 EP 1204 DI 10.1007/s10803-012-1664-z PG 9 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800018 PM 23008058 ER PT J AU Pugliese, CE White, BA White, SW Ollendick, TH AF Pugliese, Cara E. White, Bradley A. White, Susan W. Ollendick, Thomas H. TI Social Anxiety Predicts Aggression in Children with ASD: Clinical Comparisons with Socially Anxious and Oppositional Youth SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Asperger's; Aggression; Child; Social anxiety ID PERVASIVE DEVELOPMENTAL DISORDERS; HIGH-FUNCTIONING CHILDREN; AUTISM SPECTRUM DISORDER; ASPERGER-SYNDROME; DSM-IV; INTERVIEW SCHEDULE; PARENT VERSIONS; ADOLESCENTS; RELIABILITY; SYMPTOMS AB The present study examined the degree to which social anxiety predicts aggression in children with high functioning autism spectrum disorders (HFASD, n = 20) compared to children with Social Anxiety Disorder (SAD, n = 20) or with Oppositional Defiant Disorder or Conduct Disorder (ODD/CD, n = 20). As predicted, children with HFASD reported levels of humiliation/rejection fears commensurate with children with SAD and exhibited aggression at levels commensurate with ODD/CD, and a curvilinear relationship between social fears and aggression was found in the HFASD group only. Results indicate the possibility of an optimal level of social-evaluative fears that is unique for children with HFASD; too little social fear or too much may contribute to problems with aggression. C1 [Pugliese, Cara E.; White, Bradley A.; White, Susan W.; Ollendick, Thomas H.] Virginia Polytech State Inst & Univ, Dept Psychol, Blacksburg, VA 24060 USA. RP Pugliese, CE (reprint author), Virginia Polytech State Inst & Univ, Dept Psychol, 109 Williams Hall, Blacksburg, VA 24060 USA. 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PD MAY PY 2013 VL 43 IS 5 BP 1205 EP 1213 DI 10.1007/s10803-012-1666-x PG 9 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800019 PM 23008059 ER PT J AU Al-Farsi, YM Waly, MI Al-Sharbati, MM Al-Shafaee, M Al-Farsi, O Al-Fahdi, S Ouhtit, A Al-Khaduri, M Al-Adawi, S AF Al-Farsi, Yahya M. Waly, Mostafa I. Al-Sharbati, Marwan M. Al-Shafaee, Mohamed Al-Farsi, Omar Al-Fahdi, Samiya Ouhtit, Allal Al-Khaduri, Maha Al-Adawi, Samir TI Variation in Socio-Economic Burden for Caring of Children with Autism Spectrum Disorder in Oman: Caregiver Perspectives SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Socio-economic burden; Autism; ASD; Caregiver; Oman ID HEALTH-CARE UTILIZATION; PARENTS; EXPENDITURES; DISABILITIES; SERVICES; PROFILE AB A cross-sectional study was conducted to investigate whether caregiver's variations in socioeconomic status (SES) has direct bearing on challenges of nurturing children with autism spectrum disorder (ASD) in Oman. A cadre of caregivers (n = 150) from two types of SES (low-income and middle-high income) were compared based on four domains: (1) accessing and perception of remedial services, (2) utilization and perception of psychiatric services, (3) constraints for being a caregiver of children with ASD and (4) financial expenses of taking care of children with ASD. There is little indication that any particular SES fare well on these domains. Factors to mitigate such predicaments are therefore imperative in order to improve quality of life for caregivers among children with ASD. C1 [Al-Farsi, Yahya M.; Al-Shafaee, Mohamed; Al-Farsi, Omar; Al-Fahdi, Samiya] Sultan Qaboos Univ, Dept Family Med & Publ Hlth, Coll Med & Hlth Sci, Al Khoud 123, Oman. [Waly, Mostafa I.] Sultan Qaboos Univ, Dept Nutr & Food Sci, Coll Agr & Marine Sci, Muscat, Oman. [Waly, Mostafa I.] Univ Alexandria, Dept Nutr, High Inst Publ Hlth, Alexandria, Egypt. [Al-Sharbati, Marwan M.; Al-Adawi, Samir] Sultan Qaboos Univ, Dept Behav Med, Coll Med & Hlth Sci, Muscat, Oman. [Ouhtit, Allal] Sultan Qaboos Univ, Dept Genet, Coll Med & Hlth Sci, Muscat, Oman. [Al-Khaduri, Maha] Sultan Qaboos Univ, Dept Obstet & Gynecol, Coll Med & Hlth Sci, Muscat, Oman. RP Al-Farsi, YM (reprint author), Sultan Qaboos Univ, Dept Family Med & Publ Hlth, Coll Med & Hlth Sci, POB 35, Al Khoud 123, Oman. 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PD MAY PY 2013 VL 43 IS 5 BP 1214 EP 1221 DI 10.1007/s10803-012-1667-9 PG 8 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800020 PM 23001768 ER PT J AU Sachse, M Schlitt, S Hainz, D Ciaramidaro, A Schirman, S Walter, H Poustka, F Bolte, S Freitag, CM AF Sachse, Michael Schlitt, Sabine Hainz, Daniela Ciaramidaro, Angela Schirman, Shella Walter, Henrik Poustka, Fritz Bolte, Sven Freitag, Christine M. TI Executive and Visuo-motor Function in Adolescents and Adults with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Executive functions; Reaction time; Movement time; Information processing; CANTAB ID SPATIAL WORKING-MEMORY; OBSESSIVE-COMPULSIVE DISORDER; CARD SORTING TEST; ASPERGER-SYNDROME; COGNITIVE INFLEXIBILITY; INHIBITORY CONTROL; CENTRAL COHERENCE; CHILDREN; PERFORMANCE; MOVEMENT AB This study broadly examines executive (EF) and visuo-motor function in 30 adolescent and adult individuals with high-functioning autism spectrum disorder (ASD) in comparison to 28 controls matched for age, gender, and IQ. ASD individuals showed impaired spatial working memory, whereas planning, cognitive flexibility, and inhibition were spared. Pure movement execution during visuo-motor information processing also was intact. In contrast, execution time of reading, naming, and of visuo-motor information processing tasks including a choice component was increased in the ASD group. Results of this study are in line with previous studies reporting only minimal EF difficulties in older individuals with ASD when assessed by computerized tasks. The finding of impaired visuo-motor information processing should be accounted for in further neuropsychological studies in ASD. C1 [Sachse, Michael; Schlitt, Sabine; Hainz, Daniela; Ciaramidaro, Angela; Schirman, Shella; Poustka, Fritz; Bolte, Sven; Freitag, Christine M.] Univ Frankfurt Main, Dept Child & Adolescent Psychiat, D-60528 Frankfurt, Germany. [Walter, Henrik] Univ Frankfurt Main, Dept Psychiat Psychosomat & Psychotherapy, D-60528 Frankfurt, Germany. RP Freitag, CM (reprint author), Univ Frankfurt Main, Dept Child & Adolescent Psychiat, Deutschordenstr 50, D-60528 Frankfurt, Germany. 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Autism Dev. Disord. PD MAY PY 2013 VL 43 IS 5 BP 1222 EP 1235 DI 10.1007/s10803-012-1668-8 PG 14 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800021 PM 23011252 ER PT J AU Mazefsky, CA McPartland, JC Gastgeb, HZ Minshew, NJ AF Mazefsky, C. A. McPartland, J. C. Gastgeb, H. Z. Minshew, N. J. TI Brief Report: Comparability of DSM-IV and DSM-5 ASD Research Samples SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Diagnosis; Assessment; DSM-5; Autism Diagnostic Observation Schedule (ADOS); Autism Diagnostic Interview (ADI) ID AUTISM SPECTRUM DISORDERS; DIAGNOSTIC INTERVIEW; CRITERIA; CHILDREN AB Diagnostic and Statistical Manual (DSM-5) criteria for ASD have been criticized for being too restrictive, especially for more cognitively-able individuals. It is unclear, however, if high-functioning individuals deemed eligible for research via standardized diagnostic assessments would meet DSM-5 criteria. This study investigated the impact of DSM-5 on the diagnostic status of 498 high-functioning participants with ASD research diagnoses. The percent of participants satisfying all DSM-5-requirements varied significantly with reliance on data from the Autism Diagnostic Observation Schedule (ADOS; 33 %) versus Autism Diagnostic Interview-Revised (ADI-R; 83 %), highlighting the impact of diagnostic methodology on ability to document DSM-5 symptoms. Utilizing combined ADOS/ADI-R data, 93 % of participants met DSM-5 criteria, which suggests likely continuity between DSM-IV and DSM-5 research samples characterized with these instruments in combination. C1 [Mazefsky, C. A.; Gastgeb, H. Z.; Minshew, N. J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [McPartland, J. C.] Yale Univ, Yale Child Study Ctr, New Haven, CT USA. [Minshew, N. J.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. RP Mazefsky, CA (reprint author), Univ Pittsburgh, Dept Psychiat, Webster Hall,Suite 300,3811 OHara St, Pittsburgh, PA 15213 USA. 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Autism Dev. Disord. PD MAY PY 2013 VL 43 IS 5 BP 1236 EP 1242 DI 10.1007/s10803-012-1665-y PG 7 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800022 PM 23011251 ER PT J AU Douglas, JF Sanders, KB Benneyworth, MH Smith, JL DeJean, VM McGrew, SG Veenstra-VanderWeele, J AF Douglas, Jessica F. Sanders, Kevin B. Benneyworth, M. Hannah Smith, Jessica L. DeJean, Virginia M. McGrew, Susan G. Veenstra-VanderWeele, Jeremy TI Brief Report: Retrospective Case Series of Oxcarbazepine for Irritability/Agitation Symptoms in Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Antiepileptic; Anticonvulsant; Mood stabilizer; Sodium channel; Pervasive developmental disorder ID PERVASIVE DEVELOPMENTAL DISORDERS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; PSYCHOACTIVE MEDICINES; PSYCHIATRIC-DISORDERS; ANTIEPILEPTIC DRUGS; BIPOLAR DISORDER; CHILDREN; ADOLESCENTS; CARBAMAZEPINE AB We examined response to oxcarbazepine prescribed for irritability/agitation symptoms in a retrospective case series of 30 patients with Autism Spectrum Disorder (ASD). The average patient was 12.0 years old (range 5-21) and taking two other psychotropic medications (range 0-4). Fourteen patients (47 %) had a clinical global impression of improvement score of 'much improved' during treatment. Ten patients (33 %) showed an improvement on their clinical global impression of severity score. Seven patients (23 %) had a clinically significant adverse event or side effect leading to oxcarbazepine discontinuation. Without a placebo group, it is not possible to evaluate whether oxcarbazepine provides benefit for irritability/agitation symptoms in ASD. The high rate of adverse events suggests its use should be accompanied by caution. C1 [Douglas, Jessica F.; Sanders, Kevin B.; Benneyworth, M. Hannah; Smith, Jessica L.; DeJean, Virginia M.; Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN 37232 USA. [Sanders, Kevin B.; McGrew, Susan G.; Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. RP Veenstra-VanderWeele, J (reprint author), 7158 MRB 3,465 21st Ave S, Nashville, TN 37232 USA. 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Autism Dev. Disord. PD MAY PY 2013 VL 43 IS 5 BP 1243 EP 1247 DI 10.1007/s10803-012-1661-2 PG 5 WC Psychology, Developmental SC Psychology GA 122YX UT WOS:000317355800023 PM 22976374 ER PT J AU Simonoff, E Taylor, E Baird, G Bernard, S Chadwick, O Liang, H Whitwell, S Riemer, K Sharma, K Sharma, SP Wood, N Kelly, J Golaszewski, A Kennedy, J Rodney, L West, N Walwyn, R Jichi, F AF Simonoff, Emily Taylor, Eric Baird, Gillian Bernard, Sarah Chadwick, Oliver Liang, Holan Whitwell, Susannah Riemer, Kirsten Sharma, Kishan Sharma, Santvana Pandey Wood, Nicky Kelly, Joanna Golaszewski, Ania Kennedy, Juliet Rodney, Lydia West, Nicole Walwyn, Rebecca Jichi, Fatima TI Randomized controlled double-blind trial of optimal dose methylphenidate in children and adolescents with severe attention deficit hyperactivity disorder and intellectual disability SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Attention deficit disorder with hyperactivity; Randomized controlled trial; autism; mental retardation; intellectual disability; methylphenidate; stimulants ID MENTAL-RETARDATION; DEFICIT/HYPERACTIVITY DISORDER; ADHD; SYMPTOMS; EFFICACY AB Background: Attention deficit hyperactivity disorder is increased in children with intellectual disability. Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4weeks. Method: One hundred and twenty two drug-free children aged 715 with hyperkinetic disorder and IQ 3069 were recruited to a double-blind, placebo-controlled trial that randomized participants using minimization by probability, stratified by referral source and IQ level in a one to one ratio. Methylphenidate was compared with placebo. Dose titration comprised at least 1week each of low (0.5mg/kg/day), medium (1.0mg/kg/day) and high dose (1.5mg/kg/day). Parent and teacher Attention deficit hyperactivity disorder (ADHD) index of the Conners Rating Scale-Short Version at 16weeks provided the primary outcome measures. Clinical response was determined with the Clinical Global Impressions scale (CGI-I). Adverse effects were evaluated by a parent-rated questionnaire, weight, pulse and blood pressure. Analyses were by intention to treat. Trial registration: ISRCTN 68384912. Results: Methylphenidate was superior to placebo with effect sizes of 0.39 [95% confidence intervals (CIs) 0.09, 0.70] and 0.52 (95% CIs 0.23, 0.82) for the parent and teacher Conners ADHD index. Four (7%) children on placebo versus 24 (40%) of those on methylphenidate were judged improved or much improved on the CGI. IQ and autistic symptoms did not affect treatment efficacy. Active medication was associated with sleep difficulty, loss of appetite and weight loss but there were no significant differences in pulse or blood pressure. Conclusions: Optimal dosing of methylphenidate is practical and effective in some children with hyperkinetic disorder and intellectual disability. Adverse effects typical of methylphenidate were seen and medication use may require close monitoring in this vulnerable group. C1 [Simonoff, Emily; Taylor, Eric; Chadwick, Oliver; Liang, Holan; Whitwell, Susannah; Riemer, Kirsten; Sharma, Kishan; Sharma, Santvana Pandey; Wood, Nicky; Golaszewski, Ania; Kennedy, Juliet; Rodney, Lydia; West, Nicole] Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London SE5 8AF, England. [Baird, Gillian] Guys & St Thomas NHS Fdn Trust, London, England. [Bernard, Sarah] South London & Maudsley NHS Fdn Trust, London, England. [Kelly, Joanna; Walwyn, Rebecca; Jichi, Fatima] Kings Coll London, Inst Psychiat, Dept Biostat, London SE5 8AF, England. RP Simonoff, E (reprint author), Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, DeCrespigny Pk, London SE5 8AF, England. EM emily.simonoff@kcl.ac.uk FU Health Foundation [1978]; King's College FX The work was funded by The Health Foundation, formerly the PPP Foundation, reference number 1978, and sponsored by King's College. The independent Trial Steering Committee comprised Professor Patricia Howlin (Chair 2004-2005), Professor Chris Oliver (Chair 2005-2008), Professor Jeremy Turk, Dr Frank Besag (2006-2008), Mr Brian McGinnis (representing carer views 2004-2006), Dr Michael Fitzpatrick (representing carer views 2006-2008) and Dr Gill Dale (representing the Sponsor). The independent Data Monitoring Committee comprised Dr Ruth Pickering (Chair), Dr David Coghill and Dr Claire Sturge. The Mental Health and Neurosciences Clinical Trials Unit, King's College London undertook randomization, database development and assisted with project management. Clare Rutterford contributed to the development of the statistical analysis plan, data oversight and initial analyses. Professor Andrew Pickles supervised the statistical analyses for this paper. We thank all the doctors who referred participants to the trial and the participants and their families. None of the authors of the manuscript has any conflict of interest, including specific financial interests, relationships or affiliations relevant to the subject of the manuscript. CR AMAN MG, 1993, J AM ACAD CHILD PSY, V32, P851, DOI 10.1097/00004583-199307000-00022 Aman MG, 2003, J CHILD ADOL PSYCHOP, V13, P29, DOI 10.1089/104454603321666171 ANGOLD A, 1995, PSYCHOL MED, V25, P739 Barkley R., 1992, PEDIATRICS, V86, P184 Campbell M., 1978, AUTISM REAPPRAISAL C, P337 Carlin JB, 2008, STATA J, V8, P49 Conners C. K., 1989, CONNERS RATING SCALE Corners C. 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TI Early diagnosis of autism spectrum disorder: stability and change in clinical diagnosis and symptom presentation SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Autism spectrum disorder; developmental delay; diagnosis; development; assessment ID OBSERVATION SCHEDULE; 2ND YEAR; CHILDREN; AGE; LIFE AB Background: Although a diagnosis of autism spectrum disorder (ASD) appears to be stable in children as young as age three, few studies have explored stability of a diagnosis in younger children. Predictive value of diagnostic tools for toddlers and patterns of symptom change are important considerations for clinicians making early diagnoses. Most findings come from high-risk samples, but reports on children screened in community settings are also needed. Methods: Stability of diagnosis and Autism Diagnostic Observation Schedule Toddler Module (ADOS-T) classifications and scores was examined across two time points in a sample of 82 children identified through the FIRST WORDS (R) Project. Children received two comprehensive diagnostic evaluations at average ages of 19.39 (SD=2.12) and 36.89 (SD=3.85)months. Results: Stability was 100% when confirming and ruling out a diagnosis of ASD based on a comprehensive diagnostic evaluation that included clinic and home observations, although diagnosis was initially deferred for 17% of the sample. Receiver Operating Characteristic curves revealed excellent sensitivity and acceptable specificity for the ADOS-T compared to concurrent diagnosis. Logistic regressions indicated good predictive value of initial ADOS-T scores for follow-up diagnosis. Finally, both ASD and Non-ASD children demonstrated a decrease in Social Affect scores (i.e., improvement), whereas children with ASD demonstrated an increase in Restricted and Repetitive Behavior scores (i.e., worsening), changes that were accounted for by nonverbal developmental level in mixed model analyses. Conclusions: Short-term stability was documented for children diagnosed at 19months on average, although a minority of children initially showed unclear diagnostic presentations. Findings highlight utility of the ADOS-T in making early diagnoses and predicting follow-up diagnoses. Children with ASD demonstrated improvement in social communication behaviors and unfolding of repetitive behaviors, suggesting that certain early patterns of change in symptoms may be characteristic of ASD. C1 [Guthrie, Whitney; Swineford, Lauren B.; Nottke, Charly; Wetherby, Amy M.] Florida State Univ, Autism Inst, Coll Med, Tallahassee, FL 32303 USA. RP Guthrie, W (reprint author), Florida State Univ, Autism Inst, 1940 North Monroe St,Suite 72, Tallahassee, FL 32303 USA. EM whitney.guth-rie@med.fsu.edu FU NICHD [R01HD065272]; NIDCD [R01DC007462]; CDC [U01DD000304] FX This research was supported in part by NICHD R01HD065272, NIDCD R01DC007462, and CDC U01DD000304 awarded to Amy M. Wetherby. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD, NIDCD, the NIH, or the CDC. 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M., 2009, INT M AUT RES IMFAR Wetherby AM, 2002, COMMUNICATION SYMBOL Wetherby AM, 2004, J AUTISM DEV DISORD, V34, P473, DOI 10.1007/s10803-004-2544-y Woolfenden S, 2012, RES AUTISM SPECT DIS, V6, P345, DOI 10.1016/j.rasd.2011.06.008 Yoder P, 2009, J AUTISM DEV DISORD, V39, P1381, DOI 10.1007/s10803-009-0753-0 NR 33 TC 11 Z9 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD MAY PY 2013 VL 54 IS 5 BP 582 EP 590 DI 10.1111/jcpp.12008 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 127EN UT WOS:000317679500011 PM 23078094 ER PT J AU Richman, DM Barnard-Brak, L Bosch, A Thompson, S Grubb, L Abby, L AF Richman, D. M. Barnard-Brak, L. Bosch, A. Thompson, S. Grubb, L. Abby, L. TI Predictors of self-injurious behaviour exhibited by individuals with autism spectrum disorder SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE autism spectrum disorder; impulsivity; intellectual and developmental disabilities; negative affect; self-injurious behaviour; stereotypy ID INTELLECTUAL DISABILITIES; CHALLENGING BEHAVIORS; YOUNG-CHILDREN; REPETITIVE BEHAVIOR; FUNCTIONAL-ANALYSIS; EXECUTIVE FUNCTIONS; MENTAL-RETARDATION; RISK MARKERS; MISSING DATA; PREVALENCE AB Background Presence of an autism spectrum disorder is a risk factor for development of self-injurious behaviour (SIB) exhibited by individuals with developmental disorders. The most salient SIB risk factors historically studied within developmental disorders are level of intellectual disability, communication deficits and presence of specific genetic disorders. Recent SIB research has expanded the search for risk factors to include less commonly studied variables for people with developmental disorders: negative affect, hyperactivity and impulsivity. Method A heterogeneous sample of 617 individuals with autism spectrum disorder diagnoses was derived from the National Database of Autism Research. Latent constructs were estimated from items of the community version of the Aberrant Behaviour Checklist. Structural equation modelling was used to assess whether impulsivity, hyperactivity, negative affect, severity of stereotypy, intellectual functioning or severity of autism symptoms predicted severity of SIB. Results Impulsivity (=0.46), followed by intellectual functioning (=0.39), and stereotypy (=0.23) were the variables most highly predictive of increased SIB; impulsivity and stereotypy remained significant predictors of SIB after severity of autism symptoms and intelligence quotient (IQ) were controlled for. Conclusions High levels of impulsivity and stereotypy were significant predictors of SIB in a large and diverse sample of people with confirmed autism diagnoses. Future research is needed on the effects of reducing impulsivity and stereotypy on the outcomes of treatment, early intervention and attempts to prevent the development of SIB. C1 [Richman, D. M.; Barnard-Brak, L.; Bosch, A.; Thompson, S.; Grubb, L.; Abby, L.] Texas Tech Univ, Burkhart Ctr Autism Educ & Res, Lubbock, TX 79409 USA. RP Richman, DM (reprint author), Texas Tech Univ, Burkhart Ctr Autism Educ & Res, 3008 18th St,Room 113,TTU Mailstop 1071, Lubbock, TX 79409 USA. 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TI Using administrative health data to identify individuals with intellectual and developmental disabilities: a comparison of algorithms SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE administrative data; cohort algorithms; intellectual disability; standardised differences; surveillance ID AUTISM SPECTRUM DISORDERS; MENTAL-RETARDATION; RISK-FACTORS; PREVALENCE; ONTARIO; EPIDEMIOLOGY; SURVEILLANCE; SERVICES; CHILDREN; ADULTS AB Background Individuals with intellectual and developmental disabilities (IDD) experience high rates of physical and mental health problems; yet their health care is often inadequate. Information about their characteristics and health services needs is critical for planning efficient and equitable services. A logical source of such information is administrative health data; however, it can be difficult to identify cases with IDD in these data. The purpose of this study is to evaluate three algorithms for case finding of IDD in health administrative data. Methods The three algorithms were created following existing approaches in the literature which ranged between maximising sensitivity versus balancing sensitivity and specificity. The algorithm required only one IDD service contact across all available data and time periods, the algorithm added the restriction of a minimum of two physician visits while the algorithm added a further restriction that the time period be limited to 2006 onward. The resulting three cohorts were compared according to socio-demographic and clinical characteristics. Comparisons on different subgroups for a hypothetical population of 50000 individuals with IDD were also carried out: this information may be relevant for planning specialised treatment or support programmes. Results The prevalence rates of IDD per 100 were 0.80, 0.52 and 0.18 for the , and algorithms, respectively. Except for percentage with psychiatric co-morbidity', the three cohorts had similar characteristics (standardised differences<0.1). More stringent thresholds increased the percentage of psychiatric co-morbidity and decreased the percentages of women and urban residents in the identified cohorts (standardised differences=0.12 to 0.46). More concretely, using the algorithm to indirectly estimate the number of individuals with IDD, a practice not uncommon in planning and policy development, classified nearly 7000 more individuals with psychiatric co-morbidities than using the algorithm. Conclusions The prevalence rate produced by the algorithm most closely approximated the reported literature rate suggesting the value of imposing a two-physician visit minimum but not restricting the time period covered. While the statistical differences among the algorithms were generally minor, differences in the numbers of individuals in specific population subgroups may be important particularly if they have specific service needs. Health administrative data can be useful for broad-based service planning for individuals with IDD and for population level comparisons around their access and quality of care. C1 [Lin, E.] Ctr Addict & Mental Hlth, Prov Syst Support Program, Toronto, ON M5S 2S1, Canada. [Balogh, R.] Univ Ontario, Inst Technol, Oshawa, ON, Canada. [Cobigo, V.] Univ E Anglia, Sch Nursing Sci, Norwich NR4 7TJ, Norfolk, England. [Ouellette-Kuntz, H.] Queens Univ, Kingston, ON, Canada. [Wilton, A. S.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Lunsky, Y.] Ctr Addict & Mental Hlth, Dual Diag Program, Toronto, ON M5S 2S1, Canada. RP Lin, E (reprint author), Ctr Addict & Mental Hlth, Prov Syst Support Program, Room T314,33 Russell St, Toronto, ON M5S 2S1, Canada. 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PD MAY PY 2013 VL 57 IS 5 BP 462 EP 477 DI 10.1111/jir.12002 PG 16 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 123AY UT WOS:000317361600007 PM 23116328 ER PT J AU Grant, R Nozyce, M AF Grant, Roy Nozyce, Molly TI Proposed Changes to the American Psychiatric Association Diagnostic Criteria for Autism Spectrum Disorder: Implications for Young Children and Their Families SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Autism; Asperger's Disorder; Pervasive Developmental Disorder; Early childhood; Psychiatric diagnosis ID PERVASIVE DEVELOPMENTAL DISORDERS; EARLY INTERVENTION; ASPERGER-SYNDROME; OUTCOMES; DSM-5; IDENTIFICATION; STABILITY; PROGRAMS; TODDLERS; BEHAVIOR AB The American Psychiatric Association has revised the diagnostic criteria for their DSM-5 manual. Important changes have been made to the diagnosis of the current (DSM-IV) category of Pervasive Developmental Disorders. This category includes Autistic Disorder (autism), Asperger's Disorder, and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS). The DSM-5 deletes Asperger's Disorder and PDD-NOS as diagnostic entities. This change may have unintended consequences, including the possibility that the new diagnostic framework will adversely affect access to developmental interventions under Individuals with Disabilities Education Act (IDEA) programs, Early Intervention (for birth to 2 years olds) and preschool special education (for 3 and 4 years olds). Changing the current diagnosis of PDD-NOS to a "Social Communication Disorder" focused on language pragmatics in the DSM-5 may restrict eligibility for IDEA programs and limit the scope of services for affected children. Young children who meet current criteria for PDD-NOS require more intensive and multi-disciplinary services than would be available with a communication domain diagnosis and possible service authorization limited to speech-language therapy. Intensive behavioral interventions, inclusive group setting placements, and family support services are typically more available for children with an autism spectrum disorder than with diagnoses reflecting speech-language delay. The diagnostic distinction reflective of the higher language and social functioning between Asperger's Disorder and autism is also undermined by eliminating the former as a categorical diagnosis and subsuming it under autism. This change may adversely affect treatment planning and misinform parents about prognosis for children who meet current criteria for Asperger's Disorder. C1 [Grant, Roy] Childrens Hlth Fund, New York, NY 10027 USA. 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TI An epigenetic framework for neurodevelopmental disorders: From pathogenesis to potential therapy SO NEUROPHARMACOLOGY LA English DT Review DE Epigenopathy; Histone; Chromatin; Methylation; Acetylation; MiRNA; SnoRNA; Noncoding RNA; Autism; Schizophrenia ID FRAGILE-X-SYNDROME; AUTISM SPECTRUM DISORDERS; PRADER-WILLI-SYNDROME; LINKED MENTAL-RETARDATION; LONG-TERM-MEMORY; HISTONE DEACETYLASE INHIBITORS; RUBINSTEIN-TAYBI-SYNDROME; TUBEROUS SCLEROSIS COMPLEX; ACTIVE DNA DEMETHYLATION; PLURIPOTENT STEM-CELLS AB Neurodevelopmental disorders (NDDs) are characterized by aberrant and delayed early-life development of the brain, leading to deficits in language, cognition, motor behaviour and other functional domains, often accompanied by somatic symptoms. Environmental factors like perinatal infection, malnutrition and trauma can increase the risk of the heterogeneous, multifactorial and polygenic disorders, autism and schizophrenia. Conversely, discrete genetic anomalies are involved in Down, Rett and Fragile X syndromes, tuberous sclerosis and neurofibromatosis, the less familiar Phelan-McDermid, Sotos, Kleefstra, Coffin-Lowry and "ATRX" syndromes, and the disorders of imprinting, Angelman and Prader-Willi syndromes. NDDs have been termed "synaptopathies" in reference to structural and functional disturbance of synaptic plasticity, several involve abnormal Ras-Kinase signalling ("rasopathies"), and many are characterized by disrupted cerebral connectivity and an imbalance between excitatory and inhibitory transmission. However, at a different level of integration, NDDs are accompanied by aberrant "epigenetic" regulation of processes critical for normal and orderly development of the brain. Epigenetics refers to potentially-heritable (by mitosis and/or meiosis) mechanisms controlling gene expression without changes in DNA sequence. In certain NDDs, prototypical epigenetic processes of DNA methylation and covalent histone marking are impacted. Conversely, others involve anomalies in chromatin-modelling, mRNA splicing/editing, mRNA translation, ribosome biogenesis and/or the regulatory actions of small nucleolar RNAs and micro-RNAs. Since epigenetic mechanisms are modifiable, this raises the hope of novel therapy, though questions remain concerning efficacy and safety. The above issues are critically surveyed in this review, which advocates a broad-based epigenetic framework for understanding and ultimately treating a diverse assemblage of NDDs ("epigenopathies") lying at the interface of genetic, developmental and environmental processes. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. (c) 2012 Elsevier Ltd. All rights reserved. C1 IDR Servier, Unit Res & Discover Neurosci, F-78290 Paris, France. RP Millan, MJ (reprint author), IDR Servier, Unit Res & Discover Neurosci, 125 Chemin Ronde, F-78290 Paris, France. 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TI Fragile X syndrome: From targets to treatments SO NEUROPHARMACOLOGY LA English DT Review DE Neurodevelopmental disorders; Fragile X Syndrome; Autism spectrum disorder; Intellectual disability ID MENTAL-RETARDATION PROTEIN; METABOTROPIC GLUTAMATE RECEPTORS; LONG-TERM DEPRESSION; FMR1 KNOCKOUT MICE; PRIMARY SOMATOSENSORY CORTEX; MOUSE MODEL; FULL MUTATION; DENDRITIC SPINES; CGG-REPEAT; MINOCYCLINE TREATMENT AB Fragile X syndrome (FXS) is one of the most prevalent and well-studied monogenetic causes of intellectual disability and autism and, although rare, its high penetrance makes it a desirable model for the study of neurodevelopmental disorders more generally. Indeed recent studies suggest that there is functional convergence of a number of genes that are implicated in intellectual disability and autism indicating that an understanding of the cellular and biochemical dysfunction that occurs in monogenic forms of these disorders are likely to reveal common targets for therapeutic intervention. Fundamental research into FXS has provided a wealth of information about how the loss of function of the fragile X mental retardation protein results in biochemical, anatomical and physiological dysfunction leading to the discovery of interventions that correct many of the core pathological phenotypes associated with animal models of FXS. Most promisingly such strategies have led to development of drugs that are now in clinical trials. This review highlights how progress in understanding disorders such as FXS has led to a new era in which targeted molecular treatment towards neurodevelopmental disorders is becoming a reality. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Wijetunge, Lasani S.; Wyllie, David J. A.; Kind, Peter C.] Univ Edinburgh, Ctr Integrat Physiol, Patrick Wild Ctr, Edinburgh EH8 9XD, Midlothian, Scotland. [Chattarji, Sumantra] Tata Inst Fundamental Res, Natl Ctr Biol Sci, Bangalore, Karnataka, India. [Chattarji, Sumantra] Inst Stem Cell Biol & Regenerat Med, Ctr Neurodev Synaptopathies, Bangalore, Karnataka, India. RP Kind, PC (reprint author), Univ Edinburgh, Ctr Integrat Physiol, Patrick Wild Ctr, Hugh Robson Bldg,George Sq, Edinburgh EH8 9XD, Midlothian, Scotland. EM pkind@ed.ac.uk FU Patrick Wild Centre; Medical Research Council UK FX We would like to thank Dr Emily Osterweil and Dr. Andrew Stanfield along with the anonymous reviewers for their helpful comments. We would also like to thank Professor Randi Hagerman and Dr. Mary Jacena S. Leigh for sharing their data from the minocycline trials. We acknowledge the support from the Patrick Wild Centre and the Medical Research Council UK. We would also like to thank Dr. Gus Alusi and Reem Waines for their continued support and helpful insights into living with FXS. 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Neuropsychiatric conditions, including intellectual disability, autism and epilepsy, are highly prevalent in TSC populations. Here, I review recent findings that shed light on some of the neurobiological mechanisms that may contribute to the pathogenesis of TSC-associated neuropsychiatric impairments. Emerging intervention studies in animal models show striking effects of mTORC1 inhibitors on TSC-related CNS manifestations. Translational studies that assess the effects of mTORC1 inhibitors on neuropsychiatric phenotypes in human TSC individuals are underway. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. (c) 2012 Elsevier Ltd. All rights reserved. C1 DZNE, German Ctr Neurodegenerat Dis, D-53175 Bonn, Germany. RP Ehninger, D (reprint author), DZNE, German Ctr Neurodegenerat Dis, Ludwig Erhard Allee 2, D-53175 Bonn, Germany. 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Kawamura, Masahito, Jr. Cote, Jessica L. Williams, Rebecca B. Ruskin, David N. TI Adenosine and autism: A spectrum of opportunities SO NEUROPHARMACOLOGY LA English DT Review DE Adenosine; Anxiety; Autism; ATP; Ketogenic diet; Metabolism ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; KETOGENIC DIET; DOUBLE-BLIND; REFRACTORY EPILEPSY; RECEPTOR AGONISTS; A(1) RECEPTORS; ALLOPURINOL AUGMENTATION; CAFFEINE TREATMENT; RAT HIPPOCAMPUS AB In rodents, insufficient adenosine produces behavioral and physiological symptoms consistent with several comorbidities of autism. In rodents and humans, stimuli postulated to increase adenosine can ameliorate these comorbidities. Because adenosine is a broad homeostatic regulator of cell function and nervous system activity, increasing adenosine's influence might be a new therapeutic target for autism with multiple beneficial effects. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Masino, Susan A.; Cote, Jessica L.; Ruskin, David N.] Trinity Coll, Neurosci Program, Life Sci Ctr, Hartford, CT 06106 USA. [Masino, Susan A.; Williams, Rebecca B.; Ruskin, David N.] Trinity Coll, Dept Psychol, Hartford, CT 06106 USA. [Kawamura, Masahito, Jr.] Jikei Univ, Sch Med, Dept Pharmacol, Minato Ku, Tokyo 1058461, Japan. RP Masino, SA (reprint author), Trinity Coll, Neurosci Program, Life Sci Ctr, 300 Summit St, Hartford, CT 06106 USA. EM susan.masino@trincoll.edu FU National Institutes of Health from the National Institute of Neurological Disorders and Stroke (NINDS) [NS065957, NS066932]; National Science Foundation [IOS-0843585] FX This work was supported by National Institutes of Health Grants NS065957 and NS066932 from the National Institute of Neurological Disorders and Stroke (NINDS) and IOS-0843585 from the National Science Foundation. 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Hossein TI The involvement of Reelin in neurodevelopmental disorders SO NEUROPHARMACOLOGY LA English DT Review DE Reelin; Schizophrenia; Autism; Bipolar disorder; Major depression; Lissencephaly; Alzheimer's disease; Treatment ID POLYMORPHIC GGC REPEAT; CAJAL-RETZIUS CELLS; CAUSES DIFFERENTIAL EXPRESSION; DAB1 TYROSINE PHOSPHORYLATION; MENTAL-RETARDATION PROTEIN; CORTICAL PLATE DEVELOPMENT; AUTISM SPECTRUM DISORDERS; PRENATAL IMMUNE CHALLENGE; MESSENGER-RNA EXPRESSION; MINOR PHYSICAL ANOMALIES AB Reelin is a glycoprotein that serves important roles both during development (regulation of neuronal migration and brain lamination) and in adulthood (maintenance of synaptic function). A number of neuropsychiatric disorders including autism, schizophrenia, bipolar disorder, major depression, Alzheimer's disease and lissencephaly share a common feature of abnormal Reelin expression in the brain. Altered Reelin expression has been hypothesized to impair neuronal connectivity and synaptic plasticity, leading ultimately to the cognitive deficits present in these disorders. The mechanisms for abnormal Reelin expression in some of these disorders are currently unknown although possible explanations include early developmental insults, mutations, hypermethylation of the promoter for the Reelin gene (RELN), miRNA silencing of Reelin mRNA, FMRP underexpression and Reelin processing abnormalities. Increasing Reelin expression through pharmacological therapies may help ameliorate symptoms resulting from Reelin deficits. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Folsom, Timothy D.; Fatemi, S. Hossein] 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), Univ Minnesota, Dept Psychiat, 420 Delaware St SE,MMC 392, Minneapolis, MN 55455 USA. EM folso013@umn.edu; fatem002@umn.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [5R01HD052074-01A2]; National Institute of Mental Health [5R01MH086000-01A2]; Minnesota Medical Foundation Alfred and Ingrid Lenz Harrison Initiative Fund FX Grant support by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R01HD052074-01A2) and the National Institute of Mental Health (5R01MH086000-01A2) and the Minnesota Medical Foundation Alfred and Ingrid Lenz Harrison Initiative Fund to SHF is gratefully acknowledged. Dr. Fatemi has several United States patents (7341844) on the use of Reelin as a diagnostic marker in psychiatric disorders but has not derived any financial gains from these patents. 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NEUROPHARMACOLOGY JI Neuropharmacology PD MAY PY 2013 VL 68 SI SI BP 122 EP 135 DI 10.1016/j.neuropharm.2012.08.015 PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 123EL UT WOS:000317371100007 PM 22981949 ER PT J AU Gray, SJ AF Gray, Steven James TI Gene therapy and neurodevelopmental disorders SO NEUROPHARMACOLOGY LA English DT Review DE Gene therapy; AAV; Neurodevelopmental disorder; Rett syndrome; Angelman syndrome; Lysosomal storage disease ID ADENOASSOCIATED VIRUS VECTORS; LYSOSOMAL STORAGE DISEASES; CENTRAL-NERVOUS-SYSTEM; RETT-SYNDROME; MOUSE MODEL; EFFICIENT TRANSDUCTION; REGULATED EXPRESSION; DIRECTED EVOLUTION; ADENOVIRAL VECTORS; ANGELMAN-SYNDROME AB With a number of recent clinical successes, gene therapy is quickly becoming a realistic treatment option for neurological disorders. Advancements in global central nervous system (CNS) gene delivery, in particular, have accelerated to the point that treatments for neurological disorders such as lysosomal storage diseases seem within reach. Other neurodevelopmental disorders, such as Rett Syndrome, Fragile X, and autism still face significant obstacles to overcome before a viable human gene therapy can be considered. This review focuses on the most common CNS gene delivery vehicle, adeno-associated virus (AAV), and the current state of AAV vector design and delivery for CNS gene therapy. Relevant examples of gene therapy studies for neurodevelopmental disorders, as well as outstanding challenges, are discussed. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. (c) 2012 Elsevier Ltd. All rights reserved. C1 Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA. RP Gray, SJ (reprint author), Univ N Carolina, Gene Therapy Ctr, 7109 Thurston Bowles,104 Manning Dr, Chapel Hill, NC 27599 USA. EM graysj@email.unc.edu FU International Rett Syndrome Foundation; New Hope Research Foundation; Legacy of Angels Foundation; Hannah's Hope Fund; Jasper Against Batten FX SJG would like to acknowledge support from the International Rett Syndrome Foundation, the New Hope Research Foundation, the Legacy of Angels Foundation, Hannah's Hope Fund, and Jasper Against Batten. 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It has been proposed that the symptoms of autism spectrum disorders (ASDs) are the result of deficient GABA neurotransmission, possibly including reduced expression of GABA(A) receptors. However, this hypothesis has not been directly tested in living adults with ASD. In this preliminary investigation, we used Positron Emission Tomography (PET) with the benzodiazepine receptor PET ligand [C-11]Ro15-4513 to measure alpha 1 and alpha 5 subtypes of the GABA(A) receptor levels in the brain of three adult males with well-characterized high-functioning ASD compared with three healthy matched volunteers. We found significantly lower [C-11]Ro15-4513 binding throughout the brain of participants with ASD (p < 0.0001) compared with controls. Planned region of interest analyses also revealed significant reductions in two limbic brain regions, namely the amygdala and nucleus accumbens bilaterally. Further analysis suggested that these results were driven by lower levels of the GABA(A) alpha 5 subtype. These results provide initial evidence of a GABA(A) alpha 5 deficit in ASD and support further investigations of the GABA system in this disorder. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Mendez, Maria Andreina; Horder, Jamie; Coghlan, Suzanne; Murphy, Declan] Kings Coll London, Dept Forens & Neurodev Sci, Inst Psychiat, London SES 8AF, England. [Mendez, Maria Andreina; Stokes, Paul; Erritzoe, David; Lingford-Hughes, Anne; Nutt, David] Univ London Imperial Coll Sci Technol & Med, Ctr Pharmacol & Therapeut, Div Expt Med, Neuropsychopharmacol Unit, London W12 0NN, England. [Myers, Jim] Univ Bristol, Sch Social & Community Med, Psychopharmacol Unit, Bristol BS8 2BN, Avon, England. [Howes, Oliver] MRC Clin Sci Ctr, Psychiat Imaging Grp, London W12 0NN, England. RP Horder, J (reprint author), Kings Coll London, Dept Forens & Neurodev Sci, Inst Psychiat, POB 50,De Crespigny Pk, London SES 8AF, England. EM jamie.horder@kcl.ac.uk FU National Institute for Health Research (NIHR); Biomedical Research Centre; Medical Research Council AIMS Network; Wellcome Trust [091300]; Medical Research Council, UK grant [MC-A656-5QD30] FX We wish to thank the volunteers for their patience and collaboration with the study, and we are grateful for the technical support and assistance provided by Hammersmith Imanet. This project was supported by a program grant from National Institute for Health Research (NIHR) and the Biomedical Research Centre. The MRI component of this project was funded by the Medical Research Council AIMS Network and also by a grant from the Wellcome Trust (Reference 091300). The PET scans were funded by a Medical Research Council, UK grant to Dr Oliver Howes (Grant code: MC-A656-5QD30). 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TI GABAergic activity in autism spectrum disorders: An investigation of cortical inhibition via transcranial magnetic stimulation SO NEUROPHARMACOLOGY LA English DT Article DE Autistic disorder; Asperger's disorder; Primary motor cortex; Transcranial magnetic stimulation; GABA; Electromyography ID HIGH-FUNCTIONING AUTISM; DORSOLATERAL PREFRONTAL CORTEX; MAJOR DEPRESSIVE DISORDER; HUMAN MOTOR CORTEX; SILENT PERIOD; INTRACORTICAL INHIBITION; ASPERGERS-DISORDER; TOURETTE-SYNDROME; WHITE-MATTER; TMS-EEG AB Mounting evidence suggests a possible role for gamma-aminobutyric acid (GABA) in the neuropathophysiology of autism spectrum disorders (ASD), but the extent of this impairment is unclear. A non-invasive, in vivo measure of GABA involves transcranial magnetic stimulation (TMS) of the primary motor cortex to probe cortical inhibition. Individuals diagnosed with ASD (high-functioning autism or Asperger's disorder) (n = 36 [28 male); mean age: 26.00 years) and a group of healthy individuals (n = 34 [23 male]; mean age: 26.21 years) (matched for age, gender, and cognitive function) were administered motor cortical TMS paradigms putatively measuring activity at GABA(A) and GABA(B) receptors (i.e., short and long interval paired pulse TMS, cortical silent period). All cortical inhibition paradigms yielded no difference between ASD and control groups. There was, however, evidence for short interval cortical inhibition (SICI) deficits among those ASD participants who had experienced early language delay, suggesting that GABA may be implicated in an ASD subtype. The current findings do not support a broad role for GABA in the neuropathophysiology of ASD, but provide further indication that GABA(A) could be involved in ASD where there is a delay in language acquisition. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Enticott, Peter G.; Kennedy, Hayley A.; Fitzgerald, Paul B.] The Alfred, Monash Alfred Psychiat Res Ctr, Melbourne, Vic 3004, Australia. [Enticott, Peter G.; Kennedy, Hayley A.; Fitzgerald, Paul B.] Monash Univ, Cent Clin Sch, Melbourne, Vic 3004, Australia. [Enticott, Peter G.; Rinehart, Nicole J.; Tonge, Bruce J.; Bradshaw, John L.] Monash Univ, Sch Psychol & Psychiat, Ctr Dev Psychiat & Psychol, Clayton, Vic 3800, Australia. RP Enticott, PG (reprint author), Monash Alfred Psychiat Res Ctr, Level 4,607 St Kilda Rd, Melbourne, Vic 3004, Australia. EM peter.enticott@monash.edu RI Fitzgerald, Paul/A-1225-2008 OI Fitzgerald, Paul/0000-0003-4217-8096 FU Clinical Research Fellowship from the National Health and Medical Research Council (NHMRC), Australia; Practitioner Fellowship from the NHMRC FX The authors wish to thank Dr. Richard Thomson, Dr. Bernadette Fitzgibbon, and Ms. Bronwyn Harrison for their assistance with the processing of EMG signals. The authors also thank all those who took part in the study and those who assisted with participant recruitment, including Prof. Tony Attwood, Ms. Tracel Devereux (Alpha Autism), Dr. Richard Eisenmajer, Mr. Dennis Freeman (Wesley College Melbourne), Ms. Pam Langford, Dr. Kerryn Saunders, Ms. Linke Smedts-Kreskas (S.P.O.C.A.A.S.), Autism Victoria, Autism Asperger's Advocacy Australia (A4), Autism Spectrum Australia (ASPECT), and the Asperger Syndrome Support Network. Dr. Enticott is funded by a Clinical Research Fellowship from the National Health and Medical Research Council (NHMRC), Australia. Prof. Fitzgerald is funded by a Practitioner Fellowship from the NHMRC. 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However, in preclinical studies of mGluR5 compounds tested in our laboratory and others, increased locomotion following mGluR5 modulation has been observed. Understanding the influence of general activity on sociability and repetitive behaviors will increase the accuracy of interpretations of positive outcomes measured from pharmacological treatment that produces locomotor activating or sedating effects. In the present studies, dose-response curves for D-amphetamine (AMPH)-induced hyperlocomotion were similar in standard B6 mice and in the BTBR mouse model of autism. AMPH produced significant, robust reductions in the high level of repetitive self-grooming that characterizes BTBR, and also reduced the low baseline grooming in B6, indicating that AMPH-induced hyperlocomotion competes with time spent engaged in self-grooming. We then tested AMPH in B6 and BTBR on the 3-chambered social approach task. One component of sociability, the time spent in the chamber with the novel mouse, in B6 mice was reduced, while the sniffing time component of sociability in BTBR mice was enhanced. This finding replicated across multiple cohorts treated with AMPH and saline vehicle. In-depth analysis revealed that AMPH increased the number and decreased the duration of sniffing bouts in BTBR, suggesting BTBR treated with AMPH mostly engaged in brief sniffs rather than true social interactions with the novel mouse during the social approach task. Our data suggest that compounds with stimulant properties may have some direct benefits on reducing repetitive behaviors in autism spectrum disorders, particularly in the subset of autistic individuals with hyperactivity. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. Published by Elsevier Ltd. 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Helenius, Hans Suominen, Auli Gissler, Mika Brown, Alan S. Sourander, Andre TI Smoking during Pregnancy and Risk of Autism Spectrum Disorder in a Finnish National Birth Cohort SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE maternal smoking; Autism Spectrum Disorders; childhood autism; Asperger's syndrome; pervasive developmental disorders; fetal; risk factors; epidemiology ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDER; DEFICIT HYPERACTIVITY DISORDER; PERINATAL FACTORS; MATERNAL SMOKING; NICOTINE REPLACEMENT; INFANTILE-AUTISM; EXPOSURE; CONSEQUENCES; PREVALENCE AB Background Results of previous population-based studies examining associations between smoking during pregnancy and autism spectrum disorders (ASD) are contradictory. Furthermore, there is a lack of population-based studies examining the relationship between smoking during pregnancy and the main diagnostic subtypes of ASD. Methods We conducted a population-based nested casecontrol study based on the Finnish Prenatal Study of Autism (FIPS-A) among liveborn infants delivered in Finland between 1987 and 2005. Data on maternal smoking during pregnancy were available from the Finnish Medical Birth Register (FMBR) since October 1990. Data on ASD in the offspring were obtained from the Finnish Hospital Discharge Register (FHDR). Results Among the three subtypes of ASD, maternal smoking during the whole pregnancy was associated with an increased risk of pervasive developmental disorder (PDD) (odds ratio 1.2, 95% confidence interval 1.0, 1.5). The increase in odds persisted after controlling for maternal age, mother's socio-economic and psychiatric status, and infant's weight for gestational age. However, smoking exposure limited to the first trimester was not associated with PDD or any of the other ASD subtypes. Conclusions Maternal smoking is related to a modest increase in risk of PDD, while no associations were observed for childhood autism and Asperger's syndrome. C1 [Phuong Lien Tran] Univ Grenoble 1, Grenoble, France. [Phuong Lien Tran; Lehti, Venla; Lampi, Katja M.; Suominen, Auli; Sourander, Andre] Univ Turku, Dept Child Psychiat, Turku 20014, Finland. [Helenius, Hans; Sourander, Andre] Univ Turku, Dept Biostat, Turku 20014, Finland. [Sourander, Andre] Turku Univ Hosp, Dept Child Psychiat, Turku, Finland. [Gissler, Mika] Natl Inst Hlth & Welf THL, Helsinki, Finland. [Brown, Alan S.] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat,Joseph L Mailman Sch Publ Hlth, New York, NY USA. RP Sourander, A (reprint author), Univ Turku, Dept Child Psychiat, Itainen Pitkakatu 1 Varia, Turku 20014, Finland. EM andre.sourander@utu.fi FU Autism Speaks Foundation, USA; Sigrid Juselius Foundation, Finland; NIMH [1K02-MH65422] FX This study was supported by grants from Autism Speaks Foundation, USA (A. S.), the Sigrid Juselius Foundation, Finland (A. S.); and NIMH 1K02-MH65422) (A.S.B.). 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Soc. Psychol. Rev. PD MAY PY 2013 VL 17 IS 2 BP 142 EP 157 DI 10.1177/1088868312472607 PG 16 WC Psychology, Social SC Psychology GA 126QI UT WOS:000317635900003 PM 23348982 ER PT J AU Escudero-Sanz, A Carranza-Carnicero, JA Huescar-Hernandez, E AF Escudero-Sanz, Alfonso Carranza-Carnicero, Jose A. Huescar-Hernandez, Elisa TI Emergence and development of Joint Attention in infancy SO ANALES DE PSICOLOGIA LA Spanish DT Article DE Joint attention; mother-child interaction; language; children ID EARLY LANGUAGE-ACQUISITION; VISUAL-ATTENTION; INDIVIDUAL-DIFFERENCES; YOUNG-CHILDREN; MOTHER-INFANT; NEUROCOGNITIVE FUNCTION; GAZE PERCEPTION; GESTURE; OBJECT; AUTISM AB Joint Attention is the first step to build communication. Hence, its study is of great interest due to its influence on cognitive, social, emotional, and language development. 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PD MAY PY 2013 VL 29 IS 2 BP 404 EP 412 DI 10.6018/analesps.29.2.136871 PG 9 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 114VD UT WOS:000316770000012 ER PT J AU Quintin, EM Bhatara, A Poissant, H Fombonne, E Levitin, DJ AF Quintin, Eve-Marie Bhatara, Anjali Poissant, Helene Fombonne, Eric Levitin, Daniel J. TI Processing of musical structure by high-functioning adolescents with autism spectrum disorders SO CHILD NEUROPSYCHOLOGY LA English DT Article DE Perception of structure; Musical structure; Music cognition; Global processing; Autism spectrum disorders ID COGNITIVE MECHANISMS; WILLIAMS-SYNDROME; CENTRAL COHERENCE; CHILDREN; PERCEPTION; INDIVIDUALS; REPRESENTATION; PERFORMANCE; LISTENERS; PHENOTYPE AB Enhanced pitch perception and memory have been cited as evidence of a local processing bias in autism spectrum disorders (ASD). This bias is argued to account for enhanced perceptual functioning (Mottron & Burack, 2001; Mottron, Dawson, Soulieres, Hubert, & Burack, 2006) and central coherence theories of ASD (Frith, 1989; Happe & Frith, 2006). A local processing bias confers a different cognitive style to individuals with ASD (Happe, 1999), which accounts in part for their good visuospatial and visuoconstructive skills. Here, we present analogues in the auditory domain, audiotemporal or audioconstructive processing, which we assess using a novel experimental task: a musical puzzle. This task evaluates the ability of individuals with ASD to process temporal sequences of musical events as well as various elements of musical structure and thus indexes their ability to employ a global processing style. Musical structures created and replicated by children and adolescents with ASD (1019 years old) and typically developing children and adolescents (717 years old) were found to be similar in global coherence. Presenting a musical template for reference increased accuracy equally for both groups, with performance associated to performance IQ and short-term auditory memory. The overall pattern of performance was similar for both groups; some puzzles were easier than others and this was the case for both groups. Task performance was further found to be correlated with the ability to perceive musical emotions, more so for typically developing participants. Findings are discussed in light of the empathizing-systemizing theory of ASD (Baron-Cohen, 2009) and the importance of describing the strengths of individuals with ASD (Happe, 1999; Heaton, 2009). C1 [Quintin, Eve-Marie] Stanford Univ, Sch Med, Ctr Interdisciplinary Brain Sci Res, Stanford, CA 94305 USA. [Bhatara, Anjali] Univ Paris, Lab Psychol Percept, F-75252 Paris, France. [Poissant, Helene] Univ Quebec, Dept Psychol, Montreal, PQ H3C 3P8, Canada. [Fombonne, Eric] McGill Univ, Dept Psychiat, Montreal, PQ H3A 1B1, Canada. [Levitin, Daniel J.] McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada. RP Levitin, DJ (reprint author), McGill Univ, Dept Psychol, Stewart Biol Bldg,1205 Dr Penfield Ave, Montreal, PQ H3A 1B1, Canada. EM daniel.levitin@mcgill.ca FU FQRSC; Canadian Autism Research Training Program; CIHR; Autism Speaks; NSERC; Google FX This article was submitted in partial fulfillment of the requirements for the PhD in Psychology by the first author. The research was supported in part by a doctoral grant to EMQ by FQRSC and the Canadian Autism Research Training Program (funded by CIHR) and by research grants to DJL from NAAR (now Autism Speaks), NSERC, Google, and John and Ethelene Gareau. EF has been an expert witness for vaccine manufacturers and for the U. S. Department of Justice and the U. S. Department of Health and Social Services in U. S. Thimerosal litigation. None of his research has ever been funded by the industry. 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PD MAY 1 PY 2013 VL 19 IS 3 BP 250 EP 275 DI 10.1080/09297049.2011.653540 PG 26 WC Clinical Neurology SC Neurosciences & Neurology GA 122BS UT WOS:000317290900003 PM 22397615 ER PT J AU Toth, ZE Heinzlmann, A Hashimoto, H Koves, K AF Toth, Zsuzsanna E. Heinzlmann, Andrea Hashimoto, Hitoshi Koeves, Katalin TI Distribution of Secretin Receptors in the Rat Central Nervous System: an in situ Hybridization Study SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Brain stem; Forebrain; In vitro transcription; Radioactive labeling; Mapping ID BRAIN; AUTISM; CEREBELLUM; EXPRESSION; TERMINALIS; NUCLEUS; BINDING AB Secretin shows a wide distribution in the brain. Functional significance of central secretin is stressed since it has been associated with autism and schizophrenia. The presence of the secretin receptor was previously demonstrated in the brain by different methods. Neurons in the cerebellum, hypothalamic paraventricular and supraoptic nuclei, and in the vascular organ of lamina terminalis were shown to express secretin receptor mRNA by using in situ hybridization with digoxigenin-labeled probe. In this work, we used a very sensitive radioactive in situ hybridization technique and systematically mapped the expression of secretin receptor mRNA in the brain. The densest labeling was observed in the nucleus of solitary tract and in the laterodorsal thalamic nucleus, where decreasing number of receptors was seen in the vascular organ of lamina terminalis, and the lateral habenular complex, and then in the supraoptic nucleus. Only a few scattered labeled cells were observed in the median frontal gyrus, entorhinal cortex, hypothalamic paraventricular nucleus, perifornical region, lateral hypothalamic area, head of the caudate nucleus, spinal trigeminal nucleus, and cerebellum. Secretin receptor mRNA showed a far wider distribution than was known before, suggesting a more significant functional relevance than thought earlier. C1 [Toth, Zsuzsanna E.] Semmelweis Univ, Dept Anat Histol & Embryol, Neuromorphol & Neuroendocrine Res Lab, H-1094 Budapest, Hungary. [Toth, Zsuzsanna E.] Hungarian Acad Sci, H-1094 Budapest, Hungary. [Heinzlmann, Andrea; Koeves, Katalin] Semmelweis Univ, Dept Human Morphol & Dev Biol, H-1094 Budapest, Hungary. [Hashimoto, Hitoshi] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Med Pharmacol, Suita, Osaka, Japan. RP Koves, K (reprint author), Semmelweis Univ, Dept Human Morphol & Dev Biol, Tuzolto U 58, H-1094 Budapest, Hungary. EM koves.katalin@med.semmelweis-univ.hu RI Hashimoto, Hitoshi/D-1209-2010 OI Hashimoto, Hitoshi/0000-0001-6548-4016 FU ETT [495/09]; Department of Human Morphology and Developmental Biology, Semmelweis University FX We are grateful to Mrs. Anna Takacs and Judit Kerti for their excellent technical assistance. This work was supported by ETT grant 495/09 to ZE Toth and by the Department of Human Morphology and Developmental Biology, Semmelweis University. 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Mol. Neurosci. PD MAY PY 2013 VL 50 IS 1 BP 172 EP 178 DI 10.1007/s12031-012-9895-1 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 123DD UT WOS:000317367700017 PM 23065333 ER PT J AU Travers, JC Tincani, M Krezmien, MP AF Travers, Jason C. Tincani, Matt Krezmien, Michael P. TI A Multiyear National Profile of Racial Disparity in Autism Identification SO JOURNAL OF SPECIAL EDUCATION LA English DT Article DE autism; race; disproportionate representation; prevalence; identification ID SPECIAL-EDUCATION; DIAGNOSTIC SUBSTITUTION; MINORITY-STUDENTS; PREVALENCE; EQUITY; DIVERSITY; TRENDS; RACE AB Disproportionate representation of racially diverse students in special education is a well-documented problem, yet few studies have systematically evaluated disproportionate representation of diverse students with autism. This study examined disproportionate representation of racially diverse students with autism by determining risk and logistical odds ratios among racially diverse and White students from the national population between 1998 and 2006. Although overall risk of autism increased for all racial groups every year, White students were twice as likely to be identified with autism as Hispanic and American Indian/Alaskan Native students during most years of the sample. Although initially overrepresented, the odds ratios for Asian/Pacific Islander and Black students with autism continuously declined in recent years. Hispanic and American Indian/Alaskan Native students were significantly underrepresented every year in the analysis. Potential cause and implications of underrepresentation are described, along with directions for research. C1 [Travers, Jason C.; Krezmien, Michael P.] Univ Massachusetts, Amherst, MA 01003 USA. [Tincani, Matt] Temple Univ, Philadelphia, PA 19122 USA. 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PD MAY PY 2013 VL 47 IS 1 BP 41 EP 49 DI 10.1177/0022466911416247 PG 9 WC Education, Special SC Education & Educational Research GA 119BZ UT WOS:000317073200004 ER PT J AU Clegg, J Gillott, A Jones, J AF Clegg, Jennifer Gillott, Alinda Jones, Jo TI Conceptual issues in neurodevelopmental disorders: lives out of synch SO CURRENT OPINION IN PSYCHIATRY LA English DT Review DE affective; cognitive; conceptual; embodied; neurodevelopmental disorders ID AUTISM SPECTRUM DISORDER; TOURETTE SYNDROME; INTELLECTUAL DISABILITY; CLINICAL-DIAGNOSIS; SLEEP PROBLEMS; CHILDREN; SYMPTOMS; BEHAVIOR; MOTHERS; ADULTS AB Purpose of review Current revision of the two major psychiatric classification systems has elicited particular comment on neurodevelopmental disorders, which have seen increased provision of specialist clinical services, user group activity, fictional and biographical accounts, and research. Philosophical scrutiny of autism research and literature provides an additional perspective. Recent findings Neurodevelopmental disorders show considerable overlap neuropsychologically, physiologically and genetically. They overlap diagnostically with schizophrenia, personality disorders, anxiety and depression. Of the two main diagnostic groups, there is more evidence of change with maturation in autism spectrum disorder than attention-deficit hyperactivity disorder. Interventions should combine cognitive, affective and embodied aspects of these disorders, and encompass the individual and their social environment. There is considerable evidence of the toll that caring for people with neurodevelopmental disorders exerts on parents. Summary Neurodevelopmental disorders are multifaceted: research addressed to connection rather than further Balkanization is more likely to be fruitful. Clinicians should consider which facets are displayed symptomatically to enable people to grow through rather than surrender to their impairments. Social scaffolding optimizes functional well being. Future research should take into account the tensions in the relationship between research and user groups, and examine the experiences of adults and of the spouses and partners of those affected. C1 [Clegg, Jennifer] Univ Nottingham, Nottingham NG7 2TU, England. [Clegg, Jennifer; Gillott, Alinda; Jones, Jo] Nottinghamshire Healthcare NHS Trust, Nottingham, England. RP Clegg, J (reprint author), Univ Nottingham, Inst Mental Hlth, Innovat Pk,Triumph Rd, Nottingham NG7 2TU, England. EM Jennifer.Clegg@Nottingham.ac.uk FU Asperger's syndrome FX Dr Clegg has no conflicts of interest to declare. Drs Jones and Gillott are both employed by the Nottinghamshire Healthcare NHS Trust providing a specialist service to adults with Asperger's syndrome. Dr Gillott has also received payment for preparation of court reports concerning adults with Asperger's syndrome. 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An abnormal serotonergic (5-HT) system has been implicated in the etiology of ASD. In the present study, we have examined the expression and distribution of two early inducers of 5-HT neurons in rat embryos, to elucidate the prenatal development of 5-HT neurons after VPA exposure at embryonic day (E) 9.5. Whole-embryo in situ hybridization at E11.5 showed that the expression of sonic hedgehog, one of the early inducers of 5-HT neurons, was reduced around the isthmus in the VPA-exposed group. Furthermore, whole-mount immunohistochemistry of the hindbrain and quantitative analysis of 5-HT neurons in the rostral raphe nucleus (rRN) revealed that neuronal distribution in the caudal part of the rRN was narrower at E15.5 in the VPA-exposed group than in controls. Thus, the early development of 5-HT neurons was altered after VPA exposure in utero. The observed prenatal alteration may be significant in the etiology of autism. (c) 2013 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Oyabu, Akiko; Narita, Masaaki; Tashiro, Yasura] Mie Univ, Grad Sch Med, Dept Dev & Regenerat Med, Tsu, Mie 5148507, Japan. RP Tashiro, Y (reprint author), Mie Univ, Grad Sch Med, Dept Dev & Regenerat Med, 2-174 Edobashi, Tsu, Mie 5148507, Japan. EM ytashiro@doc.medic.mie-u.ac.jp FU Ministry of Health, Labour and Welfare of the Japanese Government FX This study was supported in part by the Ministry of Health, Labour and Welfare of the Japanese Government. 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PD MAY PY 2013 VL 31 IS 3 BP 202 EP 208 DI 10.1016/j.ijdevneu.2013.01.006 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 117TG UT WOS:000316975400008 PM 23376409 ER PT J AU Ghaleiha, A Asadabadi, M Mohammadi, MR Shahei, M Tabrizi, M Hajiaghaee, R Hassanzadeh, E Akhondzadeh, S AF Ghaleiha, Ali Asadabadi, Mahtab Mohammadi, Mohammad-Reza Shahei, Maryam Tabrizi, Mina Hajiaghaee, Reza Hassanzadeh, Elmira Akhondzadeh, Shahin TI Memantine as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Autism; glutamate; memantine; NMDA; trial ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; CEREBELLAR CORTICES; ABERRANT BEHAVIOR; RATING-SCALE; ADOLESCENTS; PARIETAL; PROTEIN AB Autism is a neurodevelopmental disorder that causes significant impairment in socialization and communication. It is also associated with ritualistic and stereotypical behaviour. Recent studies propose both hyper-and hypoglutamatergic ideologies for autism. The objective of this study was to assess the effects of memantine plus risperidone in the treatment of children with autism. Children with autism were randomly allocated to risperidone plus memantine or placebo plus risperidone for a 10-wk, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 3 mg/d and memantine was titrated to 20 mg/d. Children were assessed at baseline and after 2, 4, 6, 8 and 10 wk of starting medication protocol. The primary outcome measure was the irritability subscale of Aberrant Behavior Checklist-Community (ABC-C). Difference between the two treatment arms was significant as the group that received memantine had greater reduction in ABC-C subscale scores for irritability, stereotypic behaviour and hyperactivity. Eight side-effects were observed over the trial, out of the 25 side-effects that the checklist included. The difference between the two groups in the frequency of side-effects was not significant. The present study suggests that memantine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N10; www.irct.ir) C1 [Ghaleiha, Ali] Hamadan Univ Med Sci, Res Ctr Behav Disorders & Subst Abuse, Hamadan, Iran. [Asadabadi, Mahtab; Mohammadi, Mohammad-Reza; Shahei, Maryam; Hassanzadeh, Elmira; Akhondzadeh, Shahin] Univ Tehran Med Sci, Roozbeh Hosp, Psychiat Res Ctr, Tehran 13337, Iran. [Tabrizi, Mina] Univ Tehran Med Sci, Fac Med, Dept Med Genet, Tehran 13337, Iran. [Hajiaghaee, Reza] Inst Med Plants ACECR, Tehran, Iran. RP Akhondzadeh, S (reprint author), Univ Tehran Med Sci, Roozbeh Psychiat Hosp, Psychiat Res Ctr, South Kargar St, Tehran 13337, Iran. EM s.akhond@neda.net FU Tehran University of Medical Sciences [6964] FX This study was Dr Maryam Shahei's postgraduate thesis toward the Iranian Board of Psychiatry. This study was supported by a grant from Tehran University of Medical Sciences to Professor Shahin Akhondzadeh (Grant No: 6964). 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TI Monoamine oxidase A and A/B knockout mice display autistic-like features SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Animal models; autistic-spectrum disorders; monoamine oxidase ID PERVASIVE DEVELOPMENTAL DISORDERS; PURKINJE-CELL LOSS; A-DEFICIENT MICE; SPECTRUM DISORDERS; MOUSE MODEL; INFANTILE-AUTISM; CORPUS-CALLOSUM; SOMATOSENSORY CORTEX; REPETITIVE BEHAVIOR; MENTAL-RETARDATION AB Converging lines of evidence show that a sizable subset of autism-spectrum disorders (ASDs) is characterized by increased blood levels of serotonin (5-hydroxytryptamine, 5-HT), yet the mechanistic link between these two phenomena remains unclear. The enzymatic degradation of brain 5-HT is mainly mediated by monoamine oxidase (MAO)A and, in the absence of this enzyme, by its cognate isoenzyme MAOB. MAOA and A/B knockout (KO) mice display high 5-HT levels, particularly during early developmental stages. Here we show that both mutant lines exhibit numerous behavioural hallmarks of ASDs, such as social and communication impairments, perseverative and stereotypical responses, behavioural inflexibility, as well as subtle tactile and motor deficits. Furthermore, both MAOA and A/B KO mice displayed neuropathological alterations reminiscent of typical ASD features, including reduced thickness of the corpus callosum, increased dendritic arborization of pyramidal neurons in the prefrontal cortex and disrupted microarchitecture of the cerebellum. The severity of repetitive responses and neuropathological aberrances was generally greater in MAOA/B KO animals. These findings suggest that the neurochemical imbalances induced by MAOA deficiency (either by itself or in conjunction with lack of MAOB) may result in an array of abnormalities similar to those observed in ASDs. 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PD MAY PY 2013 VL 125 SU 1 SI SI BP 11 EP 11 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700016 ER PT J AU Ashwood, P AF Ashwood, P. TI Is there are link between immune dysfunction and autism? SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Ashwood, P.] Univ Calif Davis, Dept Med Microbiol & Immunol, Sacramento, CA 95817 USA. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. 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PD MAY PY 2013 VL 125 SU 1 SI SI BP 248 EP 248 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700575 ER PT J AU Essa, MM Braidy, N Vijayan, KR Subash, S Guillemin, GJ AF Essa, M. M. Braidy, N. Vijayan, K. R. Subash, S. Guillemin, G. J. TI Excitotoxicity in the Pathogenesis of Autism SO NEUROTOXICITY RESEARCH LA English DT Review DE Autism; Excitotoxicity; Glutamatergic receptors; Membrane potential; Neurotransmitter; Ion channel; Free radicals ID METHYL-D-ASPARTATE; NEUROTROPHIC FACTOR; SPECTRUM DISORDERS; CALCIUM-CHANNEL; GLUTAMATE NEUROTOXICITY; ALZHEIMERS-DISEASE; LIPID-PEROXIDATION; NEURONAL INJURY; NMDA RECEPTORS; NERVOUS-SYSTEM AB Autism is a debilitating neurodevelopment disorder characterised by stereotyped interests and behaviours, and abnormalities in verbal and non-verbal communication. It is a multifactorial disorder resulting from interactions between genetic, environmental and immunological factors. Excitotoxicity and oxidative stress are potential mechanisms, which are likely to serve as a converging point to these risk factors. Substantial evidence suggests that excitotoxicity, oxidative stress and impaired mitochondrial function are the leading cause of neuronal dysfunction in autistic patients. Glutamate is the primary excitatory neurotransmitter produced in the CNS, and overactivity of glutamate and its receptors leads to excitotoxicity. The over excitatory action of glutamate, and the glutamatergic receptors NMDA and AMPA, leads to activation of enzymes that damage cellular structure, membrane permeability and electrochemical gradients. The role of excitotoxicity and the mechanism behind its action in autistic subjects is delineated in this review. C1 [Essa, M. M.; Vijayan, K. R.; Subash, S.] Sultan Qaboos Univ, Coll Agr & Marine Sci, Dept Food Sci & Nutr, Muscat, Oman. [Essa, M. M.; Guillemin, G. J.] Univ NSW, Sch Med Sci, Fac Med, Dept Pharmacol, Sydney, NSW 2052, Australia. [Braidy, N.] Univ New S Wales, Sch Psychiat, Fac Med, Sydney, NSW, Australia. [Guillemin, G. J.] St Vincents Hosp, Peter Duncan Neurosci Unit, St Vincents Ctr Appl Med Res, Sydney, NSW 2010, Australia. RP Guillemin, GJ (reprint author), Univ NSW, Sch Med Sci, Fac Med, Dept Pharmacol, Sydney, NSW 2052, Australia. EM g.guillemin@unsw.edu.au FU Sultan Qaboos University; Research Council; Oman [RC/AGR/FOOD/11/01]; National Health and Medical Research Council (NHMRC); Rebecca Cooper foundation (Australia); Alzheimer's Australia Viertel Foundation Postdoctoral Research Fellowship at the University of New South Wales; [IG/AGR/FOOD/11/02] FX The project was supported by Sultan Qaboos University; Oman in the form of internal grant is gratefully acknowledged (IG/AGR/FOOD/11/02) and also partly supported by the Research Council; Oman (Grant # RC/AGR/FOOD/11/01) as Post-Doctoral fellowship to Dr. Subash S. The scholarship given by Sultan Qaboos University to Vijayan KR is gratefully acknowledged. This work has been also supported by the National Health and Medical Research Council (NHMRC) and by the Rebecca Cooper foundation (Australia). Dr. Nady Braidy is the recipient of an Alzheimer's Australia Viertel Foundation Postdoctoral Research Fellowship at the University of New South Wales. 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Res. PD MAY PY 2013 VL 23 IS 4 BP 393 EP 400 DI 10.1007/s12640-012-9354-3 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 114TC UT WOS:000316764400008 PM 23065398 ER PT J AU Kong, NY Carta, JJ AF Kong, Na Young Carta, Judith J. TI Responsive Interaction Interventions for Children With or at Risk for Developmental Delays: A Research Synthesis SO TOPICS IN EARLY CHILDHOOD SPECIAL EDUCATION LA English DT Article DE responsiveness; responsive interaction; responsive parenting; young children with developmental delays; research synthesis ID PRELINGUISTIC COMMUNICATION INTERVENTIONS; RELATIONSHIP-FOCUSED INTERVENTION; AUTISM SPECTRUM DISORDERS; LANGUAGE IMPAIRMENT; EARLY-CHILDHOOD; YOUNG-CHILDREN; INTENTIONAL COMMUNICATION; MATERNAL BEHAVIORS; SOCIAL-SKILLS; DISABILITIES AB The purpose of this article is to synthesize the available studies regarding responsive interaction intervention (RII) for children with or at risk for developmental delays with a focus on six dimensions: (a) the characteristics of participants, (b) the features of RII, (c) the measurement of treatment fidelity, (d) the overall effectiveness of RII as reflected by the percentage of studies reporting significant changes in adult or child outcomes, (e) the measurement of maintenance and generalization of RII effects, and (f) the social validity or level of acceptability. Through a search of articles from 1990 to 2010, the authors identified 26 studies (31 articles) employing group experimental or quasiexperimental designs incorporating these dimensions. Overall, the results of the reviewed studies indicated that implementation of RII resulted in significant positive changes in adults' responsive behaviors and children's emotional and social-communicative outcomes. Although the most frequently reported child outcomes were in the social-communication domain, the most consistently significant positive outcomes for parent and child outcomes were in the emotional domain. The authors identify several gaps in this literature and suggest areas where research is needed. C1 [Kong, Na Young] Univ Kansas, Lawrence, KS 66045 USA. [Kong, Na Young; Carta, Judith J.] Univ Kansas, Juniper Gardens Childrens Project, Kansas City, KS 66101 USA. 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Early Child. Spec. Educ. PD MAY PY 2013 VL 33 IS 1 BP 4 EP 17 DI 10.1177/0271121411426486 PG 14 WC Education, Special SC Education & Educational Research GA 118GD UT WOS:000317011500001 ER PT J AU Hamlyn, J Duhig, M McGrath, J Scott, J AF Hamlyn, Jess Duhig, Michael McGrath, John Scott, James TI Modifiable risk factors for schizophrenia and autism - Shared risk factors impacting on brain development SO NEUROBIOLOGY OF DISEASE LA English DT Review DE Schizophrenia; Autism; Neurodevelopmental disorder; Epidemiology; Prevention ID VITAMIN-D; SPECTRUM DISORDERS; MATERNAL INFECTION; PATERNAL AGE; CHILDHOOD ADVERSITIES; IMMUNE INVOLVEMENT; PRENATAL EXPOSURE; METAANALYSIS; PSYCHOSIS; BIRTH AB Schizophrenia and autism are two poorly understood clinical syndromes that differ in age of onset and clinical profile. However, recent genetic and epidemiological research suggests that these two neurodevelopmental disorders share certain risk factors. The aims of this review are to describe modifiable risk factors that have been identified in both disorders, and, where available, collate salient systematic reviews and meta-analyses that have examined shared risk factors. Based on searches of Medline, Embase and PsycINFO, inspection of review articles and expert opinion, we first compiled a set of candidate modifiable risk factors associated with autism. Where available, we next collated systematic-reviews (with or without meta-analyses) related to modifiable risk factors associated with both autism and schizophrenia. We identified three modifiable risk factors that have been examined in systematic reviews for both autism and schizophrenia. Advanced paternal age was reported as a risk factor for schizophrenia in a single meta-analysis and as a risk factor in two meta-analyses for autism. With respect to pregnancy and birth complications, for autism one meta-analysis identified maternal diabetes and bleeding during pregnancy as risks factors for autism whilst a meta-analysis of eight studies identified obstetric complications as a risk factor for schizophrenia. Migrant status was identified as a risk factor for both autism and schizophrenia. Two separate meta-analyses were identified for each disorder. Despite distinct clinical phenotypes, the evidence suggests that at least some non-genetic risk factors are shared between these two syndromes. In particular, exposure to drugs, nutritional excesses or deficiencies and infectious agents lend themselves to public health interventions. Studies are now needed to quantify any increase in risk of either autism or schizophrenia that is associated with these modifiable environmental factors. (C) 2012 Elsevier Inc. All rights reserved. C1 [Hamlyn, Jess] Gold Coast Hosp, Southport, Qld 4215, Australia. [Duhig, Michael; McGrath, John; Scott, James] Queensland Ctr Mental Hlth Res, Pk Ctr Mental Hlth, Wacol, Qld 4075, Australia. [Duhig, Michael; Scott, James] Univ Queensland, Clin Res Ctr, Brisbane, Qld 4006, Australia. [McGrath, John; Scott, James] Univ Queensland, Discipline Psychiat, St Lucia, Qld 4067, Australia. [McGrath, John] Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4067, Australia. RP Scott, J (reprint author), Royal Brisbane & Womens Hosp, Level 3 UQCCR, Herston, Qld 4029, Australia. 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Dis. PD MAY PY 2013 VL 53 SI SI BP 3 EP 9 DI 10.1016/j.nbd.2012.10.023 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 109LX UT WOS:000316371200002 PM 23123588 ER PT J AU Raver, SA Hester, P Michalek, AMP Cho, DN Anthony, N AF Raver, Sharon A. Hester, Peggy Michalek, Anne M. P. Cho, Dana Anthony, Nicole TI Impact of an Activity Mini-Schedule on the Inattention of Preschoolers with Cochlear Implants during a Group Activity SO EDUCATION AND TREATMENT OF CHILDREN LA English DT Article DE Mini-Schedules; Evidence-Based Practice; Preschoolers; Cochlear Implants; Hearing Loss; Attention ID PHOTOGRAPHIC ACTIVITY SCHEDULES; VISUAL-ATTENTION; COMMUNICATION INTERVENTION; CHILDREN; AUTISM; HEARING; SKILLS; AUDITION; DEAF AB This pilot study evaluated the effectiveness of using an activity mini-schedule which divided a circle time activity into four sub-activities with four preschoolers who were deaf and had received cochlear implants. Often preschoolers with cochlear implants display difficulty directing attention to appropriate stimuli during large group activities (Chute & Nevins, 2003). It was hypothesized that the use of an activity mini-schedule would decrease inattention. Using a multiple baseline design across participants, an activity mini-schedule was introduced to each participant sequentially by a paraeducator who sat behind the children during circle time. Participants' behaviors were videotaped and coded. The introduction of an activity mini-schedule decreased inattention in all participants, yet individual outcomes varied. Although this study offers some evidence that activity mini-schedules may positively impact attention in young children, more research is needed. C1 [Raver, Sharon A.; Hester, Peggy; Michalek, Anne M. P.; Cho, Dana; Anthony, Nicole] Old Dominion Univ, Norfolk, VA 23529 USA. 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Treat. Child. PD MAY PY 2013 VL 36 IS 2 BP 15 EP 32 PG 18 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AP0JI UT WOS:000341747200002 ER PT J AU Carlile, KA Reeve, SA Reeve, KF Debar, RM AF Carlile, Kelly A. Reeve, Sharon A. Reeve, Kenneth F. DeBar, Ruth M. TI Using Activity Schedules on the iPod touch to Teach Leisure Skills to Children with Autism SO EDUCATION AND TREATMENT OF CHILDREN LA English DT Article DE Activity Schedules; Autism; Independence; iPod Touch; Leisure Skills; Proximity Fading ID DISABILITIES; CLASSROOM; STUDENTS AB Although activity schedules are often presented to learners in book form, this format may be cumbersome and socially stigmatizing to a child with autism. Conversely, presenting an activity schedule on an iPod touch may provide a more socially acceptable format, in that it would be more discreet and allow for easy portability, especially if supports, such as prompts and an adult's presence, are eventually removed. The present study investigated whether an iPod touch could be used to effectively teach activity schedule following involving independent leisure activities to four children with autism. Manual prompts, progressive time-delay procedures, and reinforcement were also used. Prompts were faded using a progressive time-delay procedure, and experimenter proximity to the participants was faded until she was no longer present. A multiple-probe-across-participants design was used. Prior to intervention, none of the participants followed the schedule and they rarely engaged in on-task behavior. Following intervention, all participants learned to independently follow leisure activity schedules presented on the iPod touch and increased their on-task behavior. In addition, these skills generalized to novel settings and novel schedules, and maintained over time. Social validity measures suggested that the participants preferred to follow activity schedules using the iPod touch. Community members also rated the use of the device as more typical of age-related peers and more socially acceptable in the community. The implications of incorporating technology to increase independence in children with autism are discussed. C1 [Carlile, Kelly A.; Reeve, Sharon A.; Reeve, Kenneth F.; DeBar, Ruth M.] Caldwell Coll, Caldwell, NJ 07006 USA. RP Reeve, SA (reprint author), Caldwell Coll, Dept Appl Behav Anal, 120 Bloomfield Ave, Caldwell, NJ 07006 USA. EM sreeve@caldwell.edu CR Blood E., 2011, EDUC TREAT CHILD, V34, P299 Caldwell L. 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A., 2010, EDUC TREAT CHILD, V33, P351, DOI DOI 10.1353/ETC.0.0103 Rehfeldt RA, 2004, J APPL BEHAV ANAL, V37, P115, DOI 10.1901/jaba.2004.37-115 SCHLEIEN SJ, 1981, J APPL BEHAV ANAL, V14, P513, DOI 10.1901/jaba.1981.14-513 Shabani DB, 2002, J APPL BEHAV ANAL, V35, P79, DOI 10.1901/jaba.2002.35-79 STOKES TF, 1977, J APPL BEHAV ANAL, V10, P349, DOI 10.1901/jaba.1977.10-349 Stromer R., 2006, FOCUS AUTISM OTHER D, V21, P14, DOI 10.1177/10883576060210010301 NR 21 TC 3 Z9 3 PU WEST VIRGINIA UNIV PRESS PI MORGANTOWN PA COMMUNICATIONS BLDG PATTESON DR, PO BOX 6295, MORGANTOWN, WV 26506-6295 USA SN 0748-8491 EI 1934-8924 J9 EDUC TREAT CHILD JI Educ. Treat. Child. PD MAY PY 2013 VL 36 IS 2 BP 33 EP 57 PG 25 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AP0JI UT WOS:000341747200003 ER PT J AU Green, VA Drysdale, H Boelema, T Smart, E van der Meer, L Achmadi, D Prior, T O'Reilly, M Diddert, R Lancioni, G AF Green, Vanessa A. Drysdale, Heather Boelema, Tanya Smart, Emily van der Meer, Larah Achmadi, Donna Prior, Tessa O'Reilly, Mark Diddert, Robert Lancioni, Guilio TI Use of Video Modeling to Increase Positive Peer Interactions of Four Preschool Children with Social Skills Difficulties SO EDUCATION AND TREATMENT OF CHILDREN LA English DT Article DE Pre-School Children; Social Skills; Play; Video Modeling; Peer Group Entry; Social Withdrawal ID AUTISM SPECTRUM DISORDERS; ALTERNATIVE TREATMENTS; INTERVENTIONS; METAANALYSIS; BEHAVIOR; ACCEPTABILITY; EFFICACY; RESPONSIVENESS; ADOLESCENTS; COMPETENCE AB Difficulties initiating and maintaining positive social interactions with peers represents a significant problem for many preschool children. The present study sought to evaluate the use of a video modeling intervention for increasing positive peer interactions among four preschool boys who were assessed as having poor social skills. The video modeling intervention was evaluated in a delayed multiple probe across participants design. The video depicted successful entry of a peer in a play routine and maintenance of positive play behavior by the peer. Positive outcomes were achieved for two participants and variable outcomes for the remaining two children. Teachers and parents rated the intervention as acceptable. The results suggest an improvement in the amount of time engaged in positive social interactions with peers for two of the four participants with the onset of the video modeling intervention. The findings are discussed in relation to implications for early childhood practice and future research in the area. C1 [Green, Vanessa A.; Drysdale, Heather; Boelema, Tanya; Smart, Emily; van der Meer, Larah; Achmadi, Donna; Prior, Tessa] Victoria Univ Wellington, Wellington, New Zealand. [O'Reilly, Mark] Univ Texas Austin, Austin, TX 78712 USA. 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PD MAY PY 2013 VL 36 IS 2 BP 59 EP 85 PG 27 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AP0JI UT WOS:000341747200004 ER PT J AU Carbone, VJ O'Brien, L Sweeney-Kerwin, EJ Albert, KM AF Carbone, Vincent J. O'Brien, Leigh Sweeney-Kerwin, Emily J. Albert, Kristin M. TI Teaching Eye Contact to Children with Autism: A Conceptual Analysis and Single Case Study SO EDUCATION AND TREATMENT OF CHILDREN LA English DT Article DE Eye Contact; Social Skills; Mands; Extinction; Autism; Motivating Operations ID INDUCED RESPONSE VARIABILITY; SOCIAL-COMMUNICATIVE SKILLS; JOINT ATTENTION; DEVELOPMENTAL-DISABILITIES; GAZE BEHAVIOR; EXTINCTION; LANGUAGE; INTERVENTION; ADOLESCENTS; STRATEGIES AB Eye contact occurs very early in development and serves many functions for the young child. It has been implicated in the development of social, cognitive, and language skills. A substantial number of children with autism fail to develop this important skill and therefore experimenters with both developmental and behavior analytic perspectives have researched methods to teach eye contact. However, only a few researchers have recently attempted to condition the response of the communication partner as a reinforcer for social behavior and thereby arrange the conditions under which typical children develop social responses. The purpose of this case study was to extend the analysis of typical development of social skills to the teaching of eye contact as a language pragmatic skill to a child with autism. Data from a single case study of a child with autism are provided. C1 [Carbone, Vincent J.; O'Brien, Leigh; Sweeney-Kerwin, Emily J.; Albert, Kristin M.] Carbone Clin, Valley Cottage, NY 10989 USA. RP Carbone, VJ (reprint author), Carbone Clin, 614 Corp Way,Suite 1, Valley Cottage, NY 10989 USA. 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PD MAY PY 2013 VL 36 IS 2 BP 139 EP 159 PG 21 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AP0JI UT WOS:000341747200008 ER PT J AU Cox, A Taliercio, A Zacharyczuk, C AF Cox, Amber Taliercio, Adam Zacharyczuk, Colleen TI Additional CDC Data Dispell Vaccine-Autism Link SO PEDIATRIC ANNALS LA English DT Editorial Material CR DeStefano F, 2013, J PEDIATR-US, V163, P561, DOI 10.1016/j.jpeds.2013.02.001 NR 1 TC 0 Z9 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 EI 1938-2359 J9 PEDIATR ANN JI Pediatr. Annu. PD MAY PY 2013 VL 42 IS 5 BP 178 EP 178 PG 1 WC Pediatrics SC Pediatrics GA 186ZD UT WOS:000322083600006 ER PT J AU Stein, LI Polido, JC Cermak, SA AF Stein, Leah I. Polido, Jose C. Cermak, Sharon A. TI Oral Care and Sensory Over-responsivity in Children with Autism Spectrum Disorders SO PEDIATRIC DENTISTRY LA English DT Article DE AUTISM SPECTRUM DISORDER; SENSORY DISORDERS; DENTAL CARE FOR DISABLED; OCCUPATIONAL THEARPY; ACCESS TO HEALTH CARE ID PROCESSING DISORDERS; YOUNG-CHILDREN; TYPICAL DEVELOPMENT; MENTAL-RETARDATION; INTEGRATION; DESENSITIZATION; ABNORMALITIES; PREVALENCE; BEHAVIORS; PATTERNS AB Purpose: The purpose of this study was to investigate the relationship between sensory sensitivities and oral care difficulties in children with autism spectrum disorders (ASDs) or typical development (TD). Methods: Participants included 396 parents of 2- to 18-year-old children with ASDs or TD who completed a questionnaire about oral care in the home and dental office. Descriptive and bivariate analyses were conducted to examine the association between sensory sensitivities and oral care variables. Results: Both hypotheses were supported: (1) ASDs children vs. TD children were reported to have a significantly greater prevalence of sensory over-responsivity across all sensory domains; and (2) ASDs children characterized as "sensory over-responders" exhibited a significantly greater prevalence of oral care difficulty in the home and dental office vs. ASDs children who responded more typically to sensory stimuli ("sensory not over-responders"). Conclusions: This study provides further evidence for the impact of sensory processing problems on oral care, both in the home and dental office. Methods to best serve children with autism spectrum disorders may include strategies that alter the sensory characteristics of the dental environment as well as interventions to reduce children's sensory sensitivities. C1 [Stein, Leah I.; Cermak, Sharon A.] Univ So Calif, Herman Ostrow Sch Dent, Div Occupat Sci & Occupat Therapy, Los Angeles, CA USA. [Polido, Jose C.] Univ So Calif, Herman Ostrow Sch Dent, Div Dent, Childrens Hosp Los Angeles, Los Angeles, CA USA. RP Stein, LI (reprint author), Univ So Calif, Herman Ostrow Sch Dent, Div Occupat Sci & Occupat Therapy, Los Angeles, CA USA. 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Dent. PD MAY-JUN PY 2013 VL 35 IS 3 BP 230 EP 235 PG 6 WC Dentistry, Oral Surgery & Medicine; Pediatrics SC Dentistry, Oral Surgery & Medicine; Pediatrics GA AS8TL UT WOS:000344520800002 PM 23756306 ER PT J AU Oranje, B Lahuis, B van Engeland, H van der Gaag, RJ Kemner, C AF Oranje, Bob Lahuis, Bertine van Engeland, Herman van der Gaag, Rutger Jan Kemner, Chantal TI Sensory and sensorimotor gating in children with multiple complex developmental disorders (MCDD) and autism SO PSYCHIATRY RESEARCH LA English DT Article DE Auditory evoked responses; P50 suppression; Prepulse inhibition (PPI); Startle reflex ID PREPULSE INHIBITION; SCHIZOPHRENIC-PATIENTS; 1ST-EPISODE SCHIZOPHRENIA; ANTIPSYCHOTIC-NAIVE; BORDERLINE SYNDROME; P50; STARTLE; SUPPRESSION; CLASSIFICATION; ABNORMALITIES AB Multiple Complex Developmental Disorder (MCDD) is a well-defined and validated behavioral subtype of autism with a proposed elevated risk of developing a schizophrenic spectrum disorder. The current study investigated whether children with MCDD show the same deficits in sensory gating that are commonly reported in schizophrenia, or whether they are indistinguishable from children with autism in this respect. P50 suppression and prepulse inhibition (PPI) of the startle reflex were assessed in children with MCDD (n=14) or autism (n=13), and healthy controls (n=12), matched on age and IQ. All subjects showed high levels of PPI and P50 suppression. However, no group differences were found. No abnormalities in sensory filtering could be detected in children with autism or MCDD. Since sensory gating deficits are commonly regarded as possible endophenotypic markers for schizophrenia, the current results do not support a high level of similarity between schizophrenia and MCDD. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Oranje, Bob] Copenhagen Univ Hosp, Ctr Clin Intervent & Neuropsychiat Schizophrenia, Univ Psychiat Ctr Glostrup, DK-2600 Glostrup, Denmark. [Oranje, Bob] Univ Copenhagen, Fac Hlth Sci, Dept Neurol Psychiat & Sensory Sci, DK-1168 Copenhagen, Denmark. [Lahuis, Bertine; van Engeland, Herman; Kemner, Chantal] Univ Med Ctr, Dept Child & Adolescent Psychiat, Utrecht, Netherlands. [van der Gaag, Rutger Jan] Univ Med Ctr, Nijmegen, Netherlands. [Kemner, Chantal] Univ Utrecht, Dept Dev Psychol, NL-3508 TC Utrecht, Netherlands. RP Oranje, B (reprint author), Copenhagen Univ Hosp, Ctr Clin Intervent & Neuropsychiat Schizophrenia, Univ Psychiat Ctr Glostrup, Ndr Ringvej 29-67, DK-2600 Glostrup, Denmark. 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PD APR 30 PY 2013 VL 7 AR 57 DI 10.3389/fncel.2013.00057 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 134NR UT WOS:000318218200001 PM 23641197 ER PT J AU Bozdagi, O Tavassoli, T Buxbaum, JD AF Bozdagi, Ozlem Tavassoli, Teresa Buxbaum, Joseph D. TI Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay SO MOLECULAR AUTISM LA English DT Article DE Pharmacotherapy; Personalized medicine; Individualized medicine; 22q13 deletion syndrome; Phelan-McDermid syndrome ID MUTANT MICE; SHANK3 AB Background: Haploinsufficiency of SHANK3, due to either hemizygous gene deletion (termed 22q13 deletion syndrome or Phelan-McDermid syndrome) or to gene mutation, accounts for about 0.5% of the cases of autism spectrum disorder (ASD) and/or developmental delay, and there is evidence for a wider role for SHANK3 and glutamate signaling abnormalities in ASD and related conditions. Therapeutic approaches that reverse deficits in SHANK3-haploinsufficiency may therefore be broadly beneficial in ASD and in developmental delay. Findings: We observed that daily intraperitoneal injections of human insulin-like growth factor 1 (IGF-1) over a 2-week period reversed deficits in hippocampal alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) signaling, long-term potentiation (LTP), and motor performance that we had previously reported in Shank3-deficient mice. Positive effects were observed with an IGF-1 peptide derivative as well. Conclusions: We observed significant beneficial effects of IGF-1 in a mouse model of ASD and of developmental delay. Studies in mouse and human neuronal models of Rett syndrome also show benefits with IGF-1, raising the possibility that this compound may have benefits broadly in ASD and related conditions, even with differing molecular etiology. 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EM joseph.buxbaum@mssm.edu FU Seaver Foundation; Simons Foundation; NIMH [R01MH093725] FX This work was supported by the Seaver Foundation, the Simons Foundation, the NIMH (grant R01MH093725 to JDB), and by a gift from William Gibson and Paulina Rychenkova, PhD. We thank Catalina Betancur for helpful comments. Aspects of this work were presented at annual meetings of The Society for Neuroscience (2010, 2011) and the American Society of Human Genetics (2010), and at Phelan-McDermid Syndrome symposia (2011, 2012). 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Although psychiatric disorders place a large economic burden on society, the drugs available to treat them are often palliative with variable efficacy and intolerable side-effects. The development of novel drugs has been hindered by a lack of knowledge about the etiology of these diseases. It is thus necessary to further investigate psychiatric disorders using a combination of human molecular genetics, gene-by-environment studies, in vitro pharmacological and biochemistry experiments, animal models, and investigation of the non-biological basis of these diseases, such as environmental effects. Many psychiatric disorders, including autism spectrum disorder, attention-deficit/hyperactivity disorder, mental retardation, and schizophrenia can be triggered by alterations to neural development. The zebrafish is a popular model for developmental biology that is increasingly used to study human disease. Recent work has extended this approach to examine psychiatric disorders as well. However, since psychiatric disorders affect complex mental functions that might be human specific, it is not possible to fully model them in fish. In this review, I will propose that the suitability of zebrafish for developmental studies, and the genetic tools available to manipulate them, provide a powerful model to study the roles of genes that are linked to psychiatric disorders during neural development. The relative speed and ease of conducting experiments in zebrafish can be used to address two areas of future research: the contribution of environmental factors to disease onset, and screening for novel therapeutic compounds. C1 Univ Leicester, Coll Med Biol Sci & Psychiat, Dept Biol, Leicester LE1 7RH, Leics, England. RP Norton, WHJ (reprint author), Univ Leicester, Coll Med Biol Sci & Psychiat, Dept Biol, Univ Rd, Leicester LE1 7RH, Leics, England. 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Neural Circuits PD APR 26 PY 2013 VL 7 AR 79 DI 10.3389/fncir.2013.00079 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 143JN UT WOS:000318863800001 PM 23637652 ER PT J AU Cooper, NR Simpson, A Till, A Simmons, K Puzzo, I AF Cooper, Nicholas R. Simpson, Andrew Till, Amy Simmons, Kelly Puzzo, Ignazio TI Beta event-related desynchronization as an index of individual differences in processing human facial expression: further investigations of autistic traits in typically developing adults SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE alpha; beta; mu; EEG; ERD; autism; emotion ID MIRROR-NEURON SYSTEM; PRIMARY MOTOR CORTEX; MU-RHYTHM; SENSORIMOTOR CORTEX; SPECTRUM DISORDERS; ALPHA OSCILLATIONS; GENERAL-POPULATION; EEG; FACE; IMITATION AB The human mirror neuron system (hMNS) has been associated with various forms of social cognition and affective processing including vicarious experience. It has also been proposed that a faulty hMNS may underlie some of the deficits seen in the autism spectrum disorders (ASDs). In the present study we set out to investigate whether emotional facial expressions could modulate a putative EEG index of hMNS activation (mu suppression) and if so, would this differ according to the individual level of autistic traits [high versus low Autism Spectrum Quotient (AQ) score]. Participants were presented with 3s films of actors opening and closing their hands (classic hMNS mu-suppression protocol) while simultaneously wearing happy, angry, or neutral expressions. Mu-suppression was measured in the alpha and low beta bands. The low AQ group displayed greater low beta event-related desynchronization (ERD) to both angry and neutral expressions. The high AQ group displayed greater low beta ERD to angry than to happy expressions. There was also significantly more low beta ERD to happy faces for the low than for the high AQ group. In conclusion, an interesting interaction between AQ group and emotional expression revealed that hMNS activation can be modulated by emotional facial expressions and that this is differentiated according to individual differences in the level of autistic traits. The EEG index of hMNS activation (mu suppression) seems to be a sensitive measure of the variability in facial processing in typically developing individuals with high and low self-reported traits of autism. C1 [Cooper, Nicholas R.; Simpson, Andrew; Till, Amy; Simmons, Kelly] Univ Essex, Dept Psychol, Ctr Brain Sci, Colchester CO4 3SQ, Essex, England. [Puzzo, Ignazio] Univ Reading, Sch Psychol & Clin Language Sci, Ctr Integrat Neurosci & Neurodynam, Reading, Berks, England. RP Cooper, NR (reprint author), Univ Essex, Dept Psychol, Ctr Brain Sci, Wivenhoe Pk, Colchester CO4 3SQ, Essex, England. 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PD APR 25 PY 2013 VL 7 AR 159 DI 10.3389/fnhum.2013.00159 PG 8 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 136CI UT WOS:000318337100001 PM 23630489 ER PT J AU Chen, CP Lin, CJ Chang, TY Chern, SR Wu, PS Chen, YT Su, JW Lee, CC Chen, LF Wang, W AF Chen, Chih-Ping Lin, Chen-Ju Chang, Tung-Yao Chern, Schu-Rern Wu, Peih-Shan Chen, Yu-Ting Su, Jun-Wei Lee, Chen-Chi Chen, Li-Feng Wang, Wayseen TI Prenatal diagnosis of ring chromosome 2 with lissencephaly and 2p25.3 and 2q37.3 microdeletions detected using array comparative genomic hybridization SO GENE LA English DT Article DE 2p25.3 deletion; 2q37.3 deletion; Lissencephaly; Ring chromosome 2 ID MOLECULAR CYTOGENETIC CHARACTERIZATION; MENTAL-RETARDATION SYNDROME; INTELLECTUAL DISABILITY; DELETION; PATIENT; AUTISM; FISH; DUPLICATION; MOSAICISM; MONOSOMY AB We present rapid aneuploidy diagnosis of ring chromosome 2 with 2p25.3 and 2q37.3 microdeletions by aCGH using uncultured amniocytes in a fetus with IUGR, microcephaly, lissencephaly and ambiguous external genitalia. Our case adds lissencephaly to the list of CNS abnormalities in ring chromosome 2 with 2p25.3 and 2q37.3 microdeletions. We discuss the consequence of haploinsufficiency of HDAC4, KIF1A, PASK, HDLBP, FRAP2 and D2HGDH on 2q37.3, and haploinsufficiency of MYT1L, SNTG2 and TPO on 2p25.3 in this case. (C) 2013 Elsevier B.V. All rights reserved. C1 [Chen, Chih-Ping; Lin, Chen-Ju; Su, Jun-Wei; Lee, Chen-Chi; Chen, Li-Feng] Mackay Mem Hosp, Dept Obstet & Gynecol, Taipei, Taiwan. [Chen, Chih-Ping; Chern, Schu-Rern; Chen, Yu-Ting; Wang, Wayseen] Mackay Mem Hosp, Dept Med Res, Taipei, Taiwan. [Chen, Chih-Ping] Mackay Med Coll, Dept Med, New Taipei City, Taiwan. [Chen, Chih-Ping] Asia Univ, Dept Biotechnol, Taichung, Taiwan. [Chen, Chih-Ping] China Med Univ, Coll Chinese Med, Sch Chinese Med, Taichung, Taiwan. [Chen, Chih-Ping] Natl Yang Ming Univ, Inst Clin & Community Hlth Nursing, Taipei 112, Taiwan. [Chen, Chih-Ping] Natl Yang Ming Univ, Dept Obstet & Gynecol, Sch Med, Taipei 112, Taiwan. [Chang, Tung-Yao] Taiji Fetal Med Ctr, Taipei, Taiwan. [Wu, Peih-Shan] Gene Biodesign Co Ltd, Taipei, Taiwan. [Su, Jun-Wei] China Med Univ Hosp, Dept Obstet & Gynecol, Taichung, Taiwan. [Wang, Wayseen] Tatung Univ, Dept Bioengn, Taipei 104, Taiwan. RP Chen, CP (reprint author), Mackay Mem Hosp, Dept Obstet & Gynecol, 92,Sect 2,Chung Shan North Rd, Taipei, Taiwan. EM cpc_mmh@yahoo.com FU National Science Council [NSC-99-2628-B-195-001-MY3, NSC-101-2314-B-195-011-MY3]; Mackay Memorial Hospital, Taipei, Taiwan [MMH-E-101-04] FX This work was supported by research grants NSC-99-2628-B-195-001-MY3 and NSC-101-2314-B-195-011-MY3 from the National Science Council and MMH-E-101-04 from Mackay Memorial Hospital, Taipei, Taiwan. 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Neal, Sarah J. Lin, Qian Hughes, Zoe A. Smith, Daniel G. TI The BTBR Mouse Model of Autism Spectrum Disorders Has Learning and Attentional Impairments and Alterations in Acetylcholine and Kynurenic Acid in Prefrontal Cortex SO PLOS ONE LA English DT Article ID T PLUS TF/J; REACTION-TIME-TASK; COMPUTER-GRAPHIC STIMULI; DEFICIT/HYPERACTIVITY DISORDER; CEREBROSPINAL-FLUID; UNUSUAL REPERTOIRE; BASAL FOREBRAIN; T+TF/J MICE; RAT; LESIONS AB Autism is a complex spectrum of disorders characterized by core behavioral deficits in social interaction, communication, repetitive stereotyped behaviors and restricted interests. Autism frequently presents with additional cognitive symptoms, including attentional deficits and intellectual disability. Preclinical models are important tools for studying the behavioral domains and biological underpinnings of autism, and potential treatment targets. The inbred BTBR T+tf/J (BTBR) mouse strain has been used as an animal model of core behavioral deficits in autism. BTBR mice exhibit repetitive behaviors and deficits in sociability and communication, but other aspects of their cognitive phenotype, including attentional performance, are not well characterized. We examined the attentional abilities of BTBR mice in the 5-choice serial reaction time task (5-CSRTT) using an automated touchscreen testing apparatus. The 5-CSRTT is an analogue of the human continuous performance task of attention, and so both the task and apparatus have translational relevance to human touchscreen cognitive testing. We also measured basal extracellular levels of a panel of neurotransmitters within the medial prefrontal cortex, a brain region critically important for performing the 5-CSRTT. We found that BTBR mice have increased impulsivity, defined as an inability to withhold responding, and decreased motivation, as compared to C57Bl/6J mice. Both of these features characterize attentional deficit disorders in humans. BTBR mice also display decreased accuracy in detecting short stimuli, lower basal levels of extracellular acetylcholine and higher levels of kynurenic acid within the prefrontal cortex. Intact cholinergic transmission in prefrontal cortex is required for accurate performance of the 5-CSRTT, consequently this cholinergic deficit may underlie less accurate performance in BTBR mice. Based on our findings that BTBR mice have attentional impairments and alterations in a key neural substrate of attention, we propose that they may be valuable for studying mechanisms for treatment of cognitive dysfunction in individuals with attention deficits and autism. C1 [McTighe, Stephanie M.; Neal, Sarah J.; Lin, Qian; Hughes, Zoe A.; Smith, Daniel G.] Pfizer Global Res & Dev, Neurosci Res Unit, Cambridge, MA USA. RP McTighe, SM (reprint author), Pfizer Global Res & Dev, Neurosci Res Unit, Cambridge, MA USA. 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of survival and reproduction and improve the quality of life. However, it is often difficult to identify optimal behaviors in real life due to the complexity of the decision maker's environment and social dynamics. As a result, although many different brain areas and circuits are involved in decision making, evolutionary and learning solutions adopted by individual decision makers sometimes produce suboptimal outcomes. Although these problems are exacerbated in numerous neurological and psychiatric disorders, their underlying neurobiological causes remain incompletely understood. In this review, theoretical frameworks in economics and machine learning and their applications in recent behavioral and neurobiological studies are summarized. Examples of such applications in clinical domains are also discussed for substance abuse, Parkinson's disease, attention-deficit/hyperactivity disorder, schizophrenia, mood disorders, and autism. Findings from these studies have begun to lay the foundations necessary to improve diagnostics and treatment for various neurological and psychiatric disorders. C1 Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA. RP Lee, D (reprint author), Yale Univ, Sch Med, Dept Neurobiol, 333 Cedar St, New Haven, CT 06510 USA. EM daeyeol.lee@yale.edu RI Lee, Daeyeol/A-6794-2008 OI Lee, Daeyeol/0000-0003-3474-019X FU National Institute of Health [DA029330, DA027844] FX I am grateful to Amy Arnsten, Min Whan Jung, Matt Kleinman, Ifat Levy, Mike Petrowicz, Joey Schnurr, and Hyojung Seo for their helpful comments on the manuscript. The author's research is supported by the National Institute of Health (DA029330 and DA027844). 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However, prenatal exposure to valproate may increase the risk of autism. Objective To determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring. Design, Setting, and Participants Population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). We analyzed the risks associated with all autism spectrum disorders as well as childhood autism. Data were analyzed by Cox regression adjusting for potential confounders (maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity). Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first. Main Outcomes and Measures Absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy. Results Of 655 615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI, 2.59%-7.46%) for autism spectrum disorder (adjusted HR, 2.9 [95% CI, 1.7-4.9]) and an absolute risk of 2.50% (95% CI, 1.30%-4.81%) for childhood autism (adjusted HR, 5.2 [95% CI, 2.7-10.0]). When restricting the cohort to the 6584 children born to women with epilepsy, the absolute risk of autism spectrum disorder among 432 children exposed to valproate was 4.15% (95% CI, 2.20%-7.81%) (adjusted HR, 1.7 [95% CI, 0.9-3.2]), and the absolute risk of childhood autism was 2.95% (95% CI, 1.42%-6.11%) (adjusted HR, 2.9 [95% CI, 1.4-6.0]) vs 2.44% (95% CI, 1.88%-3.16%) for autism spectrum disorder and 1.02% (95% CI, 0.70%-1.49%) for childhood autism among 6152 children not exposed to valproate. Conclusions and Relevance Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control. JAMA. 2013;309(16):1696-1703 www.jama.com C1 [Christensen, Jakob] Aarhus Univ Hosp, Dept Neurol, DK-8000 Aarhus C, Denmark. [Christensen, Jakob] Aarhus Univ Hosp, Dept Clin Pharmacol, DK-8000 Aarhus C, Denmark. [Gronborg, Therese Koops; Parner, Erik Thorlund] Aarhus Univ, Inst Publ Hlth, Dept Biostat, Aarhus, Denmark. [Pedersen, Lars Henning] Aarhus Univ, Inst Publ Hlth, Dept Epidemiol, Aarhus, Denmark. [Pedersen, Lars Henning] Aarhus Univ, Inst Clin Med, Dept Obstet & Gynaecol, Aarhus, Denmark. [Vestergaard, Mogens] Aarhus Univ, Inst Publ Hlth, Res Unit, Aarhus, Denmark. [Vestergaard, Mogens] Aarhus Univ, Inst Publ Hlth, Sect Gen Practice, Aarhus, Denmark. [Sorensen, Merete Juul] Aarhus Univ Hosp, Reg Ctr Child & Adolescent Psychiat, Risskov, Denmark. [Schendel, Diana] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Christensen, J (reprint author), Aarhus Univ Hosp, Dept Neurol, Norrebrogade 44, DK-8000 Aarhus C, Denmark. EM jakob@farm.au.dk RI Vestergaard, Mogens/M-9333-2014 OI Vestergaard, Mogens/0000-0001-8830-2174 FU UCB Nordic; Danish Epilepsy Association; Danish Council for Independent Research; European Research Council (European Union) [260242]; Danish Medical Research Council [09-072986] FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Christensen reported receiving honoraria for serving on the scientific advisory boards of UCB Nordic and Eisai AB; receiving lecture honoraria from UCB Nordic and Eisai AB; and receiving travel funding from UCB Nordic. Dr Parner reported receiving grants from Autism Speaks and the National Institutes of Health. No other authors reported disclosures.Dr Christensen receives research support from the Danish Epilepsy Association. Dr Pedersen is supported by a Sapere Aude-Postdoctoral grant from the Danish Council for Independent Research. This study was supported by grants from the European Research Council (the European Union Seventh Framework Programme, ERC-2010-StG No. 260242) and the Danish Medical Research Council (09-072986). 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Am. Med. Assoc. PD APR 24 PY 2013 VL 309 IS 16 BP 1696 EP 1703 DI 10.1001/jama.2013.2270 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 130IG UT WOS:000317906700026 PM 23613074 ER PT J AU van Boxtel, JJA Lu, HJ AF van boxtel, Jeroen J. A. Lu, Hongjing TI Impaired global, and compensatory local, biological motion processing in people with high levels of autistic traits SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE biological motion perception; autism spectrum disorder; attention; individual differences; predictive coding; adaptation; dual-task ID SACCADIC EYE-MOVEMENTS; POINT-LIGHT DISPLAYS; SPECTRUM DISORDERS; VISUAL-PERCEPTION; CHILDREN; ADAPTATION; BRAIN; RECOGNITION; COHERENCE; INTEGRATION AB People with Autism Spectrum Disorder (ASD) are hypothesized to have poor high-level processing but superior low-level processing, causing impaired social recognition, and a focus on non-social stimulus contingencies. Biological motion perception provides an ideal domain to investigate exactly how ASD modulates the interaction between low and high-level processing, because it involves multiple processing stages, and carries many important social cues. We investigated individual differences among typically developing observers in biological motion processing, and whether such individual differences associate with the number of autistic traits. In Experiment 1, we found that individuals with fewer autistic traits were automatically and involuntarily attracted to global biological motion information, whereas individuals with more autistic traits did not show this pre-attentional distraction. We employed an action adaptation paradigm in the second study to show that individuals with more autistic traits were able to compensate for deficits in global processing with an increased involvement in local processing. Our findings can be interpreted within a predictive coding framework, which characterizes the functional relationship between local and global processing stages, and explains how these stages contribute to the perceptual difficulties associated with ASD. C1 [van boxtel, Jeroen J. A.; Lu, Hongjing] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Lu, Hongjing] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90095 USA. RP van Boxtel, JJA (reprint author), Univ Calif Los Angeles, Dept Psychol, Franz Hall 6550, Los Angeles, CA 90095 USA. 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TI Proteomic Profiling in Drosophila Reveals Potential Dube3a Regulation of the Actin Cytoskeleton and Neuronal Homeostasis SO PLOS ONE LA English DT Article ID UBIQUITIN-PROTEIN LIGASE; ANGELMAN-SYNDROME; PROXIMAL 15Q; GLIAL-CELLS; GENE UBE3A; DEGRADATION; EXPRESSION; DUPLICATION; MUTATIONS; SYNAPSE AB The molecular defects associated with Angelman syndrome (AS) and 15q duplication autism are directly correlated to expression levels of the E3 ubiquitin ligase protein UBE3A. Here we used Drosophila melanogaster to screen for the targets of this ubiquitin ligase under conditions of both decreased (as in AS) or increased (as in dup(15)) levels of the fly Dube3a or human UBE3A proteins. Using liquid phase isoelectric focusing of proteins from whole fly head extracts we identified a total of 50 proteins that show changes in protein, and in some cases transcriptional levels, when Dube3a fluctuates. We analyzed head extracts from cytoplasmic, nuclear and membrane fractions for Dube3a regulated proteins. Our results indicate that Dube3a is involved in the regulation of cellular functions related to ATP synthesis/metabolism, actin cytoskeletal integrity, both catabolism and carbohydrate metabolism as well as nervous system development and function. Sixty-two percent of the proteins were > 50% identical to homologous human proteins and 8 have previously be shown to be ubiquitinated in the fly nervous system. Eight proteins may be regulated by Dube3a at the transcript level through the transcriptional co-activation function of Dube3a. We investigated one autism-associated protein, ATP alpha, and found that it can be ubiquitinated in a Dube3a dependent manner. We also found that Dube3a mutants have significantly less filamentous actin than wild type larvae consistent with the identification of actin targets regulated by Dube3a. The identification of UBE3A targets is the first step in unraveling the molecular etiology of AS and duplication 15q autism. C1 [Jensen, Laura; Farook, M. Febin; Reiter, Lawrence T.] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA. [Reiter, Lawrence T.] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. [Reiter, Lawrence T.] Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA. RP Reiter, LT (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA. EM lreiter@uthsc.edu FU Autism Speaks; NIH NINDS [R01 NS059902-03]; Neurosciences Institute at UTHSC; NIH NCRR [1 S10 RR027221-01] FX This work was supported by an Autism Speaks grant and NIH NINDS grant R01 NS059902-03 to LTR. Additional support was provided by the Neurosciences Institute at UTHSC and by NIH NCRR grant 1 S10 RR027221-01 to William E. Armstrong. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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However, little attention has been paid to ToM in patients with cerebral infarction. In this study, we investigated the ability of ToM in patients with temporal lobe cerebral infarction (TLCI) using a variety of tests. Methods: In the study, 19 patients with TLCI and 20 healthy controls (HC) were examined using the Recognition of faux pas and the Reading the Mind in the Eyes (RME) tasks, to assess their ability of ToM. Results: The results of the study indicated that the TLCI group performed significantly worse compared with the HC group as revealed in the total faux pas-related score and in emotion recognition (Mind Reading). Conclusions: Our results implied that patients with TLCI had difficulty in ToM. Our data provided new evidence that the temporal lobe may be involved in processing ToM inferences. C1 [Xi, Chunhua; Zhu, Chunyan; Wang, Yongguang; Wang, Kai] Anhui Med Univ, Neuropsychol Lab, Dept Neurol, Affiliated Hosp 1, Hefei 230022, Anhui, Peoples R China. [Xi, Chunhua; Zhu, Youling; Song, Daohui] Anhui Med Univ, Dept Neurol, Affiliated Hosp 3, Hefei 230061, Anhui, Peoples R China. [Wang, Yongguang] Zhejiang Univ, Dept Psychol & Behav Sci, Hangzhou 310028, Peoples R China. RP Wang, K (reprint author), Anhui Med Univ, Neuropsychol Lab, Dept Neurol, Affiliated Hosp 1, Jixi Rd, Hefei 230022, Anhui, Peoples R China. EM wangkai1964@yahoo.com RI Wang, Yongguang/G-9548-2013 FU Natural Science Foundation of China [91232717, 81171273, 31100812, 10080703040]; Educational Commission of Anhui Province [KJ2011Z198] FX This research was supported by the Natural Science Foundation of China (91232717, 81171273, 31100812), (10080703040) and Educational Commission of Anhui Province (KJ2011Z198). 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Brain Funct. PD APR 22 PY 2013 VL 9 AR 15 DI 10.1186/1744-9081-9-15 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 145AT UT WOS:000318985700001 PM 23607361 ER PT J AU Mareschal, I Calder, AJ Clifford, CWG AF Mareschal, Isabelle Calder, Andrew J. Clifford, Colin W. G. TI Humans Have an Expectation That Gaze Is Directed Toward Them SO CURRENT BIOLOGY LA English DT Article ID EYE CONTACT; TEMPORAL CORTEX; PERCEPTION; AUTISM; ORIENTATION; LOOKING; MOTION; FACES; CELLS; ME AB Many animals use cues from another animal's gaze to help distinguish friend from foe [1-3]. In humans, the direction of someone's gaze provides insight into their focus of interest and state of mind [4] and there is increasing evidence linking abnormal gaze behaviors to clinical conditions such as schizophrenia and autism [5-11]. This fundamental role of another's gaze is buoyed by the discovery of specific brain areas dedicated to encoding directions of gaze in faces [12-14]. Surprisingly, however, very little is known about how others' direction of gaze is interpreted. Here we apply a Bayesian framework that has been successfully applied to sensory and motor domains [15-19] to show that humans have a prior expectation that other people's gaze is directed toward them. This expectation dominates perception when there is high uncertainty, such as at night or when the other person is wearing sunglasses. We presented participants with synthetic faces viewed under high and low levels of uncertainty and manipulated the faces by adding noise to the eyes. Then, we asked the participants to judge relative gaze directions. We found that all participants systematically perceived the noisy gaze as being directed more toward them. This suggests that the adult nervous system internally represents a prior for gaze and highlights the importance of experience in developing our interpretation of another's gaze. C1 [Mareschal, Isabelle; Clifford, Colin W. G.] Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia. [Mareschal, Isabelle; Clifford, Colin W. G.] Univ Sydney, Australian Ctr Excellence Vis Sci, Sydney, NSW 2006, Australia. [Calder, Andrew J.] MRC, Cognit & Brain Sci Unit, Cambridge CB2 7EF, England. RP Mareschal, I (reprint author), Queen Mary Univ London, Sch Biol & Chem Sci, London E1 4NS, England. EM i.mareschal@qmul.ac.uk FU Australian Research Council [DP120102589, FT110100150]; Medical Research Council, UK [MC_US_A060_5PQ50] FX This work is supported by the Australian Research Council Discovery Project (DP120102589) to C.C. and A.C. C.C. is supported by an Australian Research Council Future Fellowship (FT110100150). A.C. is supported by the Medical Research Council, UK (MC_US_A060_5PQ50). 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Biol. PD APR 22 PY 2013 VL 23 IS 8 BP 717 EP 721 DI 10.1016/j.cub.2013.03.030 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 131ND UT WOS:000317999500027 PM 23562265 ER PT J AU Smoller, JW Craddock, N Kendler, K Lee, PH Neale, BM Nurnberger, JI Ripke, S Santangelo, S Sullivan, PF AF Smoller, Jordan W. Craddock, Nicholas Kendler, Kenneth Lee, Phil Hyoun Neale, Benjamin M. Nurnberger, John I. Ripke, Stephan Santangelo, Susan Sullivan, Patrick F. CA Psychiatric Genomics Consortium TI Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis SO LANCET LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; BIPOLAR DISORDER; GENE-EXPRESSION; SCHIZOPHRENIA; ASSOCIATION; METAANALYSIS; POPULATION; CACNA1C; DEPRESSION AB Background Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. Methods We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33 332 cases and 27 888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples. Findings SNPs at four loci surpassed the cutoff for genome-wide significance (p<5x10(-8)) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported effects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all five disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers. Interpretation Our findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause. C1 [Smoller, Jordan W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Simches Res Bldg, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu RI Franke, Barbara/D-4836-2009; Sonuga-Barke, Edmund/D-9137-2011; Kuntsi, Jonna/G-9750-2011; van Grootheest, Gerard/C-6942-2014; Sigurdsson, Engilbert/D-2486-2014; Kahler, Anna/J-2874-2012; McQuillin, Andrew/C-1623-2008; Nolen, Willem/E-9006-2014; Zhang, Peng/N-2920-2014; Breen, Gerome/A-5540-2010; Medland, Sarah/C-7630-2013; Hansen, Thomas/O-5965-2014; Lesch, Klaus-Peter/J-4906-2013; Mowry, Bryan /G-5046-2010; Holmans, Peter/F-4518-2015 OI Franke, Barbara/0000-0003-4375-6572; van Grootheest, Gerard/0000-0003-4350-6661; Sigurdsson, Engilbert/0000-0001-9404-7982; McQuillin, Andrew/0000-0003-1567-2240; Zhang, Peng/0000-0003-1182-1392; Breen, Gerome/0000-0003-2053-1792; Medland, Sarah/0000-0003-1382-380X; Hansen, Thomas/0000-0001-6703-7762; Lesch, Klaus-Peter/0000-0001-8348-153X; Holmans, Peter/0000-0003-0870-9412 FU NIMH [U01 MH085520]; National Institutes of Health (USA); National Institute of Mental Health FX National Institute of Mental Health.We thank the study participants, and the research staff at the many study sites. 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TI Challenges in comparing the safety of different vaccination schedules SO VACCINE LA English DT Article DE Epidemiologic methods; Immunization schedule; Vaccination ID CASE SERIES; VACCINES; INFANTS; PHYSICIANS; PARENTS; AUTISM; DESIGN; RISK AB As vaccine hesitancy has increased in the United States, various authors have begun proposing alternatives to the Advisory Committee on Immunization Practices' recommended childhood immunization schedule. Because parents may believe the safety claims made by such authors, evaluations of the safety of alternative vaccination schedules are needed. However, comparing the safety of different vaccination schedules has numerous methodologic challenges. These challenges include defining vaccination history, defining safety, appropriately modeling interactions between vaccines, and appropriately handling age effects. Failure to properly address these challenges can result in biased results. (C) 2013 Elsevier Ltd. All rights reserved. C1 Grp Hlth Res Inst, Seattle, WA 98101 USA. RP Jackson, ML (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM jackson.ml@ghc.org FU America's Health Insurance Plans (AHIP) from the Centers for Disease Control and Prevention (CDC) [200-2002-00732] FX This work was supported by a subcontract with America's Health Insurance Plans (AHIP) under contract 200-2002-00732 from the Centers for Disease Control and Prevention (CDC). 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Dalman, Christina Golding, Jean Lewis, Glyn Magnusson, Cecilia TI Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; COMPREHENSIVE METAANALYSIS; PSYCHIATRIC-DISORDERS; SOCIOECONOMIC-STATUS; FETAL-GROWTH; EXPOSURE; OUTCOMES; REGISTER; BIRTH; MISCLASSIFICATION AB Objective To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring. Design Population based nested case-control study. Setting Stockholm County, Sweden, 2001-07. Participants 4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43 277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16 845 controls with data on maternal antidepressant use nested within a cohort (n=589 114) of young people aged 0-17 years. Main outcome measure A diagnosis of autism spectrum disorder, with or without intellectual disability. Exposures Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards. Results A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder. Conclusions In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases. C1 [Rai, Dheeraj; Lewis, Glyn] Univ Bristol, Sch Social & Community Med, Ctr Mental Hlth Addict & Suicide Res, Bristol BS8 2BN, Avon, England. [Rai, Dheeraj; Dalman, Christina; Magnusson, Cecilia] Karolinska Inst, Dept Publ Hlth Sci, Div Publ Hlth Epidemiol, Stockholm, Sweden. [Rai, Dheeraj] Avon & Wiltshire Partnership Mental Hlth NHS Trus, Bristol, Avon, England. [Lee, Brian K.] Drexel Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Golding, Jean] Univ Bristol, Sch Social & Community Med, Ctr Child & Adolescent Hlth, Bristol BS8 2BN, Avon, England. RP Rai, D (reprint author), Univ Bristol, Sch Social & Community Med, Ctr Mental Hlth Addict & Suicide Res, Bristol BS8 2BN, Avon, England. EM dheeraj.rai@bristol.ac.uk RI Lewis, Glyn/E-9944-2012 OI Lewis, Glyn/0000-0001-5205-8245 FU Swedish Research Council [2012-3017, 523-2010-1052]; Stockholm County Council [2007008]; Swedish Council for Working Life and Social Research [2007-2064]; Swedish Regional agreement on medical training and clinical research (ALF) FX This study was funded by the Swedish Research Council (grant No 2012-3017). The data linkages and staff costs have also been supported by grants from the Stockholm County Council (2007008), Swedish Council for Working Life and Social Research (2007-2064), Swedish Research Council (523-2010-1052), and Swedish Regional agreement on medical training and clinical research (ALF). No funder had any role in the study design; data collection, analysis, or interpretation; in the writing of the report; or in the decision to submit the article for publication. The views expressed are those of the authors and not necessarily those of any of the funders or organisations they represent. 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FXS is a genetic cause of intellectual impairment and is an autism spectrum disorder. Human studies with auditory evoked potentials indicate that FXS is associated with abnormal auditory processing. The Fmr1 knock-out (KO) mouse is a useful model for studying FXS. The KO mice show acoustic hypersensitivity and propensity for audiogenic seizures, suggesting altered auditory responses. However, the nature of changes at the neuronal level is not known. Here we conducted in vivo single unit extracellular electrophysiology in the auditory cortex of urethane/xylazine-anesthetized Fmr1 KO mice in response to tones and frequency modulated (FM) sweeps. Using tones as stimuli, we report expanded frequency tuning, enhanced response magnitude, and more variable first spike latencies in Fmr1 KO mice compared to wild-type controls. FM sweep stimuli revealed altered sensitivity to the rate of frequency change indicating abnormal spectrotemporal processing. There was no difference in FM sweep direction selectivity. Consistent with studies of the somatosensory cortex, these data point to hyper-responsiveness of auditory neurons as a key processing abnormality in FXS. Auditory neural responses can serve as outcome measures in preclinical trials of therapeutics for FXS as well as serve as physiological probes to study their mechanisms of action. (C) 2013 Elsevier B.V. All rights reserved. C1 [Razak, Khaleel] Univ Calif Riverside, Grad Program Neurosci, Riverside, CA 92521 USA. Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA. RP Razak, K (reprint author), Univ Calif Riverside, Grad Program Neurosci, Riverside, CA 92521 USA. EM khaleel@ucr.edu FU FRAXA Research Foundation FX This work was supported by the FRAXA Research Foundation. We thank members of the Razak lab for useful discussions on the data and the manuscript. We also thank Dr. Iryna Ethell for providing mice for experiments and discussions of the data. 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PD APR 19 PY 2013 VL 1506 BP 12 EP 24 DI 10.1016/j.brainres.2013.02.038 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 134KJ UT WOS:000318208800002 PM 23458504 ER PT J AU Yang, W Liu, J Zheng, FF Jia, MX Zhao, LN Lu, TL Ruan, YY Zhang, JS Yue, WH Zhang, D Wang, LF AF Yang, Wen Liu, Jing Zheng, Fanfan Jia, Meixiang Zhao, Linnan Lu, Tianlan Ruan, Yanyan Zhang, Jishui Yue, Weihua Zhang, Dai Wang, Lifang TI The Evidence for Association of ATP2B2 Polymorphisms with Autism in Chinese Han Population SO PLOS ONE LA English DT Article ID PLASMA-MEMBRANE CA2+-ATPASE; PERVASIVE DEVELOPMENTAL DISORDERS; COMMON GENETIC-VARIANTS; GENOME-WIDE; LINKAGE DISEQUILIBRIUM; DISEASE GENES; RAT-BRAIN; SPECTRUM DISORDERS; INFANTILE-AUTISM; COMPLEX DISEASES AB Background: Autism is a neurodevelopmental disorder with a high estimated heritability. ATP2B2, located on human chromosome 3p25.3, encodes the plasma membrane calcium-transporting ATPase 2 which extrudes Ca2+ from cytosol into extracellular space. Recent studies reported association between ATP2B2 and autism in samples from Autism Genetic Resource Exchange (AGRE) and Italy. In this study, we investigated whether ATP2B2 polymorphisms were associated with autism in Chinese Han population. Methods: We performed a family based association study between five SNPs (rs35678 in exon, rs241509, rs3774180, rs3774179, and rs2278556 in introns) in ATP2B2 and autism in 427 autism trios of Han Chinese descent. All SNPs were genotyped using the Sequenom genotyping platform. The family-based association test (FBAT) program was used to perform association test for SNPs and haplotype analyses. Results: This study demonstrated a preferential transmission of T allele of rs3774179 to affected offsprings under an additive model (T>C, Z = 2.482, p = 0.013). While C allele of rs3774179 showed an undertransmission from parents to affected children under an additive and a dominant model, respectively (Z = -2.482, p = 0.013; Z = -2.591, p = 0.0096). Haplotype analyses revealed that three haplotypes were significantly associated with autism. The haplotype C-C (rs3774180-rs3774179) showed a significant undertransmission from parents to affected offsprings both in specific and global haplotype FBAT (Z = -2.037, p = 0.042; Global p = 0.03). As for the haplotype constructed by rs3774179 and rs2278556, C-A might be a protective haplotype (Z = -2.206, p = 0.027; Global p = 0.04), while T-A demonstrated an excess transmission from parents to affected offsprings (Z = 2.143, p = 0.032). These results were still significant after using the permutation method to obtain empirical p values. Conclusions: Our research suggested that ATP2B2 might play a role in the etiology of autism in Chinese Han population. C1 [Yang, Wen; Liu, Jing; Zheng, Fanfan; Jia, Meixiang; Zhao, Linnan; Lu, Tianlan; Ruan, Yanyan; Yue, Weihua; Zhang, Dai; Wang, Lifang] Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing 100871, Peoples R China. [Yang, Wen; Liu, Jing; Zheng, Fanfan; Jia, Meixiang; Zhao, Linnan; Lu, Tianlan; Ruan, Yanyan; Yue, Weihua; Zhang, Dai; Wang, Lifang] Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China. [Zhang, Jishui] Capital Univ Med Sci, Beijing Childrens Hosp, Beijing, Peoples R China. [Zhang, Dai] Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China. RP Zhang, D (reprint author), Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing 100871, Peoples R China. EM daizhang@bjmu.edu.cn; lifangwang@bjmu.edu.cn FU National Basic Research Development Program of China (973 program) [2010CB833905]; National Natural Science Foundation [81071110] FX This research was supported by research grants from the National Basic Research Development Program of China (973 program 2010CB833905), and National Natural Science Foundation (grant number 81071110). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Results: By assuming a recessive model of inheritance, we identified seven candidate genes shared by the two probands. We also evaluated a different analytical strategy that does not require the assumption of disease model, and identified a list of 59 candidate variants that may increase susceptibility to autism. Manual examination of this list identified ANK3 as the most likely candidate gene. Finally, we identified 33 prioritized non-coding variants such as those near SMG6 and COQ5, based on evolutionary constraint and experimental evidence from ENCODE. Although we were unable to confirm rigorously whether any of these genes indeed contribute to the disease, our analysis provides a prioritized shortlist for further validation studies. Conclusions: Our study represents one of the first whole-genome sequencing studies in autism leveraging a large family-based pedigree. These results provide for a discussion on the relative merits of finding de-novo mutations in sporadic cases versus finding inherited mutations in large pedigrees, in the context of neuropsychiatric and neurodevelopmental diseases. C1 [Shi, Lingling; Wang, Kai] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Psychiat, Los Angeles, CA 90089 USA. [Zhang, Xu] S China Univ Technol, Sch Biosci & Bioengn, Guangzhou 510641, Guangdong, Peoples R China. [Zhang, Xu; He, Mingze] BGI Tianjin, Tianjin 300308, Peoples R China. [Golhar, Ryan; Otieno, Frederick G.; Hou, Cuiping; Kim, Cecilia; Keating, Brendan; Lyon, Gholson J.; Wang, Kai; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Lyon, Gholson J.] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, New York, NY 11724 USA. [Hakonarson, Hakon] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. RP Wang, K (reprint author), Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Psychiat, Los Angeles, CA 90089 USA. EM kaiwang@usc.edu; hakonarson@email.chop.edu RI Lyon, Gholson/D-2765-2014 OI Lyon, Gholson/0000-0002-5869-0716 FU NIH/NHGRI [R01 HG006465]; PADOH [4100047863]; Lurie Foundation; Margaret Q Landenberger Foundation FX The authors thank members of the Wang and Hakonarson lab for helpful discussions and comments. This study is in part supported by NIH/NHGRI grant number R01 HG006465 and by PADOH grant 4100047863 for autism genetics. We also thank the Lurie Foundation and the Margaret Q Landenberger Foundation for their support. 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TI Male-Biased Autosomal Effect of 16p13.11 Copy Number Variation in Neurodevelopmental Disorders SO PLOS ONE LA English DT Article ID RARE CHROMOSOMAL DELETIONS; END RULE PATHWAY; HUMAN GENOME; DE-NOVO; DEVELOPMENTAL DELAY; RECURRENT MICRODELETIONS; GENERALIZED EPILEPSIES; GENETIC ARCHITECTURE; SPECTRUM DISORDERS; BIPOLAR DISORDER AB Copy number variants (CNVs) at chromosome 16p13.11 have been associated with a range of neurodevelopmental disorders including autism, ADHD, intellectual disability and schizophrenia. Significant sex differences in prevalence, course and severity have been described for a number of these conditions but the biological and environmental factors underlying such sex-specific features remain unclear. We tested the burden and the possible sex-biased effect of CNVs at 16p13.11 in a sample of 10,397 individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridisation (aCGH); cases were compared with 11,277 controls. In order to identify candidate phenotype-associated genes, we performed an interval-based analysis and investigated the presence of ohnologs at 16p13.11; finally, we searched the DECIPHER database for previously identified 16p13.11 copy number variants. In the clinical referral series, we identified 46 cases with CNVs of variable size at 16p13.11, including 28 duplications and 18 deletions. Patients were referred for various phenotypes, including developmental delay, autism, speech delay, learning difficulties, behavioural problems, epilepsy, microcephaly and physical dysmorphisms. CNVs at 16p13.11 were also present in 17 controls. Association analysis revealed an excess of CNVs in cases compared with controls (OR = 2.59; p = 0.0005), and a sex-biased effect, with a significant enrichment of CNVs only in the male subgroup of cases (OR = 5.62; p = 0.0002), but not in females (OR = 1.19, p = 0.673). The same pattern of results was also observed in the DECIPHER sample. Interval-based analysis showed a significant enrichment of case CNVs containing interval II (OR = 2.59; p = 0.0005), located in the 0.83 Mb genomic region between 15.49-16.32 Mb, and encompassing the four ohnologs NDE1, MYH11, ABCC1 and ABCC6. Our data confirm that duplications and deletions at 16p13.11 represent incompletely penetrant pathogenic mutations that predispose to a range of neurodevelopmental disorders, and suggest a sex-limited effect on the penetrance of the pathological phenotypes at the 16p13.11 locus. C1 [Tropeano, Maria; Dobson, Richard J. B.; Breen, Gerome; Rucker, James; Dixit, Abhishek; McGuffin, Peter; Farmer, Anne; Vassos, Evangelos; Curran, Sarah; Collier, David A.] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Ahn, Joo Wook; Ogilvie, Caroline Mackie] Guys & St Thomas NHS Fdn Trust, Dept Cytogenet, London, England. [Pal, Deb K.] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, London WC2R 2LS, England. [White, Peter S.] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA. [White, Peter S.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Andrieux, Joris] CHRU Lille, Inst Genet Med, Lille, France. [Collier, David A.] Eli Lilly & Co Ltd, Discovery Neurosci Res, Lilly Res Labs, Windlesham, Surrey, England. RP Tropeano, M (reprint author), Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. EM maria.tropeano@kcl.ac.uk; collier_david_andrew@lilly.com RI Vassos, Evangelos/F-9825-2013; McGuffin, Peter/A-1565-2012; Tropeano, Maria/E-7611-2011; Dobson, Richard/C-9269-2011; Breen, Gerome/A-5540-2010 OI Vassos, Evangelos/0000-0001-6363-0438; McGuffin, Peter/0000-0002-9888-2907; Tropeano, Maria/0000-0002-5156-7539; Dobson, Richard/0000-0003-4224-9245; Breen, Gerome/0000-0003-2053-1792 FU South London and Maudsley Trust NIHR specialist Biomedical Research Centre; Guys and St Thomas Trust NIHR comprehensive Biomedical Research Centre; European Commission Seventh Framework project PsychCNVs [HEALTH-2007-2.2.1-10-223423]; Wellcome Trust (Wellcome Trust Case control consortium; WTCCC2) FX This project and the BBGRE database (BBGRE.org) was funded through a strategic partnership of the South London and Maudsley Trust NIHR specialist Biomedical Research Centre and the Guys and St Thomas Trust NIHR comprehensive Biomedical Research Centre. DAC is funded by the European Commission Seventh Framework project PsychCNVs (http://www.psych-cnv.eu/; Grant agreement number HEALTH-2007-2.2.1-10-223423). This work was supported by the Wellcome Trust (Wellcome Trust Case control consortium; WTCCC2) (DAC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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NEUTRON-ACTIVATION ANALYSIS; DIABETES-MELLITUS PATIENTS; BONE-MINERAL DENSITY; ATOMIC-ABSORPTION-SPECTROMETRY; PLASMA-MASS SPECTROMETRY; TRACE-ELEMENT EXPOSURE; BREAST-CANCER PATIENTS; CHRONIC-RENAL-FAILURE; BLOOD MERCURY LEVEL AB Background: Hair analysis is used for estimation of the nutritional status of individuals. In the present work, a systematic review on the relation between the mineral composition of hair and the physical or mental disorders is discussed. Detailed information of examined populations, methods of sample preparations and analytical techniques are presented. Methods: A systematic literature search in four electronic databases Scopus, PubMed, Web of Science and Medline (from 1997 to 2012/01/31) for English language articles was performed. In addition, a reference list and manual search was undertaken. Results: The following number of studies was included: 66. Most of the authors reported that there exists a correlation between deficiency or excess of some elements in hair and occurrence of some diseases, such as: autism, cancer, hypertension, myocardial infarction, kidney disease and diabetes mellitus. However, not all results were consistent. Conclusions: Most of the authors concluded that the profile of hair mineral imbalance might be useful as a diagnostic tool for the early diagnosis of many diseases. However, it seems that there is a need to standardize sample preparation procedures, in particular washing and mineralization methods. (C) 2013 Elsevier B.V. All rights reserved. C1 [Wolowiec, Paulina; Michalak, Izabela; Chojnacka, Katarzyna] Wroclaw Univ Technol, Inst Inorgan Technol & Mineral Fertilizers, PL-50372 Wroclaw, Poland. [Mikulewicz, Marcin] Med Acad Wroclaw, Dept Dentofacial Orthopead & Orthodont, PL-50425 Wroclaw, Poland. RP Michalak, I (reprint author), Wroclaw Univ Technol, Inst Inorgan Technol & Mineral Fertilizers, Smoluchowskiego 25, PL-50372 Wroclaw, Poland. EM paulina.wolowiec@pwr.wroc.pl; izabela.michalak@pwr.wroc.pl; katarzyna.chojnacka@pwr.wroc.pl; mikulewicz.marcin@gmail.com FU National Centre for Research and Development in Poland [N R13 0006 10] FX The work was supported by The National Centre for Research and Development in Poland - project no. N R13 0006 10. 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Chim. Acta PD APR 18 PY 2013 VL 419 BP 139 EP 171 DI 10.1016/j.cca.2013.02.001 PG 33 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 134EK UT WOS:000318192700027 PM 23415695 ER PT J AU Dominguez, LG Velazquez, JLP Galan, RF AF Dominguez, Luis Garcia Velazquez, Jose Luis Perez Galan, Roberto Fernandez TI A Model of Functional Brain Connectivity and Background Noise as a Biomarker for Cognitive Phenotypes: Application to Autism SO PLOS ONE LA English DT Article ID SPATIAL-ORGANIZATION; PREFRONTAL CORTEX; SPECTRUM DISORDER; COMPLEXITY; NETWORKS; SYNCHRONIZATION; SPECIFICITY; DYNAMICS AB We present an efficient approach to discriminate between typical and atypical brains from macroscopic neural dynamics recorded as magnetoencephalograms (MEG). Our approach is based on the fact that spontaneous brain activity can be accurately described with stochastic dynamics, as a multivariate Ornstein-Uhlenbeck process (mOUP). By fitting the data to a mOUP we obtain: 1) the functional connectivity matrix, corresponding to the drift operator, and 2) the traces of background stochastic activity (noise) driving the brain. We applied this method to investigate functional connectivity and background noise in juvenile patients (n = 9) with Asperger's syndrome, a form of autism spectrum disorder (ASD), and compared them to age-matched juvenile control subjects (n = 10). Our analysis reveals significant alterations in both functional brain connectivity and background noise in ASD patients. The dominant connectivity change in ASD relative to control shows enhanced functional excitation from occipital to frontal areas along a parasagittal axis. Background noise in ASD patients is spatially correlated over wide areas, as opposed to control, where areas driven by correlated noise form smaller patches. An analysis of the spatial complexity reveals that it is significantly lower in ASD subjects. Although the detailed physiological mechanisms underlying these alterations cannot be determined from macroscopic brain recordings, we speculate that enhanced occipital-frontal excitation may result from changes in white matter density in ASD, as suggested in previous studies. We also venture that long-range spatial correlations in the background noise may result from less specificity (or more promiscuity) of thalamo-cortical projections. All the calculations involved in our analysis are highly efficient and outperform other algorithms to discriminate typical and atypical brains with a comparable level of accuracy. Altogether our results demonstrate a promising potential of our approach as an efficient biomarker for altered brain dynamics associated with a cognitive phenotype. C1 [Dominguez, Luis Garcia] Univ Toronto, Temerty Ctr Therapeut Brain Intervent, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Velazquez, Jose Luis Perez] Univ Toronto, Hosp Sick Children, Brain & Behav Ctr, Neurosci & Mental Hlth Programme,Div Neurol, Toronto, ON M5G 1X8, Canada. [Velazquez, Jose Luis Perez] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. [Velazquez, Jose Luis Perez] Univ Toronto, Dept Paediat, Toronto, ON M5S 1A1, Canada. [Galan, Roberto Fernandez] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. RP Galan, RF (reprint author), Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. EM rfgalan@case.edu FU Natural Sciences and Engineering Research Council of Canada [227059-2012]; Mt. Sinai Health Care Foundation; NSERC FX This study was funded in part by a grant (number 227059-2012) of the Natural Sciences and Engineering Research Council of Canada, NSERC (JLPV) and a scholarship of The Mt. Sinai Health Care Foundation (RFG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Kravitz, Dwight J. Freyberg, Jan Baron-Cohen, Simon Baker, Chris I. TI Tunnel Vision: Sharper Gradient of Spatial Attention in Autism SO JOURNAL OF NEUROSCIENCE LA English DT Article ID VISUAL-ACUITY; CONTRAST SENSITIVITY; SPECTRUM DISORDERS; PERCEPTION; MECHANISMS; CHILDREN; SEARCH; DORSAL; FIELD AB Enhanced perception of detail has long been regarded a hallmark of autism spectrum conditions (ASC), but its origins are unknown. Normal sensitivity on all fundamental perceptual measures-visual acuity, contrast discrimination, and flicker detection-is strongly established in the literature. If individuals with ASC do not have superior low-level vision, how is perception of detail enhanced? We argue that this apparent paradox can be resolved by considering visual attention, which is known to enhance basic visual sensitivity, resulting in greater acuity and lower contrast thresholds. Here, we demonstrate that the focus of attention and concomitant enhancement of perception are sharper in human individuals with ASC than in matched controls. Using a simple visual acuity task embedded in a standard cueing paradigm, we mapped the spatial and temporal gradients of attentional enhancement by varying the distance and onset time of visual targets relative to an exogenous cue, which obligatorily captures attention. Individuals with ASC demonstrated a greater fall-off in performance with distance from the cue than controls, indicating a sharper spatial gradient of attention. Further, this sharpness was highly correlated with the severity of autistic symptoms in ASC, as well as autistic traits across both ASC and control groups. These findings establish the presence of a form of "tunnel vision" in ASC, with far-reaching implications for our understanding of the social and neurobiological aspects of autism. C1 [Robertson, Caroline E.; Kravitz, Dwight J.; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Robertson, Caroline E.; Freyberg, Jan; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. RP Robertson, CE (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr, Bethesda, MD 20892 USA. EM caroline.robertson@nih.gov FU National Institute of Mental Health; NIH-Cambridge Fellowship; MRC; Wellcome Trust FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, and was conducted in association with the NIHR CLAHRC for Cambridgeshire and Peterborough NHS Foundation Trust. We gratefully acknowledge the Gates-Cambridge Trust and the NIH-Cambridge Fellowship (to C. E. R.). S.B-C. was supported by the MRC and the Wellcome Trust during the period of this work. We thank Bonnie Auyeung, Marlene Behrmann, Alex Martin, John Mollon, Kate Plaisted-Grant, and Teresa Tavassoli for their comments, Carrie Allison for help with recruitment, and Steffen Losch, Andra Adams, Richard Bethlehem, and Orian Welling for their help with stimulus design. 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TI Behavioral deficits in an Angelman syndrome model: Effects of genetic background and age SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Angelman syndrome; Conditioned fear; Inbred strain; Morris water maze; Reversal learning; UBE3A ID LONG-TERM POTENTIATION; FMR1 KNOCKOUT MICE; FRAGILE-X-SYNDROME; MOUSE MODEL; UBIQUITIN LIGASE; UBE3A; AUTISM; REVERSAL; CHILDREN; HIPPOCAMPAL AB Angelman syndrome (AS) is a severe neurodevelopmental disorder associated with disruption of maternally inherited UBE3A (ubiquitin protein ligase E3A) expression. At the present time, there is no effective treatment for AS. Mouse lines with loss of maternal Ube3a (Ube3a(m-/P+)) recapitulate multiple aspects of the clinical AS profile, including impaired motor coordination, learning deficits, and seizures. Thus, these genetic mouse models could serve as behavioral screens for preclinical efficacy testing, a critical component of drug discovery for AS intervention. However, the severity and consistency of abnormal phenotypes reported in Ube3a(m-/P+) mice can vary, dependent upon age and background strain, which is problematic for the detection of beneficial drug effects. As part of an ongoing AS drug discovery initiative, we characterized Ube3a(m-/P+) mice on either a 129S7/SvEvBrd-Hprt(b-m2) (129) or C57BL/6J (B6) background across a range of functional domains and ages to identify reproducible and sufficiently large phenotypes suitable for screening therapeutic compounds. The results from the study showed that Ube3a(m-/P+) mice have significant deficits in acquisition and reversal learning in the Morris water maze. The findings also demonstrated that Ube3a(m-/P+) mice exhibit motor impairment in a rotarod task, hypoactivity, reduced rearing and marble-burying, and deficient fear conditioning. Overall, these profiles of abnormal phenotypes can provide behavioral targets for evaluating effects of novel therapeutic strategies relevant to AS. (C) 2013 Elsevier B.V. All rights reserved. C1 [Huang, Hsien-Sung; Burns, Andrew J.; Riday, Thorfinn T.; Yashiro, Koji; Philpot, Benjamin D.] Univ N Carolina, Sch Med, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA. [Nonneman, Randal J.; Baker, Lorinda K.; Riddick, Natallia V.; Philpot, Benjamin D.; Moy, Sheryl S.] Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. [Baker, Lorinda K.; Riddick, Natallia V.; Nikolova, Viktoriya D.; Moy, Sheryl S.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. [Philpot, Benjamin D.] Univ N Carolina, Sch Med, UNC Neurosci Ctr, Chapel Hill, NC 27599 USA. RP Philpot, BD (reprint author), Univ N Carolina, Sch Med, CB 7545,115 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM bphilpot@med.unc.edu; ssmoy@med.unc.edu FU Simons Foundation; Angelman Syndrome Foundation; NIMH [1R01MH093372]; NICHD [P3OHD03110] FX The authors wish to thank Dr. Yong-hui Jiang for his kind generosity in providing Ube3a breeding pairs for our colony. This work was supported by the Simons Foundation, the Angelman Syndrome Foundation, NIMH grant 1R01MH093372 to BDP, and NICHD grant P3OHD03110 to Dr. Joe Piven. These sponsors did not have involvement in study design, data collection, analysis, or interpretation, writing the report, or decision to submit the article for publication. 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Brain Res. PD APR 15 PY 2013 VL 243 BP 79 EP 90 DI 10.1016/j.bbr.2012.12.052 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 125MH UT WOS:000317543400012 PM 23295389 ER PT J AU Vazquez-Sanroman, D Sanchis-Segura, C Toledo, R Hernandez, ME Manzo, J Miquel, M AF Vazquez-Sanroman, D. Sanchis-Segura, C. Toledo, R. Hernandez, M. E. Manzo, J. Miquel, M. TI The effects of enriched environment on BDNF expression in the mouse cerebellum depending on the length of exposure SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Cerebellum; Mice; Enriched environment; BDNF; Purkinje ID NEUROTROPHIC FACTOR; HIPPOCAMPAL NEUROGENESIS; DENTATE GYRUS; C57BL/6J MICE; BRAIN; INCREASES; BEHAVIOR; NEURONS; RATS; RECEPTOR AB Environmental enrichment (EE) has been proposed as a factor that improves neuronal connectivity and brain plasticity. The induction of molecular mechanisms that takes place in the cortex, nucleus accumbens and hippocampus resulting from exposure to EE has been attributed partly to the role of neurotrophins as brain-derived neurotrophic factor (BDNF). Recent data directly implicate this neurotrophin in the modulation of plasticity changes in the cerebellum produced by living under environmental enrichment. In the present study, we aimed to assess the effects of different lengths of exposure to EE on cerebellar BDNF expression and western blotting analysis. On the whole, the present data has shown that BDNF increased under EE. However, changes in expression as a result of extending the duration of EE were only seen in Purkinje neurons. In Purkinje neurons, long-term exposure was required in order to fully express this neurotrophin. These data support BDNF as one of the long-term plasticity mechanisms induced by environment, suggesting that cerebellar plasticity can be stimulated as a response to challenges generated by environment. Our findings could have functional implications for various neurodegenerative disorders such as spinocerebellar ataxias, autism, schizophrenia and certain prion encephalopathies, most of them pathologies which have demonstrated to be characterized by alterations in Purkinje neurons and to show a partial recovery by exposure to EE. (C) 2013 Elsevier B.V. All rights reserved. C1 [Vazquez-Sanroman, D.; Sanchis-Segura, C.; Miquel, M.] Univ Jaume 1, Area Psicobiol, Castellon De La Plana, Spain. [Toledo, R.; Hernandez, M. E.; Manzo, J.] Univ Veracruzana, Ctr Invest Cerebrates, Xalapa 91000, Veracruz, Mexico. RP Miquel, M (reprint author), Univ Jaume 1, Area Psicobiol, Ave Sos Baynat S-N, Castellon de La Plana 12071, Spain. EM miquel@psb.uji.es RI MIQUEL, MARTA/A-6522-2008 OI MIQUEL, MARTA/0000-0001-9670-4210 FU El Ministerio de Ciencia e Innovacion [PSI2008-01317/PSIC]; Secretaria General de Universidades del Ministerio de Educacion [SAB2009-0159]; Bancaixa [P1.1A2008-17, P1.1B2011-42] FX This work was supported by grants from El Ministerio de Ciencia e Innovacion [PSI2008-01317/PSIC]; Secretaria General de Universidades del Ministerio de Educacion [SAB2009-0159]; Bancaixa [P1.1A2008-17] and Bancaixa (P1.1B2011-42). 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Brain Res. PD APR 15 PY 2013 VL 243 BP 118 EP 128 DI 10.1016/j.bbr.2012.12.047 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 125MH UT WOS:000317543400017 PM 23295397 ER PT J AU Pearson, BL Corley, MJ Vasconcellos, A Blanchard, DC Blanchard, RJ AF Pearson, Brandon L. Corley, Michael J. Vasconcellos, Amy Blanchard, D. Caroline Blanchard, Robert J. TI Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Autism; Postmortem; Subventricular zone; Extracellular matrix; Heparan sulfate; Neurogenesis ID AGE-RELATED-CHANGES; NEURAL STEM-CELLS; PLUS TF/J MICE; SPECTRUM DISORDERS; ADULT BRAIN; RAT-BRAIN; CHILDREN; PROTEOGLYCANS; NUMBER; NICHE AB Abnormal cellular growth and organization have been characterized in postmortem tissue from brains of autistic individuals, suggestive of pathology in a critical neurogenic niche, the subventricular zone (SVZ) of the brain lateral ventricles (LV). We examined cellular organization, cell proliferation, and constituents of the extracellular matrix such as N-sulfated heparan sulfate (HS) and laminin (LAM) in postmortem brain tissue from the LV-SVZ of young to elderly individuals with autism (n = 4) and age-matched typically developing (TD) individuals (n = 4) using immunofluorescence techniques. Strong and systematic reductions in HS immunofluorescence were observed in the LV-SVZ of the TD individuals with increasing age. For young through mature, but not elderly, autistic pair members, HS was reduced compared to their matched TDs. Cellular proliferation (Ki67+) was higher in the autistic individual of the youngest age-matched pair. These preliminary data suggesting that HS may be reduced in young to mature autistic individuals are in agreement with previous findings from the BTBR T+ tf/J mouse, an animal model of autism; from mice with genetic modifications reducing HS; and with genetic variants in HS-related genes in autism. They suggest that aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism, and potentially involved in the etiology of the disorder. (C) 2013 Elsevier B.V. All rights reserved. C1 [Pearson, Brandon L.; Corley, Michael J.; Blanchard, Robert J.] Univ Hawaii, Dept Psychol, Honolulu, HI 96822 USA. [Pearson, Brandon L.] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA. [Corley, Michael J.; Vasconcellos, Amy; Blanchard, D. Caroline] Univ Hawaii, Pacific Biosci Res Inst, Honolulu, HI 96822 USA. RP Blanchard, DC (reprint author), Univ Hawaii, Pacific Biosci Res Inst, 1993 East West Rd, Honolulu, HI 96822 USA. EM blanchar@hawaii.edu FU NIH [R01 MH081845]; PHS [R24 MH 068855]; NICHD Brain and Tissue Bank FX Funded by NIH R01 MH081845 to RJB. We are grateful for the contributions of Autism Tissue Program of Autism Speaks, the Harvard Brain Tissue Resource Center, which is supported in part by PHS grant number R24 MH 068855, and the NICHD Brain and Tissue Bank. We are especially grateful to the families who donated specimens. 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Li, Jiang Katz, Adam M. Weber, Michael D. Sen, Saunak Crawley, Jacqueline Sherr, Elliott H. TI Quantitative Trait Loci for Interhemispheric Commissure Development and Social Behaviors in the BTBR T+ tf/J Mouse Model of Autism SO PLOS ONE LA English DT Article ID CORPUS-CALLOSUM; SPECTRUM DISORDERS; WHITE-MATTER; T+TF/J MICE; STRAINS; SOCIABILITY; RECURRENCE; PHENOTYPES; AGENESIS; DEFICITS AB Background: Autism and Agenesis of the Corpus Callosum (AgCC) are interrelated behavioral and anatomic phenotypes whose genetic etiologies are incompletely understood. We used the BTBR T+ tf/ J (BTBR) strain, exhibiting fully penetrant AgCC, a diminished hippocampal commissure, and abnormal behaviors that may have face validity to autism, to study the genetic basis of these disorders. Methods: We generated 410 progeny from an F2 intercross between the BTBR and C57BL/ 6J strains. The progeny were phenotyped for social behaviors (as juveniles and adults) and commisural morphology, and genotyped using 458 markers. Quantitative trait loci (QTL) were identified using genome scans; significant loci were fine-mapped, and the BTBR genome was sequenced and analyzed to identify candidate genes. Results: Six QTL meeting genome-wide significance for three autism-relevant behaviors in BTBR were identified on chromosomes 1, 3, 9, 10, 12, and X. Four novel QTL for commissural morphology on chromosomes 4, 6, and 12 were also identified. We identified a highly significant QTL (LOD score = 20.2) for callosal morphology on the distal end of chromosome 4. Conclusions: We identified several QTL and candidate genes for both autism-relevant traits and commissural morphology in the BTBR mouse. Twenty-nine candidate genes were associated with synaptic activity, axon guidance, and neural development. This is consistent with a role for these processes in modulating white matter tract development and aspects of autism-relevant behaviors in the BTBR mouse. Our findings reveal candidate genes in a mouse model that will inform future human and preclinical studies of autism and AgCC. C1 [Jones-Davis, Dorothy M.; Rider, Eric; Osbun, Nathan C.; da Gente, Gilberto J.; Li, Jiang; Sherr, Elliott H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yang, Mu; Katz, Adam M.; Weber, Michael D.; Crawley, Jacqueline] NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Sen, Saunak] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Sherr, EH (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. EM sherre@neuropeds.ucsf.edu FU Pfizer, Inc. [P0030953]; MH02179 from the National Institute of Mental Health Intramural Research Program [MH02179]; National Institutes of Health [K02NS052192, NS062173]; National Institute of General Medical Sciences/National Institutes of Health [K12GM081266] FX This work was supported by Grant P0030953 from Pfizer, Inc.(http://www.pfizer.com) to Dr. Elliott Sherr. Dr. Mathew Pletcher (employed by Pfizer, Inc.) provided suggestions in the design and interpretation of the study, and Dr. Nicholas Brandon (employed by Pfizer, Inc.) provided a critical reading of the manuscript. This work was also supported by Award MH02179 from the National Institute of Mental Health Intramural Research Program to Dr. Jacqueline Crawley and Dr. Mu Yang, National Institutes of Health Awards K02NS052192 and NS062173 to Dr.Elliott Sherr, and Award Number K12GM081266 from the National Institute of General Medical Sciences/National Institutes of Health (http://projectreporter.nih.gov/project_ info_ description.cfm? aid = 7869455& icde = 12962536& ddparam = & ddvalue = & ddsub = & cr = 443& csb = GNA& cs = ASC) to Dr. Dorothy Jones-Davis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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In the healthy brain these coherent patterns (also termed resting state functional connectivity) often exhibit spatial similarity to the large scale organization of task-induced functional networks. However, it is not clear to what extent the resting state patterns can also reflect task-induced abnormalities in cortical activations which are often detected in various brain pathologies. Here we examined whether an abnormal visual activation pattern is recapitulated in the resting state functional connectivity. We examined LG, a sighted young adult with developmental object agnosia and no apparent cortical structural abnormality. We have previously reported that upon visual stimulation, LG's intermediate visual areas (V2, V3) are paradoxically deactivated. Here, examining LG's resting state functional connectivity revealed the same pattern of functional abnormality including a strong atypical decorrelation between areas V2-V3 and the rest of the visual system. 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Henkelman, R. Mark Lerch, Jason P. Crawley, Jacqueline N. TI Neuroanatomical analysis of the BTBR mouse model of autism using magnetic resonance imaging and diffusion tensor imaging SO NEUROIMAGE LA English DT Article DE BTBR T plus tf/J mice; Magnetic resonance imaging; Diffusion tensor imaging; Behavior ID T PLUS TF/J; CORPUS-CALLOSUM; ULTRASONIC VOCALIZATIONS; BEHAVIORAL PHENOTYPES; REPETITIVE BEHAVIOR; UNUSUAL REPERTOIRE; INBRED STRAINS; SCENT-MARKING; C57BL/6J MICE; SOCIAL BRAIN AB Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. Autism-relevant phenotypes in the inbred mouse strain BTBR T + tf/J (BTBR) offer translational tools to discover biological mechanisms underlying unusual mouse behaviors analogous to symptoms of autism. Two of the most consistent findings with BTBR are lack of sociability as measured by the three-chamber social approach task and increased amount of time engaged in self-grooming in an empty cage. Here we evaluated BTBR as compared to two typical inbred strains with high sociability and low self-grooming, C57BL/6J (B6) and FVB/AntJ (FVB), on both the automated three-chambered social approach task and repetitive self-grooming assays. Brains from the behaviorally tested mice were analyzed using magnetic resonance imaging and diffusion tensor imaging to investigate potential neuroanatomical abnormalities throughout the brain; specifically, to discover neuroanatomical mechanisms which could explain the autism-relevant behavioral abnormalities. Significant differences in volume and white matter microstructure were detected in multiple anatomical regions throughout the brain of BTBR compared to B6 and FVB. Further, significant correlations were found between behavioral measures and areas of the brain known to be associated with those behaviors. For example, striatal volume was strongly correlated to time spent in self-grooming across strains. Our findings suggest that neuropathology exists in BTBR beyond the previously reported white matter abnormalities in the corpus callosum and hippocampal commissure and that these brain differences may be related to the behavioral abnormalities seen in BTBR. (C) 2013 Elsevier Inc. All rights reserved. C1 [Ellegood, Jacob; Henkelman, R. Mark; Lerch, Jason P.] Hosp Sick Children, Mouse Imaging Ctr, Toronto, ON M5T 3H7, Canada. [Henkelman, R. Mark; Lerch, Jason P.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Babineau, Brooke A.; Crawley, Jacqueline N.] NIMH, Bethesda, MD 20892 USA. RP Ellegood, J (reprint author), Hosp Sick Children, Mouse Imaging Ctr, 25 Orde St, Toronto, ON M5T 3H7, Canada. EM jacob@phenogenomics.ca RI Henkelman, Mark/F-3662-2011 FU Ontario Mental Health Foundation (OMHF); Canadian Institute for Health Research (CIHR); National Institute of Mental Health Intramural Research Program; Ontario Brain Institute (OBI); Ontario government FX We would like to thank Christine Laliberte for her assistance with the MRI scanning, Matthijs van Eede and Jan Scholz for help with different stages of the analysis, and Mu Yang and Jill Silverman for their assistance with the behavioral tasks and perfusions. We also acknowledge the Ontario Mental Health Foundation (OMHF) for salary support (Jacob Ellegood). This research was conducted with the support of the Canadian Institute for Health Research (CIHR), the National Institute of Mental Health Intramural Research Program, and the Ontario Brain Institute (OBI). OBI was created to become an internationally recognized centre of excellence in brain and neuroscience research. This independent non-profit corporation, funded partially by the Ontario government, is dedicated to improving approaches to the prevention, early diagnosis, treatment and management of neurological, and psychiatric disorders. The opinions, results, and conclusions are those of the authors and no endorsement by any of the agencies is intended or should be inferred. 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ID HIGH-FUNCTIONING AUTISM; MIRROR NEURON SYSTEM; DEVELOPMENTAL COORDINATION DISORDER; JOINT ATTENTION; YOUNG-CHILDREN; SENTENCE COMPREHENSION; LANGUAGE-DEVELOPMENT; ASPERGERS SYNDROME; BIOLOGICAL MOTION; VISUAL-PERCEPTION AB In classical approaches to cognition, sensory, motor, and emotional experiences are stripped of domain-specific perceptual and sensorimotor information, and represented in a relatively abstract form. 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Al-Ayadhi, Laila TI The neurotoxic effect of clindamycin - induced gut bacterial imbalance and orally administered propionic acid on DNA damage assessed by the comet assay: protective potency of carnosine and carnitine SO GUT PATHOGENS LA English DT Article DE Propionic acid; Clindamycin; Tail length; Tail moment; Carnosine; Carnitine; Autism; Neurotoxicity ID AUTISTIC SPECTRUM DISORDERS; ANTIOXIDANT ACTIVITY; SOCIAL-BEHAVIOR; RATS RELEVANCE; CHILDREN; BRAIN; METABOLISM; DIPEPTIDES; HISTIDINE; PRODUCT AB Background: Comet assay is a quick method for assessing DNA damage in individual cells. It allows the detection of single and double DNA strand breaks, which represent the direct effect of some damaging agents. This study uses standard comet quantification models to compare the neurotoxic effect of orally administered propionic acid (PA) to that produced as a metabolite of bacterial overgrowth induced by clindamycin. Additionally, the protective effect of carnosine and carnitine as natural dietary supplements is assessed. Methods: Single cell gel electrophoresis (comet assays) were performed on brain cortex and medulla samples after removal from nine groups of hamsters including: a control (untreated) group; PA-intoxicated group; clindamycin treated group; clindamycin-carnosine group and; clindamycin-carnitine group. Results: There were significant double strand breaks recorded as tail length, tail moment and % DNA damage in PA and clindamycin-treated groups for the cortex and medulla compared to the control group. Neuroprotective effects of carnosine and carnitine were observed. Receiver Operating Characteristics curve (ROC) analysis showed satisfactory values of sensitivity and specificity of the comet assay parameters. Conclusion: Percentage DNA damage, tail length, and tail moment are adequate biomarkers of PA neurotoxicity due to oral administration or as a metabolite of induced enteric bacterial overgrowth. Establishing biomarkers of these two exposures is important for protecting children's health by documenting the role of the imbalance in gut microbiota in the etiology of autism through the gut-brain axis. These outcomes will help efforts directed at controlling the prevalence of autism, a disorder recently related to PA neurotoxicity. C1 [El-Ansary, Afaf; El-Gezeery, Amina R.] King Saud Univ, Coll Sci, Dept Biochem, Riyadh 11495, Saudi Arabia. [El-Ansary, Afaf; Al-Ayadhi, Laila] King Saud Univ, Fac Med, Dept Physiol, Riyadh 11495, Saudi Arabia. [Al-Ayadhi, Laila] Autism Res & Treatment Ctr, Riyadh, Saudi Arabia. [El-Ansary, Afaf; Al-Ayadhi, Laila] King Saud Univ, Shaik AL Amodi Autism Res Chair, Riyadh 11495, Saudi Arabia. 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In this review we discuss what is known about MNs from the work using single-cell recordings in the adult monkey, the evidence for the putative MN system in humans, and the extent to which research using electroencephalography (EEG) methods has contributed to our understanding of the development of these motor systems and their role in the social behaviors postulated by the MN hypothesis. We conclude with directions for future research that will improve our understanding of the putative human MN system and the functional role of MNs in social development. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Vanderwert, Ross E.; Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. [Ferrari, Pier F.] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. [Vanderwert, Ross E.] Childrens Hosp Boston, Div Dev Med, Labs Cognit Neurosci, Boston, MA USA. RP Ferrari, PF (reprint author), Univ Parma, Dipartimento Neurosci, Via Volturno 39, I-43100 Parma, Italy. 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Skills Battery in 110 children with and without ASD. Social attention was assessed using infrared eye gaze tracking during passive viewing of movies of facial expressions and objects displayed together on a computer screen. Face processing skills were significantly correlated with measures of attention to faces and with social skills as measured by the Social Communication Questionnaire (SCQ). Consistent with prior research, children with ASD scored significantly lower on face processing skills tests but, unexpectedly, group differences in amount of attention to faces (vs. objects) were not found. We discuss possible methodological contributions to this null finding. We also highlight the importance of a dimensional approach for understanding the developmental origins of reduced face perception skills, and emphasize the need for longitudinal research to truly understand how social motivation and social attention influence the development of social perceptual skills. C1 [Parish-Morris, Julia; Schultz, Robert T.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Parish-Morris, Julia; Schultz, Robert T.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Parish-Morris, Julia; Chevallier, Coralie; Tonge, Natasha; Pandey, Juhi; Schultz, Robert T.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. [Letzen, Janelle] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. RP Schultz, RT (reprint author), Childrens Hosp Philadelphia, Ctr Autism Res, 3535 Market St,8th Floor,Suite 860, Philadelphia, PA 19104 USA. 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Psychol. PD APR 10 PY 2013 VL 4 AR 185 DI 10.3389/fpsyg.2013.00185 PG 7 WC Psychology, Multidisciplinary SC Psychology GA AA1HE UT WOS:000330846400001 PM 23596436 ER PT J AU Babineau, BA Yang, M Berman, RF Crawley, JN AF Babineau, Brooke A. Yang, Mu Berman, Robert F. Crawley, Jacqueline N. TI Low home cage social behaviors in BTBR T plus tf/J mice during juvenile development SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Inbred strain; Home cage observation; Social interaction ID INBRED MOUSE STRAINS; ULTRASONIC VOCALIZATIONS; UNUSUAL REPERTOIRE; SCENT-MARKING; T+TF/J MICE; AUTISM; MODEL; C57BL/6J; SOCIABILITY; PHENOTYPES AB BTBR T+tf/J (BTBR) is a genetically homogenous inbred strain of mice that displays abnormal social behaviors, deficits in vocalizations, and high levels of repetitive behaviors, relevant to the three diagnostic symptoms of autism spectrum disorder, leading to the use of this strain as a mouse model of autism. Comprehensive observations of BTBR social behaviors within the home cage during early stages of development have not been conducted. Here we evaluate the home cage behaviors of BTBR in two laboratory environments (NIMH, Bethesda, Maryland vs. UC Davis, Davis, California), starting from the day of weaning and continuing into adulthood. Extensive ethogram parameters were scored for BTBR in home cages that contained four BTBR conspecifics, versus home cages that contained four C57BL/6 J (B6) conspecifics. BTBR were considerably less interactive than B6 in the home cage at both sites, as measured during the early dark stage of their circadian cycle. A novel home cage behavioral measure, frequency of long interactions, was found to be more frequent and of longer duration in B6 versus BTBR home cages across experimental sites. Significant strain differences in the occurrence of investigative and affiliative behaviors were also seen, however these findings were not fully consistent across the two testing sites. At the end of the 30-day home cage observation period, each seven-week old subject mouse was tested in the three-chambered social approach task. BTBR displayed lack of sociability and B6 displayed significant sociability, consistent with previous reports. Our findings reveal that BTBR engaged in lower levels of some components of spontaneous conspecific social interactions in the home cage environment throughout juvenile development, consistent with their deficits in juvenile and adult sociability as measured in specialized social tasks. (C) 2013 Elsevier Inc. All rights reserved. C1 [Babineau, Brooke A.; Yang, Mu; Crawley, Jacqueline N.] NIMH, Intramural Res Program, Lab Behav Neurosci, Bethesda, MD 20892 USA. [Berman, Robert F.] Univ Calif Davis, Dept Neurol Surg, Davis, CA 95616 USA. RP Babineau, BA (reprint author), Univ Calif San Francisco, Sch Med, 513 Parnassus Ave HSE-901, San Francisco, CA 94143 USA. EM Brooke.Babineau@ucsf.edu FU National Institute of Mental Health FX Supported by the National Institute of Mental Health Intramural Research Program. CR Amodeo DA, 2012, BEHAV BRAIN RES, V227, P64, DOI 10.1016/j.bbr.2011.10.032 Bolivar VJ, 2007, BEHAV BRAIN RES, V176, P21, DOI 10.1016/j.bbr.2006.09.007 Chadman KK, 2011, PHARMACOL BIOCHEM BE, V97, P586, DOI 10.1016/j.pbb.2010.09.012 Chadman KK, 2008, AUTISM RES, V1, P147, DOI 10.1002/aur.22 Crawley JN, 2007, BRAIN PATHOL, V17, P448, DOI 10.1111/j.1750-3639.2007.00096.x Defensor EB, 2011, BEHAV BRAIN RES, V217, P302, DOI 10.1016/j.bbr.2010.10.033 GRANT E. 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Behav. PD APR 10 PY 2013 VL 114 BP 49 EP 54 DI 10.1016/j.physbeh.2013.03.006 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 156VZ UT WOS:000319853300008 PM 23510981 ER PT J AU Kohlstadt, I Wharton, G AF Kohlstadt, Ingrid Wharton, Gerold TI Clinician uptake of obesity-related drug information: a qualitative assessment using continuing medical education activities SO NUTRITION JOURNAL LA English DT Article DE Medication effects on appetite; Insulin resistance; Drug-related weight gain; Mental illness as a risk factor for obesity; Adverse metabolic drug effects; Drug safety research; Nutrition knowledge of primary care practitioners ID SAFETY; ADOLESCENTS; CHILDREN; TRIALS AB Background: Medications necessary for disease management can simultaneously contribute to weight gain, especially in children. Patients with preexisting obesity are more susceptible to medication-related weight gain. How equipped are primary care practitioners at identifying and potentially reducing medication-related weight gain? To inform this question germane to public health we sought to identify potential gaps in clinician knowledge related to metabolic adverse drug effects of weight gain. Methods: The study analyzed practitioner responses to the pre-activity questions of six continuing medical education (CME) activities from May 2009 through August 2010. Results: The 20,705 consecutive, self-selected respondents indicated varied levels of familiarity with adverse metabolic effects and psychiatric indications of atypical antipsychotics. Correct responses were lower than predicted for drug indications pertaining to autism (-17% predicted); drug effects on insulin resistance (-62% predicted); chronic disease risk in mental illness (-34% predicted); and drug safety research (-40% predicted). Pediatrician knowledge scores were similar to other primary care practitioners. Conclusions: Clinicians' knowledge of medication-related weight gain may lead them to overestimate the benefits of a drug in relation to its metabolic risks. The knowledge base of pediatricians appears comparable to their counterparts in adult medicine, even though metabolic drug effects in children have only become prevalent recently. C1 [Kohlstadt, Ingrid] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Annapolis, MD 21401 USA. [Wharton, Gerold] US FDA, Off Pediat Therapeut, Silver Spring, MD USA. RP Kohlstadt, I (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, 198 Prince George St, Annapolis, MD 21401 USA. 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TI Modeling Autism by SHANK Gene Mutations in Mice SO NEURON LA English DT Review ID POSTSYNAPTIC DENSITY PROTEINS; DE-NOVO MUTATIONS; DENDRITIC SPINE MORPHOLOGY; 22Q13.3 DELETION SYNDROME; INSULIN-RECEPTOR SUBSTRATE; PHELAN-MCDERMID SYNDROME; SPECTRUM DISORDERS; MOUSE MODELS; SCAFFOLDING PROTEINS; MUTANT MICE AB Shank family proteins (Shank1, Shank2, and Shank3) are synaptic scaffolding proteins that organize an extensive protein complex at the postsynaptic density (PSD) of excitatory glutamatergic synapses. Recent human genetic studies indicate that SHANK family genes (SHANK1, SHANK2, and SHANK3) are causative genes for idiopathic autism spectrum disorders (ASD). Neurobiological studies of Shank mutations in mice support a general hypothesis of synaptic dysfunction in the pathophysiology of ASD. However, the molecular diversity of SHANK family gene products, as well as the heterogeneity in human and mouse phenotypes, pose challenges to modeling human SHANK mutations. Here, we review the molecular genetics of SHANK mutations in human ASD and discuss recent findings where such mutations have been modeled in mice. Conserved features of synaptic dysfunction and corresponding behaviors in Shank mouse mutants may help dissect the pathophysiology of ASD, but also highlight divergent phenotypes that arise from different mutations in the same gene. C1 [Jiang, Yong-hui] Duke Univ, Sch Med, Dept Pediat, Durham, NC 27710 USA. [Jiang, Yong-hui] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA. [Ehlers, Michael D.] Pfizer Worldwide Res & Dev, Neurosci Res Unit, Cambridge, MA 02139 USA. RP Jiang, YH (reprint author), Duke Univ, Sch Med, Dept Pediat, Durham, NC 27710 USA. EM yong-hui.jiang@duke.edu; michael.ehlers@pfizer.com FU Autism Speaks; Phelan-McDermid Syndrome Foundation; NIH [5K12-HD0043494-08, R01MH098114-01]; Pfizer, Inc. FX We thank Juliet Hernandez, Benjamin Philpot, Dan Smith, Julia Sommer, and William Wetsel for critical review of the manuscript. We thank Xiaoming Wang and Alexandra Bey for help preparing tables and comments. Work in the lab of Y.-h.J. is supported by Autism Speaks, Phelan-McDermid Syndrome Foundation, and NIH grants 5K12-HD0043494-08 and R01MH098114-01. Work in the lab of M.D.E. is supported by Pfizer, Inc., and M.D.E. is an employee and shareholder of Pfizer, Inc. 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Sharp, Stephen J. Auyeung, Bonnie Baron-Cohen, Simon Brayne, Carol TI Prevalence of autism in mainland China, Hong Kong and Taiwan: a systematic review and meta-analysis SO MOLECULAR AUTISM LA English DT Review DE Autism spectrum conditions; Prevalence; Screening; Diagnosis; Chinese population ID PERVASIVE DEVELOPMENTAL DISORDERS; RATING-SCALE CARS; SPECTRUM DISORDERS; CHILDHOOD AUTISM; SCREENING INSTRUMENTS; PSYCHOMETRIC PROPERTIES; BEHAVIOR CHECKLIST; INFANTILE-AUTISM; YOUNG-CHILDREN; VERSION AB Background: The prevalence of autism spectrum conditions (ASC) is 1% in developed countries, but little data are available from mainland China, Hong Kong and Taiwan. This study synthesizes evidence relating to the prevalence of ASC in these areas and assesses the effects of research methodology on prevalence estimates. Methods: Systematic literature searches were conducted in PubMed, Web of Knowledge, China Web of Knowledge and Weipu databases, as well as relevant papers published from 1987 to 2011, reporting prevalence estimates of ASC or childhood autism in mainland China, Hong Kong and Taiwan. Summary estimates of prevalence were calculated with a random effects model. The effects of research methodology on the prevalence estimates were assessed using a meta-regression model. Results: There were 25 studies eligible for review, 18 of which were suitable for inclusion in a meta-analysis. Pooled prevalence of childhood autism was 11.8 per 10,000 individuals (95% confidence interval (CI): 8.2, 15.3) in mainland China. Pooled prevalence of ASC was 26.6 per 10,000 (95% CI: 18.5, 34.6) in three areas. Substantial heterogeneity was identified between studies (I-2>75%). The prevalence estimate of childhood autism was most strongly associated with the choice of screening instrument. After adjustment for age group, the odds ratio for prevalence estimates when using the Autism Behavior Checklist (ABC) as the screening instrument compared with those using the Clancy Autism Behavior Scale (CABS) was 0.29 (95% CI: 0.12, 0.69), and 1.79 (95% CI: 0.70, 4.55; P= 0.20) when using the Checklist for Autism in Toddlers (CHAT) compared to the CABS. Conclusions: The available studies investigating the prevalence of ASC in China, Hong Kong and Taiwan have focused mainly on childhood autism rather than the whole spectrum. The prevalence estimates are lower than estimates from developed countries. Studies using more recently developed screening instruments reported higher prevalence than older ones. However, available studies have methodological weaknesses and therefore these results lack comparability with those from developed countries. Our findings indicate a potential under-diagnosis and under-detection of ASC in mainland China, Hong Kong and Taiwan, and a need to adopt more advanced methods for research of ASC in these areas. C1 [Sun, Xiang; Brayne, Carol] Univ Cambridge, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Cambridge CB2 0SR, England. [Sun, Xiang; Allison, Carrie; Auyeung, Bonnie; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 2AH, England. [Matthews, Fiona E.] Inst Publ Hlth, MRC Biostat Unit, Cambridge CB2 0SR, England. [Sharp, Stephen J.] Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge CB2 0QQ, England. RP Sun, X (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Forvie Site,Robinson Way, Cambridge CB2 0SR, England. EM xs227@medschl.cam.ac.uk FU Waterloo Foundation; Peking University First Hospital; Cambridge Commonwealth Trust; Clare Hall, University of Cambridge; Great Britain-China Educational Trust; Medical Research Council UK; Wellcome Trust; NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) FX We thank Yu-Tzu Wu for valuable discussions throughout this report. This study was funded by The Waterloo Foundation and the Peking University First Hospital. XS was partly funded by the Cambridge Commonwealth Trust and Clare Hall, University of Cambridge and the Great Britain-China Educational Trust.. SBC, CA, and BA were funded by the Medical Research Council UK, the Wellcome Trust, and the team was funded by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Cambridgeshire and Peterborough NHS Foundation Trust during the period of this work. FM was funded by Medical Research Council UK. 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Autism PD APR 9 PY 2013 VL 4 AR 7 DI 10.1186/2040-2392-4-7 PG 13 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 254UN UT WOS:000327193400001 PM 23570419 ER PT J AU Theoharides, TC Asadi, S Patel, AB AF Theoharides, Theoharis C. Asadi, Shahrzad Patel, Arti B. TI Focal brain inflammation and autism SO JOURNAL OF NEUROINFLAMMATION LA English DT Review ID HUMAN MAST-CELLS; PERVASIVE DEVELOPMENTAL DISORDERS; CORTICOTROPIN-RELEASING HORMONE; TUMOR-NECROSIS-FACTOR; SPECTRUM DISORDERS; MITOCHONDRIAL DYSFUNCTION; ATYPICAL ANTIPSYCHOTICS; NEUROTENSIN RECEPTOR-3; IMMUNE DYSREGULATION; REPETITIVE BEHAVIOR AB Increasing evidence indicates that brain inflammation is involved in the pathogenesis of neuropsychiatric diseases. Autism spectrum disorders (ASD) are characterized by social and learning disabilities that affect as many as 1/80 children in the USA. There is still no definitive pathogenesis or reliable biomarkers for ASD, thus significantly curtailing the development of effective therapies. Many children with ASD regress at about age 3 years, often after a specific event such as reaction to vaccination, infection, stress or trauma implying some epigenetic triggers, and may constitute a distinct phenotype. ASD children respond disproportionally to stress and are also affected by food and skin allergies. Corticotropin-releasing hormone (CRH) is secreted under stress and together with neurotensin (NT) stimulates mast cells and microglia resulting in focal brain inflammation and neurotoxicity. NT is significantly increased in serum of ASD children along with mitochondrial DNA (mtDNA). NT stimulates mast cell secretion of mtDNA that is misconstrued as an innate pathogen triggering an auto-inflammatory response. The phosphatase and tensin homolog (PTEN) gene mutation, associated with the higher risk of ASD, which leads to hyper-active mammalian target of rapamycin (mTOR) signalling that is crucial for cellular homeostasis. CRH, NT and environmental triggers could hyperstimulate the already activated mTOR, as well as stimulate mast cell and microglia activation and proliferation. The natural flavonoid luteolin inhibits mTOR, mast cells and microglia and could have a significant benefit in ASD. C1 [Theoharides, Theoharis C.; Asadi, Shahrzad; Patel, Arti B.] Tufts Univ, Sch Med, Dept Mol Physiol & Pharmacol, Mol Immunopharmacol & Drug Discovery Lab, Boston, MA 02111 USA. [Asadi, Shahrzad] Tufts Med Ctr, Dept Pharm, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Dept Internal Med, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Med Ctr, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Dept Psychiat, Boston, MA 02111 USA. [Patel, Arti B.] Tufts Univ, Sackler Sch Grad Biomed Sci, Grad Program Biochem, Boston, MA 02111 USA. RP Theoharides, TC (reprint author), Tufts Univ, Sch Med, Dept Mol Physiol & Pharmacol, Mol Immunopharmacol & Drug Discovery Lab, Suite J304,136 Harrison Ave, Boston, MA 02111 USA. EM theoharis.theoharides@tufts.edu FU Autism Research Institute; National Autism Association, Safe Minds; Theta Biomedical Consulting and Development Co. Inc. (Brookline, MA) FX Aspects of the work discussed were funded in part by the Autism Research Institute, the National Autism Association, Safe Minds, and Theta Biomedical Consulting and Development Co. Inc. (Brookline, MA). 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Neuroinflamm. PD APR 9 PY 2013 VL 10 AR 46 DI 10.1186/1742-2094-10-46 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 127ES UT WOS:000317680200001 PM 23570274 ER PT J AU Fox, SE Wagner, JB Shrock, CL Tager-Flusberg, H Nelson, CA AF Fox, Sharon E. Wagner, Jennifer B. Shrock, Christine L. Tager-Flusberg, Helen Nelson, Charles A. TI Neural processing of facial identity and emotion in infants at high-risk for autism spectrum disorders SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism; fNIRS; face processing; near-infrared spectroscopy; cognitive development ID INDEPENDENT COMPONENT ANALYSIS; NEAR-INFRARED SPECTROSCOPY; 6-MONTH-OLD INFANTS; FACE PERCEPTION; HUMAN BRAIN; RECOGNITION; ACTIVATION; CORTEX; GAZE; CIRCUITRY AB Deficits in face processing and social impairment are core characteristics of autism spectrum disorder. The present work examined 7-month-old infants at high-risk for developing autism and typically developing controls at low-risk, using a face perception task designed to differentiate between the effects of face identity and facial emotions on neural response using functional Near-Infrared Spectroscopy. In addition, we employed independent component analysis, as well as a novel method of condition-related component selection and classification to identify group differences in hemodynamic waveforms and response distributions associated with face and emotion processing. The results indicate similarities of waveforms, but differences in the magnitude, spatial distribution, and timing of responses between groups. These early differences in local cortical regions and the hemodynamic response may, in turn, contribute to differences in patterns of functional connectivity. C1 [Fox, Sharon E.] MIT, Cambridge, MA 02139 USA. [Fox, Sharon E.; Wagner, Jennifer B.; Nelson, Charles A.] Childrens Hosp Boston, Boston, MA USA. [Wagner, Jennifer B.] CUNY Coll Staten Isl, New York, NY USA. [Shrock, Christine L.] Harvard Univ, Cambridge, MA 02138 USA. [Tager-Flusberg, Helen] Boston Univ, Boston, MA 02215 USA. RP Nelson, CA (reprint author), Harvard Univ, Labs Cognit Neurosci, Sch Med,Boston Childrens Hosp, Richard David Scott Chair Pediat Dev Med Res, 1Autumn St,Off AU621,Mailbox 713, Boston, MA 02115 USA. EM charles.nelson@childrens.harvard.edu FU Autism Speaks; Simons Foundation; NIDCD [R21 DC 08637, R01 DC 10290]; Helen Tager-Flusberg; NIMH; NARSAD; Hugh Hampton Young Memorial Foundation; NIH FX This work was made possible, in part, by grants from Autism Speaks, the Simons Foundation, and the NIDCD (R21 DC 08637 and R01 DC 10290) to Helen Tager-Flusberg and Charles A. Nelson, the NIMH-funded Stuart T. Hauser Research Training Program in Biological and Social Psychiatry and a NARSAD Abrams Young Investigator Award (to Jennifer B. Wagner) and the Hugh Hampton Young Memorial Foundation, the NIH-funded Advanced Multimodal Neuroimaging Training Program, and the NIH-funded Neuroimaging Training Program (to Sharon E. Fox). Direct correspondence to the last author at Charles.nelson@childrens.harvard.edu. CR Akgul CB, 2006, MED BIOL ENG COMPUT, V44, P945, DOI 10.1007/s11517-006-0116-3 Amaral DG, 2008, TRENDS NEUROSCI, V31, P137, DOI 10.1016/j.tins.2007.12.005 Aslin R. 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Hum. Neurosci. PD APR 9 PY 2013 VL 7 AR 89 DI 10.3389/fnhum.2013.00089 PG 18 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 122RM UT WOS:000317335500001 PM 23576966 ER PT J AU Pardo, CA Buckley, A Thurm, A Lee, LC Azhagiri, A Neville, DM Swedo, SE AF Pardo, Carlos A. Buckley, Ashura Thurm, Audrey Lee, Li-Ching Azhagiri, Arun Neville, David M. Swedo, Susan E. TI A pilot open-label trial of minocycline in patients with autism and regressive features SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Minocycline; Microglia; Neuroinflammation; Clinical trial; Cytokines; Chemokines; Metalloproteinases; Neurotrophins; BDNF ID AMYOTROPHIC-LATERAL-SCLEROSIS; PREFRONTAL CORTEX; MOUSE MODEL; MICROGLIA; BRAIN; DISORDERS; DISEASE; NEUROPROTECTION; SPECTRUM; COMMUNICATION AB Background: Minocycline is a tetracycline derivative that readily crosses the blood brain barrier and appears to have beneficial effects on neuroinflammation, microglial activation and neuroprotection in a variety of neurological disorders. Both microglial activation and neuroinflammation have been reported to be associated with autism. The study was designed to evaluate the effects of minocycline treatment on markers of neuroinflammation and autism symptomatology in children with autism and a history of developmental regression. Methods: Eleven children were enrolled in an open-label trial of six months of minocycline (1.4 mg/kg). Ten children completed the trial. Behavioral measures were collected and cerebrospinal fluid (CSF), serum and plasma were obtained before and at the end of minocycline treatment and were analyzed for markers of neuroinflammation. Results: Clinical improvements were negligible. The laboratory assays demonstrated significant changes in the expression profile of the truncated form of brain derived neurotrophic factor (BDNF) (P = 0.042) and hepatic growth factor (HGF) (P = 0.028) in CSF. In serum, the ratio of the truncated BDNF form and alpha-2 macroglobulin (alpha-2 M), was also significantly lower (P = 0.028) while the mature BDNF/alpha-2 M ratio revealed no difference following treatment. Only the chemokine CXCL8 (IL-8) was significantly different (P = 0.047) in serum while no significant changes were observed in CSF or serum in chemokines such as CCL2 (MCP-1) or cytokines such as TNF-alpha, CD40L, IL-6, IFN-gamma and IL-1 beta when pre- and post-treatment levels of these proteins were compared. No significant pre-and post-treatment changes were seen in the profiles of plasma metalloproteinases, putative targets of the effects of minocycline. Conclusions: Changes in the pre-and post-treatment profiles of BDNF in CSF and blood, HGF in CSF and CXCL8 (IL-8) in serum, suggest that minocycline may have effects in the CNS by modulating the production of neurotrophic growth factors. However, in this small group of children, no clinical improvements were observed during or after the six months of minocycline administration. C1 [Pardo, Carlos A.; Azhagiri, Arun] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. [Buckley, Ashura; Thurm, Audrey; Neville, David M.; Swedo, Susan E.] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA. [Lee, Li-Ching] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. RP Pardo, CA (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, 600 North Wolfe St, Baltimore, MD 21287 USA. EM cpardov1@jhmi.edu FU National Institute of Mental Health; NIH [HHSN271200700179]; Bart McLean Fund for Neuroimmunology Research; Peter Emch Fund for Autism Research FX The research was funded by the Intramural Research Program of the National Institute of Mental Health. Dr. Pardo's laboratory received support from NIH contract HHSN271200700179, The Bart McLean Fund for Neuroimmunology Research and The Peter Emch Fund for Autism Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. 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PD APR 7 PY 2013 VL 245 MA 922-CHED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851302712 ER PT J AU Jakab, A Emri, M Spisak, T Szeman-Nagy, A Beres, M Kis, SA Molnar, P Berenyi, E AF Jakab, Andras Emri, Miklos Spisak, Tamas Szeman-Nagy, Anita Beres, Monika Kis, Sandor Attila Molnar, Peter Berenyi, Ervin TI Autistic Traits in Neurotypical Adults: Correlates of Graph Theoretical Functional Network Topology and White Matter Anisotropy Patterns SO PLOS ONE LA English DT Article ID VOXEL-BASED MORPHOMETRY; POSTERIOR CINGULATE CORTEX; ASPERGER-SYNDROME; SPECTRUM DISORDER; FUSIFORM GYRUS; BRAIN NETWORKS; BASAL GANGLIA; CONNECTIVITY PATTERNS; CEREBRAL-CORTEX; FRONTAL-CORTEX AB Attempts to explicate the neural abnormalities behind autism spectrum disorders frequently revealed impaired brain connectivity, yet our knowledge is limited about the alterations linked with autistic traits in the non-clinical population. In our study, we aimed at exploring the neural correlates of dimensional autistic traits using a dual approach of diffusion tensor imaging (DTI) and graph theoretical analysis of resting state functional MRI data. Subjects were sampled from a public neuroimaging dataset of healthy volunteers. Inclusion criteria were adult age (age: 18-65), availability of DTI and resting state functional acquisitions and psychological evaluation including the Social Responsiveness Scale (SRS) and Autistic Spectrum Screening Questionnaire (ASSQ). The final subject cohort consisted of 127 neurotypicals. Global brain network structure was described by graph theoretical parameters: global and average local efficiency. Regional topology was characterized by degree and efficiency. We provided measurements for diffusion anisotropy. The association between autistic traits and the neuroimaging findings was studied using a general linear model analysis, controlling for the effects of age, gender and IQ profile. Significant negative correlation was found between the degree and efficiency of the right posterior cingulate cortex and autistic traits, measured by the combination of ASSQ and SRS scores. Autistic phenotype was associated with the decrease of whole-brain local efficiency. Reduction of diffusion anisotropy was found bilaterally in the temporal fusiform and parahippocampal gyri. Numerous models describe the autistic brain connectome to be dominated by reduced long-range connections and excessive short-range fibers. Our finding of decreased efficiency supports this hypothesis although the only prominent effect was seen in the posterior limbic lobe, which is known to act as a connector hub. The neural correlates of the autistic trait in neurotypicals showed only limited similarities to the reported findings in clinical populations with low functioning autism. C1 [Jakab, Andras; Beres, Monika; Berenyi, Ervin] Univ Debrecen Med & Hlth Sci Ctr, Dept Biomed Lab & Imaging Sci, Debrecen, Hungary. [Emri, Miklos; Spisak, Tamas; Kis, Sandor Attila] Univ Debrecen Med & Hlth Sci Ctr, Inst Nucl Med, Debrecen, Hungary. [Szeman-Nagy, Anita] Univ Debrecen, Dept Personal & Clin Psychol, Inst Psychol, H-4012 Debrecen, Hungary. [Molnar, Peter] Univ Debrecen Med & Hlth Sci Ctr, Dept Behav Sci, Debrecen, Hungary. RP Jakab, A (reprint author), Univ Debrecen Med & Hlth Sci Ctr, Dept Biomed Lab & Imaging Sci, Debrecen, Hungary. EM jakaba@med.unideb.hu FU ENIAC CSI project [120209]; New York State Office of Mental Health; Research Foundation for Mental Hygiene; NKI Center for Advanced Brain Imaging (CABI); Brain Research Foundation (Chicago, IL); Stavros Niarchos Foundation; NIH [P50 MH086385-S1] FX This work was partly supported by the ENIAC CSI project (No. 120209). The authors would like to thank the efforts of F. Xavier Castellanos, Bennett Leventhal, Michael Milham who played a fundamental role in creating the Nathan Kline Institute Rockland Sample. Funding for the above mentioned key personnel was provided in part by the New York State Office of Mental Health and Research Foundation for Mental Hygiene. Additional project support was provided by the NKI Center for Advanced Brain Imaging (CABI), the Brain Research Foundation (Chicago, IL), the Stavros Niarchos Foundation, and NIH grant P50 MH086385-S1. 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 146RZ UT WOS:000319109800115 PM 23593367 ER PT J AU Kushki, A Drumm, E Mobarak, MP Tanel, N Dupuis, A Chau, T Anagnostou, E AF Kushki, Azadeh Drumm, Ellen Mobarak, Michele Pla Tanel, Nadia Dupuis, Annie Chau, Tom Anagnostou, Evdokia TI Investigating the Autonomic Nervous System Response to Anxiety in Children with Autism Spectrum Disorders SO PLOS ONE LA English DT Article ID AMYGDALA VOLUME; HEART-RATE; ASSOCIATION; ACTIVATION; SYMPTOMS; BEHAVIOR; DEFICITS; AROUSAL; STRESS; STROOP AB Assessment of anxiety symptoms in autism spectrum disorders (ASD) is a challenging task due to the symptom overlap between the two conditions as well as the difficulties in communication and awareness of emotions in ASD. This motivates the development of a physiological marker of anxiety in ASD that is independent of language and does not require observation of overt behaviour. In this study, we investigated the feasibility of using indicators of autonomic nervous system (ANS) activity for this purpose. Specially, the objectives of the study were to 1) examine whether or not anxiety causes significant measurable changes in indicators of ANS in an ASD population, and 2) characterize the pattern of these changes in ASD. We measured three physiological indicators of the autonomic nervous system response (heart rate, electrodermal activity, and skin temperature) during a baseline (movie watching) and anxiety condition (Stroop task) in a sample of typically developing children (n = 17) and children with ASD (n = 12). The anxiety condition caused significant changes in heart rate and electrodermal activity in both groups, however, a differential pattern of response was found between the two groups. In particular, the ASD group showed elevated heart rate during both baseline and anxiety conditions. Elevated and blunted phasic electrodermal activity were found in the ASD group during baseline and anxiety conditions, respectively. Finally, the ASD group did not show the typical decrease in skin temperature in response to anxiety. These results suggest that 1) signals of the autonomic nervous system may be used as indicators of anxiety in children with ASD, and 2) ASD may be associated with an atypical autonomic response to anxiety that is most consistent with sympathetic over-arousal and parasympathetic under-arousal. C1 [Kushki, Azadeh; Drumm, Ellen; Mobarak, Michele Pla; Tanel, Nadia; Dupuis, Annie; Chau, Tom; Anagnostou, Evdokia] Holland Bloorview Kids Rehabil Hosp, Bloorview Res Inst, Toronto, ON, Canada. [Dupuis, Annie] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Chau, Tom] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON, Canada. [Anagnostou, Evdokia] Univ Toronto, Dept Pediat, Toronto, ON M5S 1A1, Canada. RP Kushki, A (reprint author), Holland Bloorview Kids Rehabil Hosp, Bloorview Res Inst, Toronto, ON, Canada. EM akushki@hollandbloorview.ca FU Bloorview Research Institute; Ontario Brain Institute; Seaside Therapeutics FX This study was funded in part by the Bloorview Research Institute and the Ontario Brain Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The authors AK, ED, MM, NT, AD and TC have declared that no competing interests exist. EA has consulted without fees to Proximagen, Neuropharm and NOVARTIS and has received a consultation fee from Seaside Therapeutics. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. 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Fatemi, S. Hossein TI Viral infection, inflammation and schizophrenia SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE Autism; Inflammation; Influenza; Schizophrenia; Viral infection ID PRENATAL IMMUNE ACTIVATION; NECROSIS-FACTOR-ALPHA; SYNAPTOSOMAL-ASSOCIATED PROTEIN; ANTIOXIDANT ENZYME LEVELS; INFLUENZA A/WSN/33 VIRUS; PLACEBO-CONTROLLED TRIAL; BIPOLAR DISORDER; OXIDATIVE STRESS; SOUTHERN-HEMISPHERE; NEONATAL MICE AB Schizophrenia is a severe neurodevelopmental disorder with genetic and environmental etiologies. Prenatal viral/bacterial infections and inflammation play major roles in the genesis of schizophrenia. In this review, we describe a viral model of schizophrenia tested in mice whereby the offspring of mice prenatally infected with influenza at E7, E9, E16, and El8 show significant gene, protein, and brain structural abnormalities postnatally. Similarly, we describe data on rodents exposed to bacterial infection or injected with a synthetic viral mimic (Polyl:C) also demonstrating brain structural and behavioral abnormalities. Moreover, human serologic data has been indispensible in supporting the viral theory of schizophrenia. Individuals born seropositive for bacterial and viral agents are at a significantly elevated risk of developing schizophrenia. While the specific mechanisms of prenatal viral/bacterial infections and brain disorder are unclear, recent findings suggest that the maternal inflammatory response may be associated with fetal brain injury. Preventive and therapeutic treatment options are also proposed. This review presents data related to epidemiology, human serology, and experimental animal models which support the viral model of schizophrenia (C) 2012 Elsevier Inc. All rights reserved. C1 [Kneeland, Rachel E.; Fatemi, S. Hossein] 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 knee0030@umn.edu; fatem002@umn.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [5R01HD046589-04, 3R01HD046589-04S1]; Young & the Phyllis and Perry Schwartz Established Investigator Awards from NARSAD FX We would like to thank Tim Folsom for the critical review of this manuscript. The work of S.H. Fatemi was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grants 5R01HD046589-04, 3R01HD046589-04S1, and Young & the Phyllis and Perry Schwartz Established Investigator Awards from NARSAD. 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Neuro-Psychopharmacol. Biol. Psychiatry PD APR 5 PY 2013 VL 42 SI SI BP 35 EP 48 DI 10.1016/j.pnpbp2012.02.001 PG 14 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 111JP UT WOS:000316517900004 PM 22349576 ER PT J AU Allen, R Walsh, R Zangwill, N AF Allen, Rory Walsh, Reubs Zangwill, Nick TI The same, only different: what can responses to music in autism tell us about the nature of musical emotions? SO FRONTIERS IN PSYCHOLOGY LA English DT Editorial Material ID ALEXITHYMIA; EXPERIENCE; LANGUAGE; ADULTS C1 [Allen, Rory] Univ London, Dept Psychol, London, England. [Walsh, Reubs] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England. [Zangwill, Nick] Univ Durham, Dept Philosophy, Durham, England. RP Allen, R (reprint author), Univ London, Dept Psychol, London, England. 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PD APR 4 PY 2013 VL 4 AR 156 DI 10.3389/fpsyg.2013.00156 PG 4 WC Psychology, Multidisciplinary SC Psychology GA AA1FM UT WOS:000330841900001 PM 23576996 ER PT J AU Yadav, R Hillman, BG Gupta, SC Suryavanshi, P Bhatt, JM Pavuluri, R Stairs, DJ Dravid, SM AF Yadav, Roopali Hillman, Brandon G. Gupta, Subhash C. Suryavanshi, Pratyush Bhatt, Jay M. Pavuluri, Ratnamala Stairs, Dustin J. Dravid, Shashank M. TI Deletion of Glutamate Delta-1 Receptor in Mouse Leads to Enhanced Working Memory and Deficit in Fear Conditioning SO PLOS ONE LA English DT Article ID AUTISM SPECTRUM DISORDER; FRAGILE-X-SYNDROME; INHIBITORY PRESYNAPTIC DIFFERENTIATION; MEDIAL TEMPORAL-LOBE; LONG-TERM DEPRESSION; MORRIS WATER MAZE; SYNAPTIC PLASTICITY; KAINATE RECEPTORS; CANDIDATE GENES; NMDA RECEPTORS AB Glutamate delta-1 (GluD1) receptors are expressed throughout the forebrain during development with high levels in the hippocampus during adulthood. We have recently shown that deletion of GluD1 receptor results in aberrant emotional and social behaviors such as hyperaggression and depression-like behaviors and social interaction deficits. Additionally, abnormal expression of synaptic proteins was observed in amygdala and prefrontal cortex of GluD1 knockout mice ( GluD1 KO). However the role of GluD1 in learning and memory paradigms remains unknown. In the present study we evaluated GluD1 KO in learning and memory tests. In the eight-arm radial maze GluD1 KO mice committed fewer working memory errors compared to wildtype mice but had normal reference memory. Enhanced working memory in GluD1 KO was also evident by greater percent alternation in the spontaneous Y-maze test. No difference was observed in object recognition memory in the GluD1 KO mice. In the Morris water maze test GluD1 KO mice showed no difference in acquisition but had longer latency to find the platform in the reversal learning task. GluD1 KO mice showed a deficit in contextual and cue fear conditioning but had normal latent inhibition. The deficit in contextual fear conditioning was reversed by D-Cycloserine (DCS) treatment. GluD1 KO mice were also found to be more sensitive to foot-shock compared to wildtype. We further studied molecular changes in the hippocampus, where we found lower levels of GluA1, GluA2 and GluK2 subunits while a contrasting higher level of GluN2B in GluD1 KO. Additionally, we found higher postsynaptic density protein 95 (PSD95) and lower glutamate decarboxylase 67 (GAD67) expression in GluD1 KO. We propose that GluD1 is crucial for normal functioning of synapses and absence of GluD1 leads to specific abnormalities in learning and memory. These findings provide novel insights into the role of GluD1 receptors in the central nervous system. C1 [Yadav, Roopali; Hillman, Brandon G.; Gupta, Subhash C.; Suryavanshi, Pratyush; Bhatt, Jay M.; Pavuluri, Ratnamala; Dravid, Shashank M.] Creighton Univ, Dept Pharmacol, Omaha, NE 68178 USA. [Stairs, Dustin J.] Creighton Univ, Dept Psychol, Omaha, NE 68178 USA. RP Dravid, SM (reprint author), Creighton Univ, Dept Pharmacol, Omaha, NE 68178 USA. EM ShashankDravid@creighton.edu FU Health Future Foundation; National Alliance for Research on Schizophrenia and Depression; National Center for Research Resources [G20RR024001] FX This work was supported by the Health Future Foundation (SMD) and the National Alliance for Research on Schizophrenia and Depression (SMD). The project was also supported by G20RR024001 from National Center for Research Resources. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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TI Decoding moral judgments from neural representations of intentions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE functional MRI; morality; theory of mind ID TEMPORO-PARIETAL JUNCTION; AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; VOXEL PATTERN-ANALYSIS; SOCIAL COGNITION; LANGUAGE COMPREHENSION; ASPERGER-SYNDROME; FMRI DATA; MIND; BRAIN AB Intentional harms are typically judged to be morally worse than accidental harms. Distinguishing between intentional harms and accidents depends on the capacity for mental state reasoning (i.e., reasoning about beliefs and intentions), which is supported by a group of brain regions including the right temporo-parietal junction (RTPJ). Prior research has found that interfering with activity in RTPJ can impair mental state reasoning for moral judgment and that high-functioning individuals with autism spectrum disorders make moral judgments based less on intent information than neurotypical participants. Three experiments, using multivoxel pattern analysis, find that (i) in neurotypical adults, the RTPJ shows reliable and distinct spatial patterns of responses across voxels for intentional vs. accidental harms, and (ii) individual differences in this neural pattern predict differences in participants' moral judgments. These effects are specific to RTPJ. By contrast, (iii) this distinction was absent in adults with autism spectrum disorders. We conclude that multivoxel pattern analysis can detect features of mental state representations (e. g., intent), and that the corresponding neural patterns are behaviorally and clinically relevant. C1 [Koster-Hale, Jorie; Saxe, Rebecca] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Koster-Hale, Jorie; Saxe, Rebecca] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Dungan, James; Young, Liane L.] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. RP Koster-Hale, J (reprint author), MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jorie@mit.edu FU National Institutes of Health [1R01 MH096914-01A1]; Simons Foundation; National Science Foundation [095518]; John Merck Scholars grant; Dana Foundation; National Science Foundation Graduate Research Fellowship [0645960] FX We thank our participants; Lee Marvos and Caitlin Malloy for recruiting help; and Nancy Kanwisher, Ev Fedorenko, Hilary Richardson, Nick Dufour, members of the Massachusetts Institute of Technology (MIT) Saxelab, the Boston College Morality Laboratory, and the Brown Moral Psychology Research Laboratory for useful comments and discussion. Data were collected at the Athinoula A. Martinos Imaging Center at the McGovern Institute for Brain Research, MIT. This material is based on work supported by National Institutes of Health Grant 1R01 MH096914-01A1, the Simons Foundation, National Science Foundation Grant 095518, a John Merck Scholars grant, the Dana Foundation, and National Science Foundation Graduate Research Fellowship Grant 0645960. 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Govindarajan, Arvind Choi, Se-Young Tonegawa, Susumu TI Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE drug discovery; neurodevelopmental disorder ID AUTISM SPECTRUM DISORDERS; DENDRITIC SPINE; KNOCKOUT MICE; P21-ACTIVATED KINASE; MENTAL-RETARDATION; MOUSE MODEL; PROTEIN; HIPPOCAMPAL; EPILEPSY; CHILDREN AB Fragile X syndrome (FXS) is the most common inherited form of autism and intellectual disability and is caused by the silencing of a single gene, fragile X mental retardation 1 (Fmr1). The Fmr1 KO mouse displays phenotypes similar to symptoms in the human condition-including hyperactivity, repetitive behaviors, and seizures-as well as analogous abnormalities in the density of dendritic spines. Here we take a hypothesis-driven, mechanism-based approach to the search for an effective therapy for FXS. We hypothesize that a treatment that rescues the dendritic spine defect in Fmr1 KO mice may also ameliorate autism-like behavioral symptoms. Thus, we targeted a protein that regulates spines through modulation of actin cytoskeleton dynamics: p21-activated kinase (PAK). Our results demonstrate that a potent small molecule inhibitor of group I PAKs reverses dendritic spine phenotypes in Fmr1 KO mice. Moreover, this PAK inhibitor-which we call FRAX486-also rescues seizures and behavioral abnormalities such as hyperactivity and repetitive movements, thereby supporting the hypothesis that a drug treatment that reverses the spine abnormalities can also treat neurological and behavioral symptoms. Finally, a single administration of FRAX486 is sufficient to rescue all of these phenotypes in adult Fmr1 KO mice, demonstrating the potential for rapid, post-diagnostic therapy in adults with FXS. C1 [Dolan, Bridget M.; Lin, Gregory G.; Govindarajan, Arvind; Tonegawa, Susumu] MIT, Dept Biol, Picower Inst Learning & Memory, RIKEN MIT Ctr Neural Circuit Genet, Cambridge, MA 02139 USA. [Dolan, Bridget M.; Lin, Gregory G.; Govindarajan, Arvind; Tonegawa, Susumu] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Duron, Sergio G.; Campbell, David A.; Vollrath, Benedikt] Afraxis Inc, La Jolla, CA 92037 USA. [Rao, B. S. Shankaranarayana] Natl Inst Mental Hlth & Neurosci, Dept Neurophysiol, Bangalore 560029, Karnataka, India. [Ko, Hui-Yeon; Choi, Se-Young] Seoul Natl Univ, Sch Dent, Dept Physiol, Seoul 110749, South Korea. RP Dolan, BM (reprint author), MIT, Dept Biol, Picower Inst Learning & Memory, RIKEN MIT Ctr Neural Circuit Genet, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM bdolan@alum.mit.edu; tonegawa@mit.edu FU National Institutes of Health [R01-MH078821, P50-MH58880]; RIKEN Brain Science Institute; Simons Center for the Social Brain at the Massachusetts Institute of Technology FX We thank Alexander J. Rivest, Junghyup Suh, and Jennie Young for their insightful comments. This work was supported by National Institutes of Health Grants R01-MH078821 and P50-MH58880 (to S. T.), the RIKEN Brain Science Institute, and the Simons Center for the Social Brain at the Massachusetts Institute of Technology. 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Natl. Acad. Sci. U. S. A. PD APR 2 PY 2013 VL 110 IS 14 BP 5671 EP 5676 DI 10.1073/pnas.1219383110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 131ZP UT WOS:000318037800089 PM 23509247 ER PT J AU Schutzius, G Bleckmann, D Kapps-Fouthier, S di Giorgio, F Gerhartz, B Weiss, A AF Schutzius, Gabi Bleckmann, Dorothee Kapps-Fouthier, Sandra di Giorgio, Francesco Gerhartz, Bernd Weiss, Andreas TI A quantitative homogeneous assay for fragile X mental retardation 1 protein SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Fragile X syndrome; FMRP; Time-resolved Forster's resonance energy transfer; Immunoassay ID FMR1 AB Background: Hypermethylation of the fragile X mental retardation 1 gene FMR1 results in decreased expression of FMR1 protein FMRP, which is the underlying cause of Fragile X syndrome - an incurable neurological disorder characterized by mental retardation, anxiety, epileptic episodes and autism. Disease-modifying therapies for Fragile X syndrome are thus aimed at treatments that increase the FMRP expression levels in the brain. We describe the development and characterization of two assays for simple and quantitative detection of FMRP protein. Method: Antibodies coupled to fluorophores that can be employed for time-resolved Forster's resonance energy transfer were used for the development of homogeneous, one-step immunodetection. Purified recombinant human FMRP and patient cells were used as control samples for assay development. Results: The assays require small sample amounts, display high stability and reproducibility and can be used to quantify endogenous FMRP in human fibroblasts and peripheral blood mononuclear cells. Application of the assays to FXS patient cells showed that the methods can be used both for the characterization of clinical FXS patient samples as well as primary readouts in drug-discovery screens aimed at increasing endogenous FMRP levels in human cells. Conclusion: This study provides novel quantitative detection methods for FMRP in FXS patient cells. Importantly, due to the simplicity of the assay protocol, the method is suited to be used in screening applications to identify compounds or genetic interventions that result in increased FMRP levels in human cells. C1 [Schutzius, Gabi; Bleckmann, Dorothee; di Giorgio, Francesco; Weiss, Andreas] Novartis Pharma AG, Novartis Inst Biomed Res, Neurosci Discovery, CH-4002 Basel, Switzerland. [Schutzius, Gabi; Bleckmann, Dorothee; di Giorgio, Francesco] Novartis Pharma AG, Novartis Inst Biomed Res, Dev & Mol Pathways, CH-4002 Basel, Switzerland. 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RP Hobson, RP (reprint author), Tavistock Clin, Adult Dept, 120 Belsize Lane, London NW3 5BA, England. EM r.hobson@ucl.ac.uk NR 0 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1754-0739 EI 1754-0747 J9 EMOT REV JI Emot. Rev. PD APR PY 2013 VL 5 IS 2 BP 224 EP 224 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 298DF UT WOS:000330303500020 ER PT J AU Gouin, JP Paquin, C Thaw, A Barker, ET AF Gouin, Jean-Philippe Paquin, Chantal Thaw, Amanda Barker, Erin T. TI DAILY STRESSORS AND CRP PRODUCTION AMONG PARENTS OF CHILDREN WITH AN AUTISM SPECTRUM DISORDER SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-Psychosomatic-Society CY MAR 13-16, 2013 CL Miami, FL SP Amer Psychosomat Soc C1 [Gouin, Jean-Philippe; Paquin, Chantal; Thaw, Amanda; Barker, Erin T.] Concordia Univ, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2013 VL 75 IS 3 BP A52 EP A53 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 300MG UT WOS:000330467400170 ER PT J AU Dempsey, I Davies, M AF Dempsey, Ian Davies, Michael TI National test performance of young Australian children with additional educational needs SO AUSTRALIAN JOURNAL OF EDUCATION LA English DT Article DE Special education; special needs students; learning disabilities; achievement tests; national competency tests; national norms ID STUDENTS; DISABILITIES; PROPORTION; SCHOOLS AB While the national testing of Australian school students is now well-entrenched, the educational outcomes of students with additional needs in this country are unknown. Students with a disability may be exempted from national testing and, in the absence of consistent standards for test accommodations and alternative tests, Australian educational authorities continue to be unaccountable for these students. Using secondary data from the Longitudinal Study of Australian Children, it is estimated that 12.3% of study children had additional educational needs (predominantly learning disabilities, emotional and behavioural disabilities and autism) that required specialist services. More than a third of students with additional needs did not participate in national testing. Those students with additional needs who did participate performed at a significantly lower level in comparison to students without additional needs. Further, students with additional needs in public schools were much more likely to have poorer academic outcomes than their counterparts in the Catholic and Independent education sectors. 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PD APR PY 2013 VL 15 IS 2 BP 147 EP 166 DI 10.1177/1461445612471472 PG 20 WC Communication SC Communication GA 281AD UT WOS:000329071000002 ER PT J AU Lohr, WD Tanguay, P AF Lohr, W. David Tanguay, Peter TI DSM-5 and Proposed Changes to the Diagnosis of Autism SO PEDIATRIC ANNALS LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDER; ASPERGER-SYNDROME; CRITERIA; IV; VALIDITY; BEHAVIOR; CHILDREN; DOMAIN C1 [Lohr, W. David] Univ Louisville, Sch Med, Div Child & Adolescent Psychiat & Psychol, Louisville, KY 40202 USA. [Lohr, W. David; Tanguay, Peter] Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Louisville, KY 40202 USA. [Lohr, W. David] Univ Louisville, Autism Ctr, Sch Med, Louisville, KY 40202 USA. RP Lohr, WD (reprint author), Univ Louisville, Autism Ctr, 200 E Chestnut St, Louisville, KY 40202 USA. 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Annu. PD APR PY 2013 VL 42 IS 4 BP 161 EP 166 DI 10.3928/00904481-20130326-12 PG 6 WC Pediatrics SC Pediatrics GA 273RB UT WOS:000328552900017 PM 23556529 ER PT J AU Kloosterman, PH Summerfeldt, LJ Parker, JDA Holden, JJA AF Kloosterman, Patricia H. Summerfeldt, Laura J. Parker, James D. A. Holden, Jeanette J. A. TI The obsessive-compulsive trait of Incompleteness in parents of children with autism spectrum disorders SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Incompleteness; Autism spectrum disorders; Obsessive-compulsive; Repetitive behaviors ID REPETITIVE BEHAVIORS; DIAGNOSTIC INTERVIEW; HARM AVOIDANCE; SYMPTOMS; SCALE; INDIVIDUALS; ASSOCIATION; RELIABILITY; INVENTORY; FAMILIES AB The obsessive-compulsive behaviors central to Obsessive-Compulsive Disorder (OCD) are not uncommon in Autism Spectrum Disorders (ASD), however the association between these disorders is not yet clear. One construct which may be useful in delineating their overlapping characteristics is "Incompleteness" or a sense of things feeling "not just right". Incompleteness has been related to a constellation of symptoms in OCD, but its association with ASD has not yet been examined. In this study parents with two or more children with ASD (P-MC) (n=115) were compared to an independent sample of parents having a single child with an ASD (P-SC), matched by age and gender, on level of Incompleteness. Results indicate that P-MC parents scored significantly higher in Incompleteness than P-SC parents. Incompleteness scores were also associated with a profile of behaviors in their children with ASD (n=357) characterized by high scores on the empirically derived repetitive sensory motor actions and resistance to change domains of the Autism Diagnostic Interview-Revised (Cuccaro et al., 2003). We discuss the implications of Incompleteness found in parents of children with an ASD, as well as its utility as a possible endophenotype for both ASD and OCD. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Kloosterman, Patricia H.; Summerfeldt, Laura J.; Parker, James D. A.] Trent Univ, Dept Psychol, Peterborough, ON K0L 1Y0, Canada. [Holden, Jeanette J. A.] Queens Univ, Dept Psychiat, Kingston, ON K7L 3N6, Canada. [Holden, Jeanette J. A.] Queens Univ, Dept Physiol, Kingston, ON K7L 3N6, Canada. [Holden, Jeanette J. A.] Ongwanada, Autism Res Program, Kingston, ON K7M 8A6, Canada. RP Kloosterman, PH (reprint author), Trent Univ, Dept Psychol, Peterborough, ON K9J 7B8, Canada. EM patriciakloosterman@trentu.ca FU CIHR Interdisciplinary Health Research Team grant [RT-43820] FX We extend our sincere appreciation to the families who participated in this study. This work was supported by a CIHR Interdisciplinary Health Research Team grant (RT-43820) to the Autism Spectrum Disorders Canadian-American Research Consortium (ASD-CARC: www.AutismResearch.ca) (JJAH, principal investigator). The authors also wish to thank Melissa Hudson for data management, Henderika Penning for collecting some of the data, and Kateryna Keefer for assisting with the statistical analyses. 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TI Social Inclusion Enhances Biological Motion Processing: A Functional Near-Infrared Spectroscopy Study SO BRAIN TOPOGRAPHY LA English DT Article DE Social exclusion; Magnetic resonance imaging; Optical topography; Cognition; Biological motion ID BLOOD-PRESSURE; HUMAN BRAIN; PERCEPTION; OXYTOCIN; EXCLUSION; AUTISM; FMRI; BEHAVIOR; HUMANS; ACTIVATION AB Humans are especially tuned to the movements of other people. Neural correlates of this social attunement have been proposed to lie in and around the right posterior superior temporal sulcus (STS) region, which robustly responds to biological motion in contrast to a variety of non-biological motions. This response persists even when no form information is provided, as in point-light displays (PLDs). The aim of the current study was to assess the ability of functional near-infrared spectroscopy (fNIRS) to reliably measure brain responses to PLDs of biological motion, and determine the sensitivity of these responses to interpersonal contextual factors. To establish reliability, we measured brain activation to biological motion with fNIRS and functional magnetic resonance imaging (fMRI) during two separate sessions in an identical group of 12 participants. To establish sensitivity, brain responses to biological motion measured with fNIRS were subjected to an additional social manipulation where participants were either socially included or excluded before viewing PLDs of biological motion. Results revealed comparable brain responses to biological motion using fMRI and fNIRS in the right supramarginal gyrus. Further, social inclusion increased brain responses to biological motion in right supramarginal gyrus and posterior STS. 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PD APR PY 2013 VL 26 IS 2 BP 315 EP 325 DI 10.1007/s10548-012-0253-y PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 211LV UT WOS:000323910200009 PM 22941501 ER PT J AU Droucker, D Curtin, S Vouloumanos, A AF Droucker, Danielle Curtin, Suzanne Vouloumanos, Athena TI Linking Infant-Directed Speech and Face Preferences to Language Outcomes in Infants at Risk for Autism Spectrum Disorder SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE autism spectrum disorder; speech perception; high-risk infants ID JOINT VISUAL-ATTENTION; FACIAL EXPRESSIONS; AUDITORY PREFERENCES; RECURRENCE RISK; CROSS-LANGUAGE; 1ST YEAR; CHILDREN; NEWBORNS; RECOGNITION; MOTHERS AB Purpose: In this study, the authors aimed to examine whether biases for infant-directed (ID) speech and faces differ between infant siblings of children with autism spectrum disorder (ASD) (SIBS-A) and infant siblings of typically developing children (SIBS-TD), and whether speech and face biases predict language outcomes and risk group membership. Method: Thirty-six infants were tested at ages 6, 8, 12, and 18 months. Infants heard 2 ID and 2 adult-directed (AD) speech passages paired with either a checkerboard or a face. The authors assessed expressive language at 12 and 18 months and general functioning at 12 months using the Mullen Scales of Early Learning (Mullen, 1995). Results: Both infant groups preferred ID to AD speech and preferred faces to checkerboards. SIBS-TD demonstrated higher expressive language at 18 months than did SIBS-A, a finding that correlated with preferences for ID speech at 12 months. Although both groups looked longer to face stimuli than to the checkerboard, the magnitude of the preference was smaller in SIBS-A and predicted expressive vocabulary at 18 months in this group. Infants' preference for faces contributed to risk-group membership in a logistic regression analysis. Conclusion: Infants at heightened risk of ASD differ from typically developing infants in their preferences for ID speech and faces, which may underlie deficits in later language development and social communication. C1 [Droucker, Danielle] Univ Calgary, Sch & Appl Child Psychol, Calgary, AB T2N 1N4, Canada. [Curtin, Suzanne] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Vouloumanos, Athena] NYU, New York, NY USA. RP Curtin, S (reprint author), Univ Calgary, Calgary, AB T2N 1N4, Canada. EM scurtin@ucalgary.ca FU Alberta Centre for Child, Family, and Community Research; New York University FX This research was supported by funds from the Alberta Centre for Child, Family, and Community Research (awarded to the second author) and New York University (awarded to the third author). 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Speech Lang. Hear. Res. PD APR 1 PY 2013 VL 56 IS 2 BP 567 EP 576 DI 10.1044/1092-4388(2012/11-0266) PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 191WO UT WOS:000322445700016 PM 23690567 ER PT J AU Plumb, AM Wetherby, AM AF Plumb, Allison M. Wetherby, Amy M. TI Vocalization Development in Toddlers With Autism Spectrum Disorder SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE autism; autism spectrum disorder (ASD); vocalizations; early identification ID 2ND YEAR; YOUNG-CHILDREN; COMMUNICATION; PROFILES; LIFE; AGE; INTERVENTION; PREDICTORS AB Purpose: In this study, the authors aimed to examine the vocalizations of children with autism spectrum disorder (ASD) in the second year of life and their relationship to other areas of development. Method: Vocalizations were examined in 125 children between ages 18 and 24 months: 50 later diagnosed with ASD, 25 with developmental delays (DD) in which ASD was ruled out, and 50 with typical development (TD). Precise measures of vocalizations were obtained through coding of video-recorded behavior samples from the Communication and Symbolic Behavior Scales Developmental Profile (Wetherby & Prizant, 2002b). Results: The ASD group used a significantly lower proportion of vocalizations with speech sounds and a significantly higher proportion of atypical vocalizations than children with TD. The ASD group used a significantly higher proportion of distress vocalizations than the TD and DD groups. For the ASD group, the frequency of vocalizations with speech sounds correlated significantly with developmental levels both concurrently and predictively. In the ASD group, communicative vocalizations late in the second year were found to uniquely predict expressive language outcome at age 3 years above noncommunicative vocalizations. Conclusions: Further examination of distress vocalizations as a potential early indicator of ASD is recommended. In addition, the importance of early communicative vocalizations for later language development is highlighted. C1 [Plumb, Allison M.] Auburn Univ, Auburn, AL 36849 USA. [Wetherby, Amy M.] Florida State Univ, Tallahassee, FL 32306 USA. RP Plumb, AM (reprint author), Auburn Univ, Auburn, AL 36849 USA. EM amp0016@auburn.edu FU National Institute on Deafness and Other Communication Disorders (NIDCD) [R01 DC007462]; U.S. Department of Education (USDOE) Office of Special Education and Rehabilitation Services [H324C030112]; Centers for Disease Control and Prevention (CDC) [1U10DD000064] FX This research was supported in part by National Institute on Deafness and Other Communication Disorders (NIDCD) Grant R01 DC007462; U.S. Department of Education (USDOE) Office of Special Education and Rehabilitation Services Grant H324C030112; and Cooperative Agreement 1U10DD000064 from the Centers for Disease Control and Prevention (CDC). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIDCD, USDOE, or CDC. We thank the families and children who participated in this research project. 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Biol. PD APR PY 2013 VL 11 IS 4 AR e1001544 DI 10.1371/journal.pbio.1001544 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 140WT UT WOS:000318687800022 PM 23630456 ER PT J AU Williams, TA Langdon, R Porter, MA AF Williams, Tracey A. Langdon, Robyn Porter, Melanie A. TI Hyper-reactivity in fragile X syndrome females: Generalised or specific to socially-salient stimuli? A skin conductance study SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE Fragile X syndrome; FXS; Skin conductance; Electrodermal response; Social salience; Hyperarousal; Anxiety ID PHYSIOLOGICAL AROUSAL; AMYGDALA DYSFUNCTION; CHILDREN; BEHAVIOR; PREMUTATION; REACTIVITY; RESPONSES; AUTISM; BRAIN; GIRLS AB Fragile X syndrome (FXS) is characterised by hyper-reactivity, autistic tendencies and social anxiety. It has been hypothesised that the FXS social phenotype is secondary to a generalised hyper-reactivity that leads to social avoidance. No study, however, has investigated whether hyperarousal in FXS is generalised or more specific to socially salient information. We recorded skin conductance responses (SCRs) while females with FXS, as well as chronological age-(CA-) and mental age-(MA-) matched controls, viewed two sets of visual images: direct-gaze emotional faces and affectively arousing scenes. Explicit emotion recognition and subjective ratings of emotions aroused by images were also recorded. Overall, females with FXS displayed hyper-reactivity only when viewing the more socially salient stimuli (emotional faces), compared to CA-matched controls, but not MA-matched controls. Moreover, females with FXS also displayed atypical emotion recognition abilities and subjective ratings of their own emotional states. 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J. Psychophysiol. PD APR PY 2013 VL 88 IS 1 BP 26 EP 34 DI 10.1016/j.ijpsycho.2012.12.009 PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 154ZX UT WOS:000319716300003 PM 23298451 ER PT J AU Spiegel, DR AF Spiegel, David R. TI N-Methyl-D-aspartate receptors and glutamate neurotransmission: an overview in pathological conditions and treatment SO ACTA NEUROPSYCHIATRICA LA English DT Editorial Material ID NMDA; SCHIZOPHRENIA; BEHAVIORS; AUTISM; MICE C1 Eastern Virginia Med Sch, Dept Psychiat & Behav Sci, Norfolk, VA 23507 USA. RP Spiegel, DR (reprint author), Eastern Virginia Med Sch, Dept Psychiat & Behav Sci, Norfolk, VA 23507 USA. 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PD APR PY 2013 VL 25 IS 2 BP 63 EP 64 DI 10.1017/neu.2013.8 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 166JK UT WOS:000320550500001 ER PT J AU Bremaud, N AF Bremaud, Nicolas TI Islet of competence and "synthetical Other" in an Asperger case SO EVOLUTION PSYCHIATRIQUE LA French DT Article DE Psychoanalysis; Autism; Aspergers's syndrome; Competence; Other; Clinical case; Literature; J. Verne; Theorical study AB The famous case of P.-F. is an extraordinary example about Asperger autism. This case gives us with precision the fundamental symptoms described by Kanner (aloneness and sameness), but also many symptoms we can find into international or American classifications. According to a structural approach (see "L'autiste et sa voix" by J.-C. Maleval), this case clearly explains the specifical construction of "islet of competence" and the construction of a "synthetical Other". (C) 2012 Elsevier Masson SAS. All rights reserved. C1 [Bremaud, Nicolas] Lab Psychopathol Nouveaux Symptomes & Lien Social, EA Rennes Haute Bretagne 4050 2, F-85300 Challans, France. [Bremaud, Nicolas] IME Le Marais, F-85300 Challans, France. [Bremaud, Nicolas] IME Les Terres Noires, F-85000 La Roche Sur Yon, France. RP Bremaud, N (reprint author), Lab Psychopathol Nouveaux Symptomes & Lien Social, EA Rennes Haute Bretagne 4050 2, 13 Rue St Dominique, F-85300 Challans, France. EM bremaudnicolas@yahoo.fr CR Bruno P., 1992, SERIES DECOUVERTE FR, V8, P289 Grandin T., 1997, PENSER IMAGES Lacan J, 2001, AUTRES ECRITS, P191 Maleval JC, 2009, AUSTISTE SA VOIX Verne J., 1969, TOUR MONDE 80 JOURS Williams D., 1992, SI ME TOUCHE JE NEXI NR 6 TC 0 Z9 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0014-3855 J9 EVOL PSYCHIATR JI Evol. Psychiatr. PD APR-JUN PY 2013 VL 78 IS 2 BP 243 EP 248 DI 10.1016/j.evopsy.2012.09.006 PG 6 WC Psychiatry SC Psychiatry GA 168YO UT WOS:000320744100005 ER PT J AU Mellier, D AF Mellier, Denis TI The violence of the rage in clinical practices in institution SO EVOLUTION PSYCHIATRIQUE LA French DT Article DE Affect; Therapeutic relation; Violence; Destructivity; Intersubjectivity; Psychic envelope; Practice analysis; Nursing staff; Institution; Clinical case AB In institution, the teams have difficulties to cope with the violent demonstrations of the rage. The analysis of the rage in its intersubjective dimension brings a comprehensive model to their containing work. The rage replies to an attempt of differentiation of the subject, according to the process of the destruction of the primary object: 1) The rage has been theoretically defined by Kohut as an impulsive reaction facing a narcissistic injury. The need of the other becomes inside its own movement with the model of the "destruction of the object", extracted by Roussillon from the works of Winnicott on "the use of an object"; 2) Four vignettes put to the test this hypothesis. These clinical interventions come from the analysis of practices or the supervision of team (psychiatry services, home of handicapped adults or children, foster home); 3) Finally, the analysis shows that the rage is linked with the psychic envelope's dynamic. The rage appears in very different structures in psychopathology. It is as an explosive movement which jumbles the borders or the psychic envelopes. Its different forms are concomitant to the variations of the subject object differentiation according to pathologies (autism, psychosis, borderline pathologies). It is an attempt of repeated differentiation of the psychic envelops or spaces between the subject and his objects. So, in institution, its transformation depends on the recognition of its origin (the "ruthless love" in primitive relations) by the containing function of the team. (C) 2013 Elsevier Masson SAS. All rights reserved. C1 Univ Franche Comte, MSHE, EA 3188, Lab Psychol,SFPPG, F-25000 Besancon, France. RP Mellier, D (reprint author), Univ Franche Comte, MSHE, EA 3188, Lab Psychol,SFPPG, 30 Rue Megevand, F-25000 Besancon, France. 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Legal Med. PD APR 1 PY 2013 VL 34 IS 2 BP 215 EP 233 DI 10.1080/01947648.2013.800798 PG 19 WC Law; Social Sciences, Biomedical SC Government & Law; Biomedical Social Sciences GA 166QH UT WOS:000320571700003 PM 23980747 ER PT J AU Penprase, B Oakley, B Ternes, R Driscoll, D AF Penprase, Barbara Oakley, Barbara Ternes, Reuben Driscoll, Dana TI Empathy as a Determining Factor for Nursing Career Selection SO JOURNAL OF NURSING EDUCATION LA English DT Article ID HIGH-FUNCTIONING AUTISM; NORMAL SEX-DIFFERENCES; SYSTEMATIZING QUOTIENT; ASPERGER-SYNDROME; PROGRAM; ADULTS; STYLE; SELF AB The ability to empathize with others is a highly desirable characteristic for the delivery of quality care by nurses. Little research is available that explores the empathy characteristics of students who are attracted to nursing. The purpose of this study is to explore whether empathizing and systemizing characteristics are important factors underlying students' self-selection into and continuing success in nursing programs and whether the importance of these characteristics tends to differ for men and women who choose nursing as a career. A descriptive correlative design was used for this study of 1,872 undergraduates enrolled in a variety of majors, including nursing, at a large midwestern U. S. research university. Findings supported that nursing students had significantly higher empathy characteristics than students in other disciplines. C1 [Penprase, Barbara] Oakland Univ, Sch Nursing, Rochester, MI 48309 USA. [Oakley, Barbara] Oakland Univ, Dept Engn, Rochester, MI 48309 USA. [Ternes, Reuben] Oakland Univ, Dept Inst Res, Rochester, MI 48309 USA. [Driscoll, Dana] Oakland Univ, Dept Writing & Rhetor, Rochester, MI 48309 USA. RP Penprase, B (reprint author), Oakland Univ, Sch Nursing, 2200 N Squirrel Rd,2002 HHB, Rochester, MI 48309 USA. EM penprase@oakland.edu CR Abendroth M., 2006, J HOSP PALLIAT NURS, V8, P346, DOI 10.1097/00129191-200611000-00007 ALLIGOOD MR, 2005, ANN REV NURSING ED, V3, P299 *AM ASS COLL NURS, 2010, ENH DIV WORKF Baron-Cohen S., 2003, ESSENTIAL DIFFERENCE Baron-Cohen S, 2004, J AUTISM DEV DISORD, V34, P163, DOI 10.1023/B:JADD.0000022607.19833.00 Baron-Cohen S, 2002, TRENDS COGN SCI, V6, P248, DOI 10.1016/S1364-6613(02)01904-6 Baron-Cohen S, 2003, PHILOS T ROY SOC B, V358, P361, DOI 10.1098/rstb.2002.1206 BARONCOHEN S, 2007, ESSENTIAL DIFFERENCE Batson CD, 2009, SOCIAL NEUROSCIENCE OF EMPATHY, P3 Beecroft PC, 2001, J NURS ADMIN, V31, P575, DOI 10.1097/00005110-200112000-00008 Benner P., 2009, EXPERTISE NURSING PR Billington J, 2007, LEARN INDIVID DIFFER, V17, P260, DOI 10.1016/j.lindif.2007.02.004 Buxbaum JD, 2010, MOL AUTISM, V1, DOI 10.1186/2040-2392-1-1 CHAKRABARTI B, 2011, DNA SOCIAL COGNITION, P22 Chura LR, 2010, PSYCHONEUROENDOCRINO, V35, P122, DOI 10.1016/j.psyneuen.2009.09.009 Cliff B, 2012, J HEALTHC MANAG, V57, P86 Brunero Scott, 2010, Nurs Inq, V17, P65, DOI 10.1111/j.1440-1800.2009.00482.x Decety J, 2011, EMOT REV, V3, P92, DOI 10.1177/1754073910374662 Decety J, 2011, EMOT REV, V3, P115, DOI 10.1177/1754073910384160 Decety J, 2009, SOCIAL NEUROSCIENCE OF EMPATHY, P1 Eley D, 2011, J CLIN NURS, V20, P563, DOI 10.1111/j.1365-2702.2009.03122.x FAIRBANKS L, 2010, MALE NURSES ARE STIL Halpern J, 2001, DETACHED EMPATHY HUM Kovner CT, 2007, AM J NURS, V107, P58 Lawrence EJ, 2004, PSYCHOL MED, V34, P911, DOI 10.1017/S0033291703001624 Lombardo MV, 2010, J COGNITIVE NEUROSCI, V22, P1623, DOI 10.1162/jocn.2009.21287 Madhavan G., 2012, PATHOLOGICAL ALTRUIS *MIN NURS, 2011, MIN NURS STAT Newton SE, 2007, J NURS EDUC, V46, P439 OAKLEY B, 2011, COLD BLOODED KINDNES Reynolds WJ, 1999, J ADV NURS, V30, P1177, DOI 10.1046/j.1365-2648.1999.01191.x Shamay-Tsoory Simone G, 2011, Neuroscientist, V17, P18, DOI 10.1177/1073858410379268 STEINPARBURY J, 2005, PATIENT PERSON DEV I Taylor C., 2008, FUNDAMENTALS NURSING Ward Julia, 2009, J Nurs Meas, V17, P73 Wheelwright S, 2006, BRAIN RES, V1079, P47, DOI 10.1016/j.brainres.2006.01.012 WILLIAMS A, 2010, NY TIMES, pST1 Wilson T., 2011, REDIRECT SURPRISING Yu JP, 2008, J ADV NURS, V64, P440, DOI 10.1111/j.1365-2648.2008.04831.x Yu JP, 2009, J ADV NURS, V65, P1790, DOI 10.1111/j.1365-2648.2009.05071.x Zachariae R, 2003, BRIT J CANCER, V88, P658, DOI 10.1038/sj.bjc.6600798 Zahn-Waxler C, 2008, ANNU REV CLIN PSYCHO, V4, P275, DOI [10.1146/annurev.clinpsy.3.022806.091358, 10.1146/annurev.clinpsy.3.022806.0913] NR 42 TC 0 Z9 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0148-4834 J9 J NURS EDUC JI J. Nurs. Educ. PD APR PY 2013 VL 52 IS 4 BP 192 EP 197 DI 10.3928/01484834-20130314-02 PG 6 WC Nursing SC Nursing GA 161MW UT WOS:000320198200003 PM 23480066 ER PT J AU Aldridge, K George, ID Austin, JR Duan, Y Miles, JH AF Aldridge, Kristina George, Ian D. Austin, Jordan R. Duan, Ye Miles, Judith H. TI Patterns of morphological integration of the face in boys with autism spectrum disorders SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Aldridge, Kristina; George, Ian D.; Austin, Jordan R.; Miles, Judith H.] Univ Missouri, Sch Med, Columbia, MO USA. [Duan, Ye; Miles, Judith H.] Thompson Ctr Autism Neurodev Disorders, Columbia, MO USA. [Duan, Ye] Univ Missouri, Columbia, MO 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 2013 VL 27 MA 963.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883502549 ER PT J AU Al-Farsi, YM Al-Khaduri, M Al-Sumri, H Al-Farsi, O Al-Sharbati, M Waly, M Ouhtit, A Al-Shafaee, M AF Al-Farsi, Yahya M. Al-Khaduri, Maha Al-Sumri, Hanaa Al-Farsi, Omar Al-Sharbati, Marwan Waly, Mostafa Ouhtit, Allal Al-Shafaee, Mohammed TI Association of gestational diabetes mellitus with occurrence of Autism: A Cohort Study SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Al-Farsi, Yahya M.] Sultan Qaboos Univ, Coll Med, Muscat, Oman. [Al-Khaduri, Maha; Al-Sumri, Hanaa; Al-Farsi, Omar; Al-Sharbati, Marwan; Waly, Mostafa; Ouhtit, Allal; Al-Shafaee, Mohammed] Sultan Qaboos Univ, Muscat, Oman. 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 2013 VL 27 MA lb111 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883503125 ER PT J AU Bandini, L Curtin, C Anderson, S Philips, S Must, A AF Bandini, Linda Curtin, Carol Anderson, Sarah Philips, Sarah Must, Aviva TI Food as a reward and weight status in children with autism SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Bandini, Linda; Curtin, Carol] Univ Massachusetts, Sch Med, Eunice Kennedy Shriver Ctr, Waltham, MA USA. [Bandini, Linda] Boston Univ, Dept Hlth Sci, Boston, MA 02215 USA. [Anderson, Sarah] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA. [Philips, Sarah; Must, Aviva] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 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 2013 VL 27 MA 1063.11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883505295 ER PT J AU Charvet, C Finlay, BL AF Charvet, Christine Finlay, Barbara L. TI Phylogenetic based variation in autism SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Charvet, Christine; Finlay, Barbara L.] Cornell Univ, Ithaca, NY 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 2013 VL 27 MA 755.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860501287 ER PT J AU Dobson, S AF Dobson, Seth TI Neuroanatomical causes and social consequences of variation in facial motor control: what comparative primatology can teach us about autism spectrum disorders SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Dobson, Seth] Dartmouth Coll, Dept Anthropol, Hanover, NH 03755 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 2013 VL 27 MA 192.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883501179 ER PT J AU Ekvall, SM Fugazzi, P Stevens, F Ekvall, V AF Ekvall, Shirley Maxine Fugazzi, Patricia Stevens, Florence Ekvall, Valli TI Anthropometric Measurements, Dietary Intakes, Mealtime and Other Behaviors of Children with Autism SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Ekvall, Shirley Maxine] Univ Cincinnati, Dept Nutr, Cincinnati, OH USA. [Fugazzi, Patricia; Stevens, Florence; Ekvall, Valli] Childrens Hosp, Med Ctr, Cincinnati, OH 45229 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 2013 VL 27 MA 1060.25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883504482 ER PT J AU Rubio-Marrero, EN Falivelli, G Kim, H Comoletti, D AF Rubio-Marrero, Eva N. Falivelli, Giulia Kim, Hyuck Comoletti, Davide TI Interaction of TAG1 and CASPR2, Proteins Associated to Autism Disorder? SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Rubio-Marrero, Eva N.; Kim, Hyuck; Comoletti, Davide] Child Hlth Inst New Jersey, New Brunswick, NJ USA. [Falivelli, Giulia] Univ Calif San Diego, La Jolla, CA 92093 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 2013 VL 27 MA 553.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883505605 ER PT J AU Molero, Y Gumpert, C Serlachius, E Lichtenstein, P Walum, H Johansson, D Anckarsater, H Westberg, L Eriksson, E Halldner, L AF Molero, Y. Gumpert, C. Serlachius, E. Lichtenstein, P. Walum, H. Johansson, D. Anckarsater, H. Westberg, L. Eriksson, E. Halldner, L. TI A study of the possible association between adenosine A(2A) receptor gene polymorphisms and attention-deficit hyperactivity disorder traits SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Adenosine A(2A) receptor (ADORA2A); ADHD; association study; gene polymorphisms ID GENOME-WIDE ASSOCIATION; SPONTANEOUSLY HYPERTENSIVE-RATS; CAFFEINE-INDUCED ANXIETY; DEFICIT/HYPERACTIVITY DISORDER; MOLECULAR-GENETICS; TELEPHONE INTERVIEW; NERVOUS-SYSTEM; AUTISM-TICS; A-TAC; METAANALYSIS AB The adenosine A(2A) receptor (ADORA2A) is linked to the dopamine neurotransmitter system and is also implicated in the regulation of alertness, suggesting a potential association with attention-deficit hyperactivity disorder (ADHD) traits. Furthermore, animal studies suggest that the ADORA2A may influence ADHD-like behavior. For that reason, the ADORA2A gene emerges as a promising candidate for studying the etiology of ADHD traits. The aim of this study was to examine the relationship between ADORA2A gene polymorphisms and ADHD traits in a large population-based sample. This study was based on the Child and Adolescent Twin Study in Sweden (CATSS), and included 1747 twins. Attention-deficit hyperactivity disorder traits were assessed through parental reports, and samples of DNA were collected. Associations between six single nucleotide polymorphisms (SNPs) and ADHD traits were examined, and results suggested a nominal association between ADHD traits and three of these SNPs: rs3761422, rs5751876 and rs35320474. For one of the SNPs, rs35320474, results remained significant after correction for multiple comparisons. These results indicate the possibility that the ADORA2A gene may be involved in ADHD traits. However, more studies replicating the present results are warranted before this association can be confirmed. C1 [Molero, Y.; Gumpert, C.; Serlachius, E.] Karolinska Inst, Dept Clin Neurosci, SE-17177 Stockholm, Sweden. [Lichtenstein, P.; Walum, H.; Halldner, L.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Johansson, D.; Westberg, L.; Eriksson, E.] Univ Gothenburg, Dept Pharmacol, Gothenburg, Sweden. [Anckarsater, H.] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden. [Halldner, L.] Karolinska Inst, Ctr Neurodev Disorders KIND, SE-17177 Stockholm, Sweden. RP Molero, Y (reprint author), Karolinska Inst, MEB, Box 281, SE-17177 Stockholm, Sweden. EM yasmina.molero.samuelson@ki.se RI Serlachius, Eva/E-8956-2013 OI Serlachius, Eva/0000-0001-7115-6422 FU Karolinska Institutet; Karolinska Institutet Center of Neurodevelopmental Disorders (KIND); Swedish Department of Higher Education; Swedish Council For Working Life and Social Research; Swedish Research Council; Soderberg's foundation; Hallstens Foundation; Swedish Brain Foundation FX Funding for this study was provided by Karolinska Institutet, Karolinska Institutet Center of Neurodevelopmental Disorders (KIND), the Swedish Department of Higher Education, the Swedish Council For Working Life and Social Research, the Swedish Research Council, Soderberg's foundation, Hallstens Foundation and the Swedish Brain Foundation. Dr Staffan Nilsson is gratefully acknowledged for valuable statistical advice, and Dr Patrik Magnusson is gratefully acknowledged for valuable advice on methodological aspects of genetic association studies. The authors declare no conflicts of interest. 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PD APR PY 2013 VL 12 IS 3 BP 305 EP 310 DI 10.1111/gbb.12015 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 156PG UT WOS:000319834200003 PM 23332182 ER PT J AU Douglas-Escobar, M Elliott, E Neu, J AF Douglas-Escobar, Martha Elliott, Elizabeth Neu, Josef TI Effect of Intestinal Microbial Ecology on the Developing Brain SO JAMA PEDIATRICS LA English DT Review ID GUT MICROBIOTA; NECROTIZING ENTEROCOLITIS; BEHAVIOR; DISEASE; MICE; COLONIZATION; ACTIVATION; INFANCY; OBESITY; HEALTH AB he mammalian gastrointestinal tract harbors a highly diverse microbial population that plays a major role in nutrition, metabolism, protection against pathogens, and development of the immune system. It is estimated that at least 1000 different bacterial species cohabit the human intestinal tract. Most recently, the Human Microbiome Project, using new genomic technologies, has started a catalog of specific microbiome composition and its correlation with health and specific diseases. Herein we provide a brief review of the intestinal microbiome, with a focus on new studies showing that there is an important link between the microbes that inhabit the intestinal tract and the developing brain. With future research, an understanding of this link may help us to treat various neurobehavioral problems such as autism, schizophrenia, and anxiety. C1 [Douglas-Escobar, Martha; Elliott, Elizabeth; Neu, Josef] Univ Florida, Dept Pediat, Div Neonatol, Gainesville, FL 32610 USA. RP Neu, J (reprint author), Univ Florida, Dept Pediat, Div Neonatol, 1600 SW Archer Rd,Human Dev Bldg,HD 112, Gainesville, FL 32610 USA. EM neuj@peds.ufl.edu FU National Institute of Child Health and Human Development [RO1 HD 059143] FX This work was supported by the National Institute of Child Health and Human Development (grant RO1 HD 059143 to Dr Neu). 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PD APR PY 2013 VL 167 IS 4 BP 374 EP 379 DI 10.1001/jamapediatrics.2013.497 PG 6 WC Pediatrics SC Pediatrics GA 156MH UT WOS:000319825800011 PM 23400224 ER PT J AU Krieger, AE Saias, T Adrien, JL AF Krieger, A. -E. Saias, T. Adrien, J. -L. TI Promoting family-professional partnership in institutions for children with autism SO ENCEPHALE-REVUE DE PSYCHIATRIE CLINIQUE BIOLOGIQUE ET THERAPEUTIQUE LA French DT Article DE Parents-professionals partnership; Autism; Enabling; Empowerment AB Objective. - The present study aims to evaluate the impact of the Family-Professional Partnership Model on parents' perception of being enabled and empowered in the treatment of their autistic children. In the context of treatment for children with autism, the Family-Professional Partnership Model strives to create an egalitarian relationship between parents and mental health professionals and it encourages parents to actively participate in their child's treatment. To evaluate the effectiveness of the Family-Professional Partnership Model at enabling and empowering parents of autistic children at the IME, parents of autistic children (n = 18) completed the EPS and the PES. Method. - For the purposes of this study, the EPS and the PES were translated into French. Eighteen parent couples of autistic children (ages 4-13 years) receiving treatment at the IME for 1 to 2 years agreed to participate. Participants' responses to the EPS were correlated with their responses to the PES. Results. - Parent scores on the EPS significantly correlated with their scores on the PES. Father scores on the two measurements correlated significantly, Whereas the correlation between mother scores on these measurements remained insignificant. Conclusion. - The findings of this study are limited by the small sample size (n = 18) but they suggest that the Family-Professional Partnership Model had a positive impact on parent enablement and empowerment in taking care of their autistic children. Future studies should evaluate enablement and empowerment in a larger sample of subjects. They should also evaluate specific factors in the Family-Professional Partnership that lead to parent empowerment. (C) L'Encephale, Paris, 2012. C1 [Krieger, A. -E.; Saias, T.; Adrien, J. -L.] Univ Paris 05, Lab Psychopathol & Proc Sante, F-92774 Boulogne, France. [Saias, T.] Univ Quebec, Montreal, PQ H3C 3P8, Canada. RP Krieger, AE (reprint author), Univ Paris 05, Lab Psychopathol & Proc Sante, 71 Ave Edouard Vaillant, F-92774 Boulogne, France. EM anne.emmanuelle.krieger@gmail.com; th.saias@gmail.com CR Akey TM, 2000, EDUC PSYCHOL MEAS, V60, P429 Boudreault P, 1998, COMPRENDRE FAMILLE Brookman-Frazee L, 2004, J POSIT BEHAV INTERV, V6, P195, DOI 10.1177/10983007040060040201 Chatelanat G, 2003, ED FRANCOPHONIE, V31, P56 Chatelanat G, 2003, ED ENSEIGNEMENT SPEC Daudelin G, 2001, EMPOWERMENT COMME TE Dempsey Ian, 1995, Australia and New Zealand Journal of Developmental Disabilities, V20, P67 Dunst C., 2007, INT J DISABIL DEV ED, V54, P305, DOI 10.1080/10349120701488772 Kerr KP, 2000, EARLY CHILD DEV CARE, V163, P125, DOI 10.1080/0300443001630109 Rage B, 2008, AUTISME COMPRENDRE A NR 10 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 APR PY 2013 VL 39 IS 2 BP 130 EP 136 DI 10.1016/j.encep.2012.06.002 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 149IM UT WOS:000319312200008 PM 23095583 ER PT J AU Minjarez, MB Mercier, EM Williams, SE Hardan, AY AF Minjarez, Mendy Boettcher Mercier, Emma M. Williams, Sharon E. Hardan, Antonio Y. TI Impact of Pivotal Response Training Group Therapy on Stress and Empowerment in Parents of Children With Autism SO JOURNAL OF POSITIVE BEHAVIOR INTERVENTIONS LA English DT Article DE autism; pivotal; applied behavior analysis; parent training; parent education ID SOCIAL SUPPORT; EDUCATION; MOTHERS; PATHWAYS; PROGRAM; HEALTH AB Parents of children with autism are increasingly being considered as primary agents of intervention for their children. The goal of this study was to evaluate whether participating in a pivotal response training (PRT) group therapy program for parents of children with autism influenced related aspects of parents' lives, namely, their levels of stress and empowerment. Seventeen families participated in a 10-week therapy group designed to train parents to use PRT, with a specific focus on their children's language deficits. Measures of empowerment and stress were obtained at baseline and at the end of the trial. Ratings on the Parenting Stress Index/Short Form and the Family Empowerment Scale showed significant changes from pre- to posttreatment, indicating that parents felt higher levels of empowerment and lower levels of stress after the 10-week group program. Notably, stress related to parent-child interactions was most reduced. Possible causal factors and implications are discussed. C1 [Minjarez, Mendy Boettcher] Seattle Childrens Hosp, Seattle Childrens Res Inst, Seattle, WA USA. [Mercier, Emma M.] Univ Durham, Sch Educ, Durham DH1 3HP, England. [Williams, Sharon E.; Hardan, Antonio Y.] Stanford Univ, Sch Med, Div Child Psychiat, Stanford, CA 94305 USA. [Minjarez, Mendy Boettcher; Mercier, Emma M.; Williams, Sharon E.; Hardan, Antonio Y.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Lucile Packard Childrens Hosp, Stanford, CA 94305 USA. RP Minjarez, MB (reprint author), Seattle Childrens Autism Ctr, POB 5371,M-S CAC, Seattle, WA 98145 USA. 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Interv. PD APR PY 2013 VL 15 IS 2 BP 71 EP 78 DI 10.1177/1098300712449055 PG 8 WC Psychology, Clinical; Education, Special SC Psychology; Education & Educational Research GA 152JG UT WOS:000319527300002 ER PT J AU Muskett, T Body, R Perkins, M AF Muskett, Tom Body, Richard Perkins, Mick TI A discursive psychology critique of semantic verbal fluency assessment and its interpretation SO THEORY & PSYCHOLOGY LA English DT Article DE autism; concepts; conversation analysis; discursive psychology; verbal fluency ID NORMAL-CHILDREN; WORD FLUENCY; CATEGORIES; PROTOTYPICALITY; LANGUAGE; AUTISM AB Semantic verbal fluency (SVF), a psychological assessment method used in experimental research and clinical practice, requires participants to produce as many words as possible from a given superordinate category (e. g., "animals," "vehicles"). Features of responses, such as the prototypicality and ordering of items, are then interpreted as if revealing details about the organisation-or, in instances of ostensibly atypical performance, disorganisation-of participants' underlying conceptual and/or semantic systems. In this paper, we draw upon perspectives from Discursive Psychology, particularly the work of Derek Edwards (e. g., Edwards, 1997), to argue against this position. Following critical discussion of SVF's strongly cognitivist theoretical foundations, we present analyses of social interactions across various contexts, including the real-life administration of the paradigm with a child with autism, to suggest that performance is unavoidably socially mediated rather than solely internally driven. Our arguments challenge SVF's validity and its role in the description of "cognitive disorder." C1 [Muskett, Tom; Perkins, Mick] Univ Sheffield, Dept Human Commun Sci, Sheffield S11 7GX, S Yorkshire, England. 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PD APR PY 2013 VL 23 IS 2 BP 205 EP 226 DI 10.1177/0959354312472097 PG 22 WC Psychology, Multidisciplinary SC Psychology GA 148BZ UT WOS:000319218800004 ER PT J AU Rosqvist, HB Brownlow, C O'Dell, L AF Rosqvist, Hanna Bertilsdotter Brownlow, Charlotte O'Dell, Lindsay TI Mapping the social geographies of autism online and off-line narratives of neuro-shared and separate spaces SO DISABILITY & SOCIETY LA English DT Article DE disability geography; people with autism; neuro-separate space; neuro-shared space; online communities; self-advocacy press ID PEOPLE; CHILDREN; DISABILITIES; PARENTS; INCLUSION; EXCLUSION; IDENTITY; STIGMA; VOICES; PLACE AB This paper draws together empirical work that has been produced by the authors in two different autistic spaces: the Swedish magazine Empowerment produced by and aimed at adults with autism, and English-speaking autistic communities online. While the two points of data collection are quite different, there are important points of commonality that enable us to explore central issues concerning autistic and neurotypical space and the meanings assigned to these in different contexts. The paper aims to introduce the notion of social geographies of autism, based on talks among adults with autism and a social movement to promote autistic identities, giving examples from our previous work that has spanned both online and off-line spaces. Key issues discussed in the paper include a focus on autistic political platforms and the carving out of both social and political spaces for people with autism. In doing so, neuro-separate and neuro-shared spaces must be negotiated. C1 [Rosqvist, Hanna Bertilsdotter] Umea Univ, Dept Sociol, Umea, Sweden. [Rosqvist, Hanna Bertilsdotter] Umea Univ, Umea Ctr Gender Studies, Umea, Sweden. [Brownlow, Charlotte] Univ So Queensland, Dept Psychol, Toowoomba, Qld 4350, Australia. 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Soc. PD APR 1 PY 2013 VL 28 IS 3 BP 367 EP 379 DI 10.1080/09687599.2012.714257 PG 13 WC Rehabilitation; Social Sciences, Interdisciplinary SC Rehabilitation; Social Sciences - Other Topics GA 146OU UT WOS:000319101200006 ER PT J AU Ranick, J Persicke, A Tarbox, J Kornack, JA AF Ranick, Jennifer Persicke, Angela Tarbox, Jonathan Kornack, Jake A. TI Teaching children with autism to detect and respond to deceptive statements SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Deception; Non-literal language; Multiple exemplar training; Bullying; Relational Frame Theory ID SPECTRUM DISORDERS; MIND; ADOLESCENTS AB Previous research has shown that children with autism often have deficits in deception, both in the ability to lie to others and in the ability to detect when they are being lied to. Additionally, children with autism are frequently the victims of bullying and difficulty with understanding deception likely makes the population more vulnerable to bullying. The purpose of this study was to teach individuals with autism to identify when others were lying to them, specifically to exclude them or to take their possessions. The treatment package consisted of multiple exemplar training, including rules, modeling, role-play, and immediate feedback. The results indicated that the procedure was effective for all three participants. Additionally, generalization was demonstrated to novel, untrained lies and to same-age peer confederates who were not involved in training. (C) 2012 Elsevier Ltd. All rights reserved. EM j.tarbox@centerforautism.com CR Adachi T, 2004, BRAIN DEV-JPN, V26, P301, DOI 10.1016/S0387-7604(03)00170-0 Baron-Cohen Simon, 1995, MINDBLINDNESS ESSAY Bond CF, 2008, PSYCHOL BULL, V134, P477, DOI 10.1037/0033-2909.134.4.477 Cappadocia MC, 2012, J AUTISM DEV DISORD, V42, P266, DOI 10.1007/s10803-011-1241-x DePaulo BM, 2003, PSYCHOL BULL, V129, P74, DOI 10.1037//0033-2909.129.1.74 Emerich DM, 2003, J AUTISM DEV DISORD, V33, P253, DOI 10.1023/A:1024498232284 HALA S, 1991, CHILD DEV, V62, P83, DOI 10.1111/j.1467-8624.1991.tb01516.x HAPPE FGE, 1995, CHILD DEV, V66, P843, DOI 10.1111/j.1467-8624.1995.tb00909.x Mchugh L, 2007, PSYCHOL REC, V57, P517 National Autism Center, 2009, NAT STAND REP Persicke A, 2012, RES AUTISM SPECT DIS, V6, P913, DOI 10.1016/j.rasd.2011.12.007 Persicke A., 2013, RES AUTISM SPECT DIS, V6, P913 Pexman PM, 2011, J AUTISM DEV DISORD, V41, P1097, DOI 10.1007/s10803-010-1131-7 SODIAN B, 1992, J CHILD PSYCHOL PSYC, V33, P591, DOI 10.1111/j.1469-7610.1992.tb00893.x SODIAN B, 1991, CHILD DEV, V62, P468, DOI 10.1111/j.1467-8624.1991.tb01545.x Sterzing P. R., 2012, ARCH PEDIAT ADOL MED, P1 Stewart I., 2001, RELATIONAL FRAME THE van Roekel E, 2010, J AUTISM DEV DISORD, V40, P63, DOI 10.1007/s10803-009-0832-2 NR 18 TC 1 Z9 1 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 APR PY 2013 VL 7 IS 4 BP 503 EP 508 DI 10.1016/j.rasd.2012.12.001 PG 6 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 152OA UT WOS:000319539800001 ER PT J AU Neely, L Rispoli, M Camargo, S Davis, H Boles, M AF Neely, Leslie Rispoli, Mandy Camargo, Siglia Davis, Heather Boles, Margot TI The effect of instructional use of an iPad (R) on challenging behavior and academic engagement for two students with autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE iPad (R); Autism spectrum disorder; Challenging behavior; Academic demand ID COMPUTER-BASED INTERVENTIONS; SPECTRUM DISORDERS; INTELLECTUAL DISABILITIES; MOTIVATING OPERATIONS; CHILDREN; SKILLS; IPOD; INDIVIDUALS; CLASSROOM AB iPads (R) are increasingly used in the education of children with autism spectrum disorder. However, few empirical studies have examined the effects of iPads (R) on student behaviors. The purpose of this study was to compare academic instruction delivered with an iPad (R) to instruction delivered through traditional materials for two students with autism spectrum disorder who engaged in escape-maintained challenging behavior. An ABAB reversal design was utilized in which academic instruction with an iPad (R) and academic instruction with traditional materials were compared. Both participants demonstrated lower levels of challenging behavior and higher levels of academic engagement in the iPad (R) condition and higher levels of challenging behavior with lower levels of academic engagement during the traditional materials condition. These results suggest that the use of an iPad (R) as a means of instructional delivery may reduce escape-maintained behavior for some children with autism. Suggestions for future research directions are discussed. (C) 2013 Published by Elsevier Ltd. C1 [Neely, Leslie; Rispoli, Mandy; Camargo, Siglia; Davis, Heather; Boles, Margot] Texas A&M Univ, College Stn, TX 77843 USA. RP Neely, L (reprint author), Texas A&M Univ, Dept Educ Psychol, 4225 TAMU, College Stn, TX 77843 USA. EM cockeril@neo.tamu.edu CR Ayres KM, 2009, EDUC TRAIN DEV DISAB, V44, P493 Bondy A. S., 1994, FOCUS AUTISTIC BEHAV, V9, P1, DOI DOI 10.1177/108835769400900301 Burke RV, 2010, RES DEV DISABIL, V31, P1223, DOI 10.1016/j.ridd.2010.07.023 Cihak D, 2010, J POSIT BEHAV INTERV, V12, P103, DOI 10.1177/1098300709332346 Hammond DL, 2010, EDUC TRAIN AUTISM DE, V45, P525 Harrell A., 2010, SF WEEKLY NEWS Iwata Brian A, 2008, Behav Anal Pract, V1, P3 Johnson J. 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PD APR PY 2013 VL 7 IS 4 BP 509 EP 516 DI 10.1016/j.rasd.2012.12.004 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 152OA UT WOS:000319539800002 ER PT J AU Occelli, V Esposito, G Venuti, P Arduino, GM Zampini, M AF Occelli, Valeria Esposito, Gianluca Venuti, Paola Arduino, Giuseppe Maurizio Zampini, Massimiliano TI Attentional shifts between audition and vision in Autism Spectrum Disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Attention; Shifting; Autism Spectrum Disorders (ASDs); Multisensory; Auditory; Visual ID SENSORY OVER-RESPONSIVITY; EVENT-RELATED POTENTIALS; YOUNG-CHILDREN; ABNORMALITIES; CEREBELLAR; DEFICITS; IMPAIRMENT; HYPOPLASIA; BEHAVIOR; BINDING AB Previous evidence on neurotypical adults shows that the presentation of a stimulus allocates the attention to its modality, resulting in faster responses to a subsequent target presented in the same (vs. different) modality. People with Autism Spectrum Disorders (ASDs) often fail to detect a (visual or auditory) target in a stream of stimuli after shifting attention between modalities, possibly because they do not fully switch their attention from one modality to the other. In this study, the performance of a group of high-functioning patients with ASDs and a group of neurotypical controls was compared. Participants were asked to detect a target, auditory or visual, which was preceded, at different temporal intervals (i.e., 150, 600, 1000 ms), by an uninformative cue, either in the same or a different modality. In controls, when the target was visual, the cue modality did not affect performance. Unlike, when the target was auditory, a visual cue produced longer reaction times as compared to when it was auditory. In the ASD group, irrespectively of the modality of the cue, a slowing-down of responses to the target was observed at increasing temporal intervals. The discrepancy of performance is consistent with the 'over-focused' theory of sensory processing. Published by Elsevier Ltd. C1 [Occelli, Valeria; Esposito, Gianluca; Venuti, Paola; Zampini, Massimiliano] Univ Trent, Dept Psychol & Cognit Sci, I-38068 Rovereto, TN, Italy. [Esposito, Gianluca] RIKEN Brain Sci Inst, Kuroda Res Unit Affiliat Social Behav, Wako, Saitama 3510198, Japan. [Arduino, Giuseppe Maurizio] Ctr Autism & Asperger Syndrome, I-12084 Mondovi, CN, Italy. [Zampini, Massimiliano] Univ Trent, Ctr Mind Brain Sci, CIMeC, I-38068 Rovereto, TN, Italy. RP Occelli, V (reprint author), Emory Univ, Sch Med, Dept Neurol, Woodruff Mem Res Bldg,Suite 6209,101 Woodruff Cir, Atlanta, GA 30322 USA. 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Autism Spectr. Disord. PD APR PY 2013 VL 7 IS 4 BP 517 EP 525 DI 10.1016/j.rasd.2012.12.003 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 152OA UT WOS:000319539800003 ER PT J AU Schenning, H Knight, V Spooner, F AF Schenning, Heather Knight, Victoria Spooner, Fred TI Effects of structured inquiry and graphic organizers on social studies comprehension by students with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Moderate and severe disabilities; Moderate disability; Severe disability; Access to general curriculum; Social studies ID SIGNIFICANT COGNITIVE DISABILITIES; SEVERE DEVELOPMENTAL-DISABILITIES; GENERAL CURRICULUM; INSTRUCTION; CHILDREN; STANDARDS; HAPPENS; SCIENCE; SHIFTS; FOCUS AB In social studies, students learn about society and the culture in which they live, current and historical events, people from different backgrounds, and how to develop skills for participating in a democratic system. As people with disabilities are members of our society, participation in social studies content is an important component of their knowledge. Despite the potential benefits of learning social studies content, there is limited investigation in this area for individuals with autism spectrum disorders (ASD). In this study, three middle school students with autism spectrum disorders (ASD) who participated in alternate assessment standards testing based on alternate achievement standards (AA-AAS) learned social studies content (geographic relationships, historical perspectives, economics and development, and government and active citizenship) via structured inquiry and explicit instruction. Results from the single-case multiple probe across participants design suggest a functional relation between the implementation of structured inquiry using explicit instruction and student comprehension of social studies content. In addition, students were able to generalize to "real-world" applications. Future ;research and implications for practices are discussed. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Schenning, Heather] Charlotte Mecklenburg Sch, Alexander Graham Middle Sch, Charlotte, NC USA. [Knight, Victoria] Univ Kentucky, Dept Special Educ & Rehabil Counseling, Coll Educ, Lexington, KY 40506 USA. [Spooner, Fred] Univ N Carolina, Charlotte, NC 28223 USA. RP Knight, V (reprint author), Univ Kentucky, Dept Special Educ & Rehabil Counseling, Coll Educ, 229 Taylor Educ Bldg, Lexington, KY 40506 USA. EM v.knight@uky.edu CR Ayres KM, 2012, EDUC TRAIN AUTISM DE, V47, P14 Ayres KM, 2011, EDUC TRAIN AUTISM DE, V46, P11 Bednarz S. W., 2003, WORLD CULTURES GEOGR Browder D, 2009, EXCEPT CHILDREN, V75, P343 Browder D. 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W., 2001, WOODCOCKJOHNSON 3 TE Woodcock R. W., 1990, WOODCOCK JOHNSON TES Zakas T. L., 2010, THESIS U N CAROLINA NR 41 TC 4 Z9 4 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 APR PY 2013 VL 7 IS 4 BP 526 EP 540 DI 10.1016/j.rasd.2012.12.007 PG 15 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 152OA UT WOS:000319539800004 ER PT J AU Hassan, TH Abdelrahman, HM Fattah, NRA El-Masry, NM Hashim, HM El-Gerby, KM Fattah, NRA AF Hassan, Tamer H. Abdelrahman, Hadeel M. Fattah, Nelly R. Abdel El-Masry, Nagda M. Hashim, Haitham M. El-Gerby, Khaled M. Fattah, Nermin R. Abdel TI Blood and brain glutamate levels in children with autistic disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Blood glutamate; Brain glutamate; Autism ID GLUTAMATE-RECEPTOR-6 GENE; CEREBELLAR CORTICES; CEREBROSPINAL-FLUID; ASSOCIATION; ACID; PARIETAL; SPECTROSCOPY; DYSFUNCTION; INDUCTION; LINKAGE AB Despite of the great efforts that move forward to clarify the pathophysiologic mechanisms in autism, the cause of this disorder, however, remains largely unknown. There is an increasing body of literature concerning neurochemical contributions to the pathophysiology of autism. We aimed to determine blood and brain levels of glutamate in children with autistic disorder and to correlate between them. The study included 10 children with autism and 10 age- and sex-matched healthy controls. Blood glutamate levels were measured using high performance liquid chromatography technique. Brain glutamate levels were measured using proton magnetic resonance spectroscopy. The mean blood and brain glutamate levels were significantly higher in patients than controls (p < 0.001). There was highly significant positive correlation between blood glutamate level and brain glutamate levels in the four tested brain regions (p < 0.001). Glutamate plays an important role in the pathogenesis of autism. Further larger studies are required to support our findings. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Hassan, Tamer H.; Abdelrahman, Hadeel M.] Zagazig Univ, Fac Med, Dept Pediat, Zagazig, Egypt. [Fattah, Nelly R. Abdel; El-Masry, Nagda M.; Hashim, Haitham M.] Zagazig Univ, Fac Med, Dept Psychiat, Zagazig, Egypt. [El-Gerby, Khaled M.] Zagazig Univ, Fac Med, Dept Radiodiag, Zagazig, Egypt. [Fattah, Nermin R. Abdel] Zagazig Univ, Fac Med, Dept Med Biochem, Zagazig, Egypt. RP Hashim, HM (reprint author), Zagazig Univ, Fac Med, Dept Psychiat, Zagazig, Egypt. EM aboukhedry@yahoo.com CR Acosta M. 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Autism Spectr. Disord. PD APR PY 2013 VL 7 IS 4 BP 541 EP 548 DI 10.1016/j.rasd.2012.12.005 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 152OA UT WOS:000319539800005 ER PT J AU Pouw, LBC Rieffe, C Stockmann, L Gadow, KD AF Pouw, Lucinda B. C. Rieffe, Carolien Stockmann, Lex Gadow, Kenneth D. TI The link between emotion regulation, social functioning, and depression in boys with ASD SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Depression; Emotion regulation; Coping; Victimization ID AUTISM SPECTRUM DISORDERS; CHILDHOOD DEPRESSION; PEER VICTIMIZATION; BULLYING BEHAVIOR; PARENT-REPORT; CHILDREN; ADOLESCENTS; FRIENDSHIP; PSYCHOPATHOLOGY; INDIVIDUALS AB Purpose: Symptoms of depression are common in children and adolescents with an autism spectrum disorder (ASD), but information about underlying developmental factors is limited. Depression is often linked to aspects of emotional functioning such as coping strategies, but in children with ASD difficulties with social interactions are also a likely contributor to depressive symptoms. Methodology: We examined several aspects of emotional coping (approach, avoidant, maladaptive) and social functioning (victimization, negative friendship interactions) and their relation to depression symptoms in children with ASD (N=63) and typically developing (TD) peers (N=57). Children completed a battery of self-report questionnaires. Results: Less approach and avoidant, but more maladaptive coping strategies, and poor social functioning were uniquely associated with more symptoms of depression in children with ASD. Only less approach and more maladaptive coping were uniquely associated with depression severity in TO boys. Conclusions: Unlike TD boys, boys with ASD who report using avoidant strategies to deal with stressful situations report fewer symptoms of depression, suggesting that this may be an adaptive emotion regulation strategy. However, understanding the role of over-arousal in this process, inferences about long-term effects of this strategy, its causality and direction of effects will require additional research. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Pouw, Lucinda B. C.; Rieffe, Carolien] Leiden Univ, NL-2300 RB Leiden, Netherlands. [Rieffe, Carolien] Dutch Fdn Deaf & Hard Hearing Child, Amsterdam, Netherlands. [Stockmann, Lex] Rivierduinen, Ctr Autism, Leiden, Netherlands. [Gadow, Kenneth D.] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. RP Rieffe, C (reprint author), Leiden Univ, POB 9555, NL-2300 RB Leiden, Netherlands. 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TI Emotion regulation difficulties in anorexia nervosa: Relationship to self-perceived sensory sensitivity SO COGNITION & EMOTION LA English DT Article DE Emotion regulation; Sensory sensitivity; Sensation; Anorexia nervosa; Acceptance ID EATING-DISORDER EXAMINATION; AUTISM SPECTRUM DISORDERS; INTEROCEPTIVE AWARENESS; MODEL; PSYCHOPATHOLOGY; QUESTIONNAIRE; RECOGNITION; ACCEPTANCE; AMENORRHEA; INTERVIEW AB Changes in sensation (e.g., prickly skin) are crucial constituents of emotional experience, and the intensity of perceived changes has been linked to emotional intensity and dysregulation. The current study examined the relationship between sensory sensitivity and emotion regulation among adults with anorexia nervosa (AN), a disorder characterised by disturbance in the experience of the body. Twenty-one individuals with AN, 20 individuals with AN who were weightrestored, and 23 typical controls completed self-report measures of sensory sensitivity and emotion regulation. 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TI Evaluating Rare Variants in Complex Disorders Using Next-Generation Sequencing SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Human genetics; Genomics; Genetic architecture; Complex traits; Next-generation sequencing; Targeted enrichment; Single nucleotide variants; SNVs; Single nucleotide polymorphisms; SNPs; Structural variation; Copy number variants; CNVs; Complex neuropsychiatric disorders; Schizophrenia; Autism; Genetic disorders; Psychiatry ID COPY-NUMBER VARIATION; DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; MISSING HERITABILITY; STRUCTURAL VARIATION; COMMON VARIANTS; HUMAN-DISEASE; HUMAN EXOMES AB Determining the genetic architecture of liability for complex neuropsychiatric disorders like autism spectrum disorders and schizophrenia poses a tremendous challenge for contemporary biomedical research. Here we discuss how genetic studies first tested, and rejected, the hypothesis that common variants with large effects account for the prevalence of these disorders. We then explore how the discovery of structural variation has contributed to our understanding of the etiology of these disorders. The rise of fast and inexpensive oligonucleotide sequencing and methods of targeted enrichment and their influence on the search for rare genetic variation contributing to complex neuropsychiatric disorders is the next focus of our article. Finally, we consider the technical challenges and future prospects for the use of next-generation sequencing to reveal the complex genetic architecture of complex neuropsychiatric disorders in both research and the clinical settings. C1 [Ezewudo, Matthew; Zwick, Michael E.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. RP Zwick, ME (reprint author), Emory Univ, Dept Human Genet, Whitehead Biomed Res Bldg,Suite 301, Atlanta, GA 30322 USA. EM mezewud@emory.edu; mzwick@emory.edu FU National Institutes of Health/National Heart, Lung, and Blood Institute FX M. Ezewudo: none; M. E. Zwick: grant from National Institutes of Health/National Heart, Lung, and Blood Institute, and consultant to Henry M. Jackson Foundation. 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Findings revealed that science frames decreased over time, while policy frames increased. Medical, government, family, and nonprofit sources were most common in news coverage. Solutions were mentioned more frequently than causes; however, mobilizing information was limited. Theoretical implications and practical applications are discussed. C1 Univ S Carolina, Sch Journalism & Mass Commun, Columbia, SC 29208 USA. RP McKeever, BW (reprint author), Univ S Carolina, Sch Journalism & Mass Commun, Columbia, SC 29208 USA. 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Commun. PD APR PY 2013 VL 35 IS 2 BP 213 EP 240 DI 10.1177/1075547012450951 PG 28 WC Communication SC Communication GA 142RY UT WOS:000318816000004 ER PT J AU Chen, S Liu, CC AF Chen, Su Liu, Chengchu TI Ether Glycerophospholipids and Their Potential as Therapeutic Agents SO CURRENT ORGANIC CHEMISTRY LA English DT Article DE Ether glycerophospholipids; docosahexaenoic acid; molecular nutrition; Alzheimer's disease; autism; infertility ID PLATELET-ACTIVATING-FACTOR; AUTISM SPECTRUM DISORDERS; TANDEM MASS-SPECTROMETRY; BLOOD-BRAIN-BARRIER; ALZHEIMERS-DISEASE; DOCOSAHEXAENOIC ACID; ELECTROSPRAY-IONIZATION; FATTY-ACID; PLASMALOGEN DEFICIENCY; INTESTINAL-ABSORPTION AB Ether glycerophospholipids (GPLs) are a subclass of phospholipids, chemically characterized by the existence of an ether bond within the lipid molecules. Because ether GPLs are membrane structure components, they act as the wide-like resistance to membrane oxidation induced by chemical hypoxia and reactive oxygen species. The abnormal biosynthesis of ether GPLs in humans leads to the decreased supply of the critical lipids to various human cells, resulting in the alteration of the membrane lipid composition. Recent studies demonstrated that the level of docosahexaenoic acid (DHA) - containing ether molecular species of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in the Alzheimer's brain significantly decreased. On the other hand, the deficiency of DHA and platelet-activating factor in human sperm causes infertility in men. We propose that the supplementation of DHA ether molecular species of GPLs may prevent and treat brain disorders, such as Alzheimer's disease and autism, and infertility. The present review describes (1) procedures for the semi-synthesis of DHA - containing ether molecular species of PC and PE; (2) mass spectrometric methods for structurally identifying the lipids; (3) potential of DHA plasmanycholine species as lipid drugs for preventing and treating brain diseases and infertility; and (4) recommendation of marine oysters, monkfish liver and scallops based seafoods as DHA ether GPLs supplementation for the medical application. C1 [Chen, Su] CHAINON Neurotrophin Biotechnol Inc, San Antonio, TX 78230 USA. [Liu, Chengchu] Shanghai Ocean Univ, Coll Food Sci, Shanghai 201306, Peoples R China. [Liu, Chengchu] Shanghai Engn Res Ctr Aquat Prod Proc & Preservat, Shanghai 201306, Peoples R China. RP Chen, S (reprint author), CHAINON Neurotrophin Biotechnol Inc, 12436 Vance Jackson Suite 721, San Antonio, TX 78230 USA. 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Org. Chem. PD APR PY 2013 VL 17 IS 8 BP 802 EP 811 PG 10 WC Chemistry, Organic SC Chemistry GA 126WQ UT WOS:000317653500005 ER PT J AU Mestre, TA Zurowski, M Fox, SH AF Mestre, Tiago A. Zurowski, Mateusz Fox, Susan H. TI 5-Hydroxytryptamine 2A receptor antagonists as potential treatment for psychiatric disorders SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE 5-HT2A receptors; Alzheimer's disease; antagonist; CYR-10; depression; eplivanserin; glemanserin; insomnia; nelotanserin; Parkinson's disease; partial agonist; pimavanserin; pruvanserin; schizophrenia; serotonin; volinanserin ID OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN 5-HT2A RECEPTOR; POSITRON-EMISSION-TOMOGRAPHY; MAJOR DEPRESSIVE DISORDER; MESSENGER-RNA EXPRESSION; GENE PROMOTER POLYMORPHISM; F-18 SETOPERONE PET; ANOREXIA-NERVOSA; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE AB Introduction: 5-Hydroxytryptamine 2A receptors (5-HT2A-Rs) are widely expressed in the brain and have been implicated in mood and behavior. Based on the use of atypical antipsychotics in schizophrenia, antagonism of 5-HT2A-Rs initially emerged as a potential intervention capable of reducing the incidence of extrapyramidal symptoms, while exerting an effective antipsychotic action. More recently, highly selective 5-HT2A-R antagonists have been evaluated in the treatment of a wide range of other psychiatric disorders. Areas covered: The aim of the current review is to present important clinical studies investigating the potential therapeutic effects of 5-HT2A-R antagonists in both primary psychiatric disorders, such as schizophrenia and mood disorders, as well as in psychiatric manifestations of neurodegenerative disorders. We present an overview of 5-HT2A-Rs in normal brain function and the rationale for use in (neuro) psychiatric disease based on significant findings from genetic association studies, neuroimaging data and postmortem studies. The majority of the studies relate to schizophrenia, depression, anxiety, obsessive compulsive disorder and psychosis in Parkinson's disease and Alzheimer's disease. To date, there is sparse literature on 5-HT2A-Rs in Gilles de la burette syndrome, attention deficit hyperactivity disorder, eating disorders and autism spectrum disorders. The authors conclude by reviewing recent clinical trials investigating highly selective 5-HT2A-R antagonists in schizophrenia, psychosis in Parkinson's disease, insomnia and generalized anxiety. Expert opinion: Despite the potential, to date, 5-HT2A-R antagonists have not made an impact in the management of psychiatric disorders and psychiatric symptoms of neurodegenerative conditions. C1 [Mestre, Tiago A.; Fox, Susan H.] Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Mestre, Tiago A.; Fox, Susan H.] Movement Disorders Ctr, Div Neurol, Toronto, ON, Canada. 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Investig. Drugs PD APR PY 2013 VL 22 IS 4 BP 411 EP 421 DI 10.1517/13543784.2013.769957 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 129YF UT WOS:000317879200002 PM 23409724 ER PT J AU Moreno-De-Luca, A Myers, SM Challman, TD Moreno-De-Luca, D Evans, DW Ledbetter, DH AF Moreno-De-Luca, Andres Myers, Scott M. Challman, Thomas D. Moreno-De-Luca, Daniel Evans, David W. Ledbetter, David H. TI Developmental brain dysfunction: revival and expansion of old concepts based on new genetic evidence SO LANCET NEUROLOGY LA English DT Article ID DE-NOVO MUTATIONS; COPY NUMBER VARIANT; MENTAL-RETARDATION; CHROMOSOME 1Q21.1; DELETION SYNDROME; YOUNG-CHILDREN; AUTISM; DISORDERS; MICRODELETION; SCHIZOPHRENIA AB Neurodevelopmental disorders can be caused by many different genetic abnormalities that are individually rare but collectively common. Specific genetic causes, including certain copy number variants and single-gene mutations, are shared among disorders that are thought to be clinically distinct. This evidence of variability in the clinical manifestations of individual genetic variants and sharing of genetic causes among clinically distinct brain disorders is consistent with the concept of developmental brain dysfunction, a term we use to describe the abnormal brain function underlying a group of neurodevelopmental and neuropsychiatric disorders and to encompass a subset of various clinical diagnoses. Although many pathogenic genetic variants are currently thought to be variably penetrant, we hypothesise that when disorders encompassed by developmental brain dysfunction are considered as a group, the penetrance will approach 100%. The penetrance is also predicted to approach 100% when the phenotype being considered is a specific trait, such as intelligence or autistic-like social impairment, and the trait could be assessed using a continuous, quantitative measure to compare probands with non-carrier family members rather than a qualitative, dichotomous trait and comparing probands with the healthy population. C1 [Moreno-De-Luca, Andres; Myers, Scott M.; Challman, Thomas D.; Evans, David W.; Ledbetter, David H.] Geisinger Hlth Syst, Autism & Dev Med Inst, Danville, PA 17822 USA. [Moreno-De-Luca, Andres; Ledbetter, David H.] Geisinger Hlth Syst, Genom Med Inst, Danville, PA 17822 USA. [Moreno-De-Luca, Andres; Myers, Scott M.; Challman, Thomas D.] Geisinger Hlth Syst, Dept Pediat, Danville, PA 17822 USA. [Moreno-De-Luca, Andres; Myers, Scott M.; Challman, Thomas D.; Evans, David W.; Ledbetter, David H.] Bucknell Univ, Program Neurosci, Lewisburg, PA 17837 USA. 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A combined approach using both signal detection and an extension of Bayes theorem is a possible approach to discriminating between symptoms that have potentially a multi-causal basis, of which 22q11.2 deletion is only one possibility. Two later issues have arisen, one involving possibly at least two genetically different syndromes that result in similar autism in infancy, the other in statistical problems of prediction. Diagnosis of probable early DS 22q11.2 independent deaths as opposed to survival into adulthood can be wrongly thought to be a case of infanticide, and legal disputes have consequently arisen in the U.K., the USA, and Australia. C1 [Gregson, Robert A. M.] Australian Natl Univ, Canberra, ACT 0200, Australia. RP Gregson, RAM (reprint author), Australian Natl Univ, Dept Psychol, GPO Box 4, Canberra, ACT 0200, Australia. 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PD APR PY 2013 VL 17 IS 2 BP 173 EP 181 PG 9 WC Social Sciences, Mathematical Methods; Psychology, Mathematical SC Mathematical Methods In Social Sciences; Psychology GA 135XR UT WOS:000318324500001 PM 23517604 ER PT J AU John, A Tatard-Leitman, VM Suh, J Billingslea, EN Roberts, TP Siegel, SJ AF Saunders, John A. Tatard-Leitman, Valerie M. Suh, Jimmy Billingslea, Eddie N. Roberts, Timothy P. Siegel, Steven J. TI Knockout of NMDA Receptors in Parvalbumin Interneurons Recreates Autism-Like Phenotypes SO AUTISM RESEARCH LA English DT Article DE autism; electrophysiology; endophenotype; animal models; NMDA receptor 1 knockout ID MICE MUS-MUSCULUS; MOUSE MODELS; NEURODEVELOPMENTAL DISORDERS; ULTRASONIC VOCALIZATIONS; NEURAL SYNCHRONIZATION; SCHIZOPHRENIA; OSCILLATIONS; DEFICITS; IMPAIRMENT; POTENTIALS AB Autism is a disabling neurodevelopmental disorder characterized by social deficits, language impairment, and repetitive behaviors with few effective treatments. New evidence suggests that autism has reliable electrophysiological endophenotypes and that these measures may be caused by n-methyl-d-aspartic acid receptor (NMDAR) disruption on parvalbumin (PV)-containing interneurons. These findings could be used to create new translational biomarkers. Recent developments have allowed for cell-type selective knockout of NMDARs in order to examine the perturbations caused by disrupting specific circuits. This study examines several electrophysiological and behavioral measures disrupted in autism using a PV-selective reduction in NMDA R1 subunit. Mouse electroencephalograph (EEG) was recorded in response to auditory stimuli. Event-related potential (ERP) component amplitude and latency analysis, social testing, and premating ultrasonic vocalizations (USVs) recordings were performed. Correlations were examined between the ERP latency and behavioral measures. The N1 ERP latency was delayed, sociability was reduced, and mating USVs were impaired in PV-selective NMDA Receptor 1 Knockout (NR1 KO) as compared with wild-type mice. There was a significant correlation between N1 latency and sociability but not between N1 latency and premating USV power or T-maze performance. The increases in N1 latency, impaired sociability, and reduced vocalizations in PV-selective NR1 KO mice mimic similar changes found in autism. Electrophysiological changes correlate to reduced sociability, indicating that the local circuit mechanisms controlling N1 latency may be utilized in social function. Therefore, we propose that behavioral and electrophysiological alterations in PV-selective NR1 KO mice may serve as a useful model for therapeutic development in autism. Autism Res 2013, 6: 6977. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Saunders, John A.; Tatard-Leitman, Valerie M.; Suh, Jimmy; Billingslea, Eddie N.; Siegel, Steven J.] Univ Penn, Dept Psychiat, Translat Neurosci Program, Philadelphia, PA 19104 USA. [Saunders, John A.; Roberts, Timothy P.; Siegel, Steven J.] Univ Penn, Bioengn Grad Grp, Philadelphia, PA 19104 USA. [Roberts, Timothy P.] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. RP Siegel, SJ (reprint author), Univ Penn, Dept Psychiat, Translat Res Labs, 125 S 31st St, Philadelphia, PA 19104 USA. EM siegels@upenn.edu FU NIMH [5R01DA023210-02]; Oberkircher Family; Eli Lilly; AstraZeneca; NuPathe; Pfizer; Merck; Sanofi; Wyeth FX Grant sponsor: NIMH; Grant number: 5R01DA023210-02 (SJS).Grant sponsor: Oberkircher Family; Grant number: Oberkircher Family Endowed Chair in Pediatric Radiology (TPR).The study was supported by 5R01DA023210-02 (SJS). Dr. Roberts thanks the Oberkircher Family for the Oberkircher Family Endowed Chair in Pediatric Radiology. Steven Siegel reports having received grant support from Eli Lilly, AstraZeneca, NuPathe, and Pfizer that is unrelated to the content of this paper and consulting payments from NuPathe, Merck, Sanofi, and Wyeth that are unrelated to this work. Dr. Roberts is a consultant for prism clinical imaging. All other authors report no biomedical financial interests or potential conflicts of interest. 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PD APR PY 2013 VL 6 IS 2 BP 69 EP 77 DI 10.1002/aur.1264 PG 9 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 133DL UT WOS:000318117500001 ER PT J AU Prigge, MD Bigler, ED Fletcher, PT Zielinski, BA Ravichandran, C Anderson, J Froehlich, A Abildskov, T Papadopolous, E Maasberg, K Nielsen, JA Alexander, AL Lange, N Lainhart, J AF Prigge, Molly D. Bigler, Erin D. Fletcher, P. Thomas Zielinski, Brandon A. Ravichandran, Caitlin Anderson, Jeffrey Froehlich, Alyson Abildskov, Tracy Papadopolous, Evangelia Maasberg, Kathryn Nielsen, Jared A. Alexander, Andrew L. Lange, Nicholas Lainhart, Janet TI Longitudinal Heschl's Gyrus Growth During Childhood and Adolescence in Typical Development and Autism SO AUTISM RESEARCH LA English DT Article DE autism; Heschl's gyrus; longitudinal development; MRI ID PRIMARY AUDITORY-CORTEX; HUMAN CEREBRAL-CORTEX; NON-SPEECH SOUNDS; SPECTRUM DISORDERS; LANGUAGE IMPAIRMENT; VOLUME MEASUREMENT; PLANUM TEMPORALE; MISMATCH FIELD; CHILDREN; BRAIN AB Heightened auditory sensitivity and atypical auditory processing are common in autism. Functional studies suggest abnormal neural response and hemispheric activation to auditory stimuli, yet the neurodevelopment underlying atypical auditory function in autism is unknown. In this study, we model longitudinal volumetric growth of Heschl's gyrus gray matter and white matter during childhood and adolescence in 40 individuals with autism and 17 typically developing participants. Up to three time points of magnetic resonance imaging data, collected on average every 2.5 years, were examined from individuals 312 years of age at the time of their first scan. Consistent with previous cross-sectional studies, no group differences were found in Heschl's gyrus gray matter volume or asymmetry. However, reduced longitudinal gray matter volumetric growth was found in the right Heschl's gyrus in autism. Reduced longitudinal white matter growth in the left hemisphere was found in the right-handed autism participants. Atypical Heschl's gyrus white matter volumetric growth was found bilaterally in the autism individuals with a history of delayed onset of spoken language. Heightened auditory sensitivity, obtained from the Sensory Profile, was associated with reduced volumetric gray matter growth in the right hemisphere. Our longitudinal analyses revealed dynamic gray and white matter changes in Heschl's gyrus throughout childhood and adolescence in both typical development and autism. Autism Res 2013, 6: 7890. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Prigge, Molly D.; Froehlich, Alyson; Nielsen, Jared A.] Univ Utah, Dept Psychiat, Sch Med, Salt Lake City, UT 84108 USA. [Bigler, Erin D.; Fletcher, P. Thomas; Anderson, Jeffrey] Univ Utah, Inst Brain, Salt Lake City, UT 84108 USA. [Bigler, Erin D.; Abildskov, Tracy] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Bigler, Erin D.; Abildskov, Tracy] Brigham Young Univ, Ctr Neurosci, Provo, UT 84602 USA. [Fletcher, P. Thomas] Univ Utah, Sch Comp, Salt Lake City, UT 84108 USA. [Fletcher, P. Thomas] Univ Utah, Sci Comp & Imaging Inst, Salt Lake City, UT 84108 USA. [Zielinski, Brandon A.] Univ Utah, Dept Pediat, Salt Lake City, UT 84108 USA. [Zielinski, Brandon A.] Univ Utah, Dept Neurol, Salt Lake City, UT 84108 USA. [Ravichandran, Caitlin; Lange, Nicholas] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Anderson, Jeffrey; Nielsen, Jared A.] Univ Utah, Interdept Program Neurosci, Salt Lake City, UT 84108 USA. [Anderson, Jeffrey] Univ Utah, Dept Neuroradiol, Salt Lake City, UT 84108 USA. [Anderson, Jeffrey] Univ Utah, Dept Bioengn, Salt Lake City, UT 84108 USA. [Papadopolous, Evangelia] Univ Utah, Dept Phys, Salt Lake City, UT 84108 USA. [Maasberg, Kathryn] Univ Utah, Sch Med, Salt Lake City, UT 84108 USA. [Alexander, Andrew L.; Lainhart, Janet] Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. [Lange, Nicholas] Harvard Univ, Sch Med, Dept Biostat, Boston, MA USA. [Lange, Nicholas] McLean Hosp, Neurostat Lab, Belmont, MA 02178 USA. [Lainhart, Janet] Univ Wisconsin, Dept Psychiat, Div Child & Adolescent Psychiat, Madison, WI 53706 USA. RP Prigge, MD (reprint author), Univ Utah, Dept Psychiat, 650 Komas Dr Suite 206, Salt Lake City, UT 84108 USA. EM molly.dubray@hsc.utah.edu FU NRSA Predoctoral Fellowship NIH NIDCD [F31 DC010143]; NIH NIDCD [T32 DC008553]; NIH [RO1 NIMH MH080826, RO1 MH084795] FX We sincerely thank the participants and families for their time and participation. This research was supported by NRSA Predoctoral Fellowship NIH NIDCD F31 DC010143 (MDP), NIH NIDCD T32 DC008553, NIH RO1 NIMH MH080826, and NIH RO1 MH084795. Past data collection was supported in part by NICHD/NIDCD U19 HD035476, part of the CPEA. We thank Annahir Cariello and Jason Cooperrider for their assistance, and we acknowledge the contributions of William McMahon, Judith Miller, Michael Johnson, Jubel Morgan, and Jeffrey Lu in early stages of this work. The content of this project is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Mental Health, NICHD, NIDCD, or National Institutes of Health. 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Solomon, Marjorie TI Oxytocin and Vasopressin in Children and Adolescents With Autism Spectrum Disorders: Sex Differences and Associations With Symptoms SO AUTISM RESEARCH LA English DT Article DE neuropeptides; oxytocin; vasopressin; autism; sex differences; repetitive behaviors; anxiety ID OBSESSIVE-COMPULSIVE DISORDER; PLASMA ARGININE-VASOPRESSIN; RECEPTOR GENE OXTR; MALE PRAIRIE VOLES; SOCIAL-BEHAVIOR; CEREBROSPINAL-FLUID; HUMAN HYPOTHALAMUS; MAJOR DEPRESSION; KNOCKOUT MICE; HUMANS AB There has been intensified interest in the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in autism spectrum disorders (ASD) given their role in affiliative and social behavior in animals, positive results of treatment studies using OT, and findings that genetic polymorphisms in the AVPOT pathway are present in individuals with ASD. Nearly all such studies in humans have focused only on males. With this preliminary study, we provide basic and novel information on the involvement of OT and AVP in autism, with an investigation of blood plasma levels of these neuropeptides in 75 preadolescent and adolescent girls and boys ages 818: 40 with high-functioning ASD (19 girls, 21 boys) and 35 typically developing children (16 girls, 19 boys). We related neuropeptide levels to social, language, repetitive behavior, and internalizing symptom measures in these individuals. There were significant gender effects: Girls showed higher levels of OT, while boys had significantly higher levels of AVP. There were no significant effects of diagnosis on OT or AVP. Higher OT values were associated with greater anxiety in all girls, and with better pragmatic language in all boys and girls. AVP levels were positively associated with restricted and repetitive behaviors in girls with ASD but negatively (nonsignificantly) associated with these behaviors in boys with ASD. Our results challenge the prevailing view that plasma OT levels are lower in individuals with ASD, and suggest that there are distinct and sexually dimorphic mechanisms of action for OT and AVP underlying anxiety and repetitive behaviors. Autism Res 2013, 6: 91102. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Miller, Meghan] Univ Calif Berkeley, Dept Psychol, Berkeley, CA USA. [Miller, Meghan; Solomon, Marjorie] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA. [Bales, Karen L.; Hostetler, Caroline M.] Univ Calif Davis, Dept Psychol, Davis, CA USA. [Taylor, Sandra L.] Univ Calif Davis, Sch Med, Clin & Translat Sci Ctr, Sacramento, CA 95817 USA. [Yoon, Jong; Carter, Cameron S.; Solomon, Marjorie] Univ Calif Davis, Imaging Res Ctr, Sacramento, CA 95817 USA. RP Solomon, M (reprint author), Univ Calif Davis, MIND Inst, 2825 50th St, Sacramento, CA 95817 USA. EM marjorie.solomon@ucdmc.ucdavis.edu FU NIMH [K08 MH074967-01]; BIRCWH award [K12 HD051958] FX This work was supported by K08 MH074967-01 from NIMH and a BIRCWH award, (K12 HD051958), to Marjorie Solomon. Statistical support was made possible by UL1 RR024246 from the National Center for Research Resources, a component of the NIH and NIH Roadmap for Medical Research. The authors report no conflicts of interest. 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TI Endogenous Spatial Attention: Evidence for Intact Functioning in Adults With Autism SO AUTISM RESEARCH LA English DT Article DE attention; spatial attention; endogenous attention; psychophysics; adults; autism; autism spectrum disorders; ASD ID INCREASES CONTRAST SENSITIVITY; HUMAN VISUAL-CORTEX; COVERT ATTENTION; SELECTIVE ATTENTION; SUSTAINED ATTENTION; RESPONSE FUNCTIONS; ZOOM LENS; DEFICITS; PERFORMANCE; CHILDREN AB Rapid manipulation of the attention field (i.e. the location and spread of visual spatial attention) is a critical aspect of human cognition, and previous research on spatial attention in individuals with autism spectrum disorders (ASD) has produced inconsistent results. In a series of three psychophysical experiments, we evaluated claims in the literature that individuals with ASD exhibit a deficit in voluntarily controlling the deployment and size of the spatial attention field. We measured the spatial distribution of performance accuracies and reaction times to quantify the sizes and locations of the attention field, with and without spatial uncertainty (i.e. the lack of predictability concerning the spatial position of the upcoming stimulus). We found that high-functioning adults with autism exhibited slower reaction times overall with spatial uncertainty, but the effects of attention on performance accuracies and reaction times were indistinguishable between individuals with autism and typically developing individuals in all three experiments. These results provide evidence of intact endogenous spatial attention function in high-functioning adults with ASD, suggesting that atypical endogenous attention cannot be a latent characteristic of autism in general. Autism Res 2013, 6: 108118. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Grubb, Michael A.; Carrasco, Marisa; Heeger, David J.] NYU, Dept Psychol, New York, NY 10003 USA. [Behrmann, Marlene; Egan, Ryan] Carnegie Mellon Univ, Dept Psychol, Pittsburgh, PA 15213 USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Carrasco, Marisa; Heeger, David J.] NYU, Ctr Neural Sci, New York, NY 10003 USA. RP Heeger, DJ (reprint author), NYU, Dept Psychol, Washington Pl,8th Floor, New York, NY 10003 USA. EM david.heeger@nyu.edu FU NIH [R01-EY019693]; SFARI [177638]; ACE [HD055748]; Autism Speaks Predoctoral Fellowship [7831] FX This research was supported by NIH Grant R01-EY019693 to D. H. and M. C., by SFARI Grant 177638 to D. H. and M. B., by ACE Grant HD055748 to N.M., and by Autism Speaks Predoctoral Fellowship 7831 to M.G. 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PD APR PY 2013 VL 6 IS 2 BP 108 EP 118 DI 10.1002/aur.1269 PG 11 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 133DL UT WOS:000318117500005 PM 23427075 ER PT J AU Baruth, JM Wall, CA Patterson, MC Port, JD AF Baruth, Joshua M. Wall, Christopher A. Patterson, Marc C. Port, John D. TI Proton Magnetic Resonance Spectroscopy as a Probe into the Pathophysiology of Autism Spectrum Disorders (ASD): A Review SO AUTISM RESEARCH LA English DT Review DE Autism Spectrum Disorders; proton magnetic resonance spectroscopy; N-acetylaspartate; glutamate; myo-inositol ID N-ACETYL ASPARTATE; WHITE-MATTER; HUMAN BRAIN; ASPERGER-SYNDROME; MR SPECTROSCOPY; LOCALIZED PROTON; DOUBLE-BLIND; MITOCHONDRIAL DYSFUNCTION; MINICOLUMNAR PATHOLOGY; CEREBELLAR CORTICES AB Proton magnetic resonance spectroscopy (1H-MRS) is a safe, noninvasive way of quantifying in vivo biochemical and metabolite concentration levels in individuals with Autism Spectrum Disorders (ASD). Findings to date suggest ASD is associated with widespread reduction in N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol (mI), and glutamate plus glutamine plus gamma-Aminobutyric Acid (Glx); however, variable findings, and even substantial increases, are not uncommon depending on the study and/or region-of-interest. Widespread reduction of NAA, Cr, Cho, mI, and Glx in ASD likely reflects impaired neuronal function and/or metabolism related to abnormal neurodevelopmental processes. Future studies should attempt to relate 1H-MRS findings to histological findings and control for variability in subject age and functioning level; this would assist in evaluating the relationship between 1H-MRS metabolic levels and neuronal and glial cell densities, as well as neurodevelopmental process associated with ASD. Furthermore, more longitudinal 1H-MRS studies are needed in both control and ASD subjects to attempt to standardize metabolite levels across different developmental periods in well-defined endophenotypes. This will provide for a standard rubric for which metabolic aberrations (as well as treatment responses) can be measured. With higher magnetic field strengths and spectral-editing techniques capable of quantifying less-concentrated metabolites, 1H-MRS will continue to be an important tool in ASD research. Autism Res 2013, 6: 119133. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Baruth, Joshua M.; Wall, Christopher A.; Port, John D.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN 55905 USA. [Patterson, Marc C.] Mayo Clin, Childrens Ctr, Dept Neurol, Rochester, MN 55905 USA. [Patterson, Marc C.] Mayo Clin, Childrens Ctr, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA. [Patterson, Marc C.] Mayo Clin, Childrens Ctr, Dept Med Genet, Rochester, MN 55905 USA. [Port, John D.] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. RP Baruth, JM (reprint author), Mayo Clin, Dept Psychiat & Psychol, 200 1st St SW, Rochester, MN 55905 USA. EM jmbaru01@louisville.edu RI Port, John/I-7940-2014 OI Port, John/0000-0002-4237-7776 FU Mayo Clinic Department of Psychiatry and Psychology FX The authors have no conflicts of interest to declare. We would like to thank the Mayo Clinic Department of Psychiatry and Psychology, and especially Mark Frye, MD and Peter Jensen, MD for support of this project. 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PD APR PY 2013 VL 6 IS 2 BP 119 EP 133 DI 10.1002/aur.1273 PG 15 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 133DL UT WOS:000318117500006 PM 23436782 ER PT J AU Sasson, NJ Lam, KSL Childress, D Parlier, M Daniels, JL Piven, J AF Sasson, Noah J. Lam, Kristen S. L. Childress, Debra Parlier, Morgan Daniels, Julie L. Piven, Joseph TI The Broad Autism Phenotype Questionnaire: Prevalence and Diagnostic Classification SO AUTISM RESEARCH LA English DT Article DE autism; Broad Autism Phenotype; assessment; prevalence; genetics ID EXPLORATORY FACTOR-ANALYSIS; MULTIPLE-INCIDENCE; COGNITIVE PHENOTYPE; GENERAL-POPULATION; FAMILY-HISTORY; PARENTS; CHILDREN; TRAITS; PERSONALITY; DISORDER AB The Broad Autism Phenotype Questionnaire (BAPQ) was administered to a large community-based sample of biological parents of children with autism (PCAs) and comparison parents (CPs) (n=1,692). Exploratory factor analysis and internal consistency parameters confirmed a robust three-factor structure of the BAPQ, corresponding to the proposed aloof, pragmatic language and rigidity subscales. Based upon the distribution of Broad Autism Phenotype (BAP) features in the general population, new normative cutoff values for BAPQ subscales were established that provide increased specificity relative to those previously reported, and thus enhance the utility of the BAPQ for diagnostically classifying the BAP. These cutoffs were also used to estimate prevalence of the BAP and its three components, with rates ranging between 1423% for PCAs and between 59% for CPs. Analysis of patterns of BAP characteristics within family members revealed that BAP features were more likely to co-occur in PCAs relative to CPs. Collectively, these findings extend the utility of the BAPQ and provide additional evidence that it is an efficient and reliable tool for disaggregating the heterogeneity of autism through the identification of meaningful subgroups of parents. Autism Res 2013, 6: 134143. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Sasson, Noah J.] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 78050 USA. [Lam, Kristen S. L.; Childress, Debra; Parlier, Morgan; Daniels, Julie L.; Piven, Joseph] Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, Chapel Hill, NC USA. [Daniels, Julie L.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Sasson, NJ (reprint author), Univ Texas Dallas, Sch Behav & Brain Sci GR41, Richardson, TX 78050 USA. EM nsasson@utdallas.edu; jpiven@med.unc.edu FU National Institutes of Health, IDDRC Participant Registry Core, P30 [HD003110]; Centers for Disease Control and Prevention [U10 DD000184-06, U50/CCU422345]; Research Registry Core of the Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at UNC-Chapel Hill [HD003110] FX Grant sponsor: National Institutes of Health, IDDRC Participant Registry Core, P30 # HD003110; Centers for Disease Control and Prevention, Grant numbers: U10 DD000184-06, U50/CCU422345.We would like to thank Renee Clark and the Research Registry Core of the Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at UNC-Chapel Hill (Grant Number HD003110), as well as all the individuals who participated in this research. This work was further supported by the Centers for Disease Control and Prevention (Grant Numbers: U10 DD000184-06, U50/CCU422345). 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PD APR PY 2013 VL 6 IS 2 BP 134 EP 143 DI 10.1002/aur.1272 PG 10 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 133DL UT WOS:000318117500007 PM 23427091 ER PT J AU Ronconi, L Gori, S Ruffino, M Molteni, M Facoetti, A AF Ronconi, Luca Gori, Simone Ruffino, Milena Molteni, Massimo Facoetti, Andrea TI Zoom-out attentional impairment in children with autism spectrum disorder SO CORTEX LA English DT Article DE Spatial attention; Attentional scaling; Local processing; Pervasive developmental disorder; Social cognition ID EVENT-RELATED POTENTIALS; CONCURRENT TMS-FMRI; VISUAL-ATTENTION; PHYSIOLOGICAL CORRELATE; SELECTIVE ATTENTION; BIOLOGICAL MOTION; SPATIAL ATTENTION; COGNITIVE-STYLE; BRAIN; PERCEPTION AB Autism spectrum disorder (ASD) has long been associated with an inability to experience wholes without full attention to the constituent parts. A zoom-out attentional dysfunction might be partially responsible for this perceptual integration deficit in ASD. In the present study, the efficiency of attentional focusing mechanisms was investigated in children affected by ASD. We measured response latencies to a visual target onset displayed at three eccentricities from the fixation. Attentional resources were focused (zoom-in) or distributed (zoom-out) in the visual field presenting a small (containing only the nearest target eccentricity) or large (containing also the farthest target eccentricity) cue, 100 or 800 msec, before the target onset. Typically developing children, at the short cue-target interval, showed a gradient effect (i.e., latencies are slower at the farthest eccentricity) in the small focusing cue, but not in the large focusing cue condition. These results indicate an efficient zoom-in and zoom-out attentional mechanism. In contrast, children with ASD showed a gradient effect also in the large focusing cue condition, suggesting a specific zoom-out attentional impairment. In addition, the ASD group showed an atypical gradient effect at the long cue-target interval only in the small cue condition, suggesting a prolonged zoom-in and sluggish zoom-out attentional mechanism. This abnormal attentional focusing - probably linked to a dysfunctional top-down feedback from fronto-parietal network to the early visual areas - could contribute to the atypical visual perception associated to individuals with ASD which, in turn, could have consequences in their social-communicative development. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Ronconi, Luca; Gori, Simone; Facoetti, Andrea] Univ Padua, Dipartimento Psicol Gen, Dev & Cognit Neurosci Lab, I-35131 Padua, Italy. [Gori, Simone; Ruffino, Milena; Molteni, Massimo; Facoetti, Andrea] Ist Sci E Medea Bosisio Parini, Unita Neuropsicol Sviluppo, Lecce, Italy. RP Facoetti, A (reprint author), Univ Padua, Dipartimento Psicol Gen, Via Venezia 8, I-35131 Padua, Italy. EM andreafacoetti@unipd.it RI Facoetti, Andrea/C-2876-2009 FU University of Padua FX This work was supported by a grant from University of Padua ("Progetto di Ateneo 2009 and 2011" to A.F. and "Assegni di Ricerca 2009 and 2011" to S.G.). The contributions of staff members of "E. Medea" Scientific Institute as well as of children and their families are gratefully acknowledged. We thank Laura Zampini and Barbara Urbani for their help in recruitment. and clinical characterization of participants. Finally, we thank the Editor Mike Anderson and the two anonymous Reviewers for their valuable comments. 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The industry asserts it is minimally toxic to humans, but here we argue otherwise. Residues are found in the main foods of the Western diet, comprised primarily of sugar, corn, soy and wheat. Glyphosate's inhibition of cytochrome P450 (CYP) enzymes is an overlooked component of its toxicity to mammals. CYP enzymes play crucial roles in biology, one of which is to detoxify xenobiotics. Thus, glyphosate enhances the damaging effects of other food borne chemical residues and environmental toxins. Negative impact on the body is insidious and manifests slowly over time as inflammation damages cellular systems throughout the body. Here, we show how interference with CYP enzymes acts synergistically with disruption of the biosynthesis of aromatic amino acids by gut bacteria, as well as impairment in serum sulfate transport. Consequences are most of the diseases and conditions associated with a Western diet, which include gastrointestinal disorders, obesity, diabetes, heart disease, depression, autism, infertility, cancer and Alzheimer's disease. We explain the documented effects of glyphosate and its ability to induce disease, and we show that glyphosate is the "textbook example" of exogenous semiotic entropy: the disruption of homeostasis by environmental toxins. C1 [Seneff, Stephanie] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Seneff, S (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. EM anthonysamsel@acoustictracks.net; Seneff@csail.mit.edu FU Quanta Computers, Taipei, Taiwan, under the auspices of the Qmulus Project FX This work was funded in part by Quanta Computers, Taipei, Taiwan, under the auspices of the Qmulus Project. We thank three reviewers whose valuable comments led to a much improved version of this paper. 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TI Conditional and domain-specific inactivation of the Tsc2 gene in neural progenitor cells SO GENESIS LA English DT Article DE cortical development; mTORC1; mTORC2; rapamycin; tuberous sclerosis complex ID TUBEROUS SCLEROSIS COMPLEX; MOUSE MODEL; IN-VIVO; PHOSPHORYLATION; MUTATIONS; RAPAMYCIN; HAMARTIN; MTOR; MICE; EXPRESSION AB Tuberous sclerosis complex (TSC) is a genetic disease characterized by multiorgan benign tumors as well as neurological manifestations. Epilepsy and autism are two of the more prevalent neurological complications and are usually severe. TSC is caused by mutations in either the TSC1 (encodes hamartin) or the TSC2 (encodes tuberin) genes with TSC2 mutations being associated with worse outcomes. Tuberin contains a highly conserved GTPase-activating protein (GAP) domain that indirectly inhibits mammalian target of rapamycin complex 1 (mTORC1). mTORC1 dysregulation is currently thought to cause much of the pathogenesis in TSC but mTORC1-independent mechanisms may also contribute. We generated a novel conditional allele of Tsc2 by flanking exons 36 and 37 with loxP sites. Mice homozygous for this knock-in Tsc2 allele are viable and fertile with normal appearing growth and development. Exposure to Cre recombinase then creates an in-frame deletion involving critical residues of the GAP domain. Homozygous conditional mutant mice generated using Emx1Cre have increased cortical mTORC1 signaling, severe developmental brain anomalies, seizures, and die within 3 weeks. We found that the normal levels of the mutant Tsc2 mRNA, though GAP-deficient tuberin protein, appear unstable and rapidly degraded. This novel animal model will allow further study of tuberin function including the requirement of the GAP domain for protein stability. genesis 51:284292. (c) 2013 Wiley Periodicals, Inc. C1 [Fu, Cary; Ess, Kevin C.] Vanderbilt Univ, Div Child Neurol & Epilepsy, Sch Med, Vanderbilt Kennedy Ctr,Vanderbilt Brain Inst, Nashville, TN 37232 USA. [Fu, Cary; Ess, Kevin C.] Vanderbilt Univ, Dept Neurol, Sch Med, Vanderbilt Kennedy Ctr,Vanderbilt Brain Inst, Nashville, TN 37232 USA. RP Ess, KC (reprint author), Vanderbilt Univ, Dept Neurol, Sch Med, 465 21st Ave South,6158C MRB3, Nashville, TN 37232 USA. EM kevin.ess@vanderbilt.edu FU Tuberous Sclerosis Alliance; NINDS, NIH [1R01 NS078289]; Vanderbilt Center for Molecular Neuroscience FX Contract grant sponsor: The Tuberous Sclerosis Alliance; Contract grant sponsor: NINDS, NIH, Contract grant number: 1R01 NS078289; Contract grant sponsor: Vanderbilt Center for Molecular Neuroscience CR Balendran A, 1999, J BIOL CHEM, V274, P37400, DOI 10.1074/jbc.274.52.37400 Beaumont TL, 2012, CHILD NERV SYST, V7, P963 Benvenuto G, 2000, ONCOGENE, V19, P6306, DOI 10.1038/sj.onc.1204009 Carson RP, 2012, NEUROBIOL DIS, V45, P369, DOI 10.1016/j.nbd.2011.08.024 Chevere-Torres I, 2012, NEUROBIOL DIS, V45, P156, DOI 10.1016/j.nbd.2011.07.018 Crino PB, 2004, J CHILD NEUROL, V19, P716 Crino PB, 2006, NEW ENGL J MED, V355, P1345, DOI 10.1056/NEJMra055323 Farley FW, 2000, GENESIS, V28, P106, DOI 10.1002/1526-968X(200011/12)28:3/4<106::AID-GENE30>3.3.CO;2-K Fu C, 2012, CEREB CORTEX, V22, P2111, DOI 10.1093/cercor/bhr300 Gorski JA, 2002, J NEUROSCI, V22, P6309 Govindarajan B, 2005, J BIOL CHEM, V280, P5870, DOI 10.1074/jbc.M411768200 Hartman TR, 2009, HUM MOL GENET, V18, P151, DOI 10.1093/hmg/ddn325 Hay N, 2004, GENE DEV, V18, P1926, DOI 10.1101/gad.1212704 Hernandez O, 2007, GENESIS, V45, P101, DOI 10.1002/dvg.20271 Hodges AK, 2001, HUM MOL GENET, V10, P2899, DOI 10.1093/hmg/10.25.2899 Inoki K, 2003, GENE DEV, V17, P1829, DOI 10.1101/gad.1110003 Joinson C, 2003, PSYCHOL MED, V33, P335, DOI 10.1017/S0033291702007092 Jones AC, 1997, HUM MOL GENET, V6, P2155, DOI 10.1093/hmg/6.12.2155 Lee EC, 2001, GENOMICS, V73, P56, DOI 10.1006/geno.2000.6451 Liu PT, 2003, GENOME RES, V13, P476, DOI 10.1101/gr.749203 Magri L, 2011, CELL STEM CELL, V9, P447, DOI 10.1016/j.stem.2011.09.008 Maheshwar MM, 1997, HUM MOL GENET, V6, P1991, DOI 10.1093/hmg/6.11.1991 Meikle L, 2008, J NEUROSCI, V28, P5422, DOI 10.1523/JNEUROSCI.0955-08.2008 Momose S, 2007, BIOCHEM BIOPH RES CO, V356, P693, DOI 10.1016/j.bbrc.2007.03.036 Noonan DJ, 2002, ARCH BIOCHEM BIOPHYS, V398, P132, DOI 10.1006/abbi.2001.2682 Onda H, 1999, J CLIN INVEST, V104, P687, DOI 10.1172/JCI7319 Pullen N, 1998, SCIENCE, V279, P707, DOI 10.1126/science.279.5351.707 Rosner M, 2008, MUTAT RES-REV MUTAT, V658, P234, DOI 10.1016/j.mrrev.2008.01.001 Ruvinsky I, 2005, GENE DEV, V19, P2199, DOI 10.1101/gad.351605 Schaim SS, 2003, CURR BIOL, V13, P797, DOI 10.1016/S0960-9822(03)00329-4 Staley BA, 2011, PEDIATRICS, V127, pE117, DOI 10.1542/peds.2010-0192 Uhlmann EJ, 2002, ANN NEUROL, V52, P285, DOI 10.1002/ana.10283 Way SW, 2012, HUM MOL GENET, V21, P3226, DOI 10.1093/hmg/dds156 Zeng LH, 2011, HUM MOL GENET, V20, P445, DOI 10.1093/hmg/ddq491 NR 34 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-954X J9 GENESIS JI Genesis PD APR PY 2013 VL 51 IS 4 BP 284 EP 292 DI 10.1002/dvg.22377 PG 9 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 132NF UT WOS:000318074900007 PM 23359422 ER PT J AU Harfterkamp, M Buitelaar, JK Minderaa, RB van de Loo-Neus, G van der Gaag, RJ Hoekstra, PJ AF Harfterkamp, Myriam Buitelaar, Jan K. Minderaa, Ruud B. van de Loo-Neus, Gigi van der Gaag, Rutger-Jan Hoekstra, Pieter J. TI Long-Term Treatment with Atomoxetine for Attention-Deficit/Hyperactivity Disorder Symptoms in Children and Adolescents with Autism Spectrum Disorder: An Open-Label Extension Study SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ONCE-DAILY ATOMOXETINE; DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; PLACEBO; ADHD AB Objective: The efficacy and tolerability of long-term treatment with atomoxetine for symptoms of attention-deficit/hyperactivity disorder (ADHD) in children with autism spectrum disorder (ASD) has not been established. Methods: In this study, 88 patients 6-17 years of age, with ADHD and ASD, were treated with 1.2 mg/kg/day atomoxetine for 20 weeks as follow-up of an 8 week double-blind placebo-controlled period. Primary endpoint was the ADHD Rating Scale (ADHD-RS). Results: After 8 weeks of initial treatment, the mean total, inattention, and hyperactivity-impulsivity ADHD-RS further decreased significantly from 34.9 to 27.0 for the total ADHD-RS, from 18.3 to 14.5 for the ADHD-RS inattention subscale, and from 16.5 to 12.6 for the hyperactivity-impulsivity subscale. Adverse events were mild and tended to diminish over time during continued treatment, especially regarding nausea and fatigue. There were no serious adverse events. Conclusions: The results of the present analysis suggest that continued treatment with atomoxetine up to 28 weeks further improve ADHD symptoms in children and adolescents with ASD, while adverse events tend to subside. Future studies investigating the long-term efficacy of atomoxetine in children and adolescents with ASD should be randomized and placebo controlled. This study has been registered in ClinicalTrials.gov (www.clinicaltrials.gov) under registration number NCT00380692. C1 [Harfterkamp, Myriam; Minderaa, Ruud B.; Hoekstra, Pieter J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Buitelaar, Jan K.; van de Loo-Neus, Gigi; van der Gaag, Rutger-Jan] Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands. [Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. RP Harfterkamp, M (reprint author), Univ Med Ctr Groningen, Dept Psychiat, POB 660, NL-9700 AR Groningen, Netherlands. EM m.harfterkamp@accare.nl RI Gaag, R.J./H-8030-2014; Hoekstra, Pieter/O-4396-2014 FU Eli Lilly and company; European Society for Child and Adolescent Psychiatry (ESCAP) in Helsinki, Finland; ZonMw; EU; National Institute of Mental Health FX This study was funded by Eli Lilly and company.The paper has been presented at the International Conference sponsored by the European Society for Child and Adolescent Psychiatry (ESCAP) in Helsinki, Finland, June, 2011.Myriam Harfterkamp has accepted invitations for congress travels from Eli Lilly. Ruud B. Minderaa was advisor for Eli Lilly. Jan K. Buitelaar has been a consultant to and member of advisory board of, and/or speaker for Janssen Cilag B. V., Eli Lilly, BristolMyer Squibb, Organon/Shering Plough, UCB, Shire, Medice, Servier, and Servier. Gigi van de Loo-Neus has received honoraria for presentations or advice over the past 2 years from the pharmaceutical companies Eli Lilly, UCB Pharma B. V., and Eurocept B. V. Rutger-Jan van der Gaag has no financial disclosures. Pieter J. Hoekstra has received funding through ZonMw, EU Seventh Framework Program, and National Institute of Mental Health as well as honoraria for presentations or advice from the pharmaceutical companies Desitin, Shire, and Eli Lilly. CR Adler LA, 2009, J CLIN PSYCHOPHARM, V29, P44, DOI 10.1097/JCP.0b013e318192e4a0 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Buitelaar JK, 2007, BIOL PSYCHIAT, V61, P694, DOI 10.1016/j.biopsych.2006.03.066 Donnelly C, 2009, J AM ACAD CHILD ADOL, V48, P2 Du Paul GJ, 1998, J PSYCHOPATHOL BEHAV, V20, P3 Faries D. E., 2001, J ATTEN DISORD, V5, P107, DOI 10. 1177/1087054701005100204 Harfterkamp M, 2012, J AM ACAD CHILD PSY, V51, P733, DOI 10.1016/j.jaac.2012.04.011 Kratochvil CJ, 2006, J AM ACAD CHILD PSY, V45, P919, DOI 10.1097/01.chi0000222788.34229.68 Michelson D, 2001, PAEDIATRICS, V108, P5 Michelson D, 2002, AM J PSYCHIAT, V159, P1896, DOI 10.1176/appi.ajp.159.11.1896 Michelson D, 2004, J AM ACAD CHILD PSY, V43, P896, DOI 10.1097/01.chi.0000125089.35109.81 Montoya A, 2009, CURR MED RES OPIN, V25, P2745, DOI 10.1185/03007990903316152 Rutter M., 2003, AUTISM DIAGNOSTIC IN Svanborg P, 2009, EUR CHILD ADOLES PSY, V18, P240, DOI 10.1007/s00787-008-0725-5 Weiss M, 2005, J AM ACAD CHILD PSY, V44, P647, DOI 10.1097/01.chi.0000163280.47221.c9 Wilens TE, 2006, J PEDIATR-US, V149, P112, DOI 10.1016/j.jpeds.2006.01.052 NR 16 TC 6 Z9 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD APR PY 2013 VL 23 IS 3 BP 194 EP 199 DI 10.1089/cap.2012.0012 PG 6 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 130ZU UT WOS:000317960700006 PM 23578015 ER PT J AU Ghanizadeh, A AF Ghanizadeh, A. TI Parents reported oral sensory sensitivity processing and food preference in ADHD SO JOURNAL OF PSYCHIATRIC AND MENTAL HEALTH NURSING LA English DT Article DE ADHD; adolescents; children; parent; picky eater; responsivity ID AUTISM SPECTRUM DISORDERS; PICKY EATERS; CHILDREN; SELECTIVITY; SUBTYPES; SAMPLE AB Accessible summary center dot Oral sensory overresponsivity is frequently seen in attention deficit hyperactivity disorder (ADHD) children with oppositional behaviours. center dot Attention deficit hyperactivity disorder children with oppositional behaviours are more likely to adhere to the same foods. center dot Food preferences in ADHD children co-morbid with oppositional behaviour are more common than in those without oppositional behaviours. center dot Children with both ADHD and oppositional behaviours are less likely to try new food and have limited repertoire of foods. Behavioural and food recommendation for children with ADHD should consider their co-morbid behaviours. Abstract Oral sensory processing in children with attention deficit hyperactivity disorder (ADHD) is an area with limited research. Oppositional defiant disorder (ODD) and separation anxiety disorder (SAD) symptoms usually co-occur with ADHD. This study investigates the association of oral sensory processing problems with ODD and SAD symptoms in children with ADHD. The parents of 189 children with ADHD completed Oral Over- and Underresponsivity Behaviors Inventory reporting oral overresponsivity (OR) and underresponsivity (UR) of their children. Only ODD score predicted OR scale score. None of ADHD severity, anxiety score, age and gender predicted OR score. UR scale score was only predicted by SAD and inattention scores. ODD score and hyperactivity/impulsivity score did not predict UR score. The ODD behaviour in children with ADHD needs to be evaluated and managed more extensively and it should include oral sensory occupational therapy. Future studies should extend this research to children with ADHD and obesity and food reward system. C1 [Ghanizadeh, A.] Shiraz Univ Med Sci, Hafez Hosp, Res Ctr Psychiat & Behav Sci, Shiraz, Iran. [Ghanizadeh, A.] Shiraz Univ Med Sci, Hafez Hosp, Dept Psychiat, Shiraz, Iran. RP Ghanizadeh, A (reprint author), Shiraz Univ Med Sci, Hafez Hosp, Dept Psychiat, Res Ctr Psychiat & Behav Sci, Shiraz, Iran. EM ghanizad@sina.tums.ac.ir CR APA, 1994, AM PSYCH ASS DIAGN S Birch LL, 1998, J NUTR, V128, p407S Carruth BR, 2004, J AM DIET ASSOC, V104, pS57, DOI 10.1016/j.jada.2003.10.024 Cermak SA, 2010, J AM DIET ASSOC, V110, P238, DOI 10.1016/j.jada.2009.10.032 Darbyshire P, 1987, Nurs Times, V83, P57 Dovey TM, 2008, APPETITE, V50, P181, DOI 10.1016/j.appet.2007.09.009 Dunn W, 2002, OTJR-OCCUP PARTICI H, V22, P4 Emmons P. 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Psychiatr. Ment. Health Nurs. PD APR PY 2013 VL 20 IS 5 BP 426 EP 432 DI 10.1111/j.1365-2850.2011.01830.x PG 7 WC Nursing; Psychiatry SC Nursing; Psychiatry GA 134RC UT WOS:000318230900009 PM 22074155 ER PT J AU Chlebowski, C Robins, DL Barton, ML Fein, D AF Chlebowski, Colby Robins, Diana L. Barton, Marianne L. Fein, Deborah TI Large-Scale Use of the Modified Checklist for Autism in Low-Risk Toddlers SO PEDIATRICS LA English DT Article DE autism; M-CHAT; screening; toddlers; diagnosis ID SPECTRUM DISORDERS; YOUNG-CHILDREN; FOLLOW-UP; DIAGNOSIS; AGE; PREDICTORS AB OBJECTIVE: The purpose of the study was to examine use of the Modified Checklist for Autism in Toddlers (M-CHAT) as an autism-specific screening instrument in a large, geographically diverse pediatrics-based sample. METHODS: The M-CHAT and the M-CHAT Follow-Up (M-CHAT/F) were used to screen 18 989 toddlers at pediatric well-child visits in 2 US geographic regions. Pediatricians directly referred children to ascertain potential missed screening cases. Screen-positive children received the M-CHAT/F; children who continued to screen positive after the M-CHAT/F received a diagnostic evaluation. RESULTS: Results indicated that 54% of children who screened positive on the M-CHAT and M-CHAT/F presented with an autism spectrum disorder (ASD), and 98% presented with clinically significant developmental concerns warranting intervention. An M-CHAT total score cutoff of >= 3 identifies nearly all screen-positive cases, and for ease of scoring the use of only the M-CHAT total score cutoff is recommended. An M-CHAT total score of 7 serves as an appropriate clinical cutoff, and providers can bypass the M-CHAT/F and refer immediately to evaluation and intervention if a child obtains a score of >= 7. CONCLUSIONS: This study provides empirical support for the utility of population screening for ASD with the use of the M-CHAT in a primary care setting. Results suggest that the M-CHAT continues to be an effective screening instrument for ASD when the 2-step screening process is used. The M-CHAT is widely used at pediatric offices, and this study provides updated results to facilitate use and scoring of the M-CHAT by clinical providers. C1 [Chlebowski, Colby] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Robins, Diana L.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Barton, Marianne L.; Fein, Deborah] Univ Connecticut, Dept Psychol, Storrs, CT USA. [Fein, Deborah] Univ Connecticut, Dept Pediat, Storrs, CT USA. RP Chlebowski, C (reprint author), 3020 Childrens Way,MC 5033, San Diego, CA 92103 USA. EM cchlebowski@ucsd.edu FU National Institutes of Health (NIH) [R01 HD039961]; National Institute of Mental Health [F31 MH12550-1-2]; Maternal and Child Health Bureau [R40 MC00270]; US Department of Education student; Centers for Disease Control and Prevention-Georgia State University seed grant in the social and behavioral sciences; National Association for Autism Research FX Supported by National Institutes of Health (NIH) grant R01 HD039961, National Institute of Mental Health grant F31 MH12550-1-2, Maternal and Child Health Bureau grant R40 MC00270, a US Department of Education student-initiated research grant, a Centers for Disease Control and Prevention-Georgia State University seed grant in the social and behavioral sciences, and a grant from the National Association for Autism Research. Funded by the National Institutes of Health (NIH). CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT CDC, 2012, MMWR SURVEILL SUMM, V61, P1 Dietz C, 2006, J AUTISM DEV DISORD, V36, P713, DOI 10.1007/s10803-006-0114-1 Filipek PA, 2000, NEUROLOGY, V55, P468 Filipek PA, 1999, J AUTISM DEV DISORD, V29, P439, DOI 10.1023/A:1021943802493 Fountain C, 2011, J EPIDEMIOL COMMUN H, V65, P503, DOI 10.1136/jech.2009.104588 Harris SL, 2000, J AUTISM DEV DISORD, V30, P137, DOI 10.1023/A:1005459606120 Howard JS, 2005, RES DEV DISABIL, V26, P359, DOI 10.1016/j.ridd.2004.09.005 Johnson CP, 2007, PEDIATRICS, V120, P1183, DOI 10.1542/peds.2007-2361 Kleinman JM, 2008, J AUTISM DEV DISORD, V38, P827, DOI 10.1007/s10803-007-0450-9 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 Mandell DS, 2010, PSYCHIAT SERV, V61, P822, DOI 10.1176/appi.ps.61.8.822 Mullen E, 1995, MULLEN SCALES EARLY Myers SM, 2007, PEDIATRICS, V120, P1162, DOI 10.1542/peds.2007-2362 Pandey J, 2008, AUTISM, V12, P513, DOI 10.1177/1362361308094503 Pierce K, 2011, J PEDIATR-US, V159, P458, DOI 10.1016/j.jpeds.2011.02.036 Robins D., 1999, MODIFIED CHECKLIST A Robins DL, 2001, J AUTISM DEV DISORD, V31, P131, DOI 10.1023/A:1010738829569 Robins DL, 2008, AUTISM, V12, P537, DOI 10.1177/1362361308094502 Sallows GO, 2005, AM J MENT RETARD, V110, P417, DOI 10.1352/0895-8017(2005)110[417:IBTFCW]2.0.CO;2 SCHOPLER E, 1980, J AUTISM DEV DISORD, V10, P91, DOI 10.1007/BF02408436 Sparrow S, 1984, VINELAND ADAPTIVE BE Sparrow SS, 2005, VINELAND ADAPTIVE BE Stone WL, 2000, J AUTISM DEV DISORD, V30, P607, DOI 10.1023/A:1005647629002 NR 25 TC 18 Z9 19 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2013 VL 131 IS 4 BP E1121 EP E1127 DI 10.1542/peds.2012-1525 PG 7 WC Pediatrics SC Pediatrics GA 135EF UT WOS:000318269500010 PM 23530174 ER PT J AU Wodka, EL Mathy, P Kalb, L AF Wodka, Ericka L. Mathy, Pamela Kalb, Luther TI Predictors of Phrase and Fluent Speech in Children With Autism and Severe Language Delay SO PEDIATRICS LA English DT Article DE communication; nonverbal; autism spectrum disorders; social; repetitive ID EARLY ADULT LIFE; SPECTRUM DISORDERS; FOLLOW-UP; REPETITIVE BEHAVIORS; DIAGNOSTIC INTERVIEW; OUTCOMES; INDIVIDUALS; TODDLERS AB OBJECTIVE: To examine the prevalence and predictors of language attainment in children with autism spectrum disorder (ASD) and severe language delay. We hypothesized greater autism symptomatology and lower intelligence among children who do not attain phrase/fluent speech, with nonverbal intelligence and social engagement emerging as the strongest predictors of outcome. METHODS: Data used for the current study were from 535 children with ASD who were at least 8 years of age (mean = 11.6 years, SD = 2.73 years) and who did not acquire phrase speech before age 4. Logistic and Cox proportionate hazards regression analyses examined predictors of phrase and fluent speech attainment and age at acquisition, respectively. RESULTS: A total of 372 children (70%) attained phrase speech and 253 children (47%) attained fluent speech at or after age 4. No demographic or child psychiatric characteristics were associated with phrase speech attainment after age 4, whereas slightly older age and increased internalizing symptoms were associated with fluent speech. In the multivariate analyses, higher nonverbal IQ and less social impairment were both independently associated with the acquisition of phrase and fluent speech, as well as earlier age at acquisition. Stereotyped behavior/repetitive interests and sensory interests were not associated with delayed speech acquisition. CONCLUSIONS: This study highlights that many severely language-delayed children in the present sample attained phrase or fluent speech at or after age 4 years. These data also implicate the importance of evaluating and considering nonverbal skills, both cognitive and social, when developing interventions and setting goals for language development. Pediatrics 2013;131:e1128-e1134 C1 [Wodka, Ericka L.; Mathy, Pamela; Kalb, Luther] Kennedy Krieger Inst, Ctr Autism & Related Disorders, Baltimore, MD 21211 USA. [Wodka, Ericka L.; Mathy, Pamela] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Wodka, EL (reprint author), Kennedy Krieger Inst, Ctr Autism & Related Disorders, 3901 Greenspring Ave, Baltimore, MD 21211 USA. EM wodka@kennedykrieger.org CR Achenbach T. M., 2001, CHILD BEHAV CHECKLIS American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th Anderson DK, 2007, J CONSULT CLIN PSYCH, V75, P594, DOI 10.1037/0022-006X.75.4.594 Cox D, 1984, ANAL SURVIVAL DATA Elliot C. 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Nagaswamy, Uma Stevens, Christine Lim, Elaine Bodea, Corneliu A. Muzny, Donna Reid, Jeffrey G. Banks, Eric Coon, Hillary DePristo, Mark Dinh, Huyen Fennel, Tim Flannick, Jason Gabriel, Stacey Garimella, Kiran Gross, Shannon Hawes, Alicia Lewis, Lora Makarov, Vladimir Maguire, Jared Newsham, Irene Poplin, Ryan Ripke, Stephan Shakir, Khalid Samocha, Kaitlin E. Wu, Yuanqing Boerwinkle, Eric Buxbaum, Joseph D. Cook, Edwin H., Jr. Devlin, Bernie Schellenberg, Gerard D. Sutcliffe, James S. Daly, Mark J. Gibbs, Richard A. Roeder, Kathryn TI Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; DE-NOVO MUTATIONS; COPY-NUMBER VARIATION; SEQUENCING DATA; PRINCIPAL-COMPONENTS; FUNCTIONAL IMPACT; VARIANT ANALYSIS; COMMON VARIANTS; LARGE-SCALE; GENES AB We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD. C1 [Liu, Li; Bodea, Corneliu A.; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Sabo, Aniko; Nagaswamy, Uma; Muzny, Donna; Reid, Jeffrey G.; Dinh, Huyen; Gross, Shannon; Hawes, Alicia; Lewis, Lora; Boerwinkle, Eric; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Neale, Benjamin M.; Lim, Elaine; Ripke, Stephan; Samocha, Kaitlin E.; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Neale, Benjamin M.; Lim, Elaine; Ripke, Stephan; Samocha, Kaitlin E.; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. [Neale, Benjamin M.; Stevens, Christine; Lim, Elaine; Banks, Eric; DePristo, Mark; Fennel, Tim; Flannick, Jason; Gabriel, Stacey; Garimella, Kiran; Maguire, Jared; Poplin, Ryan; Ripke, Stephan; Shakir, Khalid; Samocha, Kaitlin E.; Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Coon, Hillary] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Makarov, Vladimir; Buxbaum, Joseph D.] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY USA. [Makarov, Vladimir; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Newsham, Irene; Wu, Yuanqing] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA. [Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Vanderbilt Brain Inst, Nashville, TN 37232 USA. [Sutcliffe, James S.] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. [Roeder, Kathryn] Carnegie Mellon Univ, Ray & Stephanie Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. RP Liu, L (reprint author), Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. EM roeder@stat.cmu.edu RI Liu, Li/G-1897-2015 FU NIH [R01MH089208, R01 MH089025, R01 MH089004, R01 MH089175, R01 MH089482, P50 HD055751, RO1 MH057881, R01 MH061009, UL1 RR024975, P30 HD015052, U54 HG003273, U54 HG003067] FX This work was directly supported by NIH grants R01MH089208, R01 MH089025, R01 MH089004, R01 MH089175, R01 MH089482, P50 HD055751, RO1 MH057881, R01 MH061009, UL1 RR024975, P30 HD015052, U54 HG003273, and U54 HG003067 (www.nih.gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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PD APR PY 2013 VL 9 IS 4 AR e1003443 DI 10.1371/journal.pgen.1003443 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 132MS UT WOS:000318073300037 PM 23593035 ER PT J AU Stosljevic, M Adamovic, M AF Stosljevic, Miodrag Adamovic, Milosav TI Dermatoglyphic characteristics of digito-palmar complex in autistic boys in Serbia SO VOJNOSANITETSKI PREGLED LA English DT Article DE dermatoglyphics; autistic disorder; child; fingers; hand; diagnostic techniques and procedures; sensitivity and specificity ID CHILDREN; SCHIZOPHRENIA; PATTERNS AB Introduction/Aim. Dermatoglyphics is a science that examines dermal patterns on volar side of both palms and soles. Since dermatoglyphs are unique for each person, by examining them a number of parameters can be determined. These parameters could help to diagnose and treat examined individulas. The aim of this study was to determine possible differences of the dermathoglyphic characteristics of digito-palmar complex (DPC) comparing the autistic boys with the healthy examinees. Methods. This study was conducted on a group of 182 boys with infantile autism, aged from 5 to 15 (average age 7.2 years) while the control group consisted of 182 healthy men from 30 to 50 years (average age 38.7 years). Within the digital scope of DPC we examined tree types of dermatoglyphic patterns on fingertips (arch, loop and whrol), as well as dermal ridge count on each finger separately (FRC - finger ridge count) and total dermal ridge count on all the ten fingers (TRC - total ridge count). Within the palmar DPC area we measured the angles between the triradius (atd, dat, adt, atb, btc, ctd), as well as dermal ridge count (RC - ridge count) between the triradius a-b, b-c and c-d. Results. The autistic boys had a significantely higher count of arches (9.17%) on fingertips of both hands when compared to the control group of examinees (4.34%), and the lower count of loops (28.40%) compared with the control group (32.42%). A higher count of arches was especially expressed on the fourth and fifth finger of both hands. Beside this characteristic, the autistic boys had a lower TRC and ab-RC as well as a wider atd angle. Conclusion. Dermatoglyphic analysis could help in diagnosing autism but only as an additional method, never as a dominant diagnostic procedure. C1 [Stosljevic, Miodrag; Adamovic, Milosav] Univ Belgrade, Fac Special Educ & Rehabil, Belgrade, Serbia. RP Stosljevic, M (reprint author), Fac Special Educ & Rehabil, Visokog Stevana 2, Belgrade 11000, Serbia. 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[Sadakata, Tetsushi] Gunma Univ, Adv Sci Res Leaders Dev Unit, Maebashi, Gumma 3718511, Japan. [Furuichi, Teiichi] RIKEN BSI, Wako, Saitama 3510198, Japan. RP Furuichi, T (reprint author), Tokyo Univ Sci, Fac Sci & Technol, Dept Appl Biol Sci, 2641 Yamazaki, Noda, Chiba 2788510, Japan. FU Japanese Ministry of Education, Culture, Sports, Science and Technology; Japan Society for the Promotion of Science; Japan Science and Technology Agency; Hamaguchi Foundation for the Advancement of Biochemistry FX This study was supported by Grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology, the Japan Society for the Promotion of Science, and the Japan Science and Technology Agency and by the Hamaguchi Foundation for the Advancement of Biochemistry. 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Anim. PD APR PY 2013 VL 62 IS 2 BP 71 EP 78 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 127PH UT WOS:000317710400001 PM 23615300 ER PT J AU Jain, R Juneja, M Sairam, S AF Jain, Rahul Juneja, Monica Sairam, Smitha TI Children With Developmental Disabilities in India: Age of Initial Concern and Referral for Rehabilitation Services, and Reasons for Delay in Referral SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE autism spectrum disorders; developmental disabilities; initial concern; referral; rehabilitation services ID EARLY INTERVENTION; PERSPECTIVE; FAMILIES; AUTISM AB This study aimed to identify the age at first concern and age at referral for rehabilitation services in children with developmental disabilities in India. Two hundred fifty-nine children were included and data were collected from the parents. In children with developmental disabilities (excluding autism spectrum disorders), median age at initial concern was 7 months and age at referral for rehabilitation services was 13 months. In children with autism spectrum disorders, median age at initial concern was 24 months and age at referral was 42 months. Physician's recognition of the condition, single child, institutional delivery and neonatal admission >= 4 days were associated with early referral. The common reasons cited by the parents for delay in services were reassurance by physicians or family members and nonreferral by the physicians. Thus, routine screening for developmental problems (including autism) and improving the awareness of these conditions among physicians and society would lead to early referral. C1 [Jain, Rahul; Juneja, Monica; Sairam, Smitha] Maulana Azad Med Coll, Child Dev Ctr, New Delhi, India. [Jain, Rahul; Juneja, Monica; Sairam, Smitha] Associated Lok Nayak Hosp, New Delhi, India. 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Child Neurol. PD APR PY 2013 VL 28 IS 4 BP 455 EP 460 DI 10.1177/0883073812447685 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 127FK UT WOS:000317682500004 PM 22752480 ER PT J AU Perovic, A Modyanova, N Wexler, K AF Perovic, Alexandra Modyanova, Nadya Wexler, Ken TI Comparison of Grammar in Neurodevelopmental Disorders: The Case of Binding in Williams Syndrome and Autism With and Without Language Impairment SO LANGUAGE ACQUISITION LA English DT Article ID SPECTRUM DISORDERS; DOWN-SYNDROME; CHILDREN; ACQUISITION; ABILITIES AB This study investigates whether distinct neurodevelopmental disorders show distinct patterns of impairments in particular grammatical abilities and the relation of those grammatical patterns to general language delays and intellectual disabilities. We studied two disorders (autism and Williams syndrome [WS]) and two distinct properties (Principle A that governs reflexives and Principle B that, together with its associated pragmatic rule, governs pronouns) of the binding module of grammar. These properties are known to have markedly different courses of acquisition in typical development. We compare the knowledge of binding in children with autism with language impairment (ALI) and those with normal language (ALN) to that of children with WS, matched on age to the ALN group, and on age and nonverbal mental age (MA) to the ALI group, as well as to two groups of typically developing (TD) controls, matched on nonverbal MA to ALI and ALN groups. Our results reveal a remarkably different pattern of comprehension of personal pronouns and reflexives in ALI as opposed to ALN, WS, and two groups of TD controls. 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Cell Dev. Biol. PD APR PY 2013 VL 24 IS 4 BP 357 EP 369 DI 10.1016/j.semcdb.2013.02.003 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 129KV UT WOS:000317838900015 PM 23466288 ER PT J AU Loucas, T Riches, N Baird, G Pickles, A Simonoff, E Chandler, S Charman, T AF Loucas, Tom Riches, Nick Baird, Gillian Pickles, Andrew Simonoff, Emily Chandler, Susie Charman, Tony TI Spoken word recognition in adolescents with autism spectrum disorders and specific language impairment SO APPLIED PSYCHOLINGUISTICS LA English DT Article ID SPEECH-PERCEPTION; PRESCHOOL-CHILDREN; GATING PARADIGM; INDIVIDUALS; FREQUENCY; COMPREHENSION; PREVALENCE; ABILITY; UPDATE; ADULTS AB Spoken word recognition, during gating, appears intact in specific language impairment (SLI). This study used gating to investigate the process in adolescents with autism spectrum disorders plus language impairment (ALI). Adolescents with ALI, SLI, and typical language development (TLD), matched on nonverbal IQ listened to gated words that varied in frequency (low/high) and number of phonological onset neighbors (low/high density). Adolescents with ALI required more speech input to initially identify low-frequency words with low competitor density than those with SLI and those with TLD, who did not differ. These differences may be due to less well specified word form representations in ALI. C1 [Loucas, Tom; Riches, Nick] Univ Reading, Reading RG6 6AL, Berks, England. [Baird, Gillian] Guys Hosp, London SE1 9RT, England. [Chandler, Susie; Charman, Tony] Inst Educ, London, England. RP Loucas, T (reprint author), Univ Reading, Sch Psychol & Clin Language Sci, Reading RG6 6AL, Berks, England. 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PD APR PY 2013 VL 34 IS 2 BP 301 EP 322 DI 10.1017/S0142716411000701 PG 22 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA 123ZQ UT WOS:000317432600004 ER PT J AU Echeverria, F Miltenberger, RG AF Echeverria, Fran Miltenberger, Raymond G. TI REDUCING RAPID EATING IN ADULTS WITH INTELLECTUAL DISABILITIES SO BEHAVIORAL INTERVENTIONS LA English DT Article ID TACTILE PROMPT; AUTISM; INITIATIONS; REDUCTION AB Rapid eating is a frequent problem among individuals with developmental disabilities that can pose a threat to health. This study sought to reduce the rate of eating behaviors in two adults diagnosed with moderate intellectual disability. Assessment of eating rate took place in the participants' group homes during lunch or dinner meals. Procedures included the use of vibrating pagers with and without verbal prompts to prompt eating and prevent rapid eating behaviors. Results demonstrate a clear reduction in rate of eating when using vibrating pagers and verbal prompts for both participants. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Echeverria, Fran; Miltenberger, Raymond G.] Univ S Florida, Tampa, FL USA. RP Miltenberger, RG (reprint author), USF MHC 2113A,13301 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM miltenbe@usf.edu CR Anglesea MM, 2008, J APPL BEHAV ANAL, V41, P107, DOI 10.1901/jaba.2008.41-107 Anson HM, 2008, BEHAV RES METHODS, V40, P1106, DOI 10.3758/BRM.40.4.1106 Azrin NH, 2008, CHILD FAM BEHAV THER, V30, P355, DOI 10.1080/07317100802483223 FAVELL JE, 1980, BEHAV MODIF, V4, P481, DOI 10.1177/014544558044004 Kedesky JH, 1998, CHILDHOOD FEEDING DI LENNOX DB, 1987, J APPL BEHAV ANAL, V20, P279, DOI 10.1901/jaba.1987.20-279 Levinson S. 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Lam, Wing Yan TI A REVIEW OF COMPARISON STUDIES IN APPLIED BEHAVIOR ANALYSIS SO BEHAVIORAL INTERVENTIONS LA English DT Article ID AUTISM SPECTRUM DISORDERS; PROBLEM-SOLVING INTERVENTIONS; DIFFERENTIAL REINFORCEMENT; SOCIAL-SKILLS; NONCONTINGENT REINFORCEMENT; INTELLECTUAL DISABILITIES; STIMULUS PREFERENCE; EXTERNAL CONTROL; YOUNG-CHILDREN; FIXED-TIME AB A commonly used research design in applied behavior analysis involves comparing two or more independent variables. Typically, the relative effectiveness of two different interventions is measured on a single dependent variable. In the current review, 54 comparison studies from seven different peer-reviewed, behavior analytic journals were evaluated between the years 2002 and 2011. Each study was evaluated across seven dimensions: (1) experimental design, (2) setting, (3) participants, (4) type of comparison, (5) number of comparisons, (6) treatment integrity, and (7) outcome. There were some consistencies across studies, with half resulting in equivalent outcomes across comparisons. In addition, most studies employed the use of an alternating treatments or multi-element single-subject design and compared a teaching methodology. On the basis of these results, the value of comparison study as well as directions for future comparison research is discussed. Overall, comparison study is a worthy and important enterprise that requires a high degree of experimental control and a careful analyses of the results, regardless of whether the outcome clearly favored one independent variable or not. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Shabani, Daniel B.] Ctr Behav Anal & Language Dev, Santa Monica, CA 90403 USA. [Lam, Wing Yan] Calif State Univ Los Angeles, Dept Psychol, Los Angeles, CA 90032 USA. RP Shabani, DB (reprint author), Ctr Behav Anal & Language Dev, 2730 Wilshire Blvd,Suite 105, Santa Monica, CA 90403 USA. 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In principle, inversions-reversals in the orientation of DNA sequences within a chromosome-should have similar detrimental potential. However, the study of inversions has been hampered by traditional approaches used for their detection, which are not particularly robust. Even with significant advances in whole genome approaches, changes in the absolute orientation of DNA remain difficult to detect routinely. Consequently, our understanding of inversions is still surprisingly limited, as is our appreciation for their frequency and involvement in human disease. Here, we introduce the directional genomic hybridization methodology of chromatid painting-a whole new way of looking at structural features of the genome-that can be employed with high resolution on a cell-by-cell basis, and demonstrate its basic capabilities for genome-wide discovery and targeted detection of inversions. Bioinformatics enabled development of sequence- and strand-specific directional probe sets, which when coupled with single-stranded hybridization, greatly improved the resolution and ease of inversion detection. We highlight examples of the far-ranging applicability of this cytogenomics-based approach, which include confirmation of the alignment of the human genome database and evidence that individuals themselves share similar sequence directionality, as well as use in comparative and evolutionary studies for any species whose genome has been sequenced. In addition to applications related to basic mechanistic studies, the information obtainable with strand-specific hybridization strategies may ultimately enable novel gene discovery, thereby benefitting the diagnosis and treatment of a variety of human disease states and disorders including cancer, autism, and idiopathic infertility. C1 [Ray, F. 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PD APR PY 2013 VL 21 IS 2 BP 165 EP 174 DI 10.1007/s10577-013-9345-0 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 127HL UT WOS:000317688800006 PM 23572395 ER PT J AU Johnson, S Wolke, D AF Johnson, Samantha Wolke, Dieter TI Behavioural outcomes and psychopathology during adolescence SO EARLY HUMAN DEVELOPMENT LA English DT Article DE Preterm; Behaviour; Autism spectrum disorders; ADHD; Anxiety; Psychiatric disorders ID LOW-BIRTH-WEIGHT; QUALITY-OF-LIFE; AGE 12 YEARS; PRETERM BIRTH; PSYCHIATRIC-DISORDERS; CHILDREN BORN; PSYCHOTIC SYMPTOMS; RISK-FACTORS; SOCIAL-CONSEQUENCES; MENTAL-DISORDERS AB Preterm birth is associated with a high risk of residual neurodevelopmental disability and cognitive impairment. These problems are closely associated with psychiatric disorders and thus it is unsurprising that preterm birth also confers high risk for poor long term mental health. The risk associated with preterm birth is not a general one, but appears to be specific to symptoms and disorders associated with anxiety, inattention and social and communication problems, and manifest in a significantly higher prevalence of emotional disorders, ADHD and Autism. Adolescence is a key period for mental health and studies have shown that problems evident in childhood persist over this time and are more stable amongst preterm individuals than term-born peers. There is also modest evidence for an increased prevalence of psychotic symptoms in preterm adolescents. The high prevalence of psychiatric disorders, present in around 25% of preterm adolescents, requires long term screening and intervention. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Johnson, Samantha] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Wolke, Dieter] Univ Warwick, Warwick Med Sch, Dept Psychol, Coventry CV4 7AL, W Midlands, England. [Wolke, Dieter] Univ Warwick, Warwick Med Sch, Div Mental Hlth & Wellbeing, Coventry CV4 7AL, W Midlands, England. RP Johnson, S (reprint author), Univ Leicester, Dept Hlth Sci, 22-28 Princess Rd West, Leicester, Leics, England. EM sjj19@le.ac.uk; d.wolke@warwick.ac.uk FU German Federal Ministry of Education and Science (BMBF) [01ER0801]; Medical Research Council (MRC) in the UK [MR\J01107x\1] FX D.W. was partly supported by grant 01ER0801 from the German Federal Ministry of Education and Science (BMBF) and grant MR\J01107x\1 from the Medical Research Council (MRC) in the UK. The opinions expressed are those of the authors and not the grant giving bodies. 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Dev. PD APR PY 2013 VL 89 IS 4 BP 199 EP 207 DI 10.1016/j.earlhumdev.2013.01.014 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 124IJ UT WOS:000317456700002 PM 23455605 ER PT J AU Nosarti, C AF Nosarti, Chiara TI Structural and functional brain correlates of behavioral outcomes during adolescence SO EARLY HUMAN DEVELOPMENT LA English DT Article DE Preterm birth; Behavioral symptoms; Brain; Magnetic resonance imaging ID LOW-BIRTH-WEIGHT; DEFICIT HYPERACTIVITY DISORDER; 1ST EPISODE SCHIZOPHRENIA; AUTISM SPECTRUM DISORDER; SCHOOL-AGE-CHILDREN; PRETERM BIRTH; WHITE-MATTER; YOUNG-ADULTS; DEVELOPMENTAL NEUROPATHOLOGY; PREFRONTAL CORTEX AB Several studies have described an association between very preterm birth and behavioral and psychiatric outcomes in childhood and adolescence. The exact mechanisms underlying this association are unknown, but impaired neurodevelopment has been proposed as a possible etiological factor. Existing research suggests a selective vulnerability of brain regions associated with a variety of behavioral and psychiatric outcomes following very preterm birth. This article reviews studies that have directly explored the structural and functional brain correlates of behavioral outcomes in ex-preterm individuals, with an emphasis on attentional problems, overall mental health functioning including internalizing and externalizing scores, and psychosocial adjustment. The focus here is on neuroimaging research conducted during adolescence, a period of life associated with the emergence and early expression of several psychiatric disorders. The neurodevelopmental hypothesis is used as a theoretical framework, according to which early brain lesions interact with the developing brain to increase later vulnerability to psychopathology. (C) 2013 Elsevier Ireland Ltd. All rights reserved. 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Dev. PD APR PY 2013 VL 89 IS 4 BP 221 EP 227 DI 10.1016/j.earlhumdev.2013.02.002 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 124IJ UT WOS:000317456700005 PM 23477720 ER PT J AU Li, YH Tottenham, N AF Li, Yuan Hang Tottenham, Nim TI Exposure to the Self-Face Facilitates Identification of Dynamic Facial Expressions: Influences on Individual Differences SO EMOTION LA English DT Article DE self-face; emotion; facial expression; dynamic expression; autism quotient ID AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; MIRROR NEURON SYSTEM; EMOTION RECOGNITION; ASPERGER-SYNDROME; NEGATIVE AFFECT; QUOTIENT AQ; VALIDITY; PERCEPTION; INVENTORY AB A growing literature suggests that the self-face is involved in processing the facial expressions of others. The authors experimentally activated self-face representations to assess its effects on the recognition of dynamically emerging facial expressions of others. They exposed participants to videos of either their own faces (self-face prime) or faces of others (nonself-face prime) prior to a facial expression judgment task. Their results show that experimentally activating self-face representations results in earlier recognition of dynamically emerging facial expression. As a group, participants in the self-face prime condition recognized expressions earlier (when less affective perceptual information was available) compared to participants in the nonself-face prime condition. There were individual differences in performance, such that poorer expression identification was associated with higher autism traits (in this neurocognitively healthy sample). However, when randomized into the self-face prime condition, participants with high autism traits performed as well as those with low autism traits. 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We propose that the effects of older PAC are likely to be broad and harmful in some domains of health but beneficial in others. Harmful effects of older PAC have received the most attention. Thus, for example, older PAC is associated with an increased risk of offspring having rare conditions such as achondroplasia and Marfan syndrome, as well as with neurodevelopmental disorders such as autism. However, newly emerging evidence in the telomere field suggests potentially beneficial effects, since older PAC is associated with a longer leukocyte telomere length (LTL) in offspring, and a longer LTL is associated with a reduced risk of atherosclerosis and with increased survival in the elderly. Thus, older PAC may cumulatively increase resistance to atherosclerosis and lengthen lifespan in successive generations of modern humans. In this paper we: (i) introduce these novel findings; (ii) discuss potential explanations for the effect of older PAC on offspring LTL; (iii) draw implications for population health and for life course; (iv) put forth an evolutionary perspective as a context for the multigenerational effects of PAC; and (v) call for broad and intensive research to understand the mechanisms underlying the effects of PAC. We draw together work across a range of disciplines to offer an integrated perspective of this issue. C1 [Aviv, Abraham] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07103 USA. [Aviv, Abraham; Susser, Ezra] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Susser, Ezra] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Aviv, A (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, 185 S Orange Ave, Newark, NJ 07103 USA. EM avivab@umdnj.edu FU NIH [AG020132, AG021593, AG030678, HD071180, AG023028, MH059114]; University of Groeningen, Germany FX The research on human telomere biology and its genetics described in this paper has been supported by NIH grants AG020132, AG021593, AG030678 and HD071180 (to A.A.). The research on paternal age and other early determinants of adult health has been supported by NIH grants AG023028, MH059114, and HD071180, and by a Dr. Lisa Oehler Visiting Professorship, University of Groeningen, Germany (to E,S,). We would like to acknowledge comments by Sarah Tishkoff, Scott Williams, Pam-Factor Litvak, and Hana Aviv that helped in the writing of this paper. 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In particular, in order to comprehend the etiological mechanisms of their characteristic behaviors, great importance should be placed on realizing how the neural networks of individuals with autistic disorders and WS are formed and work. As such, in this paper, cortical network abnormalities, based on data from a variety of research fields, are presented: psychopathological, histopathological, and clinicopathological studies, as well as structural (i.e., morphological) and functional magnetic resonance imaging studies, including functional connectivity analysis. Based on the structure of the network, we propose an etiology for ASD and WS. Finally, we explain a variety of symptoms of these two disorders, including social and nonsocial dysfunction, based on our proposed neural network. C1 [Inui, Toshio] Kyoto Univ, Kyoto 6068501, Japan. RP Inui, T (reprint author), Kyoto Univ, Dept Intelligence Sci & Technol, Grad Sch Informat, Sakyo Ku, Yoshida Honmachi, Kyoto 6068501, Japan. 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PD APR PY 2013 VL 55 IS 2 SI SI BP 99 EP 117 DI 10.1111/jpr.12004 PG 19 WC Psychology, Multidisciplinary SC Psychology GA 123QN UT WOS:000317405500002 ER PT J AU Kikuchi, Y Senju, A Hasegawa, T Tojo, Y Osanai, H AF Kikuchi, Yukiko Senju, Atsushi Hasegawa, Toshikazu Tojo, Yoshikuni Osanai, Hiroo TI The effect of spatial frequency and face inversion on facial expression processing in children with autism spectrum disorder SO JAPANESE PSYCHOLOGICAL RESEARCH LA English DT Article DE autism spectrum disorder; facial expression; local processing; spatial frequencies; inversion effect ID HIGH-FUNCTIONING AUTISM; UPSIDE-DOWN FACES; EMOTION RECOGNITION; ASPERGER-SYNDROME; IMPAIRED RECOGNITION; SELECTIVE ATTENTION; WILLIAMS-SYNDROME; COGNITIVE-STYLE; PERCEPTION; ADULTS AB To investigate whether facial expression processing in children with autism spectrum disorder (ASD) is based on local information of the stimuli, we prepared low spatial frequency (LSF) images with blurred facial features and high spatial frequency (HSF) images with rich facial features from broad (normal) spatial frequency (BSF) images. Eighteen children with ASD (mean age 11.9years) and 19 typically developing (TD) children (mean age 11.4years) matched on nonverbal IQ were presented these stimuli in upright and inverted orientations. The children with ASD had difficulty in processing facial expressions from the BSF and LSF images, but not from the HSF images. In addition, the BSF and HSF images elicited the inversion effect in the TD children, but not in the children with ASD. In contrast, the LSF images elicited the inversion effect in both groups of children. These results suggest that children with ASD are biased towards processing facial expression based on local information, even though their capacity to process facial expressions configurally is spared. C1 [Kikuchi, Yukiko; Senju, Atsushi; Hasegawa, Toshikazu] Univ Tokyo, Tokyo 1138654, Japan. [Tojo, Yoshikuni] Ibaraki Univ, Mito, Ibaraki 3108512, Japan. [Osanai, Hiroo] Musashino Higashi Ctr Educ & Res, Musashino, Tokyo, Japan. 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Psychol. Res. PD APR PY 2013 VL 55 IS 2 SI SI BP 131 EP 143 DI 10.1111/jpr.12014 PG 13 WC Psychology, Multidisciplinary SC Psychology GA 123QN UT WOS:000317405500004 ER PT J AU Takahashi, H Saito, C Okada, H Omori, T AF Takahashi, Hideyuki Saito, Chinatsu Okada, Hiroyuki Omori, Takashi TI An investigation of social factors related to online mentalizing in a human-robot competitive game SO JAPANESE PSYCHOLOGICAL RESEARCH LA English DT Article DE online mentalizing; matching pennies game; human-robot competitive game; gaze following behavior ID NEURAL BASIS; PREFRONTAL CORTEX; ASPERGER-SYNDROME; DECISION-MAKING; AUTISM; MIND; ATTRIBUTION; CHILDREN; MIMICRY; ADULTS AB Mentalizing is the ability to attribute mental states to other agents. The lack of online mentalizing, which is required in actual social contexts, may cause serious social disorders such as autism. However, the mechanism of online mentalizing is still unclear. In this study, we found that behavioral entropy (which indicates the randomness of decision making) was an efficient behavioral index for online mentalizing in a human-human competitive game. Further participants played the game with a humanoid robot; the results indicated that the entropy was significantly higher in participants whose gaze followed the robot's head turn than in those who did not, although the explicit human-likeness of the robot did not correlate with behavioral entropy. These results implied that mentalizing could be divided into two separate processes: an explicit, logical reasoning process and an implicit, intuitive process driven by perception of the other agent's gaze. We hypothesize that the latter is a core process for online mentalizing, and we argue that the social problems of autistic people are caused by dysfunction of this process. C1 [Takahashi, Hideyuki; Saito, Chinatsu; Okada, Hiroyuki; Omori, Takashi] Tamagawa Univ, Machida, Tokyo 1948610, Japan. RP Takahashi, H (reprint author), Tamagawa Univ, Brain Sci Inst, Machida, Tokyo 1948610, Japan. 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Psychol. Res. PD APR PY 2013 VL 55 IS 2 SI SI BP 144 EP 153 DI 10.1111/jpr.12007 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 123QN UT WOS:000317405500005 ER PT J AU Kozima, H AF Kozima, Hideki TI Cognitive granularity: A new perspective over autistic and non-autistic styles of development SO JAPANESE PSYCHOLOGICAL RESEARCH LA English DT Review DE autism; prediction and control; minicolumn; cognitive style ID CATEGORIES AB Individuals with autism generally show better performance on operating physical objects than in communicating with people. However, we lack a plausible model of autism that explains why their physical and social capabilities develop in separate and unbalanced ways. This paper investigates this question from the viewpoint of cognitive granularity, which refers to the size of the basic elements operable in one's cognitive system. While it is constrained by one's perceptual and motor resolution, cognitive granularity determines the level of abstraction at which one can efficiently predict and control the physical and social world. Recent findings in autism research, including preference for causal predictability and abnormalities in neuroanatomical density, suggest that individuals with autism have finer cognitive granularity; they live in a different Umwelt from that which non-autistic people experience. The difference in cognitive granularity explains not only autistic individuals' unbalanced development as well as their difficulty in understanding others' minds, but also the spectrum of developmental styles in the entire population. Finally, from this unified perspective, we also discuss possible therapeutic interventions for autism. C1 [Kozima, Hideki] Miyagi Univ, Taiwa, Miyagi 9813298, Japan. 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PD APR PY 2013 VL 34 IS 3 BP 215 EP 215 DI 10.1097/DBP.0b013e318289b0b6 PG 1 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 124RM UT WOS:000317483400011 ER PT J AU Furmanski, O Tao, F Yang, Y Li, C Skinner, J Bangash, A Worley, P Johns, R AF Furmanski, O. Tao, F. Yang, Y. Li, C. Skinner, J. Bangash, A. Worley, P. Johns, R. TI Pain processing in a mouse model of Phelan-McDermid Syndrome, an autism spectrum disorder SO JOURNAL OF PAIN LA English DT Meeting Abstract C1 [Furmanski, O.; Tao, F.; Yang, Y.; Li, C.; Skinner, J.; Bangash, A.; Worley, P.; Johns, R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD APR PY 2013 VL 14 IS 4 SU 1 BP S43 EP S43 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 126RR UT WOS:000317639400169 ER PT J AU Lees, HJ Swann, JR Wilson, ID Nicholson, JK Holmes, E AF Lees, Hannah J. Swann, Jonathan R. Wilson, Ian D. Nicholson, Jeremy K. Holmes, Elaine TI Hippurate: The Natural History of a Mammalian-Microbial Cometabolite SO JOURNAL OF PROTEOME RESEARCH LA English DT Review DE metabolic profiling; microbial metabolites; polyphenols; health ID NUCLEAR-MAGNETIC-RESONANCE; INFLAMMATORY-BOWEL-DISEASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; ECHINOSTOMA-CAPRONI INFECTION; AUTISTIC SPECTRUM DISORDERS; CAFFEIC ACID METABOLISM; RAT-LIVER MITOCHONDRIA; BLACK TEA CONSUMPTION; RENAL TUBULAR DAMAGE; BENZOIC-ACID AB Hippurate, the glycine conjugate of benzoic acid, is a normal constituent of the endogenous urinary metabolite profile and has long been associated with the microbial degradation of certain dietary components, hepatic function and toluene exposure, and is also commonly used as a measure of renal clearance. Here we discuss the potential relevance of hippurate excretion with regard to normal endogenous metabolism and trends in excretion relating to gender, age, and the intestinal microbiota. Additionally, the significance of hippurate excretion with respect to disease states including obesity, diabetes, gastrointestinal diseases, impaired renal function, psychological disorders and autism, as well as toxicity and parasitic infection, are considered. C1 [Lees, Hannah J.; Wilson, Ian D.; Nicholson, Jeremy K.; Holmes, Elaine] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Surg & Canc, London SW7 2AZ, England. [Swann, Jonathan R.] Univ Reading, Sch Chem Food & Pharm, Dept Food & Nutr Sci, Reading RG6 6AP, Berks, England. RP Holmes, E (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Surg & Canc, London SW7 2AZ, England. 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Proteome Res. PD APR PY 2013 VL 12 IS 4 BP 1527 EP 1546 DI 10.1021/pr300900b PG 20 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 122ON UT WOS:000317327500001 PM 23342949 ER PT J AU Shepherd, GMG AF Shepherd, Gordon M. G. TI Corticostriatal connectivity and its role in disease SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; OBSESSIVE-COMPULSIVE DISORDER; MOUSE MOTOR CORTEX; PYRAMIDAL PROJECTION NEURONS; DEVELOPING CEREBRAL-CORTEX; RECEPTOR TYROSINE KINASE; MEDIAL PREFRONTAL CORTEX; RANGE CORTICOFUGAL AXONS; DEEP BRAIN-STIMULATION; RAT-ASSOCIATION CORTEX AB I Corticostriatal projections are essential components of forebrain circuits and are widely involved in motivated behaviour. These axonal projections are formed by two distinct classes of cortical neurons, intratelencephalic (IT) and pyramidal tract (PT) neurons. Convergent evidence points to IT versus PT differentiation of the corticostriatal system at all levels of functional organization, from cellular signalling mechanisms to circuit topology. There is also growing evidence for IT/PT imbalance as an aetiological factor in neurodevetopmental, neuropsychiatric and movement disorders autism, amyotrophic lateral sclerosis, obsessive-compulsive disorder, schizophrenia, Huntington's and Parkinson's diseases and major depression are highlighted here. C1 Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA. RP Shepherd, GMG (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA. 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PD APR PY 2013 VL 14 IS 4 BP 278 EP 291 DI 10.1038/nrn3469 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 121OE UT WOS:000317253300010 PM 23511908 ER PT J AU Torres, EB AF Torres, Elizabeth Barbara TI Atypical signatures of motor variability found in an individual with ASD SO NEUROCASE LA English DT Article DE ASD case study; Goal-directed movements; Supplemental movements; motor variability; Log-normal distribution; Exponential distribution ID AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; ASPERGERS-DISORDER; BASAL GANGLIA; CHILDREN; CEREBELLAR; MOTION; SYSTEM; BRAIN AB We provide objective metrics of sequential movements and study a young adolescent with Autism Spectrum Disorders (ASD) in relation to novice typical controls (TC) as they learned to perform beginners' martialarts routines. We studied segments staged to hit an opponent simultaneously performed with supplemental segments. In TC instructed changes in speed had profound differential effects on the intended vs. supplemental segments that were absent in the ASD case. Moreover, the frequency-distribution of velocity and acceleration maxima in TC was well fitted by a Gamma distribution but in the ASD case the fit was exponential yielding uncannily precise motions with atypically low-range of spatio-temporal variability. C1 [Torres, Elizabeth Barbara] Rutgers State Univ, Dept Psychol, Piscataway, NJ 08854 USA. RP Torres, EB (reprint author), Rutgers State Univ, 152 Frelinghuysen Rd, Piscataway, NJ 08854 USA. EM ebtorres@rci.rutgers.edu RI McCann, Brian/N-9504-2014 FU NSF Cyber-Enabled Discovery and Innovation Type I (Idea) [0941587]; New Jersey Governor's Council for Medical Research and Treatment of Autism [10-403-SCH-E-0] FX We thank Uri Yarmush, our Psychology undergraduate martial arts expert who performed, instructed and supervised the routines in these motor experiments. We thank Amy Hansdford and the personnel at the Douglass Developmental Disability Center at Rutgers University for the clinical evaluations. We thank Prof. Jorge V. Jose for technical guidance on Statistical Mechanics and Dr. Robert W. Isenhower for useful comments. This work was funded by the NSF Cyber-Enabled Discovery and Innovation Type I (Idea) grant # 0941587 to EBT 'A novel quantitative framework to study lack of social interactions in Autism Spectrum Disorders' and by the New Jersey Governor's Council for Medical Research and Treatment of Autism grant # 10-403-SCH-E-0 'Perceptual Motor Anticipation in ASD'. 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[McDougle, Christopher J.] Lurie Ctr Autism, Lexington, MA 02421 USA. RP McDougle, CJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. 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RP Georgiades, S (reprint author), McMaster Univ, Offord Ctr Child Studies, Hamilton, ON L8S 4L8, Canada. 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RP Mandy, W (reprint author), UCL, Res Dept Clin Educ & Hlth Psychol, London, England. 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RP Dawson, G (reprint author), Univ N Carolina, 209 South Rd, Chapel Hill, NC 27599 USA. EM gdawson@autismspeaks.org CR Dawson G, 2005, DEV NEUROPSYCHOL, V27, P403, DOI 10.1207/s15326942dn2703_6 Dawson G., 2010, PEDIATRICS, V125, P17 Dawson G, 2012, J ACAD CHILD ADOLESC, V51, P1550 Dawson G, 2000, DEV PSYCHOPATHOL, V12, P695, DOI 10.1017/S0954579400004089 Dawson G, 1998, J AUTISM DEV DISORD, V28, P479, DOI 10.1023/A:1026043926488 Dawson G, 2002, CHILD DEV, V73, P700, DOI 10.1111/1467-8624.00433 Dawson G, 2008, DEV PSYCHOPATHOL, V20, P775, DOI 10.1017/S0954579408000370 McPartland J, 2004, J CHILD PSYCHOL PSYC, V45, P1235, DOI 10.1111/j.1469-7610.2004.00318.x OSTERLING J, 1994, J AUTISM DEV DISORD, V24, P247, DOI 10.1007/BF02172225 Perrin James M, 2012, Pediatrics, V130 Suppl 2, pS57, DOI 10.1542/peds.2012-0900A Rogers SJ, 2006, J AUTISM DEV DISORD, V36, P1007, DOI 10.1007/s10803-006-0142-x Rogers SJ, 2010, EARLY START DENVER M Webb SJ, 2010, CHILD NEUROPSYCHOL, V16, P255, DOI 10.1080/09297041003601454 Werner E, 2000, J AUTISM DEV DISORD, V30, P157, DOI 10.1023/A:1005463707029 NR 14 TC 1 Z9 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-2008 J9 NEUROPSYCHIATRY-LOND JI Neuropsychiatry PD APR PY 2013 VL 3 IS 2 BP 139 EP 145 DI 10.2217/NPY.13.10 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 126QM UT WOS:000317636300008 ER PT J AU Ung, D Wood, JJ Ehrenreich-May, J Arnold, EB Fujii, C Renno, P Murphy, TK Lewin, AB Mutch, PJ Storch, EA AF Ung, Danielle Wood, Jeffrey J. Ehrenreich-May, Jill Arnold, Elysse B. Fujii, Cori Renno, Patricia Murphy, Tanya K. Lewin, Adam B. Mutch, P. Jane Storch, Eric A. TI Clinical characteristics of high-functioning youth with autism spectrum disorder and anxiety SO NEUROPSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; SENSORY OVER-RESPONSIVITY; PSYCHIATRIC-DISORDERS; INTERVIEW SCHEDULE; CONTROLLED-TRIAL; CHILDREN; ADOLESCENTS; ASSOCIATION; PHENOMENOLOGY AB Aim & methods: Clinical characteristics were examined in 108 high-functioning youth (children with a full IQ scale of at least 70) with an autism spectrum disorder (ASD; aged 7-15 years) who were presenting for inclusion in one of four clinical trials examining the efficacy of cognitive behavioral therapy in youth with ASD and anxiety. Results: We present baseline characteristics of this cohort, including prevalence rates of anxiety and comorbid disorders, and correlates of anxiety (e.g., comorbid diagnoses, impairment, anxiety severity and mental health services received) as a function of age and ASD diagnosis in treatment-seeking youth. Primary anxiety disorders were: 41.7% (n = 45) social phobia, 25.9% (n = 28) generalized anxiety disorder, 15.7% (n = 17) separation anxiety disorder, 12.0% (n = 13) obsessive compulsive disorder and 4.6% (n = 5) specific phobia. Overall, 91.6% of participants (n = 99) met criteria for two or more anxiety disorders. Parents reported considerable functional impairment as measured by the Columbia Impairment Scale and anxiety severity as measured by the Pediatric Anxiety Rating Scale; this did not statistically differ as a function of ASD diagnosis or age. Anxiety severity, the number of comorbid anxiety diagnoses and total comorbid diagnoses were directly associated with parent-reported child impairment. Youth with ASD and anxiety present as a heterogeneous cohort with significant impairments and complex diagnostic presentations. Conclusion: These data provide information about the nature of anxiety in youth with ASD, which may foster the development of tailored treatment protocols. C1 [Ung, Danielle; Storch, Eric A.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. [Ung, Danielle; Arnold, Elysse B.; Murphy, Tanya K.; Lewin, Adam B.; Mutch, P. Jane; Storch, Eric A.] Univ S Florida, Dept Pediat, St Petersburg, FL 33701 USA. [Wood, Jeffrey J.; Fujii, Cori; Renno, Patricia] Univ Calif Los Angeles, Dept Educ, Los Angeles, CA 90095 USA. [Wood, Jeffrey J.; Fujii, Cori; Renno, Patricia] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Wood, Jeffrey J.; Fujii, Cori; Renno, Patricia] Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA 90095 USA. [Ehrenreich-May, Jill] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Murphy, Tanya K.; Lewin, Adam B.; Mutch, P. Jane; Storch, Eric A.] Dept Psychiat, Tampa, FL 33613 USA. [Murphy, Tanya K.; Lewin, Adam B.; Mutch, P. Jane; Storch, Eric A.] Dept Behav Neurosci, Tampa, FL 33613 USA. RP Storch, EA (reprint author), Univ S Florida, Dept Psychol, 4202 East Fowler Ave,PCD 4118G, Tampa, FL 33620 USA. EM estorch@health.usf.edu FU NIH [1R34HD065274-01, 5R34HD065274-02]; All Children Hospital Research Foundation; University of South Florida (FL, USA); CDC; Agency for Healthcare Research and Quality; National Alliance for Research on Schizophrenia and Affective Disorders; International OCD Foundation; Tourette Syndrome Association; Janssen Pharmaceuticals; Foundation for Research on Prader Willi Syndrome; University of South Florida Research Council; Joseph Drown Foundation; Forest Laboratories; All Children's Hospital Research Foundation; Shire; Transcept Pharmaceuticals Inc.; Maurice; Thelma Rothman Endowed Chair FX These studies were supported by grants awarded to EA Storch from the NIH (1R34HD065274-01), All Children Hospital Research Foundation and the University of South Florida (FL, USA) Internal Grants Program, and grants to JJ Wood and J Ehrenreich-May from the NIH (5R34HD065274-02). EA Storch has received grant funding in the last 3 years from the NIH, All Children's Hospital Research Foundation, CDC, Agency for Healthcare Research and Quality, National Alliance for Research on Schizophrenia and Affective Disorders, International OCD Foundation, Tourette Syndrome Association, Janssen Pharmaceuticals and Foundation for Research on Prader Willi Syndrome. EA Storch receives textbook honorarium from Springer publishers, American Psychological Association and Lawrence Erlbaum. EA Storch has been an educational consultant for Rogers Memorial Hospital, a consultant for Prophase Inc. and CroNos Inc., and is on the Speaker's Bureau and Scientific Advisory Board for the International OCD Foundation. J Ehrenreich-May receives grant funding from the NIH. JJ Wood receives grant funding from the NIH. AB Lewin receives grant funding from the University of South Florida Research Council, NIH, Agency for Healthcare Research and Quality, CDC, National Alliance for Research on Schizophrenia and Affective Disorders, Joseph Drown Foundation and International OCD Foundation. AB Lewin is a consultant for Prophase Inc. and has received speaker's honorariums from the Tourettes Syndrome Association. TK Murphy has received research support in the past 3 years from NIH, Forest Laboratories, Janssen Pharmaceuticals, International OCD Foundation, Tourette Syndrome Association, All Children's Hospital Research Foundation, CDC, Shire, Transcept Pharmaceuticals Inc., and National Alliance for Research on Schizophrenia and Affective Disorders. TK Murphy is on the Medical Advisory Board for Tourette Syndrome Association and Scientific Advisory Board for International OCD Foundation. TK Murphy receives textbook honorarium from Lawrence Erlbaum, and research support from the Maurice and Thelma Rothman Endowed Chair. The authors have 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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Schumann, Cynthia M. TI Is 'bench-to-bedside' realistic for autism? An integrative neuroscience approach SO NEUROPSYCHIATRY LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; FETAL-BRAIN PROTEINS; BTBR MOUSE MODEL; SPECTRUM DISORDERS; MATERNAL AUTOANTIBODIES; YOUNG-CHILDREN; ANTIBODIES; AMYGDALA; ACTIVATION; OXYTOCIN AB Given the prevalence and societal impact of autism spectrum disorder (ASD), there is an urgent need to develop innovative treatments that will improve core social deficits, for which there is currently no reliable pharmacological treatment, prevention or cure. Development of novel biological interventions will depend upon the successful translation of basic neuroscience research into safe and effective medicines. This article outlines steps to bring neuroscience research from 'the bench' to treatment at 'bedside', from phenotyping the disorder to animal models to patient treatment. Although these steps appear simplistic, this is a daunting challenge because of the inherent complexity of the human brain, our lack of understanding of disease neurobiology underlying ASD, and the incredible heterogeneity of the disorder. For ASD, perhaps more than any other neurological or psychiatric disorder, progress will depend on integrative multidisciplinary approaches between basic scientists from varying neuroscience disciplines and clinicians to make 'bench to bedside' treatment a reality. C1 [Bauman, Melissa D.; Schumann, Cynthia M.] Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. [Bauman, Melissa D.; Schumann, Cynthia M.] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA. RP Schumann, CM (reprint author), Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. 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Neurosciences & Neurology; Psychiatry GA 126QM UT WOS:000317636300010 ER PT J AU Bearss, K Lecavalier, L Minshawi, N Johnson, C Smith, T Handen, B Sukhodolsky, DG Aman, MG Swiezy, N Butter, E Scahill, L AF Bearss, Karen Lecavalier, Luc Minshawi, Noha Johnson, Cynthia Smith, Tristram Handen, Benjamin Sukhodolsky, Denis G. Aman, Michael G. Swiezy, Naomi Butter, Eric Scahill, Lawrence TI Toward an exportable parent training program for disruptive behaviors in autism spectrum disorder SO NEUROPSYCHIATRY LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; RANDOMIZED CONTROLLED-TRIAL; YOUNG-CHILDREN; PSYCHOSOCIAL INTERVENTIONS; EMOTIONAL-PROBLEMS; ADAPTIVE-BEHAVIOR; MENTAL-HEALTH; PREVALENCE; CHECKLIST; TODDLERS AB Autism spectrum disorder (ASD) is a condition of early childhood onset characterized by profound deficits in social interaction, impaired communication and repetitive behavior. The prevalence of ASD is now estimated to be one in 100 children. As the number of identified cases of ASD has grown, so have the challenges of serving these children and their families. Unfortunately, the empirical foundation for many interventions for this population is not firmly established. Thus, there is a pressing need to conduct trials that will expand the evidence base and guide clinical treatment. Investigators from the Research Units in Pediatric Psychopharmacology (RUPP; Indiana University, IN, USA; Ohio State University, OH, USA; University of Pittsburgh, PA, USA; and Yale University, CT, USA) followed a treatment development model outlined by an National Institute of Mental Health ad hoc committee to develop and test a parent training treatment manual for children with ASD accompanied by disruptive behavior problems. This article describes the process of manual development and cross-site therapist training, establishment and maintenance of treatment integrity, assessment of treatment acceptance by families as well as primary outcomes of three trials. Results suggest the structured parent training program can be delivered with a high degree of fidelity within and across therapists, is acceptable to parents and can produce significant reductions in disruptive behaviors in children with ASD. C1 [Bearss, Karen; Scahill, Lawrence] Emory Univ, Sch Med, Dept Pediat, Marcus Autism Ctr,Childrens Healthcare Atlanta, Atlanta, GA 30329 USA. [Lecavalier, Luc] Ohio State Univ, UCEDD, Nisonger Ctr, Columbus, OH 43210 USA. [Minshawi, Noha; Swiezy, Naomi] Indiana Univ Sch Med, James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. [Johnson, Cynthia] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15213 USA. [Smith, Tristram] Univ Rochester, Med Ctr, Div Neurodev & Behav Pediat, Strong Ctr Dev Disabil,Dept Pediat, Rochester, NY 14642 USA. [Handen, Benjamin] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Merck Child Outpatient Program, Pittsburgh, PA 15203 USA. [Sukhodolsky, Denis G.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Aman, Michael G.] Ohio State Univ, Nisonger Ctr UCEDD, Columbus, OH 43210 USA. [Butter, Eric] Nationwide Childrens Hosp, Westerville, OH 43081 USA. RP Bearss, K (reprint author), Emory Univ, Sch Med, Dept Pediat, Marcus Autism Ctr,Childrens Healthcare Atlanta, 1920 Briarcliff Rd NE, Atlanta, GA 30329 USA. EM karen.bearss@emory.edu RI sebastianovitsch, stepan/G-8507-2013 FU National Institute of Mental Health (NIMH) [U10MH66768, U10MH66766, U10MH66764]; Clinical and Translational Scholar Award (CTSA) from National Center for Research Resources (NCRR), a component of the NIH [UL1 RR024139, 5KL2RR024138]; NIH roadmap for Medical Research FX The authors were supported by the following cooperative agreement grants from the National Institute of Mental Health (NIMH): U10MH66768 (principal invesigator: M Aman), U10MH66766 (principal invesigator: C McDougle) and U10MH66764 (principal invesigator: L Scahill). 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B. Warfield, Marji Erickson Parish, Susan L. TI Transition to adulthood for individuals with autism spectrum disorder: current issues and future perspectives SO NEUROPSYCHIATRY LA English DT Article ID HIGH-FUNCTIONING CHILDREN; SELF-INJURIOUS-BEHAVIOR; HEALTH-CARE TRANSITION; DEVELOPMENTAL-DISABILITIES; ASPERGER-SYNDROME; NATIONAL-SURVEY; SOCIAL-INTERACTION; FINANCIAL BURDEN; ADOLESCENT BOYS; UNITED-STATES AB Rising autism prevalence rates have lent urgency to efforts to improve outcomes for individuals with autism spectrum disorder (ASD). Stakeholders have focused, in particular, on the transition to adulthood that can occur over a range of ages, typically between 18 and 22 years, and often corresponding to when the youth finishes secondary school. This represents a particularly vulnerable time, as the entitlements of the children's service system end and young adults with ASD and their families encounter fragmented and underfunded systems of care. Research across multiple domains education, vocational training and employment, social support and community involvement, housing and healthcare reveals poor outcomes for this population during the transition to adulthood, suggesting that the current models of school-based transition planning are not meeting the needs of youth with ASD. This article highlights findings from some of this literature, examines financial aspects of the transition process, and offers our perspectives on current practices and recommendations for future study. An organized program of research coupled with aggressive policy and service system changes are needed to achieve more favorable transition outcomes for the ASD population. C1 [Friedman, Nora D. B.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp Children, Boston, MA 02115 USA. [Friedman, Nora D. B.] Lurie Ctr Autism, Lexington, MA 02421 USA. [Warfield, Marji Erickson] Brandeis Univ, Heller Sch Social Policy & Management, Starr Ctr Intellectual & Dev Disabil, Waltham, MA USA. [Parish, Susan L.] Brandeis Univ, Heller Sch Social Policy & Management, Lurie Inst Disabil Policy, Waltham, MA USA. RP Friedman, NDB (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp Children, Boston, MA 02115 USA. EM ndfriedman@partners.org FU Lurie Institute for Disability Policy at Brandeis University FX SL Parish was supported by the Lurie Institute for Disability Policy at Brandeis University. The authors have 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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TI Genetic pathways to autism spectrum disorders SO NEUROPSYCHIATRY LA English DT Review ID DE-NOVO MUTATIONS; COPY-NUMBER VARIATION; PERVASIVE DEVELOPMENTAL DISORDERS; TUBEROUS SCLEROSIS COMPLEX; FRAGILE-X-SYNDROME; MENTAL-RETARDATION; DELETION SYNDROME; GENOMEWIDE SCREEN; BEHAVIORAL CHARACTERIZATION; NEURODEVELOPMENTAL GENES AB Over the past several decades, progress in understanding the genetic basis of autism spectrum disorder (ASD) has dramatically altered our conception of its genetic architecture. Once believed to be an oligogenic disorder of common susceptibility variants, autism is now considered to be a collection of distinct 'autisms' marked by profound genetic heterogeneity. While twin and family studies have demonstrated a strong genetic etiology, genome-wide linkage and association studies have been limited by the extreme underlying heterogeneity. Genome-wide association studies have identified a few variants with small effects on ASD risk, but no common variants that clearly explain the few replicated linkage signals have been identified, suggesting that common variation is unlikely to play a central role. Recent successes in characterizing genetic risk have been driven by technological advances permitting the identification of de novo variants, both single-nucleotide variants and copy number variants, occurring in sporadic autism. The power to detect modest, rare inherited effects has been achieved through growing sample sizes through large collaborations; however, the inherited risk of ASD remains largely uncharted. Several hundred risk genes for ASD have been proposed, many linked via shared physiologic pathways. While many investigators now estimate that the number of autism risk genes will reach the thousands, pathway analysis will facilitate the understanding of ASD pathophysiology, the identification of novel risk genes and the development of clinically actionable targets. Molecular diagnosis has become possible for many ASD subtypes and will continue to expand. Targeted interventions will be developed and individualized based on diagnostic data and the growing appreciation of the biology of autism. C1 [Mehta, Sunil Q.; Nurmi, Erika L.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Semel Inst Neurosci & Human Behav, Div Child & Adolescent Psychiat,Dept Psychiat & B, Los Angeles, CA 90095 USA. RP Nurmi, EL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, UCLA Semel Inst Neurosci & Human Behav, Div Child & Adolescent Psychiat,Dept Psychiat & B, Los Angeles, CA 90095 USA. 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Piven, Joseph TI On the emergence of autism: neuroimaging findings from birth to preschool SO NEUROPSYCHIATRY LA English DT Review ID FRAGILE-X-SYNDROME; FUNCTIONAL CONNECTIVITY MRI; HUMAN BRAIN-DEVELOPMENT; DE-NOVO MUTATIONS; AGE 2 YEARS; SPECTRUM DISORDER; HEAD CIRCUMFERENCE; EARLY-CHILDHOOD; GRAY-MATTER; DEFAULT NETWORK AB By definition, autism spectrum disorder (ASD) emerges early in life. Core clinical symptoms generally appear after a child's first birthday, and most children receive a diagnosis by the age of 4 years. This relatively narrow window of birth to age of onset affords the opportunity to chart the neurodevelopmental processes that give rise to ASD. Although much remains unknown, magnetic resonance brain imaging studies centered around the emergence of the disorder have yielded important clues about its pathogenesis. Prominent findings include evidence of increased cortical gray and white matter volumes, increased amygdala volumes, aberrant structural and functional connectivity, and atypical neurodevelopmental trajectories. Findings to date suggest a disrupted pattern of early brain development during an interval typically characterized by dramatic experience-dependent neurobehavioral development. Developmentally informed neuroimaging studies of ASD have the potential to improve our knowledge pertaining to etiology and early intervention. C1 [Wolff, Jason J.; Piven, Joseph] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. [Wolff, Jason J.; Piven, Joseph] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. RP Wolff, JJ (reprint author), Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. EM jason.wolff@cidd.unc.edu FU Autism Center of Excellence Network from NIH [HD055741] FX This work was supported in part by an Autism Center of Excellence Network grant to J Piven from the NIH (HD055741). The authors have 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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Neurology; Psychiatry GA 126QM UT WOS:000317636300014 ER PT J AU Mody, M Manoach, DS Guenther, FH Kenet, T Bruno, KA McDougle, CJ Stigler, KA AF Mody, Maria Manoach, Dara S. Guenther, Frank H. Kenet, Tal Bruno, Katelyn A. McDougle, Christopher J. Stigler, Kimberly Ann TI Speech and language in autism spectrum disorder: a view through the lens of behavior and brain imaging SO NEUROPSYCHIATRY LA English DT Review ID HIGH-FUNCTIONING AUTISM; WHITE-MATTER; RIGHT-HEMISPHERE; SENTENCE COMPREHENSION; CORTICAL ACTIVATION; AUDITORY LANGUAGE; EARLY RECOGNITION; EARLY-CHILDHOOD; MISMATCH FIELD; COMPLEX SOUNDS AB Numerous studies have examined the brain bases of autism; few, however, have specifically examined the neurobiology of speech and language impairments in children and adults on the spectrum, especially those characterized as low functioning or minimally verbal, due to compliance issues. With exciting new advances in the development of paradigms and tools, and the ability to image children at risk for autism as young as 6 months of age, functional neuroimaging (EEG, magnetoencephalography and functional MRI) holds tremendous promise. Findings of reduced activation and structural and functional connectivity in the language network, together with deficits in social reciprocity and motivation, and a preference for visual over verbal information, appear to be carving out a neurobiological profile for the impaired social communication brain in autism. C1 [Mody, Maria] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Mody, Maria] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mody, Maria] Lurie Ctr Autism, Charlestown, MA 02129 USA. [Mody, Maria; Manoach, Dara S.; Kenet, Tal] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Manoach, Dara S.; Kenet, Tal] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Guenther, Frank H.] Boston Univ, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA. [Guenther, Frank H.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Kenet, Tal] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Bruno, Katelyn A.] Spaulding Rehabil Hosp, Lurie Ctr Autism, Lexington, MA 02421 USA. [Bruno, Katelyn A.] Massachusetts Gen Hosp Children, Lexington, MA 02421 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp Children, Dept Psychiat, Lexington, MA 02421 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp Children, Dept Pediat, Lexington, MA 02421 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp Children, Lurie Ctr Autism, Lexington, MA 02421 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Lexington, MA 02421 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, Lexington, MA 02421 USA. [Stigler, Kimberly Ann] Indiana Univ Sch Med, James Whitcomb Riley Hosp Children, Dept Psychiat, Indianapolis, IN 46202 USA. RP Mody, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 149 13th St,CNY 2301, Charlestown, MA 02129 USA. EM maria@nmr.mgh.harvard.edu FU Bristol-Myers Squibb Co.; Eli Lilly Co.; Forest Research Institute; Janssen; Novartis; Seaside Therapeutics; SynapDx FX KA Stigler receives research support from Bristol-Myers Squibb Co., Eli Lilly & Co., Forest Research Institute, Janssen, Novartis, Seaside Therapeutics and SynapDx. The authors have 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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Williams, Lindsey W. TI Differential diagnosis and comorbidity: distinguishing autism from other mental health issues SO NEUROPSYCHIATRY LA English DT Review ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDER; DEFICIT HYPERACTIVITY DISORDER; SPECTRUM DISORDERS; PSYCHIATRIC-DISORDERS; CHALLENGING BEHAVIORS; INTELLECTUAL DISABILITY; ANXIETY DISORDERS; ASPERGER-SYNDROME; CHILDREN AB Comorbid autism spectrum disorder (ASD) and other mental health conditions are common. However, the recognition and study of this clinical issue is of recent origin. It has recently emerged that certain disorders are more likely to occur with ASD, such as ADHD, depression, anxiety and conduct disorder/challenging behaviors. Developmental factors are significant in that, while ASD presents at a very early age, this is not often the case with the co-occurring disorders noted above. The clinician should be aware of and plan for these potential concerns. Tests that are specifically designed to assess for comorbid mental health issues among persons with ASD are being developed. These methods are recommended given what we know about high rates of comorbidity in this emerging field. C1 [Matson, Johnny L.; Williams, Lindsey W.] Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. RP Matson, JL (reprint author), Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. 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Stigler, Kimberly A. TI Current state and future prospects of pharmacological interventions for autism SO NEUROPSYCHIATRY LA English DT Review ID PERVASIVE DEVELOPMENTAL DISORDERS; OPEN-LABEL TRIAL; PLACEBO-CONTROLLED TRIAL; DEFICIT HYPERACTIVITY DISORDER; PSYCHOTROPIC MEDICATION USE; SELF-INJURIOUS-BEHAVIOR; SPECTRUM DISORDERS; DOUBLE-BLIND; D-CYCLOSERINE; YOUNG-ADULTS AB Autism spectrum disorder (ASD) is a group of heterogeneous developmental disorders manifesting in early childhood. They are associated with a range of core and associated symptoms, including repetitive behaviors, hyperactivity and irritability. This review will describe the current evidence for psychopharmacological management of individuals with ASD. Additionally, some of the future treatment prospects will be discussed. Safety issues, adverse effects and limitations of the current literature will also be highlighted. C1 [Vahabzadeh, Arshya] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Buxton, David] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Boston, MA 02114 USA. [Stigler, Kimberly A.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA. [Stigler, Kimberly A.] James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. RP Stigler, KA (reprint author), Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA. EM kstigler@iupui.edu FU Bristol-Myers Squibb Co.; Eli Lilly Co.; Forest Research Institute; Janssen; Novartis; Seaside Therapeutics; SynapDx FX KA Stigler receives research support from Bristol-Myers Squibb Co., Eli Lilly & Co., Forest Research Institute, Janssen, Novartis, Seaside Therapeutics and SynapDx. The authors have 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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TI Exploring the Meaning of Parental Involvement in Physical Education for Students With Developmental Disabilities SO ADAPTED PHYSICAL ACTIVITY QUARTERLY LA English DT Article DE Autism Spectrum Disorder; children with disabilities; Down syndrome; phenomenology; qualitative research ID PERSPECTIVES AB The purpose of this phenomenological inquiry was to explore the experiences and meaning of parental involvement in physical education from the perspectives of the parents of students with developmental disabilities. The stories of four mothers of elementary aged children (3 boys, 1 girl), two mothers and one couple (mother and father) of secondary-aged youth (1 girl, 2 boys) with developmental disabilities, were gathered by using interviews, photographs, school documents, and the. researcher's journal. Bronfenbrenner's (2005) ecological system theory provided a conceptual framework to interpret the findings of this inquiry. 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B., 2005, PREPARING ED INVOLVE NR 35 TC 1 Z9 1 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 0736-5829 J9 ADAPT PHYS ACT Q JI Adapt. Phys. Act. Q. PD APR PY 2013 VL 30 IS 2 BP 147 EP 163 PG 17 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 120GZ UT WOS:000317160100003 PM 23520244 ER PT J AU Dabell, MP Rosenfeld, JA Bader, P Escobar, LF El-Khechen, D Vallee, SE Dinulos, MBP Curry, C Fisher, J Tervo, R Hannibal, MC Siefkas, K Wyatt, PR Hughes, L Smith, R Ellingwood, S Lacassie, Y Stroud, T Farrell, SA Sanchez-Lara, PA Randolph, LM Niyazov, D Stevens, CA Schoonveld, C Skidmore, D MacKay, S Miles, JH Moodley, M Huillet, A Neill, NJ Ellison, JW Ballif, BC Shaffer, LG AF Dabell, Mindy Preston Rosenfeld, Jill A. Bader, Patricia Escobar, Luis F. El-Khechen, Dima Vallee, Stephanie E. Dinulos, Mary Beth Palko Curry, Cynthia Fisher, Jamie Tervo, Raymond Hannibal, Mark C. Siefkas, Kiana Wyatt, Philip R. Hughes, Lauren Smith, Rosemarie Ellingwood, Sara Lacassie, Yves Stroud, Tracy Farrell, Sandra A. Sanchez-Lara, Pedro A. Randolph, Linda M. Niyazov, Dmitriy Stevens, Cathy A. Schoonveld, Cheri Skidmore, David MacKay, Sara Miles, Judith H. Moodley, Manikum Huillet, Adam Neill, Nicholas J. Ellison, Jay W. Ballif, Blake C. Shaffer, Lisa G. TI Investigation of NRXN1 deletions: Clinical and molecular characterization SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE neurexin 1; 2p16.3; developmental delay; autism; dysmorphic; schizophrenia; microarray ID COPY NUMBER VARIATION; EXCITATORY SYNAPSE FORMATION; NEUREXIN I-ALPHA; STRUCTURAL VARIANTS; DEVELOPMENTAL DISORDERS; DYSMORPHIC FEATURES; MENTAL-RETARDATION; BETA-NEUREXINS; HIGH-FREQUENCY; ARRAY CGH AB Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray-based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P=6.08x107), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1. (c) 2013 Wiley Periodicals, Inc. C1 [Dabell, Mindy Preston; Rosenfeld, Jill A.; Neill, Nicholas J.; Ellison, Jay W.; Ballif, Blake C.; Shaffer, Lisa G.] PerkinElmer Inc, Signature Genom Labs, Spokane, WA USA. [Bader, Patricia] Northeast Indiana Genet Counseling Ctr, Ft Wayne, IN USA. [Escobar, Luis F.; El-Khechen, Dima] Peyton Manning Childrens Hosp St Vincent, Med Genet & Neurodev Ctr, Indianapolis, IN USA. [Vallee, Stephanie E.; Dinulos, Mary Beth Palko] Dartmouth Hitchcock Med Ctr, Geisel Sch Med Dartmouth, Med Genet Sect, Dept Pediat, Lebanon, NH 03766 USA. [Curry, Cynthia; Fisher, Jamie] Genet Med Cent Calif, Fresno, CA USA. [Tervo, Raymond] Gillette Childrens Specialty Healthcare, St Paul, MN USA. [Hannibal, Mark C.] Univ Washington, Div Med Genet, Sch Med, Seattle, WA 98195 USA. [Siefkas, Kiana] Childrens Village & Yakima Valley Mem Hosp, Yakima, WA USA. [Wyatt, Philip R.; Hughes, Lauren] Orillia Soldiers Mem Hosp, Orillia, ON, Canada. [Smith, Rosemarie; Ellingwood, Sara] Maine Med Ctr, Div Genet, Portland, ME 04102 USA. [Lacassie, Yves] Louisiana State Univ, Dept Pediat, Hlth Sci Ctr, New Orleans, LA USA. [Lacassie, Yves] Childrens Hosp, New Orleans, LA USA. [Stroud, Tracy] Univ Missouri, Columbia Womens & Childrens Hosp, Columbia, MO USA. [Farrell, Sandra A.] Credit Valley Hosp, Mississauga, ON, Canada. [Sanchez-Lara, Pedro A.; Randolph, Linda M.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA. [Niyazov, Dmitriy] Ochsner Childrens Hlth Ctr, New Orleans, LA USA. [Stevens, Cathy A.] Univ Tennessee, Dept Pediat, Coll Med, Chattanooga, TN USA. [Schoonveld, Cheri] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Skidmore, David; MacKay, Sara] IWK Hlth Ctr, Maritime Med Genet Serv, Halifax, NS, Canada. [Miles, Judith H.] Univ Missouri, Thompson Ctr Autism & Neurodev Disorders, Columbia, MO USA. [Moodley, Manikum] Cleveland Clin, Ctr Pediat Neurol, Cleveland, OH 44106 USA. [Huillet, Adam] Madigan Army Med Ctr, Ft Lewis, WA USA. RP Shaffer, LG (reprint author), Genet Vet Sci Inc, 850 E Spokane Falls Blvd, Spokane, WA 99202 USA. 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J. Med. Genet. A PD APR PY 2013 VL 161A IS 4 BP 717 EP 731 DI 10.1002/ajmg.a.35780 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 112YM UT WOS:000316631300014 PM 23495017 ER PT J AU Minhas, HM Pescosolido, MF Schwede, M Piasecka, J Gaitanis, J Tantravahi, U Morrow, EM AF Minhas, Hassan M. Pescosolido, Matthew F. Schwede, Matthew Piasecka, Justyna Gaitanis, John Tantravahi, Umadevi Morrow, Eric M. TI An unbalanced translocation involving loss of 10q26.2 and gain of 11q25 in a pedigree with autism spectrum disorder and cerebellar juvenile pilocytic astrocytoma SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE autism spectrum disorder; cerebellar juvenile pilocytic astrocytoma; unbalanced translocation; t(10; 11); NTM; OPCML ID TUMOR-SUPPRESSOR; CLINICAL-FEATURES; TERMINAL DELETION; OPIOID-BINDING; OVARIAN-CANCER; OPCML; IDENTIFICATION; EXPRESSION; 10Q; SCHIZOPHRENIA AB We report on a pedigree with a pair of brothers each with minor anomalies, developmental delay, and autistic-symptoms who share an unbalanced translocation (not detectable by karyotype). The unbalanced translocation involves a 7.1Mb loss of the terminal portion of 10q, and a 4.2Mb gain of 11q. One of the brothers also developed a cerebellar juvenile pilocytic astrocytoma. The father was found to be a balanced carrier and the couple had a previous miscarriage. We demonstrate that the breakpoint for the triplicated region from chromosome 11 is adjacent to two IgLON genes, namely Neurotrimin (NTM) and Opioid Binding Protein/Cell Adhesion Molecule-like (OPCML). These genes are highly similar neural cell adhesion molecules that have been implicated in synaptogenesis and oncogenesis, respectively. The children also have a 10q deletion and are compared to other children with the 10q deletion syndrome which generally does not involve autism spectrum disorders (ASDs) or cancer. Together these data support a role for NTM and OPCML in developmental delay and potentially in cancer susceptibility. (c) 2013 Wiley Periodicals, Inc. C1 [Minhas, Hassan M.; Pescosolido, Matthew F.; Schwede, Matthew; Piasecka, Justyna; Morrow, Eric M.] Brown Univ, Warren Alpert Med Sch, Emma Pendleton Bradley Hosp, Dev Disorders Genet Res Program, Providence, RI 02912 USA. [Minhas, Hassan M.] Brown Univ, Warren Alpert Med Sch, Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Minhas, Hassan M.; Pescosolido, Matthew F.; Gaitanis, John; Morrow, Eric M.] Brown Univ, Warren Alpert Med Sch, Rhode Isl Consortium Autism Res & Treatment RI CA, Providence, RI 02912 USA. [Schwede, Matthew; Morrow, Eric M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. [Schwede, Matthew; Morrow, Eric M.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Gaitanis, John] Brown Univ, Warren Alpert Med Sch, Rhode Isl Hosp, Providence, RI 02912 USA. [Tantravahi, Umadevi] Brown Univ, Div Genet, Dept Pathol, Woman & Infants Hosp,Warren Alpert Med Sch, Providence, RI 02912 USA. RP Morrow, EM (reprint author), Brown Univ, Mol Med Lab, Box G-E4,70 Ship St, Providence, RI 02912 USA. EM eric_morrow@brown.edu FU NIMH [5K23MH080954-04]; Brown Institute for Brain Science (Mahoney Pilot Research Grant) FX Grant sponsor: NIMH; Grant number: 5K23MH080954-04; Grant sponsor: Brown Institute for Brain Science (Mahoney Pilot Research Grant). 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J. Med. Genet. A PD APR PY 2013 VL 161A IS 4 BP 787 EP 791 DI 10.1002/ajmg.a.35841 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 112YM UT WOS:000316631300022 PM 23495067 ER PT J AU Khalifa, M Stein, J Grau, L Nelson, V Meck, J Aradhya, S Duby, J AF Khalifa, Mohamed Stein, Jennifer Grau, Lance Nelson, Valery Meck, Jeanne Aradhya, Swaroop Duby, John TI Partial deletion of ANKRD11 results in the KBG phenotype distinct from the 16q24.3 microdeletion syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE KBG; 16q24; 3; microdeletion; macrodontia; MCA; MR; ANKRD11; autism; ASD; mosaicism ID DIAGNOSTIC-CRITERIA; DELINEATION AB KBG syndrome (OMIM 148050) is a very rare genetic disorder characterized by macrodontia, distinctive craniofacial abnormalities, short stature, intellectual disability, skeletal, and neurologic involvement. Approximately 60 patients have been reported since it was first described in 1975. Recently mutations in ANKRD11 have been documented in patients with KBG syndrome, and it has been proposed that haploinsufficiency of ANKRD11 is the cause of this syndrome. In addition, copy number variation in the 16q24.3 region that includes ANKRD11 results in a variable phenotype that overlaps with KBG syndrome and also includes autism spectrum disorders and other dysmorphic facial features. In this report we present a 21/2-year-old African American male with features highly suggestive of KBG syndrome. Genomic microarray identified an intragenic 154kb deletion at 16q24.3 within ANKRD11. This child's mother was mosaic for the same deletion (present in approximately 38% of cells) and exhibited a milder phenotype including macrodontia, short stature and brachydactyly. This family provides additional evidence that ANKRD11 causes KBG syndrome, and the mild phenotype in the mosaic form suggests that KBG phenotypes might be dose dependent, differentiating it from the more variable 16q24.3 microdeletion syndrome. This family has additional features that might expand the phenotype of KBG syndrome. (c) 2013 Wiley Periodicals, Inc. C1 [Khalifa, Mohamed; Stein, Jennifer; Grau, Lance] Akron Childrens Hosp, Dept Genet, Akron, OH USA. [Nelson, Valery; Meck, Jeanne; Aradhya, Swaroop] GeneDx, Gaithersburg, MD USA. [Duby, John] Akron Childrens Hosp, Akron, OH USA. RP Khalifa, M (reprint author), Northeast Ohio Med Univ, 1 Perkins Sq, Akron, OH 44308 USA. 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A PD APR PY 2013 VL 161A IS 4 BP 835 EP 840 DI 10.1002/ajmg.a.35739 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 112YM UT WOS:000316631300029 PM 23494856 ER PT J AU Sagar, A Bishop, JR Tessman, DC Guter, S Martin, CL Cook, EH AF Sagar, Angela Bishop, Jeffrey R. Tessman, D. Clare Guter, Steve Martin, Christa L. Cook, Edwin H. TI Co-occurrence of autism, childhood psychosis, and intellectual disability associated with a de novo 3q29 microdeletion SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE autism; 3q29; DLG1; PAK2; intellectual disability; psychosis ID ONSET SCHIZOPHRENIA; UBIQUITIN LIGASE; HIGH-RISK; DELETION; DUPLICATIONS; DISORDERS; FBXO45; REGION AB Some copy number variants (CNVs) are strongly implicated in both schizophrenia and autism spectrum disorders (ASDs). Childhood-onset schizophrenia (COS) occurs rarely with 0.11% of all schizophrenia diagnoses manifesting before age 10. 3q29 deletions are associated with both autism and schizophrenia, and are rarethe frequency of the deletion estimated to be 1 in 1,750 in developmental disorders. Only one patient with a 3q29 deletion was identified out of the first 1,174 families with ASDs included in the Simons Simplex Collection (SSC). We report on detailed clinical findings for this patient with a de novo 3q29 deletion who, as a young child, developed a very rare overlap of symptoms of both autism and early onset psychosis. His ASD was first diagnosed at the age of 4 years and his psychotic symptoms began at 5 years old. This is only the second case reported thus far of this rare event of co-occurring autism and very early onset psychosis in a child with a 3q29 deletion. It is also the earliest case of a child with autism developing comorbid psychosismanifesting by the age of 5 years. (c) 2013 Wiley Periodicals, Inc. C1 [Sagar, Angela; Tessman, D. Clare; Guter, Steve; Cook, Edwin H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60608 USA. [Bishop, Jeffrey R.] Univ Illinois, Coll Pharm, Dept Pharm Practice, Chicago, IL 60608 USA. [Martin, Christa L.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. RP Sagar, A (reprint author), Univ Illinois, Dept Psychiat, Inst Juvenile Res, 1747 West Roosevelt Rd,Suite 155, Chicago, IL 60608 USA. EM asagar@psych.uic.edu FU Simons Foundation; Training in the Neuroscience of Mental Health [5T32MH067631-07]; [K08MH083888] FX Grant sponsor: Simons Foundation.We thank the patient and his family for their cooperation, assistance, and support in this project. This work was supported in part by 5T32MH067631-07 Training in the Neuroscience of Mental Health (A. S.), K08MH083888 (J.R.B.), and grant support from the Simons Foundation (C.L.M., E.C.). 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A PD APR PY 2013 VL 161A IS 4 BP 845 EP 849 DI 10.1002/ajmg.a.35754 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 112YM UT WOS:000316631300031 PM 23443968 ER PT J AU Shichiji, M Ito, Y Shimojima, K Nakamu, H Oguni, H Osawa, M Yamamoto, T AF Shichiji, Minobu Ito, Yasushi Shimojima, Keiko Nakamu, Hidetsugu Oguni, Hirokazu Osawa, Makiko Yamamoto, Toshiyuki TI A cryptic microdeletion including MBD5 occurring within the breakpoint of a reciprocal translocation between chromosomes 2 and 5 in a patient with developmental delay and obesity SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE 2q23; 1 deletion syndrome; methyl-CpG-binding domain 5 gene (MBD5); pachygyria; obesity; cryptic deletion ID COMPARATIVE GENOMIC HYBRIDIZATION; MENTALLY-RETARDED PATIENT; RETARDATION; PHENOTYPE; FEATURES AB The 2q23.1 deletion syndrome has been recently recognized as a neurodevelopmental disorder associated with intellectual disability, epilepsy, and autism spectrum disorder. Recently, methyl-CpG-binding domain 5 gene (MBD5), located in the 2q23.1 region, has been considered as a single causative gene of this syndrome. We report on a female patient with a de novo reciprocal translocation between chromosomes 2 and 5. Chromosomal microarray testing revealed a cryptic 896kb deletion that included MBD5. Although clinical manifestations of this patient are compatible with those of patients with 2q23.1 deletion syndrome, a focal pachygyria revealed by brain magnetic resonance imaging has never been observed in the previously reported cases. Obesity caused by hyperphagia was observed in our patient and 28% of the previously reported patients with the 2q23.1 deletion syndrome. For better medical management, appropriate dietary guidance against hyperphagia should be given to the patients' family. (c) 2013 Wiley Periodicals, Inc. C1 [Shichiji, Minobu; Ito, Yasushi; Nakamu, Hidetsugu; Oguni, Hirokazu; Osawa, Makiko] Tokyo Womens Med Univ, Dept Pediat, Tokyo 1628666, Japan. [Shichiji, Minobu; Shimojima, Keiko; Yamamoto, Toshiyuki] Tokyo Womens Med Univ, Inst Integrated Med Sci, Tokyo 1628666, Japan. RP Yamamoto, T (reprint author), Tokyo Womens Med Univ, Inst Integrated Med Sci, 8-1 Kawada Cho, Tokyo 1628666, Japan. EM yamamoto.toshiyuki@twmu.ac.jp FU Japan Society for the Promotion of Science FX Grant sponsor: Grant-in-Aid for Scientific Research (C); Grant sponsor: Japan Society for the Promotion of Science. 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A PD APR PY 2013 VL 161A IS 4 BP 850 EP 855 DI 10.1002/ajmg.a.35768 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 112YM UT WOS:000316631300032 PM 23494922 ER PT J AU Hancarova, M Simandlova, M Drabova, J Mannik, K Kurg, A Sedlacek, Z AF Hancarova, Miroslava Simandlova, Martina Drabova, Jana Mannik, Katrin Kurg, Ants Sedlacek, Zdenek TI A patient with de novo 0.45Mb deletion of 2p16.1: The role of BCL11A, PAPOLG, REL, and FLJ16341 in the 2p15-p16.1 microdeletion syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE 2p15-p16; 1 microdeletion syndrome; autism; copy number variation; developmental delay; intellectual disability; SNP array ID COPY NUMBER; DEVELOPMENTAL DELAY; HUMAN GENOME; 2P15-16.1; GENES; DISORDERS; RESOURCES; PHENOTYPE; VARIANTS; FAMILY AB The 2p15-p16.1 microdeletion syndrome is a novel, rare disorder characterized by developmental delay, intellectual disability, microcephaly, growth retardation, facial abnormalities, and other medical problems. We report here on an 11-year-old female showing clinical features consistent with the syndrome and carrying a de novo 0.45Mb long deletion of the paternally derived 2p16.1 allele. The deleted region contains only three protein-coding RefSeq genes, BCL11A, PAPOLG, and REL, and one long non-coding RNA gene FLJ16341. Based on close phenotypic similarities with six reported patients showing typical clinical features of the syndrome, we propose that the critical region can be narrowed down further, and that these brain expressed genes can be considered candidates for the features seen in this microdeletion syndrome. (c) 2013 Wiley Periodicals, Inc. C1 [Hancarova, Miroslava; Simandlova, Martina; Drabova, Jana; Sedlacek, Zdenek] Charles Univ Prague, Fac Med 2, Dept Biol & Med Genet, Prague 15000 5, Czech Republic. [Hancarova, Miroslava; Simandlova, Martina; Drabova, Jana; Sedlacek, Zdenek] Univ Hosp Motol, Prague, Czech Republic. [Mannik, Katrin; Kurg, Ants] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. RP Sedlacek, Z (reprint author), Charles Univ Prague, Fac Med 2, Dept Biol & Med Genet, Prague 15000 5, Czech Republic. EM zdenek.sedlacek@lfmotol.cuni.cz FU European Commission [223692 CHERISH, BM1004]; Czech Ministries of Education and Health [LD11028, 00064203]; Estonian Ministry of Education and Research [SF0180027s10] FX Grant sponsor: European Commission; Grant number: 223692 CHERISH and BM1004; Grant sponsor: Czech Ministries of Education and Health; Grant numbers: LD11028 and 00064203; Grant sponsor: Estonian Ministry of Education and Research; Grant number: SF0180027s10. 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J. Med. Genet. A PD APR PY 2013 VL 161A IS 4 BP 865 EP 870 DI 10.1002/ajmg.a.35783 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 112YM UT WOS:000316631300035 PM 23495096 ER PT J AU Bekhet, AK Zauszniewski, JA AF Bekhet, Abir K. Zauszniewski, Jaclene A. TI Psychometric Assessment of the Depressive Cognition Scale Among Caregivers of Persons With Autism Spectrum Disorder SO ARCHIVES OF PSYCHIATRIC NURSING LA English DT Article ID INTELLECTUAL DISABILITY; STRESS PROLIFERATION; PRESCHOOL-CHILDREN; PARENTING STRESS; SOCIAL SUPPORT; MOTHERS; OPTIMISM; ANXIETY; FATHERS; BURDEN AB Caregivers of persons with autism spectrum disorders (ASD) are prone to depression, and early identification of cognitive depressive symptoms is important to prevent the development of clinical depression. The Depressive Cognition Scale (DCS) can be used for early detection, but the scales psychometrics has not been tested in caregivers of persons with ASD. 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TI Newborn screening for autism: in search of candidate biomarkers SO BIOMARKERS IN MEDICINE LA English DT Article DE autism; biomarkers; bloodspots; newborn; screening spectrum disorder ID THYROID-STIMULATING HORMONE; PROSTATE-SPECIFIC ANTIGEN; CENTRAL-NERVOUS-SYSTEM; GENE-RELATED PEPTIDE; DRIED BLOOD SPOTS; SPECTRUM DISORDER; OXIDATIVE STRESS; TISSUE INHIBITOR; CYTOKINE LEVELS; MATRIX METALLOPROTEINASES AB Background: Autism spectrum disorder (ASD) represents a wide range of neurodevelopmental disorders characterized by impairments in social interaction, language, communication and range of interests. Autism is usually diagnosed in children 3-5 years of age using behavioral characteristics; thus, diagnosis shortly after birth would be beneficial for early initiation of treatment. Aim: This retrospective study sought to identify newborns at risk for ASD utilizing bloodspot specimens in an immunoassay. Materials & methods: The present study utilized stored frozen specimens from ASD children already diagnosed at 15-36 months of age. The newborn specimens and controls were analyzed by immunoassay in a multiplex system that included 90 serum biomarkers and subjected to statisical analysis. Results: Three sets of five biomarkers associated with ASD were found that differed from control groups. The 15 candidate biomarkers were then discussed regarding their association with ASD. Conclusion: This study determined that a statistically selected panel of 15 biomarkers successfully discriminated presumptive newborns at risk for ASD from those of nonaffected controls. C1 [Mizejewski, Gerald J.; Lindau-Shepard, Barbara] New York State Dept Hlth, Wadsworth Ctr, Div Translat Med, Albany, NY 12201 USA. [Pass, Kenneth A.] ISNS, Bilthoven, Netherlands. RP Mizejewski, GJ (reprint author), New York State Dept Hlth, Wadsworth Ctr, Div Translat Med, POB 509, Albany, NY 12201 USA. EM mizejew@wadsworth.org FU NIH [ADB-NO1-DK-6-3430 (HHSN267200603430)]; Novel Technologies in Newborn Screening FX This work was supported by NIH Contract ADB-NO1-DK-6-3430 (HHSN267200603430), Novel Technologies in Newborn Screening to KA Pass (principal investigator). The authors have 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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Med. PD APR PY 2013 VL 7 IS 2 BP 247 EP 260 DI 10.2217/BMM.12.108 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 120FA UT WOS:000317155000018 PM 23547820 ER PT J AU Pavlova, MA Krageloh-Mann, I AF Pavlova, Marina A. Kraegeloh-Mann, Ingeborg TI Limitations on the developing preterm brain: impact of periventricular white matter lesions on brain connectivity and cognition SO BRAIN LA English DT Review DE preterm birth; brain development; cognitive functions; motor disability; brain connectivity ID LOW-BIRTH-WEIGHT; BIOLOGICAL MOTION PERCEPTION; SUPERIOR TEMPORAL SULCUS; AUTISM SPECTRUM DISORDERS; SPASTIC CEREBRAL-PALSY; INFANTS BORN PRETERM; DIFFUSION-TENSOR; CHILDREN BORN; VISUAL IMPAIRMENT; SOCIAL COGNITION AB Brain lesions to the white matter in peritrigonal regions, periventricular leukomalacia, in children who were born prematurely represent an important model for studying limitations on brain development. The lesional pattern is of early origin and bilateral, that constrains the compensatory potential of the brain. We suggest that (i) topography and severity of periventricular lesions may have a long-term predictive value for cognitive and social capabilities in preterm birth survivors; and (ii) periventricular lesions may impact cognitive and social functions by affecting brain connectivity, and thereby, the dissociable neural networks underpinning these functions. A further pathway to explore is the relationship between cerebral palsy and cognitive outcome. Restrictions caused by motor disability may affect active exploration of surrounding and social participation that may in turn differentially impinge on cognitive development and social cognition. As an outline for future research, we underscore sex differences, as the sex of a preterm newborn may shape the mechanisms by which the developing brain is affected. C1 [Pavlova, Marina A.; Kraegeloh-Mann, Ingeborg] Univ Tubingen, Sch Med, Childrens Hosp, Dept Paediat Neurol & Dev Med, D-72076 Tubingen, Germany. RP Pavlova, MA (reprint author), Univ Tubingen, Sch Med, Childrens Hosp, Dept Paediat Neurol & Dev Med, Hoppe Seyler Str 1, D-72076 Tubingen, Germany. EM marina.pavlova@uni-tuebingen.de FU Else Kroner Fresenius Foundation [P63/2008, P2010_92]; Werner Reichardt Center for Integrative Neuroscience (CIN) [2009-24]; German Research Council (DFG); Reinhold Beitlich Foundation; EU SCPE Net [20081307] FX The Else Kroner Fresenius Foundation (Grants P63/2008 and P2010_92); the Werner Reichardt Center for Integrative Neuroscience (CIN, pool project 2009-24), supported by the German Research Council (DFG), the Reinhold Beitlich Foundation to M.A.P., and EU SCPE Net 20081307 to I.K.-M. 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Evaluation of the 2nd HANDS prototype SO COMPUTERS & EDUCATION LA English DT Article DE Pedagogical issues; Secondary education; Computer mediated communication; Autistic spectrum disorders ID VIRTUAL ENVIRONMENTS; EXECUTIVE FUNCTION; SELF-EFFICACY; INDIVIDUALS; ADOLESCENTS; MIND; IMPAIRMENTS; BEHAVIOR AB Of late there has been growing interest in the potential of technology to support children with Autism Spectrum Disorders (ASD) with social and life skills. There has also been a burgeoning interest in the potential use of mobile technology in the classroom and in the use of such technology to support children with ASD. Building on these developments, the HANDS project has developed a mobile cognitive support application for smartphones, based on the principles of persuasive technology design, which supports children with ASD with social and life skills functioning - areas of ability which tend to be impaired in this population. Based on the evaluation of the implementation of an initial prototype, a second prototype was developed in the summer of 2010 and implemented in the 2010111 academic year in four special schools for children with ASD. This paper reports on a qualitative interpretivist evaluation of the second prototype, identifying which factors mediate the level of engagement with the technology by both teachers and children. Fifteen teachers and twenty six children used the second prototype. Data was gathered using from teachers (n = 15) using direct classroom observation, individual semi-structured interviews, and questionnaires. Semi-structured interviews were also used to collect data from some parents (n = 6) and children (n = 10). A number of factors identified in the first prototype are also found to be present in the second prototype. However new factors are also identified, including student awareness of difficulties and associated motivation to change, and the preference of some children with ASD to receive persuasive messages from mobile devices. Particular issues related to the cognitive structure of children with ASD are considered. Further design guidelines are proposed for future implementations of similarly purposed technology tools. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Mintz, Joseph] Univ London, Inst Educ, Fac Children & Learning, London WC1H 0LH, England. [Mintz, Joseph] London S Bank Univ, London, England. RP Mintz, J (reprint author), Univ London, Inst Educ, Fac Children & Learning, 20 Bedford Way, London WC1H 0LH, England. EM j.mintz@ioe.ac.uk FU European Commission [224216] FX This work was supported by the European Commission, [Grant No. 224216]. Thanks are due to other members of the consortium including teachers and other professionals at test site schools, for their support and assistance in the work described in this project. 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The participants were the parents of 108 children aged 6-18 years with apparently normal intelligence. The CBCL indicated abnormal behavior in 10.5 to 35.6% of the children, and T scores on both the internalizing and externalizing scales had a significant positive relation with scores on the ASSQ and ADHD-RS. It was revealed through multivariate logistic regression analysis that the persistence of seizures was significantly related with abnormality on the externalizing scale of the CBCL (p = 0.010, odds ratio: 3.48, 95% confidence interval: 1.34-9.02). Future studies are needed to determine whether seizure freedom improves behavior in children with epilepsy. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kobayashi, Katsuhiro; Endoh, Fumika; Oka, Makio; Morooka, Teruko; Yoshinaga, Harumi; Ohtsuka, Yoko] Okayama Univ, Dept Child Neurol, Grad Sch Med Dent & Pharmaceut Sci, Kita Ku, Okayama 7008530, Japan. [Kobayashi, Katsuhiro; Endoh, Fumika; Oka, Makio; Morooka, Teruko; Yoshinaga, Harumi; Ohtsuka, Yoko] Okayama Univ Hosp, Kita Ku, Okayama 7008558, Japan. [Ogino, Tatsuya] Chugokugakuen Univ, Fac Children Studies, Dept Children Studies, Okayama, Japan. [Ohtsuka, Yoko] Asahigawasou Rehabil & Med Ctr, Okayama, Japan. RP Kobayashi, K (reprint author), Okayama Univ Hosp, Dept Child Neurol, Kita Ku, 5-1 Shikatacho 2 Chome, Okayama 7008558, Japan. EM k_koba@md.okayama-u.ac.jp FU Ministry of Health and Welfare [19A-6]; Ministry of Education, Culture, Sports, Science, and Technology, Japan [24591513] FX This study is in part supported by the Research Grant (19A-6) for Nervous and Mental Disorders from the Ministry of Health and Welfare and a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (no. 24591513). 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TI Dual copy number variants involving 16p11 and 6q22 in a case of childhood apraxia of speech and pervasive developmental disorder SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID CLASSIFICATION-SYSTEM SDCS; AUTISM SPECTRUM DISORDERS; SKELETAL-MUSCLE TRIADIN; CHROMOSOME 16P11.2; MICRODELETION SYNDROME; DELETION; DELAY; GENE; MICRODUPLICATION; REARRANGEMENTS C1 [Newbury, Dianne F.; Akha, Elham Sadighi; Monaco, Anthony P.; Taylor, Jenny C.; Fisher, Simon E.; Knight, Samantha J. L.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Mari, Francesca; Renieri, Alessandra] Univ Siena, I-53100 Siena, Italy. [Mari, Francesca; Canitano, Roberto; Renieri, Alessandra] Azienda Osped Univ Senese, Siena, Italy. [Akha, Elham Sadighi; Taylor, Jenny C.; Knight, Samantha J. L.] NIHR Biomed Res Ctr, Oxford, England. [MacDermot, Kay D.] Univ London Imperial Coll Sci Technol & Med, Kennedy Galton Ctr, North West Thames Reg Genet Serv, London, England. [Fisher, Simon E.] Max Planck Inst Psycholinguist, Language & Genet Dept, Nijmegen, Netherlands. [Fisher, Simon E.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. RP Newbury, DF (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. 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J. Hum. Genet. PD APR PY 2013 VL 21 IS 4 BP 361 EP 365 DI 10.1038/ejhg.2012.166 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 119HV UT WOS:000317089300002 PM 22909776 ER PT J AU Raca, G Baas, BS Kirmani, S Laffin, JJ Jackson, CA Strand, EA Jakielski, KJ Shriberg, LD AF Raca, Gordana Baas, Becky S. Kirmani, Salman Laffin, Jennifer J. Jackson, Craig A. Strand, Edythe A. Jakielski, Kathy J. Shriberg, Lawrence D. TI Childhood Apraxia of Speech (CAS) in two patients with 16p11.2 microdeletion syndrome SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE aCGH; apraxia; dyspraxia; FOXP2; speech sound disorder ID MENTAL-RETARDATION; DISORDER; FOXP2; DELETION; AUTISM; PHENOTYPE; MUTATION; DEFICITS; MOTHER; DUPLICATIONS AB We report clinical findings that extend the phenotype of the similar to 550 kb 16p11.2 microdeletion syndrome to include a rare, severe, and persistent pediatric speech sound disorder termed Childhood Apraxia of Speech (CAS). CAS is the speech disorder identified in a multigenerational pedigree ('KE') in which half of the members have a mutation in FOXP2 that co-segregates with CAS, oromotor apraxia, and low scores on a nonword repetition task. Each of the two patients in the current report completed a 2-h assessment protocol that provided information on their cognitive, language, speech, oral mechanism, motor, and developmental histories and performance. Their histories and standard scores on perceptual and acoustic speech tasks met clinical and research criteria for CAS. Array comparative genomic hybridization analyses identified deletions at chromosome 16p11.2 in each patient. These are the first reported cases with well-characterized CAS in the 16p11.2 syndrome literature and the first report of this microdeletion in CAS genetics research. We discuss implications of findings for issues in both literatures. European Journal of Human Genetics (2013) 21, 455-459; doi:10.1038/ejhg.2012.165; published online 22 August 2012 C1 [Raca, Gordana; Laffin, Jennifer J.; Shriberg, Lawrence D.] Univ Wisconsin, Madison, WI 53705 USA. [Raca, Gordana; Laffin, Jennifer J.; Jackson, Craig A.] Univ Wisconsin, Wisconsin State Lab Hyg, Madison, WI 53706 USA. [Baas, Becky S.; Strand, Edythe A.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Kirmani, Salman] Mayo Clin, Coll Med, Rochester, MN USA. [Jakielski, Kathy J.] Augustana Coll, Rock Isl, IL 61201 USA. [Shriberg, Lawrence D.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. RP Shriberg, LD (reprint author), Univ Wisconsin, Waisman Ctr, Room 439,1500 Highland Ave, Madison, WI 53705 USA. EM shriberg@waisman.wisc.edu FU National Institute on Deafness and Other Communicative Disorders [DC000496]; National Institute of Health and Development [HD03352] FX This work was supported by a grant from the National Institute on Deafness and Other Communicative Disorders (DC000496) to Lawrence D. Shriberg and a Core Grant from the National Institute of Health and Development (HD03352) to the Waisman Center. We thank the patients and their families and the following laboratory colleagues for their contributions to this report: Sheryl Hall, Heather Karlsson, Heather Lohmeier, Jane McSweeny, Christine Tilkens, and David Wilson. 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J. Hum. Genet. PD APR PY 2013 VL 21 IS 4 BP 455 EP 459 DI 10.1038/ejhg.2012.165 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 119HV UT WOS:000317089300018 PM 22909774 ER PT J AU Barraza, JA Grewal, NS Ropacki, S Perez, P Gonzalez, A Zak, PJ AF Barraza, Jorge A. Grewal, Naomi S. Ropacki, Susan Perez, Pamela Gonzalez, Anthony Zak, Paul J. TI Effects of a 10-Day Oxytocin Trial in Older Adults on Health and Well-Being SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE oxytocin; intranasal administration; well-being; emotion; older adults ID OBSESSIVE-COMPULSIVE DISORDER; SOCIAL ANXIETY DISORDER; MINI-MENTAL STATE; INTRANASAL OXYTOCIN; BLOOD-PRESSURE; AUTISM; VASOPRESSIN; STRESS; HUMANS; LIFE AB The neuropeptide oxytocin (OT) modulates functioning of the hypothalamic-pituitary-adrenal (HPA) axis and regulates a range of social processes. Clinical studies have used intranasal OT administration to treat symptoms arising from a number of psychiatric disorders including autism, schizophrenia, and depression. Most of this research, however, has been based on single dose treatments of OT in younger adult populations. The present study examined the impact on the health and psychological well-being of a 10-day OT administration in an older adult population. Residentially housed older adults (N = 41, mean age of 80) were enrolled in a randomized, double-blind, placebo-controlled study. Participants received 40 IU intranasal OT or placebo for 10 consecutive days. No changes in mood or cardiovascular states were observed across the 10-day period. Repeated-measures ANOVAs showed that dispositional gratitude improved for the OT infused participants, although gratitude declined for placebo controls over the 10 days (p=.015). Those in the OT condition did not report a decline in physical functioning over time as was observed in the placebo condition (p=.05), and also reported less fatigue compared with controls (p=.03). No significant adverse events were reported throughout the entirety of the study, indicating that OT can be safely used with older adults. C1 [Barraza, Jorge A.; Grewal, Naomi S.; Gonzalez, Anthony; Zak, Paul J.] Claremont Grad Univ, Ctr Neuroecon Studies, Claremont, CA 91711 USA. [Ropacki, Susan] Loma Linda Univ, Dept Psychol, Loma Linda, CA 92350 USA. [Perez, Pamela] Loma Linda Univ, Dept Allied Profess, Loma Linda, CA 92350 USA. RP Zak, PJ (reprint author), Claremont Grad Univ, Ctr Neuroecon Studies, 160 East 10th St, Claremont, CA 91711 USA. EM paul.zak@cgu.edu FU National Institute of Aging (NIA) [1R21AG029871-01A2] FX This research was supported by a grant awarded to Paul J. Zak from the National Institute of Aging (NIA) grant # 1R21AG029871-01A2. The funding source had no other role other than financial support. All authors have contributed in a significant way to the manuscript and all authors have read and approved the final manuscript. There are no conflicts of interest for any of the authors including financial, personal, or other relationships with other organizations or pharmaceutical/biomedical companies that may inappropriately impact or influence the research and interpretation of the findings. We thank several people that assisted in collecting the data presented here including Dr. David Swope, Laura Beavin, Joel Kamper, and Julia Kroh. We also thank all the staff at participating active living communities who assisted in recruiting and providing us with space for data collection. CR Barraza J. 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Clin. Psychopharmacol. PD APR PY 2013 VL 21 IS 2 BP 85 EP 92 DI 10.1037/a0031581 PG 8 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 119WG UT WOS:000317129400001 PM 23421352 ER PT J AU Kohl, S Heekeren, K Klosterkotter, J Kuhn, J AF Kohl, S. Heekeren, K. Klosterkoetter, J. Kuhn, J. TI Prepulse inhibition in psychiatric disorders - Apart from schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Review DE Prepulse inhibition; Startle reflex; Psychiatric disorders; Translational research; Sensorimotor gating ID POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; ACOUSTIC STARTLE RESPONSE; SENSORIMOTOR GATING DEFICITS; INFORMATION-PROCESSING DEFICITS; VIETNAM VETERANS; BIPOLAR DISORDER; BLINK REFLEX; HUNTINGTONS-DISEASE; NOCTURNAL ENURESIS AB Prepulse inhibition (PPI) is a robust operational measure of sensorimotor gating. In schizophrenic patients PPI is deficient. The aim of our review was to investigate the state of science regarding PPI and psychiatric disorders aside from schizophrenia. We used the online database PubMed in order to search for original published reports on PPI studies. The terms "prepulse inhibition", "sensorimotor gating", "blink recovery", and "blink reflex excitability" have been combined with the names of psychiatric disorders. We found that PPI is deficient in obsessive compulsive disorder (OCD) and Gilles de la Tourette's syndrome (GTS). In bipolar disorder dysfunctional PPI seems to be rather state dependent. Studies on depression and attention deficit/hyperactivity disorder (ADHD) consistently report no alterations. Evidence regarding sensorimotor gating in anxiety, autism, fragile X syndrome, posttraumatic stress disorder (PTSD), substance disorders, and Huntington's disease is still poor. There is a strong need for further studies on PPI in psychiatric disorders. PPI is highly applicable for translational research and might also be a very useful tool to investigate the mode of action of innovative, neuro-modulative techniques. Future PPI studies should control for influencing variables such as smoking, sex, or medication. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Kohl, S.; Klosterkoetter, J.; Kuhn, J.] Univ Cologne, Dept Psychiat & Psychotherapy, D-50937 Cologne, Germany. [Heekeren, K.] Univ Zurich, Dept Gen & Social Psychiat, Zurich, Switzerland. RP Kuhn, J (reprint author), Univ Cologne, Dept Psychiat & Psychotherapy, Kerpener Str 62, D-50937 Cologne, Germany. EM Jens.kuhn@uk-koeln.de FU Walter and Marga Boll Foundation; German Research Foundation [KFO-219]; Medtronic GmbH (Meerbusch, Germany); AstraZeneca; Lilly; Lundbeck; Otsuka Pharma FX This work has been funded by the Walter and Marga Boll Foundation as well as the German Research Foundation (KFO-219 grant).Jens Kuhn received financial support for IIT-DBS studies from Medtronic GmbH (Meerbusch, Germany). Furthermore J Kuhn has occasionally received honoraria from AstraZeneca, Lilly, Lundbeck, and Otsuka Pharma for lecturing at conferences and financial support to travel to congresses. All other authors declare that they have no conflict of interest. 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Psychiatr. Res. PD APR PY 2013 VL 47 IS 4 BP 445 EP 452 DI 10.1016/j.jpsychires.2012.11.018 PG 8 WC Psychiatry SC Psychiatry GA 118LT UT WOS:000317027700003 PM 23287742 ER PT J AU Sato, JR Hoexter, MQ Oliveira, PPD Brammer, MJ Murphy, D Ecker, C AF Sato, Joao Ricardo Hoexter, Marcelo Queiroz de Magalhaes Oliveira, Pedro Paulo, Jr. Brammer, Michael John Murphy, Declan Ecker, Christine CA MRC AIMS Consortium TI Inter-regional cortical thickness correlations are associated with autistic symptoms: A machine-learning approach SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Autism; MRI; Neuroimaging; Machine learning; Pattern recognition; Connectivity ID HUMAN CEREBRAL-CORTEX; SPECTRUM DISORDER; STRUCTURAL COVARIANCE; ALZHEIMERS-DISEASE; FUNCTIONAL MRI; BRAIN ANATOMY; CLASSIFICATION; CONNECTIVITY; NEUROANATOMY; ORGANIZATION AB The investigation of neural substrates of autism spectrum disorder using neuroimaging has been the focus of recent literature. In addition, machine-learning approaches have also been used to extract relevant information from neuroimaging data. There are only few studies directly exploring the inter-regional structural relationships to identify and characterize neuropsychiatric disorders. In this study, we concentrate on addressing two issues: (i) a novel approach to extract individual subject features from inter-regional thickness correlations based on structural magnetic resonance imaging (MRI); (ii) using these features in a machine-learning framework to obtain individual subject prediction of a severity scores based on neurobiological criteria rather than behavioral information. In a sample of 82 autistic patients, we have shown that structural covariances among several brain regions are associated with the presence of the autistic symptoms. In addition, we also demonstrated that structural relationships from the left hemisphere are more relevant than the ones from the right. Finally, we identified several brain areas containing relevant information, such as frontal and temporal regions. This study provides evidence for the usefulness of this new tool to characterize neuropsychiatric disorders. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Sato, Joao Ricardo] Univ Fed ABC, Ctr Math Computat & Cognit, BR-09210170 Santo Andre, SP, Brazil. [Hoexter, Marcelo Queiroz] Univ Sao Paulo, Sch Med, Inst Psychiat, BR-05508 Sao Paulo, Brazil. [de Magalhaes Oliveira, Pedro Paulo, Jr.] Univ Sao Paulo, Sch Med, Inst Radiol, BR-05508 Sao Paulo, Brazil. [Brammer, Michael John; Murphy, Declan; Ecker, Christine] Kings Coll London, Inst Psychiat, London, England. RP Sato, JR (reprint author), Univ Fed ABC, Ctr Math Computat & Cognit, Rua Santa Adelia 166, BR-09210170 Santo Andre, SP, Brazil. EM joao.sato@ufabc.edu.br RI Ecker, Christine/E-5194-2010; Bolton, Patrick/E-8501-2010 OI Bolton, Patrick/0000-0002-5270-6262 FU FAPESP-Brazil; MRC-UK; MRC AIMS Consortium (Autism Imaging Multicentre Study); Medical Research Council UK [G0400061]; NIHR Biomedical Research Centre for Mental Health at King's College London, Institute of Psychiatry and South London & Maudsley NHS Foundation Trust FX This study received financial support from FAPESP-Brazil and MRC-UK.This work was supported by FAPESP-Brazil, the MRC AIMS Consortium (Autism Imaging Multicentre Study) funded by the Medical Research Council UK (G0400061), and the NIHR Biomedical Research Centre for Mental Health at King's College London, Institute of Psychiatry and South London & Maudsley NHS Foundation Trust. 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TI Frequency and Pattern of Documented Diagnostic Features and the Age of Autism Identification SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autism; autism spectrum disorder; identification; diagnosis; population-based ID PERVASIVE DEVELOPMENTAL DISORDER; SPECTRUM DISORDERS; REPETITIVE BEHAVIOR; GENERAL-POPULATION; 2ND YEAR; CHILDREN; SURVEILLANCE; LIFE; STABILITY; SYMPTOMS AB Objective: The DSM-IV-TR specifies 12 behavioral features that can occur in hundreds of possible combinations to meet diagnostic criteria for autism spectrum disorder (ASD). This paper describes the frequency and variability with which the 12 behavioral features are documented in a population-based cohort of 8-year-old children under surveillance for ASD, and examines whether documentation of certain features, alone or in combination with other features, is associated with earlier age of community identification of ASD. Method: Statistical analysis of behavioral features documented for a population-based sample of 2,757 children, 8 years old, with ASD in 11 geographically-defined areas in the US participating in the Autism and Developmental Disabilities Monitoring Network in 2006. Results: The median age at ASD identification was inversely associated with the number of documented behavioral features, decreasing from 8.2 years for children with only seven behavioral features to 3.8 years for children with all 12. Documented impairments in nonverbal communication, pretend play, inflexible routines, and repetitive motor behaviors were associated with earlier identification, whereas impairments in peer relations, conversational ability, and idiosyncratic speech were associated with later identification. Conclusions: The age dependence of some of the behavioral features leading to an autism diagnosis, as well as the inverse association between age at identification and number of behavioral features documented, have implications for efforts to improve early identification. Progress in achieving early identification and provision of services for children with autism may be limited for those with fewer ASD behavioral features, as well as features likely to be detected at later ages. J. Am. Acad. Child Adolesc. Psychiatry, 2013; 52(4):401-413. C1 [Maenner, Matthew J.; Durkin, Maureen S.] Univ Wisconsin Madison, Madison, WI USA. [Schieve, Laura A.; Rice, Catherine E.] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. [Cunniff, Christopher] Univ Arizona, Coll Med, Tucson, AZ USA. [Giarelli, Ellen] Drexel Univ, Philadelphia, PA USA. [Kirby, Russell S.] Univ S Florida, Tampa, FL 33620 USA. [Lee, Li-Ching] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Nicholas, Joyce S.] Med Univ S Carolina, Charleston, SC USA. [Wingate, Martha S.] Univ Alabama Birmingham, Birmingham, AL USA. RP Maenner, MJ (reprint author), 1500 Highland Ave Rm 529A, Madison, WI 53705 USA. RI Durkin, Maureen/B-7834-2015 FU Autism Science Foundation; CDC Cooperative Agreements [UR3/CCU523235, UR3/DD000078, UR3/DD000677]; University of Wisconsin-Madison; Waisman Center [P30 HD03352] FX This work was supported by a grant from the Autism Science Foundation and by the CDC Cooperative Agreements UR3/CCU523235, UR3/DD000078, and UR3/DD000677. Additional support has been provided by the University of Wisconsin-Madison and the Waisman Center (P30 HD03352, M R. Mailick, PI). We are grateful to the many staff, scientists, and clinicians that have contributed to the Autism and Developmental Disabilities Monitoring (ADDM) Network project. We also thank Mark Albanese, Ph.D., of the University of Wisconsin-Madison, for his advice regarding the descriptive analyses in this manuscript. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC. CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Avchen RN, 2011, J AUTISM DEV DISORD, V41, P227, DOI 10.1007/s10803-010-1050-7 Baron-Cohen S, 2001, J AUTISM DEV DISORD, V31, P5, DOI 10.1023/A:1005653411471 Bodfish JW, 2000, J AUTISM DEV DISORD, V30, P237, DOI 10.1023/A:1005596502855 Buitelaar JK, 1999, J AUTISM DEV DISORD, V29, P33, DOI 10.1023/A:1025966532041 Centers for Disease Control and Prevention, 2009, MMWR-MORBID MORTAL W, V58, P1 Centers for Disease Control and Prevention (CDC), LEARN SIGNS COHEN J, 1992, PSYCHOL BULL, V112, P155, DOI 10.1037/0033-2909.112.1.155 Constantino JN, 2003, ARCH GEN PSYCHIAT, V60, P524, DOI 10.1001/archpsyc.60.5.524 Cuccaro ML, 1996, J AUTISM DEV DISORD, V26, P461, DOI 10.1007/BF02172830 Cuccaro ML, 2007, AM J MED GENET B, V144B, P1022, DOI 10.1002/ajmg.b.30535 Durkin MS, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0011551 Esbensen AJ, 2009, J AUTISM DEV DISORD, V39, P57, DOI 10.1007/s10803-008-0599-x Gibbs V, 2012, J AUTISM DEV DISORD, V42, P1750, DOI 10.1007/s10803-012-1560-6 Hartley SL, 2009, J AUTISM DEV DISORD, V39, P1715, DOI 10.1007/s10803-009-0810-8 Holtmann M, 2007, DEV MED CHILD NEUROL, V49, P361 Kleinbaum D. 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Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2013 VL 52 IS 4 BP 401 EP 413 DI 10.1016/j.jaac.2013.01.014 PG 13 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 122LL UT WOS:000317319500009 PM 23582871 ER PT J AU Pescosolido, MF Gamsiz, ED Nagpal, S Morrow, EM AF Pescosolido, Matthew F. Gamsiz, Ece D. Nagpal, Shailender Morrow, Eric M. TI Distribution of Disease-Associated Copy Number Variants Across Distinct Disorders of Cognitive Development SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autism; epilepsy; intellectual disability schizophrenia; copy number variation ID DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; IDIOPATHIC GENERALIZED EPILEPSY; DEFICIT HYPERACTIVITY DISORDER; SCAFFOLDING PROTEIN SHANK3; RARE CHROMOSOMAL DELETIONS; GENOME-WIDE ANALYSIS; DRAVET SYNDROME; RECURRENT MICRODELETIONS; 15Q13.3 MICRODELETIONS AB Objective: The purpose of the present study was to discover the extent to which distinct DSM disorders share large, highly recurrent copy number variants (CNVs) as susceptibility factors. We also sought to identify gene mechanisms common to groups of diagnoses and/or specific to a given diagnosis based on associations with CNVs. Method: Systematic review of 820 PubMed articles on autism spectrum disorder (ASD), intellectual disability (ID), schizophrenia, and epilepsy produced 54 CNVs associated with one or several disorders. Pathway analysis on genes implicated by CNVs in different groupings was conducted. Results: The majority of CNVs were found in ID with the other disorders somewhat subsumed, yet certain CNVs were associated with isolated or groups of disorders. Based on genes implicated by CNVs, ID encompassed 96.8% of genes in ASD, 92.8% of genes in schizophrenia, and 100.0% of genes in epilepsy. Pathway analysis revealed that synapse processes were enriched in ASD, ID, and schizophrenia. Disease-specific processes were identified in ID (actin cytoskeleton processes), schizophrenia (ubiquitin-related processes), and ASD (synaptic vesicle transport and exocytosis). Conclusions: Intellectual disability may arise from the broadest range of genetic pathways, and specific subsets of these pathways appear to be relevant to other disorders or combinations of these disorders. It is clear that statistically significant CNVs across disorders of cognitive development are highly enriched for biological processes related to the synapse. There are also disorder-specific processes that may aid in understanding the distinct presentations and pathophysiology of these disorders. J. Am. Acad. Child Adolesc. Psychiatry; 2013;52(4):414-430. C1 [Pescosolido, Matthew F.; Gamsiz, Ece D.; Nagpal, Shailender; Morrow, Eric M.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Pescosolido, Matthew F.; Gamsiz, Ece D.; Morrow, Eric M.] Brown Univ, Emma Pendleton Bradley Hosp, Dev Disorders Genet Res Program, Providence, RI 02912 USA. [Pescosolido, Matthew F.; Gamsiz, Ece D.; Morrow, Eric M.] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA. RP Morrow, EM (reprint author), Brown Univ, Mol Med Lab, 70 Ship St, Providence, RI 02912 USA. RI Morrow, Eric/J-2767-2013 FU Career Award in Medical Science from the Burroughs Wellcome Fund; National Institute of Mental Health (NIMH) [1K23MH080954-05]; Lifespan Research Institute; Lifespan Division of Psychiatry; Brown Institute for Brain Science; Norman Prince Neurosciences Institute; Wellcome Trust FX This research received support from a Career Award in Medical Science from the Burroughs Wellcome Fund (E.M.M.) and from the National Institute of Mental Health (NIMH) grant 1K23MH080954-05 (E M M.). Dr. Gamsiz is the first Brown University Alpert Medical School Translational Neuroscience Postdoctoral Fellow jointly sponsored by the Lifespan Research Institute, the Lifespan Division of Psychiatry, the Brown Institute for Brain Science, and the Norman Prince Neurosciences Institute.This study makes use of data generated by the DECIPHER Consortium. A full list of centers that contributed to the generation of the data is available from http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Funding for the project was provided by the Wellcome Trust. 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Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2013 VL 52 IS 4 BP 414 EP 430 DI 10.1016/j.jaac.2013.01.003 PG 17 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 122LL UT WOS:000317319500010 PM 23582872 ER PT J AU Sato, K AF Sato, Kohji TI Placenta-derived hypo-serotonin situations in the developing forebrain cause autism SO MEDICAL HYPOTHESES LA English DT Article ID INDOLEAMINE 2,3-DIOXYGENASE GENE; CORTICOTROPIN-RELEASING HORMONE; DEVELOPING RAT-BRAIN; CORTICAL DEVELOPMENT; TRANSPORTER; MOUSE; EXPRESSION; TRYPTOPHAN; NEURONS; FETAL AB Autism is a pervasive developmental disorder that is characterized by the behavioral traits of impaired social cognition and communication, and repetitive and/or obsessive behavior and interests. Although there are many theories and speculations about the pathogenetic causes of autism, the disruption of the serotonergic system is one of the most consistent and well-replicated findings. Recently, it has been reported that placenta-derived serotonin is the main source in embryonic day (E) 10-15 mouse forebrain, after that period, the serotonergic fibers start to supply serotonin into the forebrain. E 10-15 is the very important developing period, when cortical neurogenesis, migration and initial axon targeting are processed. Since all these events have been considered to be involved in the pathogenesis of autism and they are highly controlled by serotonin signals, the paucity of placenta-derived serotonin should have potential importance when the pathogenesis of autism is considered. I, thus, postulate a hypothesis that placenta-derived hypo-serotonin situations in the developing forebrain cause autism. The hypothesis is as follows. Various factors, such as inflammation, dysfunction of the placenta, together with genetic predispositions cause a decrease of placenta-derived serotonin levels. The decrease of placenta-derived serotonin levels leads to hypo-serotonergic situations in the forebrain of the fetus. The paucity of serotonin in the forebrain leads to mis-wiring in important regions which are responsible for the theory of mind. The paucity of serotonin in the forebrain also causes over-growth of serotonergic fibers. These disturbances result in network deficiency and aberration of the serotonergic system, leading to the autistic phenotypes. (C) 2013 Elsevier Ltd. All rights reserved. C1 Hamamatsu Univ Sch Med, Dept Anat & Neurosci, Higashi Ku, Hamamatsu, Shizuoka 4313192, Japan. RP Sato, K (reprint author), Hamamatsu Univ Sch Med, Dept Anat & Neurosci, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan. EM ksato@hama-med.ac.jp FU Ministry of Education, Science and Culture of Japan; Shintenkai FX Grant sponsor: The Ministry of Education, Science and Culture of Japan; Shintenkai. 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Hypotheses PD APR PY 2013 VL 80 IS 4 BP 368 EP 372 DI 10.1016/j.mehy.2013.01.002 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 120IR UT WOS:000317164500007 PM 23375670 ER PT J AU Monro, JA Leon, R Puri, BK AF Monro, J. A. Leon, R. Puri, B. K. TI The risk of lead contamination in bone broth diets SO MEDICAL HYPOTHESES LA English DT Article ID OCCUPATIONAL-EXPOSURE; TOXICITY; BLOOD AB The preparation and consumption of bone broth is being increasingly recommended to patients, for example as part of the gut and psychology syndrome (GAPS) diet for autism, attention-deficit hyperactivity disorder, dyslexia, dyspraxia, depression and schizophrenia, and as part of the paleolithic diet. However, bones are known to sequester the heavy metal lead, contamination with which is widespread throughout the modern environment. Such sequestered lead can then be mobilised from the bones. We therefore hypothesised that bone broth might carry a risk of being contaminated with lead. A small, blinded, controlled study of lead concentrations in three different types of organic chicken broth showed that such broths do indeed contain several times the lead concentration of the water with which the broth is made. In particular, broth made from skin and cartilage taken off the bone once the chicken had been cooked with the bones in situ, and chicken-bone broth, were both found to have markedly high lead concentrations, of 9.5 and 7.01 mu g L-1, respectively (compared with a control value for tap water treated in the same way of 0.89 mu g L-1). In view of the dangers of lead consumption to the human body, we recommend that doctors and nutritionists take the risk of lead contamination into consideration when advising patients about bone broth diets. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Monro, J. A.; Leon, R.] Breakspear Med Grp, Hemel Hempstead, Herts, England. [Puri, B. K.] Imperial Coll London, Hammersmith Hosp, London, England. RP Puri, BK (reprint author), Hammersmith Hosp, Imaging Directorate, Du Cane Rd, London W12 0HS, England. EM basant.puri@imperial.ac.uk CR Campbell-McBride N., 2010, GUT PSYCHOL SYNDROME Fallon S., 2001, NOURISHING TRADITION Farias P, 2005, INT J ENVIRON HEAL R, V15, P21, DOI 10.1080/09603120400018782 Frassetto LA, 2009, EUR J CLIN NUTR, V63, P947, DOI 10.1038/ejcn.2009.4 Jang DH, 2011, NEUROL CLIN, V29, P607, DOI 10.1016/j.ncl.2011.05.002 Keogh JP, 2001, LEAD, P879 Morrow L, 2007, ARCH ENVIRON OCCUP H, V62, P183, DOI 10.3200/AEOH.62.4.183-186 REGAN CM, 1993, NEUROTOXICOLOGY, V14, P69 Verstraeten S, 2008, ARCH TOXICOL, V82, P789, DOI 10.1007/s00204-008-0345-3 NR 9 TC 0 Z9 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD APR PY 2013 VL 80 IS 4 BP 389 EP 390 DI 10.1016/j.mehy.2012.12.026 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 120IR UT WOS:000317164500012 PM 23375414 ER PT J AU Megremi, ASF AF Megremi, Amalia S. F. TI Is fever a predictive factor in the autism spectrum disorders? SO MEDICAL HYPOTHESES LA English DT Article ID GASTROINTESTINAL SYMPTOMS; DEVELOPMENTAL DISORDERS; OXIDATIVE STRESS; NERVOUS-SYSTEM; TNF-ALPHA; CHILDREN; ACETAMINOPHEN; PREVALENCE; ASSOCIATION; ACTIVATION AB Autism spectrum disorders (ASD) display such a marked increase in recent decades that researchers speak of "epidemic outbreak" of the disease. Although the diagnostic framework has been expanded and thus more disorders now fall within the autistic spectrum, no one disputes the increased incidence of autism in modern societies, making it a major public health problem. On the other hand, heterogeneity is a major feature of the disorder, both in terms of the etiopathogenesis as well as to the phenotypic expression, natural history and evolution. Consequently, there is considerable research interest in determining factors which are etiopathogenetically, prognostically, preventively or/and therapeutically associated with the disorder. Literature data indicate that probably there are differences in susceptibility to various infections between normal and autistic children. In addition, some autistic children show improvement in the characteristics of their autistic behavior during febrile incident and repression of fever (through antipyretics) might be associated with the onset of autistic disorder. Since fever has been associated with mental illness since the time of Hippocrates already and the presence of fever is associated with a favorable outcome in various pathologic conditions, it is assumed that there are probably two subgroups of autistic children: those who have the possibility to develop acute febrile incidents and those who develop acute incidents without fever. If this is the case, it is important to know whether there are differences between the two subgroups in various biological markers (cytokines/chemokines, autoantibodies), neuroimaging findings, personal and family history of these children (use of drugs, vaccinations, history of autoimmunity, etc.) and, if the first subgroup consists of autistic people of higher functionality and better outcome, or not. If such a classification is real, is there a possibility for the fever to be used as a predictor of the autistic disorder outcome and of whether that person will achieve an acceptable level of functionality in the future? If there are positive answers to these questions, are autistic children, who develop fever, at a very critical stage in evolutionary terms, where it is very important not to lose the defense mechanism of fever development and thus mast use the fever repression methods (antipyretic drugs for example) with caution and chariness? If it is confirmed that autistic children with high fevers are of higher functionality, it is possible for preventive intervention programs to be developed where children are exposed to the least possible chemical drugs intervention (antipyretics, antibiotics, etc.) or even selective vaccination. Further experimental, epidemiological and clinical studies are necessary to investigate the above. (C) 2013 Elsevier Ltd. All rights reserved. C1 Gen Univ Hosp Attikon, Ilion Sociomed Ctr, Athens, Greece. RP Megremi, ASF (reprint author), Gen Univ Hosp Attikon, Ilion Sociomed Ctr, Athens, Greece. 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Hypotheses PD APR PY 2013 VL 80 IS 4 BP 391 EP 398 DI 10.1016/j.mehy.2013.01.007 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 120IR UT WOS:000317164500013 PM 23394936 ER PT J AU Steinman, G Mankuta, D AF Steinman, Gary Mankuta, David TI Insulin-like growth factor and the etiology of autism SO MEDICAL HYPOTHESES LA English DT Article ID IGF-I GENE; AMYOTROPHIC-LATERAL-SCLEROSIS; HEAD CIRCUMFERENCE GROWTH; BLOOD-BRAIN-BARRIER; FOR-GESTATIONAL-AGE; LOW-BIRTH-WEIGHT; SPECTRUM DISORDERS; INFANTILE-AUTISM; CEREBROSPINAL-FLUID; CHILDREN BORN AB The basic hypothesis for this study is that reduced peripartum level of insulin-like growth factor-1 (IGF) due to genetic, epigenetic, or environmental factors is a sentinel biomarker of increased probability of later development of autism. The central objective of the resultant proposed study described here is examining if a correlation exists between the serum level of IGF in the fetus/newborn and the probability of autism developing later in the child. Mechanisms possibly causing such a decrease are considered. This would define a prospective biomarker for and possible etiology of this disorder. Insulin-like growth factor-1 directly affects the rate at which oligodendrocytes promote myelination in the central nervous system, especially in the brain. Factors which reduce the production or availability of IGF could retard normal nerve programming in the fetus or neonate. Thus, it would be desirable to arrest the pathologic processes of autism in the early neonatal stage before irreversible nerve damage occurs. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Steinman, Gary] Touro Coll Osteopath Med, Dept Biochem, New York, NY 10027 USA. [Mankuta, David] Hadassah Univ Hosp, Dept Obstet & Gynecol, IL-12000 Jerusalem, Israel. RP Steinman, G (reprint author), Touro Coll Osteopath Med, Dept Biochem, 230 West 125th St, New York, NY 10027 USA. EM gary.steinman@touro.edu FU Touro College Office of Sponsored Programs; Israel Psychobiology Fund FX Study funded by Touro College Office of Sponsored Programs and the Israel Psychobiology Fund. 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Hypotheses PD APR PY 2013 VL 80 IS 4 BP 475 EP 480 DI 10.1016/j.mehy.2013.01.010 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 120IR UT WOS:000317164500029 PM 23375408 ER PT J AU Minniti, G Lorini, R Veneselli, E Vergani, L Voci, A Calevo, MG Battaglia, FM AF Minniti, G. Lorini, R. Veneselli, E. Vergani, L. Voci, A. Calevo, M. G. Battaglia, F. M. TI Are psychobiological markers strongly correlated with allostatic load in population with autism spectrum disorders (ASD)? SO MEDICAL HYPOTHESES LA English DT Letter ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HOMOCYSTEINE; FLUORESCENCE; PLASMA C1 [Minniti, G.; Lorini, R.; Veneselli, E.; Battaglia, F. M.] Univ Genova DINOGMI, Ist Giannina Gaslini, I-16144 Genoa, Italy. [Vergani, L.; Voci, A.] Univ Genoa, Dept Biol, I-16132 Genoa, Italy. [Calevo, M. G.] Ist Giannina Gaslini, Sci Directorate, Epidemiol & Biostat Sect, I-16144 Genoa, Italy. 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Hypotheses PD APR PY 2013 VL 80 IS 4 BP 506 EP 506 DI 10.1016/j.mehy.2012.12.011 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 120IR UT WOS:000317164500037 PM 23332179 ER PT J AU Branchi, I Curley, JP D'Andrea, I Cirulli, F Champagne, FA Alleva, E AF Branchi, Igor Curley, James P. D'Andrea, Ivana Cirulli, Francesca Champagne, Frances A. Alleva, Enrico TI Early interactions with mother and peers independently build adult social skills and shape BDNF and oxytocin receptor brain levels SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Early experiences; Social; Peer; Mother; BDNF; Oxytocin; Mouse; Environment ID AUTISM SPECTRUM DISORDER; MATERNAL-CARE; INDIVIDUAL-DIFFERENCES; EPIGENETIC INFLUENCE; STRESS REACTIVITY; BEHAVIOR; MICE; GENE; ENRICHMENT; VASOPRESSIN AB The early social environment has a profound impact on developmental trajectories. Although an impoverished early environment can undermine the acquisition of appropriate social skills, the specific role played by the different components of an individual's early environment in building social competencies has not been fully elucidated. Here we setup an asynchronous communal nesting paradigm in mice to disentangle the influence of maternal care and early peer interactions on adult social behavior and neural systems reportedly involved in the regulation of social interactions. The asynchronous communal nesting consists of three mothers giving birth three days apart, generating three groups of pups - the Old, the Middle and the Young - all raised in a single nest from birth to weaning. We scored the amount of maternal and peer interactions received by these mice and by a fourth group reared under standard conditions. At adulthood, the four experimental groups have been investigated for social behavior in a social interaction test, i.e. facing an unfamiliar conspecific during five 20-min daily encounters, and for oxytocin receptor and brain derived neurotrophic factor (BDNF) levels. Results show that only individuals exposed to high levels of both maternal and peer interactions demonstrated elaborate adult agonistic competencies, i.e. the ability to promptly display a social status, and high BDNF levels in the hippocampus, frontal cortex and hypothalamus. By contrast, only individuals exposed to high levels of peer interactions showed enhanced adult affiliative behavior and enhanced oxytocin receptor levels in selected nuclei of the amygdala. Overall these findings indicate that early interactions with mother and peers independently shape specific facets of adult social behavior and neural systems involved in social interaction. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Branchi, Igor; Cirulli, Francesca; Alleva, Enrico] Ist Super Sanita, Dept Cell Biol & Neurosci, Sect Behav Neurosci, I-00161 Rome, Italy. [Curley, James P.; Champagne, Frances A.] Columbia Univ, Dept Psychol, New York, NY 10027 USA. [D'Andrea, Ivana] Neuromed Inst, Dept Neuro & Cardiovasc Pathol, I-86077 Pozzilli, IS, Italy. RP Branchi, I (reprint author), Ist Super Sanita, Dept Cell Biol & Neurosci, Sect Behav Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. EM igor.branchi@iss.it FU Italian Ministry of Health [11US/1, RF-2009-1498890]; Office of the Director, National Institutes of Health [DP2OD001675] FX This study was supported by the Italian Ministry of Health, projects 11US/1 to EA and RF-2009-1498890 to FC. FAC and JPC are supported by grant number DP2OD001675 from the Office of the Director, National Institutes of Health. The mentioned granting agencies had no further role in study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the paper for publication. 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EM cal2028@med.cornell.edu CR Abel KM, 2013, AM J PSYCHIAT, V170, P391, DOI 10.1176/appi.ajp.2012.12040543 Autism and Developmental Disabilities Monitoring Network Surveillance Principal Investigators, 2012, MMWR SURVEILL SUMM, V61, P1 Dawson G, 2010, PEDIATRICS, V125, pE17, DOI 10.1542/peds.2009-0958 Durkin MS, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0011551 Gardener H, 2011, PEDIATRICS, V128, P344, DOI 10.1542/peds.2010-1036 Idring S, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0041280 Johnson MB, 2009, NEURON, V62, P494, DOI 10.1016/j.neuron.2009.03.027 LeCouteur A, 1996, J CHILD PSYCHOL PSYC, V37, P785 Lin Sue C, 2012, Pediatrics, V130 Suppl 2, pS191, DOI 10.1542/peds.2012-0900R Magnusson C, 2012, BRIT J PSYCHIAT, V201, P109, DOI 10.1192/bjp.bp.111.095125 NR 10 TC 0 Z9 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2013 VL 170 IS 4 BP 355 EP 358 DI 10.1176/appi.ajp.2013.13010078 PG 4 WC Psychiatry SC Psychiatry GA 117AW UT WOS:000316925500002 PM 23545788 ER PT J AU Abel, KM Dalman, C Svensson, AC Susser, E Dal, H Idring, S Webb, RT Rai, D Magnusson, C AF Abel, Kathryn M. Dalman, Christina Svensson, Anna C. Susser, Ezra Dal, Henrik Idring, Selma Webb, Roger T. Rai, Dheeraj Magnusson, Cecilia TI Deviance in Fetal Growth and Risk of Autism Spectrum Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BIRTH-WEIGHT INFANTS; GESTATIONAL-AGE; SOCIOECONOMIC-STATUS; PERINATAL FACTORS; TWIN PAIRS; POPULATION; COHORT; SCHIZOPHRENIA; DISABILITIES; PREVALENCE AB Objective: Understanding the relationship between fetal growth and autism spectrum disorder (ASD) is likely to advance the search for genetic and nongenetic causes of ASD. The authors explored the associations between fetal growth, gestational age, and ASD with and without comorbid intellectual disability in a Scandinavian study population. Method: The authors conducted a matched nested case-control study within the Stockholm Youth Cohort that included all children ages 0-17 who resided in Stockholm County from 2001 to 2007 (N=589,114). The authors identified 4,283 children with ASD: 1,755 with intellectual disability and 2,528 without, and they selected 36,588 age- and sex-matched comparison subjects. ASD case subjects were ascertained from unique identifiers assigned to all Swedish residents and linkage with official registers covering all pathways of assessment or care of ASD in Stockholm County. The authors calculated z scores of deviance in fetal growth from a reference curve using records from the national Swedish Medical Birth Registry, which included ultrasound dating of gestational age as well as birth weight. Crude and adjusted odds ratios for ASD, ASD with intellectual disability, and ASD without intellectual disability were the main outcome measures. Results: ASD risk increased with fetal growth 1.50 standard deviations below and >2.00 standard deviations above the mean for gestational age; the greatest risk was for fetal growth that was less than 2.00 standard deviations below the mean (adjusted odds ratio=1.70; 95% CI=1.44-2.01) or greater than 2.00 standard deviations above the mean (adjusted. odds ratio=1.50; 95% CI=1.27-1.77). The same overall pattern was observed for ASD with and without intellectual disabilities. However, poor fetal growth (i.e., growth below the mean) was more strongly associated with ASD with intellectual disabilities than without. Regardless of fetal growth, preterm birth increased ASD risk. Conclusions: Deviance in fetal growth at either distributional extreme may be a significant antecedent to the development of ASD through genetic and/or nongenetic mechanisms. (Am J Psychiatry 2013; 170:391-398) C1 [Abel, Kathryn M.] Univ Manchester, Ctr Womens Mental Hlth, Manchester M13 9PL, Lancs, England. Univ Manchester, Manchester Acad Hlth Sci Ctr, Ctr Mental Hlth & Risk, Manchester M13 9PL, Lancs, England. Karolinska Univ Hosp, Karolinska Inst, Div Publ Hlth Epidemiol, Dept Publ Hlth Sci,Norrbacka, Stockholm, Sweden. Univ Bristol, Acad Unit Psychiat, Sch Social & Community Med, Bristol BS8 1TH, Avon, England. Avon & Wiltshire Partnership NHS Mental Hlth Trus, Bristol, Avon, England. Columbia Univ, Imprints Ctr Genet & Environm Life Course Studies, Mailman Sch Publ Hlth, New York, NY USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. RP Abel, KM (reprint author), Univ Manchester, Ctr Womens Mental Hlth, Manchester M13 9PL, Lancs, England. 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J. Psychiat. PD APR PY 2013 VL 170 IS 4 BP 391 EP 398 DI 10.1176/appi.ajp.2012.12040543 PG 8 WC Psychiatry SC Psychiatry GA 117AW UT WOS:000316925500009 PM 23545793 ER PT J AU Ritvo, ER Ritvo, RA AF Ritvo, Edward R. Ritvo, Riva Ariella TI Commentary on the Application of DSM-5 Criteria for Autism Spectrum Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Ritvo, Edward R.] Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. RP Ritvo, ER (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. CR Huerta M, 2012, AM J PSYCHIAT, V169, P1056, DOI 10.1176/appi.ajp.2012.12020276 NR 1 TC 3 Z9 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2013 VL 170 IS 4 BP 444 EP 445 DI 10.1176/appi.ajp.2013.12101376 PG 2 WC Psychiatry SC Psychiatry GA 117AW UT WOS:000316925500018 PM 23545801 ER PT J AU Huerta, M Bishop, SL Duncan, A Hus, V Lord, C AF Huerta, Marisela Bishop, Somer L. Duncan, Amie Hus, Vanessa Lord, Catherine TI Commentary on the Application of DSM-5 Criteria for Autism Spectrum Disorder Response SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Huerta, Marisela] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. Cincinnati Childrens Hosp Med, Div Dev & Behav Pediat, Cincinnati, OH USA. Univ Michigan, Dept Psychol, Ann Arbor, MI USA. RP Huerta, M (reprint author), Weill Cornell Med Coll, Dept Psychiat, White Plains, New York, NY USA. CR Grzadzinski R, MOL AUTISM IN PRESS Huerta M, 2012, AM J PSYCHIAT, V169, P1056, DOI 10.1176/appi.ajp.2012.12020276 Lord C, 2012, ARCH GEN PSYCHIAT, V69, P306, DOI 10.1001/archgenpsychiatry.2011.148 Macintosh KE, 2004, J CHILD PSYCHOL PSYC, V45, P421, DOI 10.1111/j.1469-7610.2004.00234.x Swedo SE, 2012, J AM ACAD CHILD PSY, V51, P347, DOI 10.1016/j.jaac.2012.02.013 Szatmari P, 2009, J CHILD PSYCHOL PSYC, V50, P1459, DOI 10.1111/j.1469-7610.2009.02123.x NR 6 TC 1 Z9 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2013 VL 170 IS 4 BP 445 EP 446 DI 10.1176/appi.ajp.2013.12101376r PG 2 WC Psychiatry SC Psychiatry GA 117AW UT WOS:000316925500019 PM 23545798 ER PT J AU Crump, C Rivera, D London, R Landau, M Erlendson, B Rodriguez, E AF Crump, Casey Rivera, Diana London, Rebecca Landau, Melinda Erlendson, Bill Rodriguez, Eunice TI Chronic health conditions and school performance among children and youth SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Achievement; Chronic disease; Schools; Students ID ATTENTION-DEFICIT HYPERACTIVITY; HUMAN-CAPITAL ACCUMULATION; ACADEMIC-PERFORMANCE; UNITED-STATES; MENTAL-HEALTH; FOLLOW-UP; ASTHMA; ADHD; ACHIEVEMENT; CHILDHOOD AB Purpose: Chronic health conditions are common and increasing among U.S. children and youth. We examined whether chronic health conditions are associated with low school performance. Methods: This retrospective cohort study of 22,730 children and youth (grades 2-11) in San Jose, California, was conducted from 2007 through 2010. Health conditions were defined as chronic if reported in each of the first 2 years, and school performance was measured using standardized English language arts (ELA) and math assessments. Results: Chronic health conditions were independently associated with low ELA and math performance, irrespective of ethnicity, socioeconomic status, or grade level. Adjusted odds ratios for the association between any chronic health condition and low ("basic or below") performance were 1.25 (95% confidence interval [CI], 1.16-1.36; P < .001) for ELA and 1.28 (95% CI, 1.18-1.38; P < .001) for math, relative to students without reported health conditions. Further adjustment for absenteeism had little effect on these results. The strongest associations were found for ADHD, autism, and seizure disorders, whereas a weak association was found for asthma before but not after adjusting for absenteeism, and no associations were found for cardiovascular disorders or diabetes. Conclusions: Chronic neurodevelopmental and seizure disorders, but not cardiovascular disorders or diabetes, were independently associated with low school performance among children and youth. (c) 2013 Elsevier Inc. All rights reserved. C1 [Crump, Casey] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Rivera, Diana; Rodriguez, Eunice] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [London, Rebecca] Stanford Univ, Grad Sch Educ, John W Gardner Ctr, Stanford, CA 94305 USA. [Landau, Melinda; Erlendson, Bill] San Jose Unified Sch Dist, San Jose, CA USA. RP Crump, C (reprint author), 211 Quarry Rd,Suite 405,MC 5985, Palo Alto, CA 94304 USA. EM kccrump@stanford.edu FU Lucile Packard Foundation for Children's Health; Lucile Packard Children's Hospital, Palo Alto, California FX Supported in part by grants from the Lucile Packard Foundation for Children's Health and the Lucile Packard Children's Hospital, Palo Alto, California. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. There were no conflicts of interest. 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The present study was designed to trial a procedure comprised of escape extinction combined with positive reinforcement with the aim to reduce food refusals and increase eating in a child with autism. It was predicted that the intervention package would significantly reduce food refusals and increase eating and that any increase in food acceptance would be maintained and generalised to other behaviours related to feeding on termination of the intervention. The research design was a multiple baseline across settings. The results confirmed our predictions. It was concluded that the treatment package was effective at increasing food acceptance. C1 [Bui, Lilly T. D.; Moore, Dennis W.; Anderson, Angelika] Monash Univ, Melbourne, Vic 3800, Australia. RP Bui, LTD (reprint author), Monash Univ, Krongold Ctr, Fac Educ, Clayton Campus, Melbourne, Vic 3800, Australia. 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Change PD APR PY 2013 VL 30 IS 1 BP 48 EP 55 DI 10.1017/bec.2013.5 PG 8 WC Psychology, Clinical SC Psychology GA 117VC UT WOS:000316980200005 ER PT J AU Satpute, AB Shu, J Weber, J Roy, M Ochsner, KN AF Satpute, Ajay B. Shu, Jocelyn Weber, Jochen Roy, Mathieu Ochsner, Kevin N. TI The Functional Neural Architecture of Self-Reports of Affective Experience SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Affect; emotion; fMRI; mental state attribution; neuroimaging; self-report ID AUTISM SPECTRUM DISORDERS; MEDIAL PREFRONTAL CORTEX; HUMAN AMYGDALA; EMOTIONAL RESPONSES; MAGNETIC-RESONANCE; EMPATHIC ACCURACY; COGNITIVE CONTROL; MAJOR DEPRESSION; SOCIAL COGNITION; ACTIVATION AB Background: The ability to self-report on affective experience is essential to both our everyday communication about emotion and our scientific understanding of it. However, the underlying cognitive and neural mechanisms for how people construct statements even as simple as "I feel bad!" remain unclear. We examined whether the neural architecture underlying the ability to make statements about affective experience is composed of distinct functional systems. Methods: In a novel functional magnetic neuroimaging paradigm, 20 participants were shown images varying in affective intensity; they were required either to attend to and judge the affective response versus to nonaffective aspects of the stimulus and either to categorize their response into a verbal label or report on a scale that did not require verbal labeling. Results: We found that the ability to report on affective states involves (at least) three separable systems, one for directing attention to the affective response and making attributions about it that involves the dorsomedial prefrontal cortex, one for categorizing the response into a verbal label or word that involves the ventrolateral prefrontal cortex, and one sensitive to the intensity of the affective response including the ventral anterior insula and amygdala. Conclusions: These results suggest that unified statements about affective experience rely on integrating information from several distinct neural systems. Results are discussed in the context of how disruptions to one or another of these systems may produce unique deficits in the ability to describe affective states and the implications this may hold for clinical populations. C1 [Satpute, Ajay B.] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Shu, Jocelyn; Weber, Jochen; Roy, Mathieu; Ochsner, Kevin N.] Columbia Univ, Dept Psychol, New York, NY 10025 USA. [Roy, Mathieu] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. RP Ochsner, KN (reprint author), Columbia Univ, Dept Psychol, 1190 Amsterdam Ave,MC 5501, New York, NY 10025 USA. EM ochsner@psych.columbia.edu FU National Institutes of Health [1 R01 MH076137-01 A1] FX This research was supported by National Institutes of Health Grant No. 1 R01 MH076137-01 A1 awarded to Kevin Ochsner. 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In the second case (a 12-year-old female), achalasia was diagnosed with barium swallow and esophageal manometry and was treated with Heller myotomy after two unsuccessful pneumatic endoscopic attempts (follow-up: 3 months). In the last case, a 15-year-old male underwent barium swallow and endoscopy that confirmed achalasia. He was treated with Heller myotomy, and he is asymptomatic at a 6-month follow-up. To our knowledge, this is the first report of a possible association between autism and esophageal achalasia. Because of the rarity of both diseases, their association in the same patient is unlikely to be casual even if speculation on their common etiology is impossible at present. This finding needs further confirmation, but it is sufficient, in our opinion, to indicate proper evaluation with barium swallow and/or manometry in any autistic children with eating difficulty. 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Child Adolesc. Psych. PD APR PY 2013 VL 22 IS 4 BP 217 EP 223 DI 10.1007/s00787-012-0338-x PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 118EY UT WOS:000317007400003 PM 23065028 ER PT J AU Chen, LS Xu, L Huang, TY Dhar, SU AF Chen, Lei-Shih Xu, Lei Huang, Tse-Yang Dhar, Shweta U. TI Autism genetic testing: a qualitative study of awareness, attitudes, and experiences among parents of children with autism spectrum disorders SO GENETICS IN MEDICINE LA English DT Article DE attitude; autism spectrum disorders; awareness; genetic testing; parents ID FRAGILE-X-SYNDROME; CANCER; PEDIATRICIANS; MUTATIONS; KNOWLEDGE; PHYSICIAN; BELIEFS; BRCA2 AB Purpose: The goal of this first-of-its-kind qualitative study was to examine the awareness, attitudes, and experiences among parents of autistic children regarding autism genetic testing. Methods: We conducted in-depth, individual, and semistructured interviews with 42 parents of autistic children with diverse racial/ethnic backgrounds. All interviews were audio-taped, transcribed, and coded into major themes and subthemes. Results: Approximately one-quarter of participants had two or more autistic children, and about half of them were ethnic/racial minorities. The majority of participants postulated favorable attitudes toward autism genetic testing for three main reasons: early intervention and treatment, identifying the etiology of autism, and informed family planning. Nevertheless, among parents who had taken their children for genetic testing, some expressed frustration and questioned the competency of their providers in interpreting test results. Asian parents and those with a low socioeconomic status expressed lower awareness and tended to have more limited access to autism genetic testing. Conclusion: As health-care providers play a vital role in providing genetic services and education, these professionals should be educated and be sensitive to the needs of parents with autistic children. Further quantitative research is required to examine the effects of socio-demographic factors on parents' awareness, attitudes, and experiences regarding autism genetic testing. Genet Med 2013:15(4):274-281 C1 [Chen, Lei-Shih; Xu, Lei] Texas A&M Univ, Dept Hlth & Kinesiol, College Stn, TX 77840 USA. [Huang, Tse-Yang] Natl Hsinchu Univ Educ, Dept Special Educ, Hsinchu, Taiwan. [Dhar, Shweta U.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Chen, LS (reprint author), Texas A&M Univ, Dept Hlth & Kinesiol, College Stn, TX 77840 USA. EM lace@hlkn.tamu.edu FU Texas AM University FX This study was funded through Lei-Shih Chen's grant-Texas A&M University's Program to Enhance Scholarly and Creative Activities. We thank Tung-Sung Tseng, Laura Stough, Elsa M. Gonzalez y Gonzalez, Corey Parshall, Allison Hollek, Eunju Jung, and Champa Joshi for their assistance with this study. 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Med. PD APR PY 2013 VL 15 IS 4 BP 274 EP 281 DI 10.1038/gim.2012.145 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 118OR UT WOS:000317035400006 PM 23288207 ER PT J AU Dolcetti, A Silversides, CK Marshall, CR Lionel, AC Stavropoulos, DJ Scherer, SW Bassett, AS AF Dolcetti, Alessia Silversides, Candice K. Marshall, Christian R. Lionel, Anath C. Stavropoulos, Dimitri J. Scherer, Stephen W. Bassett, Anne S. TI 1q21.1 Microduplication expression in adults SO GENETICS IN MEDICINE LA English DT Article DE 1q21.1 duplication; copy-number variation; macrocephaly; schizophrenia; tetralogy of Fallot ID COPY NUMBER VARIANTS; CONGENITAL HEART-DISEASE; DE-NOVO CNVS; CHROMOSOME 1Q21.1; BIPOLAR-DISORDER; HUMAN GENOME; SCHIZOPHRENIA; AUTISM; DUPLICATIONS; REARRANGEMENTS AB Purpose: Rare, recurrent chromosome 1q21.1 duplications have been associated with developmental delay, congenital anomalies, and macrocephaly in children. Data on adult clinical expression would help to inform genetic counseling. Methods: A systematic review of 22 studies reporting 107 individuals (59 children and 48 adults) with 1q21.1 duplications was conducted. We compiled the available phenotypic data to attempt to identify the most highly associated clinical features and to determine expression in adults. We also report on seven adult cases newly identified in the studies of schizophrenia and tetralogy of Fallot at our center. Results: Five cases were ascertained as controls, 32 as relatives of probands, and 70 as having clinical features: autism spectrum disorder (n = 15), congenital heart disease (n = 12), schizophrenia (n = 10), or other, mostly developmental, features (n = 33). The 1q21.1 duplication was significantly enriched in the cohorts with schizophrenia (P = 0.0155) and tetralogy of Fallot (P = 0.0040) at our center as compared with controls. There was a paucity of clinical data for adults; the most common features, other than those used for ascertainment, included macrocephaly and abnormalities of possible connective tissue origin (e. g., carpal tunnel syndrome). Conclusion: Further data are needed to characterize lifetime expression of 1q21.1 duplications. These initial results, however, suggest that anticipatory care should include attention to later-onset conditions such as schizophrenia. Genet Med 2013:15(4):282-289 C1 [Dolcetti, Alessia; Bassett, Anne S.] Ctr Addict & Mental Hlth, Clin Genet Res Program, Toronto, ON, Canada. [Silversides, Candice K.; Bassett, Anne S.] Univ Hlth Network, Dept Med, Div Cardiol, Toronto, ON, Canada. [Silversides, Candice K.] Toronto Gen Hosp, Toronto Congenital Cardiac Ctr Adults, Toronto, ON, Canada. [Marshall, Christian R.; Lionel, Anath C.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. [Marshall, Christian R.; Lionel, Anath C.; Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Marshall, Christian R.; Lionel, Anath C.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Marshall, Christian R.; Lionel, Anath C.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. [Stavropoulos, Dimitri J.] Hosp Sick Children, Cytogenet Lab, Dept Pediat Lab Med, Toronto, ON M5G 1X8, Canada. [Stavropoulos, Dimitri J.] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON, Canada. [Bassett, Anne S.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. RP Bassett, AS (reprint author), Ctr Addict & Mental Hlth, Clin Genet Res Program, Toronto, ON, Canada. EM anne.bassett@utoronto.ca RI Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU Canadian Institutes of Health Research [MOP-89066, MOP-53216, MOP-97800]; University of Toronto FX This study was supported by Canadian Institutes of Health Research grants (MOP-89066, MOP-53216, and MOP-97800) and a University of Toronto Excellence Award in the Social Sciences and Humanities (to A. D.). A. S. B. holds the Canada Research Chair in Schizophrenia Genetics and Genomic Disorders. The authors thank the patients and their families for their participation, research assistants and staff at the Toronto Congenital Cardiac Centre for Adults, staff at The Centre for Applied Genomics, and fellows and students who assisted in the collection and analysis of data. 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Our pilot project demonstrates how picture schedules for medical settings can relieve anxiety in children with autism and suggests that this approach should be employed as an innovative way to interact with patients with autism. (C) 2013 Elsevier Inc. All rights reserved. C1 [Chebuhar, Amy] Southeast Polk Community Sch Dist, Altoona, IA USA. [McCarthy, Ann Marie] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Bosch, Joni] Univ Iowa, Childrens Hosp, Iowa City, IA USA. [Baker, Sue] Univ Iowa, Child Hlth Specialty Clin, Iowa Dept Educ, Iowa City, IA USA. RP Chebuhar, A (reprint author), Southeast Polk Community Sch Dist, Altoona, IA USA. EM Amy.chebuhar@southeastpolk.org FU University of Iowa Hospitals and Clinics Children's Miracle Network; University of Iowa Hospitals and Clinics Process Improvement Grant FX This project was funded by the University of Iowa Hospitals and Clinics Children's Miracle Network and by a University of Iowa Hospitals and Clinics Process Improvement Grant. 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PD APR PY 2013 VL 28 IS 2 BP 125 EP 134 DI 10.1016/j.pedn.2012.05.004 PG 10 WC Nursing; Pediatrics SC Nursing; Pediatrics GA 115WN UT WOS:000316842700004 PM 22742928 ER PT J AU Hoogsteen, L Woodgate, RL AF Hoogsteen, Lindsey Woodgate, Roberta Lynne TI Centering Autism Within the Family: A Qualitative Approach to Autism and the Family SO JOURNAL OF PEDIATRIC NURSING-NURSING CARE OF CHILDREN & FAMILIES LA English DT Article DE Autism; Qualitative research method; Health care professionals ID HEALTH-CARE NEEDS; SPECTRUM DISORDERS; CHILDREN; DISABILITIES; PARENTS; MANAGEMENT; STIGMA AB The lived experience of parents of children with autism living in a rural area was explored through a phenomenological approach. Twenty-eight parents from multiple rural communities participated in semi-structured interviews. Van Manen's (1990) selective highlighting approach was used to isolate thematic statements of the experience. Findings revealed that autism became centered within the family thereby affecting how parents parented. Parenting now included: (a) multiple roles; (b) an intense focus on their child's needs; and (c) finding a balance. Although parents acquired multiple roles and faced many unmet needs, parents were determined to strive for balance within the family. (C) 2013 Elsevier Inc. All rights reserved. C1 [Hoogsteen, Lindsey; Woodgate, Roberta Lynne] Univ Manitoba, Fac Nursing, Winnipeg, MB, Canada. RP Hoogsteen, L (reprint author), Univ Manitoba, Fac Nursing, Winnipeg, MB, Canada. EM umhoogsl@cc.umanitoba.ca RI Woodgate, Roberta/B-9038-2014 FU Manitoba Health Research Council; Foundation for Registered Nurses of Manitoba Inc; Child Health Graduate Studentship FX Dr. Woodgate has a Manitoba Research Chair awarded by the Manitoba Health Research Council.The authors disclosed receipt of this following financial support for the research and/or authorship of this article: The Foundation for Registered Nurses of Manitoba Inc and the Child Health Graduate Studentship. CR Behrman RE, 2000, NELSON TXB PEDIAT Brandon P, 2007, SOC SCI MED, V65, P667, DOI 10.1016/j.socscimed.2007.04.007 Bryson SE, 2003, CAN J PSYCHIAT, V48, P506 Carbone PS, 2010, AM FAM PHYSICIAN, V81, P453 Caronna EB, 2008, ARCH DIS CHILD, V93, P518, DOI 10.1136/adc.2006.115337 Cashin A. 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TI THE BORDERLINE EMPATHY PARADOX: EVIDENCE AND CONCEPTUAL MODELS FOR EMPATHIC ENHANCEMENTS IN BORDERLINE PERSONALITY DISORDER SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID HIGH-FUNCTIONING AUTISM; EMOTIONAL INTELLIGENCE; FACIAL EXPRESSIONS; ASPERGER-SYNDROME; REJECTION SENSITIVITY; SOCIAL COGNITION; MIND; RECOGNITION; SCHIZOPHRENIA; ADULTS AB Empirical evidence and therapeutic interactions have suggested that individuals with borderline personality disorder (BPD) may demonstrate enhancements in aspects of social-emotional cognition. To assess the empirical evidence for this phenomenon, and to comprehensively evaluate alternative hypotheses for its possible role in BPD etiology and symptoms, the authors systematically searched the literature for investigations of empathy in BPD and reviewed 28 studies assessing a range of empathic abilities. Considered together, these data demonstrated comparable levels of evidence for enhanced, preserved, and reduced empathic skills in individuals with BPD. Evidence for empathic enhancements is thus substantial but inconsistent across studies, being found mainly under more socially interactive experimental paradigms. Based on the results of the review and previous explanations for BPD symptoms, the authors propose a new model for explaining the borderline paradox: that a combination of increased attention to social stimuli and dysfunctional social information processing may account in part for the specific empathic enhancements and reduced overall social functioning in BPD. C1 [Dinsdale, Natalie; Crespi, Bernard J.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. RP Crespi, BJ (reprint author), Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. 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