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PD MAY PY 2014 VL 210 IS 5 BP 496 EP 496 DI 10.1016/j.ajog.2014.02.016 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AG6EF UT WOS:000335510700044 PM 24534185 ER PT J AU Milosavljevic, N Monet, M Lena, I Brau, F Lacas-Gervais, S Feliciangeli, S Counillon, L Poet, M AF Milosavljevic, Nina Monet, Michael Lena, Isabelle Brau, Frederic Lacas-Gervais, Sandra Feliciangeli, Sylvain Counillon, Laurent Poet, Mallorie TI The Intracellular Na+/H+ Exchanger NHE7 Effects a Na+-Coupled, but Not K+-Coupled Proton-Loading Mechanism in Endocytosis SO CELL REPORTS LA English DT Article ID LYSOSOMAL STORAGE DISEASE; TRANS-GOLGI NETWORK; MENTAL-RETARDATION; H+-ATPASE; PH; ENDOSOMES; CHLORIDE; SLC9A6; MUTATION; PATHWAY AB Vesicular H+-ATPases and ClC-chloride transporters are described to acidify intracellular compartments, which also express the highly conserved Na+/H+ exchangers NHE6, NHE7, and NHE9. Mutations of these exchangers cause autism-spectrum disorders and neurodegeneration. NHE6, NHE7, and NHE9 are hypothesized to exchange cytosolic K+ for H+ and alkalinize vesicles, but this notion has remained untested in K+ because their intracellular localization prevents functional measurements. Using protonkilling techniques, we selected a cell line that expresses wild-type NHE7 at the plasma membrane, enabling measurement of the exchanger's transport parameters. We found that NHE7 transports Li+ and Na+, but not K+, is nonreversible in physiological conditions and is constitutively activated by cytosolic H+. Therefore, NHE7 acts as a proton-loading transporter rather than a proton leak. NHE7 mediates an acidification of intracellular vesicles that is additive to that of V-ATPases and that accelerates endocytosis. This study reveals an unexpected function for vesicular Na+/H+ exchangers and provides clues for understanding NHE-linked neurological disorders. C1 [Milosavljevic, Nina; Monet, Michael; Lena, Isabelle; Counillon, Laurent; Poet, Mallorie] Univ Nice Sophia Antipolis, LP2M, CNRS UMR 7370, Fac Med, F-06107 Nice, France. [Brau, Frederic; Feliciangeli, Sylvain] Univ Nice Sophia Antipolis, IPMC, CNRS UMR 7275, F-06560 Valbonne, France. [Lacas-Gervais, Sandra] Univ Nice Sophia Antipolis, CCMA, Fac Sci, F-06108 Nice, France. RP Counillon, L (reprint author), Univ Nice Sophia Antipolis, LP2M, CNRS UMR 7370, Fac Med, 28 Ave Valombrose, F-06107 Nice, France. EM laurent.counillon@unice.fr FU University of Nice-Sophia Antipolis; ANR (JCJC SVSE1 NHEint); Basileus EMECW FX This work was supported by the University of Nice-Sophia Antipolis, the ANR (JCJC SVSE1 NHEint), and the CNRS. N.M. was funded by the Basileus EMECW project. We thank Drs. Jacques Barhanin (LP2M CNRS-UMR 7370), Bruno Antonny (IPMC, CNRS-UMR 7275), and Mireille Cormont (C3M INSERM-U 1065) for fruitful discussions, Dr. Ellen Van Obberghen-Schilling (IBV CNRS-UMR 7277) for critical reading of the manuscript, and Fabien Labbal (LP2M CNRS-UMR 7370) for assistance in cell culture. 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Recently, many studies have pointed out that synaptic protein-associated mutations may lead to dysfunctions of social cognition. Dlgap2, which encodes one of the main components of scaffold proteins in postsynaptic density (PSD), has been addressed as a candidate gene in autism spectrum disorders. To elucidate the disturbance of synaptic balance arising from Dlgap2 loss-of-function in vivo, we thus generated Dlgap2(-/-) mice to investigate their phenotypes of synaptic function and social behaviors. Methods: The creation of Dlgap2(-/-) mice was facilitated by the recombineering-based method, Cre-loxP system and serial backcross. Reversal learning in a water T-maze was used to determine repetitive behaviors. The three-chamber approach task, resident-intruder test and tube task were performed to characterize the social behaviors of mutant mice. Cortical synaptosomal fraction, Golgi-Cox staining, whole-cell patch electrophysiology and transmission electron microscopy were all applied to investigate the function and structure of synapses in the orbitofrontal cortex (OFC) of Dlgap2(-/-) mice. Results: Dlgap2(-/-) mice displayed exacerbated aggressive behaviors in the resident-intruder task, and elevated social dominance in the tube test. In addition, Dlgap2(-/-) mice exhibited a clear reduction of receptors and scaffold proteins in cortical synapses. Dlgap2(-/-) mice also demonstrated lower spine density, decreased peak amplitude of miniature excitatory postsynaptic current and ultra-structural deficits of PSD in the OFC. Conclusions: Our findings clearly demonstrate that Dlgap2 plays a vital role in social behaviors and proper synaptic functions of the OFC. Moreover, these results may provide valuable insights into the neuropathology of autism. C1 [Jiang-Xie, Li-Feng; Liao, Hsiao-Mei; Chen, Chia-Hsiang; Gau, Susan Shur-Fen] Natl Taiwan Univ Hosp, Dept Psychiat, Taipei 10002, Taiwan. [Jiang-Xie, Li-Feng; Chen, Yuh-Tarng; Lee, Li-Jen; Liou, Horng-Huei; Fu, Wen-Mei; Gau, Susan Shur-Fen] Natl Taiwan Univ, Grad Inst Brain & Mind Sci, Taipei, Taiwan. [Chen, Chia-Hsiang] Chang Gung Mem Hosp Linkou, Dept Psychiat, Taoyuan, Taiwan. [Chen, Chia-Hsiang] Chang Gung Univ, Dept & Grad Inst Biomed Sci, Taoyuan, Taiwan. [Ho, Shih-Yin; Lu, Dai-Hua; Liou, Horng-Huei; Fu, Wen-Mei] Natl Taiwan Univ, Coll Med, Sch Med, Dept Pharmacol, Taipei 10051, Taiwan. [Lee, Li-Jen] Natl Taiwan Univ, Coll Med, Dept Anat & Cell Biol, Taipei, Taiwan. RP Fu, WM (reprint author), Natl Taiwan Univ Hosp, Dept Psychiat, 7 Chung Shan South Rd, Taipei 10002, Taiwan. EM wenmei@ntu.edu.tw; gaushufe@ntu.edu.tw FU National Science Council, Taiwan [NSC 97-3112-B-002-009, NSC 98-3112-B-002-004, NSC 99-3112-B-002-036, NSC 101-2314-B-002-136-MY3]; National Taiwan University Hospital [NTUH 100-S1525]; National Taiwan University (AIM for Top University Excellent Research Project) [10R81918-03101R892103, 102R892103] FX This work was supported by National Science Council, Taiwan (NSC 97-3112-B-002-009, NSC 98-3112-B-002-004, NSC 99-3112-B-002-036 and NSC 101-2314-B-002-136-MY3 to SSG), National Taiwan University Hospital (NTUH 100-S1525 to SSG) and National Taiwan University (AIM for Top University Excellent Research Project: 10R81918-03101R892103, 102R892103 to SSG). We thank the technical services provided by the Transgenic Mouse Model Core Facility of the National Core Facility Program for Biotechnology, the National Science Council and the Gene Knockout Mouse Core Laboratory of the National Taiwan University Center of Genomic Medicine. We would like to express our thanks to Su-Mei Lai for assisting in creating ultrathin sections for the electron microscopy experiments. 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This range is of interest given the functional need of the visual system both to produce good discrimination of real everyday faces and to process novel kinds of faces that we may encounter. Here, Experiment 1 establishes the boundary of faces judged as being able to occur in everyday life. Experiment 2 then shows that aftereffects increase with adaptor extremity up to this natural-range boundary, drop significantly immediately outside the boundary, and then remain stable with no drop towards zero even for highly distorted adaptors far beyond the boundary. Computational modelling shows that this unexpected pattern cannot be explained either by a simple opponent or by a classic multichannel model. However, its qualitative features can be captured either by a combination of opponent and multichannel coding (raising the possibility that not all identity-related face dimensions are opponent coded), or by a 3-pool model containing two S-shaped-response channels and a central bell-shaped channel around the average face (raising the possibility of unexpected similarities with coding of eye and head direction). (C) 2014 Elsevier Ltd. All rights reserved. C1 [McKone, Elinor] Australian Natl Univ, Res Sch Psychol, Canberra, ACT 0200, Australia. [Jeffery, Linda; Boeing, Alexandra; Rhodes, Gillian] Univ Western Australia, ARC Ctr Excellence Cognit & Its Disorders, Sch Psychol, Nedlands, WA 6009, Australia. [Clifford, Colin W. G.] Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia. RP McKone, E (reprint author), Australian Natl Univ, Sch Psychol, GPO Box 4, Canberra, ACT 0200, Australia. EM elinor.mckone@anu.edu.au FU Australian Research Council Centre of Excellence in Cognition and its Disorders [CE110001021]; ARC Professorial Fellowship [DP0877379]; ARC Queen Elizabeth II Fellowship [DP0984558]; Australian Research Council Future Fellowship [FT110100150] FX This research was supported by the Australian Research Council Centre of Excellence in Cognition and its Disorders (CE110001021), an ARC Professorial Fellowship to Rhodes (DP0877379), an ARC Queen Elizabeth II Fellowship to McKone (DP0984558), and Australian Research Council Future Fellowship to Clifford (FT110100150). We thank Eleni Avard and Stephen Pond for assistance with testing, Stephen Pond for preparing the figures and Mayu Nishimura and Daphne Maurer for co-creating the "Robbers Task". Ethical approval was granted by the Human Research Ethics Committee of the University of Western Australia. 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PD MAY PY 2014 VL 98 BP 1 EP 13 DI 10.1016/j.visres.2014.01.007 PG 13 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA AG7UJ UT WOS:000335624000001 PM 24582798 ER PT J AU Zuckerman, KE Sinche, B Mejia, A Cobian, M Becker, T Nicolaidis, C AF Zuckerman, Katharine E. Sinche, Brianna Mejia, Angie Cobian, Martiza Becker, Thomas Nicolaidis, Christina TI Latino Parents' Perspectives on Barriers to Autism Diagnosis SO ACADEMIC PEDIATRICS LA English DT Article DE autism spectrum disorder; delayed diagnosis; health services accessibility; Hispanic Americans; qualitative research ID SPECTRUM DISORDERS; ETHNIC DISPARITIES; EARLY INTERVENTION; HEALTH-CARE; SERVICE USE; CHILDREN; ACCESS; AGE; IDENTIFICATION; INFORMATION AB OBJECTIVE: Latino children are diagnosed with autism spectrum disorders (ASDs) at older ages and at the point of more severe symptoms. We sought to qualitatively describe community, family, and health care system barriers to ASD diagnosis in Latino children. METHODS: Five focus groups and 4 qualitative interviews were conducted with 33 parents of Latino children previously diagnosed with an ASD. Participants described Latino community perceptions of autism and barriers they experienced during the diagnostic process. Sessions were audiorecorded and transcribed. Transcripts were coded by 2 researchers, and data were analyzed using thematic, analysis. RESULTS: Parents reported low levels of ASD information and high levels of mental health and disability stigma in the Latino community. Parents had poor access to care as a result of poverty, limited English proficiency, and lack of empowerment to take advantage of services. Providers sometimes dismissed parents' concerns. The ASD diagnostic process itself was slow, inconvenient, confusing, and uncomfortable for the child. These factors led many parents to normalize their child's early behaviors, deny that a problem existed, and lose trust in the medical system. CONCLUSIONS: Additional educational outreach to Latino families, destigmatization of ASD, streamlining the ASD diagnostic process, and providing additional support to Latino parents of at-risk children may decrease delays in ASD diagnosis among Latino, children. C1 [Zuckerman, Katharine E.; Sinche, Brianna; Mejia, Angie; Cobian, Martiza] Oregon Hlth & Sci Univ, Child & Adolescent Hlth Measurement Initiat, Portland, OR 97239 USA. [Zuckerman, Katharine E.] Oregon Hlth & Sci Univ, Div Gen Pediat, Portland, OR 97239 USA. [Mejia, Angie] Syracuse Univ, Dept Sociol, Syracuse, NY USA. [Cobian, Martiza] Univ Pacific, Dept Psychol, Hillsboro, OR USA. [Becker, Thomas; Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Internal Med & Geriatr, Portland, OR 97239 USA. [Nicolaidis, Christina] Portland State Univ, Sch Social Work, Portland, OR 97207 USA. RP Zuckerman, KE (reprint author), Oregon Hlth & Sci Univ, 707 SW Gaines Rd,Mail Code,CDRC P, Portland, OR 97239 USA. EM zuckerma@ohsu.edu FU National Institute of Mental Health [1K23MH095828]; Academic Pediatric Association/Commonwealth Fund Young Investigator Award FX The authors would like to acknowledge Drs Ellen Lipstein and Somnath Saha for their guidance regarding qualitative methods; Dr Christina Bethell for material support; Teresa Gomez and the OHSU Autism Clinic staff for help in recruitment; and Susie Larios and Erendira Valdivia for their helpful perspectives and assistance with data analysis. Funded by grant 1K23MH095828 from the National Institute of Mental Health (PI=Zuckerman); partially funded by an Academic Pediatric Association/Commonwealth Fund Young Investigator Award (PI=Zuckerman). 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PD MAY-JUN PY 2014 VL 14 IS 3 BP 301 EP 308 DI 10.1016/j.acap.2013.12.004 PG 8 WC Pediatrics SC Pediatrics GA AG4CX UT WOS:000335368000013 PM 24767783 ER PT J AU Thakkar, KN Peterman, JS Park, S AF Thakkar, Katharine N. Peterman, Joel S. Park, Sohee TI Altered Brain Activation During Action Imitation and Observation in Schizophrenia: A Translational Approach to Investigating Social Dysfunction in Schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SCALE; PERCEPTION; MECHANISMS; DISORDERS; COGNITION; LANGUAGE; BEHAVIOR; AUTISM; MONKEY; SELF AB Objective: Social impairments are a key feature of schizophrenia, but their underlying mechanisms are poorly understood. Imitation, a process through which we understand the minds of others, involves the so-called mirror neuron system, a network comprising the inferior parietal lobe, inferior frontal gyrus, and posterior superior temporal sulcus. The authors examined mirror neuron system function in schizophrenia. Method: Sixteen medicated schizophrenia patients and 16 healthy comparison subjects performed an action imitation/observation task during functional MRI. Participants saw a video of a moving,hand or spatial cue and were instructed to either execute finger movements associated with the stimulus or simply observe. Activation in the mirror neuron system was measured during imitative versus nonimitative actions and observation of a moving hand versus a moving spatial cue. These contrasts were compared across groubs. Results: Activation in the mirror neuron system was less specific for imitation in schizophrenia. Relative to healthy subjects, patients had reduced activity in the posterior superior temporal sulcus during imitation and greater activity in the posterior superior temporal sulcus and inferior parietal lobe during nonimitative action. Patients also showed reduced activity in these regions during action observation. 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J. Psychiat. PD MAY PY 2014 VL 171 IS 5 BP 539 EP 548 DI 10.1176/appi.ajp.2013.13040498 PG 10 WC Psychiatry SC Psychiatry GA AG0SI UT WOS:000335125500012 PM 24626638 ER PT J AU Karvat, G Segal, H Barzilay, R Ganz, J Barak, N Edry, L Offen, D Kimchi, T AF Karvat, Golan Segal, Hadar Barzilay, Ran Ganz, Javier Barak, Noy Edry, Liat Offen, Daniel Kimchi, Tali TI Mesenchymal Stem Cell Transplantation Promotes Neurogenesis and Ameliorates Autism Related Behaviors in BTBR Mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autism; BTBR; Mesenchymal Stem Cells; BDNF; Neurogenesis C1 [Karvat, Golan; Barak, Noy; Edry, Liat; Offen, Daniel; Kimchi, Tali] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. [Segal, Hadar; Barzilay, Ran; Ganz, Javier] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 44 BP 15S EP 15S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800046 ER PT J AU Sakurai, T Ueda, S AF Sakurai, Takeshi Ueda, Shuhei TI Genes Involved in Williams-Beuren Syndrome and Autism Spectrum Disorders to Study Social Behavior Development SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Williams-Beuren syndrome; Autism spectrum disorders; social behavior; mouse model C1 [Sakurai, Takeshi; Ueda, Shuhei] Kyoto Univ, Grad Sch Med, Med Innovat Ctr, Kyoto, Japan. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 123 BP 38S EP 38S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800117 ER PT J AU Shevelkin, AV Abazyan, BN Button, B Rudow, GL Ross, CA Troncoso, JC Pletnikov, MV AF Shevelkin, Alexey V. Abazyan, Bagrat N. Button, Berry Rudow, Gay L. Ross, Christopher A. Troncoso, Juan C. Pletnikov, Mikhail V. TI Behavioral Phenotyping and Stereological Assessment of Transgenic Mouse Model of Inducible Expression of Mutant DISC1 in Purkinje Cells SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE autism; neurodevelopment; cerebellum; Purkinje cells; DISC1 C1 [Shevelkin, Alexey V.; Abazyan, Bagrat N.; Button, Berry; Ross, Christopher A.; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Shevelkin, Alexey V.] PK Anokhin Inst Norm Physiol, Moscow, Russia. [Rudow, Gay L.; Troncoso, Juan C.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Ross, Christopher A.; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 126 BP 39S EP 39S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800120 ER PT J AU Fineberg, NA AF Fineberg, Naomi A. TI Autistic Traits in Obsessive-compulsive Disorder: A UK Cross-sectional Survey SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Obsessive-compulsive; autistic; ASD; OCD; Autism C1 [Fineberg, Naomi A.] Univ Hertfordshire, Queen Elizabeth II Hosp, Welwyn Garden City, Herts, England. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 209 BP 65S EP 65S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800203 ER PT J AU Solomon, M Lesh, TA Niendam, TA Matter, JC Beck, JS Carter, CS Ragland, JD AF Solomon, Marjorie Lesh, Tyler A. Niendam, Tara A. Matter, John C. Beck, Jonathan S. Carter, Cameron S. Ragland, J. Daniel TI The Neural Substrates of the Generalization of Learning in Autism Spectrum Disorders (ASD) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE autism; learning; fMRI; inference; aolescence C1 [Solomon, Marjorie; Lesh, Tyler A.; Niendam, Tara A.; Matter, John C.; Beck, Jonathan S.; Carter, Cameron S.; Ragland, J. Daniel] Univ Calif Davis, Sacramento, CA 95817 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 208 BP 65S EP 65S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800202 ER PT J AU Gordon, I Vander Wyk, BC Lucas, MV Cordeaux, C Bennett, RH Eilbott, JA Zagoory-Sharon, O Leckman, JF Feldman, R Pelphrey, KA AF Gordon, Ilanit Vander Wyk, Brent C. Lucas, Molly V. Cordeaux, Cara Bennett, Randi H. Eilbott, Jeffrey A. Zagoory-Sharon, Orna Leckman, James F. Feldman, Ruth Pelphrey, Kevin A. TI The Neural Attunement Effects of Oxytocin in Children with Autism Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat C1 [Gordon, Ilanit] Bar Ilan Univ, Ramat Gan, Israel. [Gordon, Ilanit; Vander Wyk, Brent C.; Lucas, Molly V.; Cordeaux, Cara; Bennett, Randi H.; Eilbott, Jeffrey A.; Leckman, James F.; Pelphrey, Kevin A.] Yale Univ, Sch Med, New Haven, CT USA. [Zagoory-Sharon, Orna; Feldman, Ruth] Bar Ilan Univ, Gonda Brain Res Ctr, Ramat Gan, Israel. [Feldman, Ruth] Bar Ilan Univ, Dept Psychol, Ramat Gan, Israel. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 269 BP 84S EP 84S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800263 ER PT J AU Alaerts, K Geerlings, F Herremans, L Swinnen, SP Wenderoth, N AF Alaerts, Kaat Geerlings, Franca Herremans, Lynn Swinnen, Stephan P. Wenderoth, Nicole TI Functional Network Organization of the Action Observation Network in Autism Spectrum Disorders: A Graph Theory Approach. SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autism spectrum disorders; fMRI; Emotion recognition; Action observation network; Graph theory C1 [Alaerts, Kaat; Geerlings, Franca; Herremans, Lynn; Swinnen, Stephan P.] Katholieke Univ Leuven, Movement Control & Neuroplast Res Grp, Leuven, Belgium. [Wenderoth, Nicole] ETH, Neural Control Movement Lab, 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 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 271 BP 85S EP 85S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800265 ER PT J AU Nickl-Jockschat, T Rottschy, C Thommes, J Schneider, F Laird, AR Fox, PT Eickhoff, SB AF Nickl-Jockschat, Thomas Rottschy, Claudia Thommes, Johanna Schneider, Frank Laird, Angela R. Fox, Peter T. Eickhoff, Simon B. TI Evidence for Structure-function Interaction in Dysfunctional Face Processing in Autism Spectrum Disorder (ASD) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE autism; face processing; structure-function relationship; V5; meta-analysis C1 [Nickl-Jockschat, Thomas; Rottschy, Claudia; Thommes, Johanna; Schneider, Frank] Rhein Westfal TH Aachen, Aachen, Germany. [Laird, Angela R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Eickhoff, Simon B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. RI Eickhoff, Simon/K-2061-2013; Fox, Peter/B-4725-2010 OI Eickhoff, Simon/0000-0001-6363-2759; Fox, Peter/0000-0002-0465-2028 NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 274 BP 86S EP 86S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800268 ER PT J AU Koolschijn, PCM Geurts, HM AF Koolschijn, P. Cedric M. Geurts, Hilde M. TI The Neural Correlates of Perceptual Closure in Adults and Elderly with Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autism spectrum disorder; perceptual closure; face-recognition; fMRI; adults and elderly C1 [Koolschijn, P. Cedric M.; Geurts, Hilde M.] Univ Amsterdam, Dutch Autism & ADHD Res Ctr, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 319 BP 101S EP 101S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800313 ER PT J AU Hiroi, N Hiramoto, T Boku, S Takahashi, T Izumi, T Kang, G Hishimoto, A AF Hiroi, Noboru Hiramoto, Takeshi Boku, Shuken Takahashi, Tomohisa Izumi, Takeshi Kang, Gina Hishimoto, Akitoyo TI Identification of Chromosomal Segments and Specific Individual Genes Critical for Schizophrenia-related Phenotypes in Mouse Models of 22q11.2 Copy Number Variants SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE 22q11.2; Copy number variant; autism; schizophrenia; mouse model C1 [Hiroi, Noboru; Hiramoto, Takeshi; Boku, Shuken; Takahashi, Tomohisa; Izumi, Takeshi; Kang, Gina; Hishimoto, Akitoyo] Albert Einstein Coll Med, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 512 BP 139S EP 139S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801013 ER PT J AU Kana, R AF Kana, Rajesh TI Multimodal Neuroimaging Markers of Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autsim C1 [Kana, Rajesh] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 515 BP 139S EP 140S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801016 ER PT J AU Vaidya, C AF Vaidya, Chandan TI Atypical Task and State-related Modulation of Functional Connectivity in Autism Spectrum Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat C1 [Vaidya, Chandan] Georgetown Univ, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 513 BP 139S EP 139S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801014 ER PT J AU Uddin, LQ AF Uddin, Lucina Q. TI Salience-network Based Classification of Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE autism; connectivity; insula; brain network; resting state fMRI C1 [Uddin, Lucina Q.] Stanford Univ, Palo Alto, CA 94304 USA. [Uddin, Lucina Q.] Univ Miami, Coral Gables, FL 33124 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 516 BP 140S EP 140S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801017 ER PT J AU Di Martino, A Somandepalli, K Craddock, CR Milham, MP AF Di Martino, Adriana Somandepalli, Krishna Craddock, Cameron R. Milham, Michael P. TI An Emerging Paradigm for Examination of Autism in Early Brain Development SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autism; resting state; sleep; clustering; thalamus C1 [Di Martino, Adriana; Somandepalli, Krishna] NYU, Langone Med Ctr, CSC, New York, NY USA. [Craddock, Cameron R.; Milham, Michael P.] Child Mind Inst, New York, NY USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 530 BP 144S EP 145S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801031 ER PT J AU McCracken, JT AF McCracken, James T. TI Re-Thinking Clinical Trials in Autism Spectrum Disorders: The NIMH FAST-ASD Network SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autism; Clinical trials; Biomarkers; GABA C1 [McCracken, James T.] Univ Calif Los Angeles, Div Child & Adolescent Psychiat, Semel Inst, 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 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 536 BP 146S EP 146S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801037 ER PT J AU Mansour, H El-Tabei, D Shahin, O Hoffner, L Sathanoori, M Surti, U Nimgaonkar, V AF Mansour, Hader El-Tabei, Dina Shahin, Ola Hoffner, Lori Sathanoori, Malini Surti, Urvachi Nimgaonkar, Vishwajit TI First Report on a Multiplex, Consanguineous, Family with Autism and Chromosome 15 Duplication SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autism; Genetic; Consanguinity; Chromosome C1 [Mansour, Hader; Nimgaonkar, Vishwajit] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [El-Tabei, Dina; Shahin, Ola] Cairo Univ, Cairo, Egypt. [Hoffner, Lori; Sathanoori, Malini; Surti, Urvachi] Univ Pittsburgh, Magee Womens Hosp, Sch Med, Pittsburgh Cytogenet Lab, Pittsburgh, PA 15213 USA. [Nimgaonkar, Vishwajit] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 603 BP 169S EP 169S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801104 ER PT J AU Edgar, JC Chen, YH Herrington, J Bloy, L Chow, V Pandey, J Levy, S Schultz, RT Roberts, TPL AF Edgar, J. Christopher Chen, Yu-Han Herrington, John Bloy, Luke Chow, Vivian Pandey, Judi Levy, Sue Schultz, Robert T. Roberts, Timothy P. L. TI Resting-state Alpha Abnormalities in ASD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE autism spectrum disorders; alpha; resting-state; magnetoencephalography C1 [Edgar, J. Christopher; Chen, Yu-Han; Bloy, Luke; Chow, Vivian; Roberts, Timothy P. L.] Childrens Hosp Philadelphia, Lurie Family Fdn MEG Imaging Ctr, Philadelphia, PA 19104 USA. [Herrington, John; Pandey, Judi; Levy, Sue; Schultz, Robert T.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 784 BP 228S EP 228S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801284 ER PT J AU Khundrakpam, B Lewis, J Tohka, J Evans, A AF Khundrakpam, Budhachandra Lewis, John Tohka, Jussi Evans, Alan TI Dissociating Autistic from Normal Brains Based on Prediction of Biological Maturity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autism; Cortical Thickness; Structural MRI; Development; Predictive Model C1 [Khundrakpam, Budhachandra; Lewis, John; Evans, Alan] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. [Tohka, Jussi] Tampere Univ Technol, Dept Signal Proc, FIN-33101 Tampere, Finland. RI Tohka, Jussi/D-2385-2013 OI Tohka, Jussi/0000-0002-6748-5116 NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 789 BP 229S EP 229S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801289 ER PT J AU Wiggins, JL Swartz, JR Peltier, SJ Lord, C Monk, CS AF Wiggins, Jillian Lee Swartz, Johnna R. Peltier, Scott J. Lord, Catherine Monk, Christopher S. TI Context-dependent Amygdala-prefrontal Connectivity in Youth with Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE autism; amygdala; fMRI; connectivity; prefrontal C1 [Wiggins, Jillian Lee] NIH, Emot & Dev Branch, Bethesda, MD 20892 USA. [Swartz, Johnna R.] Univ N Carolina, Ctr Dev Sci, Chapel Hill, NC USA. [Swartz, Johnna R.] Duke Univ, Lab Neurogenet, Durham, NC USA. [Peltier, Scott J.] Univ Michigan, Funct MRI Lab, Ann Arbor, MI 48109 USA. [Lord, Catherine] Weill Cornell Med Coll, New York, NY USA. [Monk, Christopher S.] Univ Michigan, 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 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 791 BP 230S EP 230S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801291 ER PT J AU Kennedy, DN Mitchell, TV Hodge, S Cochran, D Frazier, JA AF Kennedy, David N. Mitchell, Teresa V. Hodge, Steven Cochran, David Frazier, Jean A. TI Altered Interhemispheric Resting- State Connectivity in Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE autism; resting state fMRI; neuroimaging; corpus callosum; interhemispheric C1 [Kennedy, David N.; Mitchell, Teresa V.; Hodge, Steven; Cochran, David; Frazier, Jean A.] Univ Massachusetts, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 795 BP 231S EP 232S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801295 ER PT J AU Carson, DS Howerton, CL Garner, JP Libove, RA Hyde, SA Phillips, JM Hardan, AY Parker, KJ AF Carson, Dean S. Howerton, Christopher L. Garner, Joseph P. Libove, Robin A. Hyde, Shellie A. Phillips, Jennifer M. Hardan, Antonio Y. Parker, Karen J. TI Plasma Vasopressin Levels Positively Predict Social Cognition in Children with Autism Spectrum Disorder but not in Siblings of Probands or Healthy Controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autism Spectrum Disorder; arginine vasopressin; biomarker; social functioning; theory of mind C1 [Carson, Dean S.; Howerton, Christopher L.; Garner, Joseph P.; Libove, Robin A.; Hyde, Shellie A.; Phillips, Jennifer M.; Hardan, Antonio Y.; Parker, Karen J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RI Garner, Joseph/C-8422-2009 NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 868 BP 255S EP 256S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801368 ER PT J AU Hollocks, MJ Howlin, P Simonoff, E AF Hollocks, Matthew J. Howlin, Patricia Simonoff, Emily TI Using Cognitive and Biological Measures to Independently and Cumulatively Predict Co-Occurring Anxiety Disorders in Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autism; Anxiety; Cortisol; ANS; Cognitive C1 [Hollocks, Matthew J.; Howlin, Patricia; Simonoff, Emily] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 866 BP 255S EP 255S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801366 ER PT J AU Dichter, GS AF Dichter, Gabriel S. TI Neural Mechanisms and Psychophysiology of Emotion Regulation Impairments in Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE autism; emotion regulation; psychophysiology; fMRI C1 [Dichter, Gabriel S.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Dichter, Gabriel S.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1016 BP 280S EP 280S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802017 ER PT J AU Rannals, MD Jaffe, AE Page, SC Campbell, M Shin, JH Tao, R Briley, A Hyde, TM Kleinman, J Weinberger, DR Maher, BJ AF Rannals, Matthew D. Jaffe, Andrew E. Page, Stephanie C. Campbell, Morganne Shin, Joo Heon Tao, Ran Briley, Aaron Hyde, Thomas M. Kleinman, Joel Weinberger, Daniel R. Maher, Brady J. TI The Schizophrenia and Autism Spectrum Disorder Gene TCF4 Regulates Neuronal Migration and Intrinsic Excitability in the Developing Neocortex SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE schizophrenia; development; autism; TCF4; electrophysiology C1 [Rannals, Matthew D.; Jaffe, Andrew E.; Page, Stephanie C.; Campbell, Morganne; Shin, Joo Heon; Tao, Ran; Briley, Aaron; Hyde, Thomas M.; Kleinman, Joel; Weinberger, Daniel R.; Maher, Brady J.] Lieber Inst Brain Dev, Baltimore, MD USA. [Jaffe, Andrew E.] Johns Hopkins Bloomberg Sch Hlth, Baltimore, MD USA. [Hyde, Thomas M.; Weinberger, Daniel R.; Maher, Brady J.] Johns Hopkins Sch Med, Baltimore, MD USA. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Inst Med Genet, Baltimore, MD USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1109 BP 308S EP 308S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802102 ER PT J AU Hollander, E Rubido, MD Khwaja, O Squassante, L Ferretti, CJ Taylor, BP Berlin, G Noone, R Antar, L McCracken, J Scahill, L Shic, F Umbricht, D AF Hollander, Eric Rubido, Marta del Valle Khwaja, Omar Squassante, Lisa Ferretti, Casara J. Taylor, Bonnie P. Berlin, Gregory Noone, Rachel Antar, Laura McCracken, James Scahill, Lawrence Shic, Frederick Umbricht, Daniel TI Affective Speech Recognition Clinical Biomarker Effects of a Novel Vasopressin 1a Receptor Antagonist Vs Placebo in Adult Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat C1 [Hollander, Eric; Ferretti, Casara J.; Taylor, Bonnie P.; Berlin, Gregory; Noone, Rachel; Antar, Laura] Univ Hosp Albert Einstein CoM, Montefiore Med Ctr, Bronx, NY USA. [Rubido, Marta del Valle] Roche, CNS Translat Med Grp, Basel, Switzerland. [Khwaja, Omar; Umbricht, Daniel] Roche, Translat Med, Basel, Switzerland. [Squassante, Lisa] Roche, Basel, Switzerland. [McCracken, James] Univ Calif Los Angeles, Los Angeles, CA USA. [Scahill, Lawrence] Emory Univ, Marcus Autism Ctr, Atlanta, GA 30322 USA. [Shic, Frederick] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1159 BP 324S EP 325S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802152 ER PT J AU Noone, RH Ferretti, CJ Taylor, BP Racine, E Kirsch, J Hollander, E AF Noone, Rachel H. Ferretti, Casara J. Taylor, Bonnie P. Racine, Emma Kirsch, Jonathan Hollander, Eric TI Modulation of the Locus Coeruleus-Noradrenergic System with Milnacipran vs Placebo in Autism Spectrum Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autism Spectrum Disorder; ASD; Milnacipran; Locus Coeruleus; Fever Response C1 [Noone, Rachel H.; Ferretti, Casara J.; Taylor, Bonnie P.; Racine, Emma; Kirsch, Jonathan; Hollander, Eric] Montefiore Med Ctr, Psychiat & Behav Sci Autism & Obsess Compuls Spec, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1158 BP 324S EP 324S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802151 ER PT J AU Ou, JJ Shi, LJ Liu, MM Luo, XR Zhao, JP AF Ou, Jianjun Shi, Lijuan Liu, Mengmeng Luo, Xuerong Zhao, Jingping TI Parental Intelligence Quotient and Autistic Behaviors in Children with Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE autism; Parental Intelligence Quotient; Autistic Behaviors C1 [Ou, Jianjun; Shi, Lijuan; Liu, Mengmeng; Luo, Xuerong; Zhao, Jingping] Cent S Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha, Hunan, Peoples R China. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1169 BP 327S EP 328S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802162 ER PT J AU Supekar, K Odriozola, P Owen, M Lynch, CJ Iuculano, T Menon, V AF Supekar, Kaustubh Odriozola, Paola Owen, Meriel Lynch, Charles J. Iuculano, Teresa Menon, Vinod TI Fusiform-Hippocampal White-Matter Pathway Predicts both Cognitive Strengths and Social Deficits in Children with Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE autism; diffusion tensor imaging; mathematics; social communication; white-matter C1 [Supekar, Kaustubh; Odriozola, Paola; Owen, Meriel; Lynch, Charles J.; Iuculano, Teresa; Menon, Vinod] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1168 BP 327S EP 327S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802161 ER PT J AU Mallya, KS Spilman, SL Laughlin, CP McCracken, JT Nurmi, EL AF Mallya, Karyn S. Spilman, Samantha L. Laughlin, Christopher P. McCracken, James T. Nurmi, Erika L. CA RUPP Autism Network TI Mounting Genetic Evidence for c-AMP Dependent Protein Kinase Signaling (PRKAR2B) in Antipsychotic-Induced Weight Gain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Pharmacogenetics; Pharmacogenomics; Antipsychotic-induced weight gain; Autism; PRKAR2B C1 [Mallya, Karyn S.; Spilman, Samantha L.; Laughlin, Christopher P.; McCracken, James T.; Nurmi, Erika L.; RUPP Autism Network] 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 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1235 BP 348S EP 348S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802228 ER PT J AU Umbricht, D Rubido, MD Shik, F McCracken, JT Scahill, L Khwaja, O Squassante, L Fontoura, P Hollander, E AF Umbricht, Daniel Rubido, Marta del Valle Shik, Fred McCracken, James T. Scahill, Lawrence Khwaja, Omar Squassante, Lisa Fontoura, Paulo Hollander, Eric TI Deficient Olfaction is Associated with Impaired Ability to Recognize Emotions in High Functioning Autistic Subjects and may be Improved by a Vasopressin 1a Receptor Antagonist SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Autism; Olfaction; Vasopressin System; Emotion Recognition; Social cognition C1 [Umbricht, Daniel; Rubido, Marta del Valle; Khwaja, Omar; Squassante, Lisa; Fontoura, Paulo] F Hoffmann La Roche & Co Ltd, Neurosci, CH-4002 Basel, Switzerland. [Shik, Fred] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. [McCracken, James T.] UCLA Semel Inst CAN Clin, Los Angeles, CA USA. [Scahill, Lawrence] Marcus Autism Ctr, Atlanta, GA USA. [Hollander, Eric] Albert Einstein Coll Med, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1359 BP 388S EP 388S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802352 ER PT J AU Rubia, K Alegria, A Brinson, H AF Rubia, Katya Alegria, Analucia Brinson, Helen TI Imaging the ADHD brain: disorder-specificity, medication effects and clinical translation SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE obsessive-compulsive disorder; atomoxetine; methylphenidate; diffusion tensor imaging; attention deficit hyperactivity disorder; conduct disorder; autism spectrum disorder; psychostimulants; MRI; functional magnetic resonance imaging; bipolar disorder ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY-DISORDER; FUNCTIONAL MAGNETIC-RESONANCE; OBSESSIVE-COMPULSIVE DISORDER; PEDIATRIC BIPOLAR DISORDER; DEFAULT-MODE NETWORK; FRONTO-STRIATAL UNDERACTIVATION; PURE CONDUCT DISORDER; 33-YEAR FOLLOW-UP; DRUG-NAIVE BOYS AB A plethora of magnetic resonance imaging studies have shown that ADHD is characterized by multiple functional and structural neural network abnormalities beyond the classical fronto-striatal model, including fronto-parieto-temporal, fronto-cerebellar and even fronto-limbic networks. There is evidence for a maturational delay in brain structure development which likely extends to brain function and structural and functional connectivity, but this needs corroboration by longitudinal imaging studies. Dysfunction of the ventrolateral prefrontal cortex seems to be more pronounced relative to other pediatric disorders and is also the most consistent target of acute psychostimulant medication. Future studies are likely to focus on using neuroimaging for clinical translation such as for individual diagnostic and prognostic classification and as a neurotherapy to reverse brain function abnormalities. C1 [Rubia, Katya; Alegria, Analucia; Brinson, Helen] Kings Coll London, Dept Child & Adolescent Psychiat, Inst Psychiat, London WC2R 2LS, England. RP Rubia, K (reprint author), Kings Coll London, Dept Child & Adolescent Psychiat, Inst Psychiat, London WC2R 2LS, England. EM katya.rubia@kcl.ac.uk FU Lilly Pharmaceuticals; National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) for Mental Health at South London; Maudsley NHS Foundation Trust; Institute of Psychiatry, Kings College London; Action Medical Research; Institute of Psychiatry PhD excellence award FX KR has received research support from Lilly Pharmaceuticals and speaker's honoraria from Lilly, Medice and Novartis. KR received support from the National Institute of Health Research (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. Dr Helen Brinson received post-doctoral support from Action Medical Research. Ms Alegria was supported by an Institute of Psychiatry PhD excellence award. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. 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PD MAY PY 2014 VL 14 IS 5 BP 519 EP 538 DI 10.1586/14737175.2014.907526 PG 20 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AF6CG UT WOS:000334801400007 PM 24738703 ER PT J AU Miniscalco, C Rudling, M Rastam, M Gillberg, C Johnels, JA AF Miniscalco, Carmela Rudling, Maja Rastam, Maria Gillberg, Christopher Johnels, Jakob Asberg TI Imitation (rather than core language) predicts pragmatic development in young children with ASD: a preliminary longitudinal study using CDI parental reports SO INTERNATIONAL JOURNAL OF LANGUAGE & COMMUNICATION DISORDERS LA English DT Article DE imitation; pre-linguistic skills; autism; development; CDI; pragmatic ID AUTISM SPECTRUM DISORDERS; COMMUNICATIVE DEVELOPMENT INVENTORY; JOINT ATTENTION; IMPAIRMENT; ENGAGEMENT; SKILLS; PLAY AB Background Research in the last decades has clearly pointed to the important role of language and communicative level when trying to understand developmental trajectories in children with autism spectrum disorders (ASD). Aims The purpose of this longitudinal study was to investigate whether (1) core language skills, measured as expressive vocabulary and grammar, and/or (2) pre-linguistic social-communicative skills, including gestures and imitation abilities, drive pragmatic language development in young children with ASD. Methods & Procedures We examined correlates and longitudinal predictors of pragmatic growth in a sample of 34 children with Autism spectrum disorder (ASD), whose parents were given parts of two MacArthur Communicative Developmental Inventories (CDI: Words & Gestures and CDI: Words & Sentences) for completion at two time points (at time 1 the mean child age was 41 months, and at time 2 it was 54 months). A novel feature in this study is that the relevant parts from both CDI forms were included at both time points, allowing us to examine whether pre-linguistic social-communication skills (e.g. imitation and gesturing) and/or core language skills (i.e. grammar and vocabulary) predict pragmatic language growth. Outcomes & Results The results show that basically all pre-linguistic, linguistic and pragmatic skills were associated concurrently. When controlling for possible confounders and for the autoregressive effect, imitation skills predicted pragmatic growth over time, whereas core language did not. This could only have been shown by the use of both CDI forms. Conclusions & Implications This preliminary study may be of both conceptual and methodological importance for research in the field of language and communication development in ASD. Imitation may play a pivotal role in the development of subsequent conversational pragmatic abilities in young children with ASD. Future research should be directed at unravelling the mechanisms underlying this association. C1 [Miniscalco, Carmela; Gillberg, Christopher; Johnels, Jakob Asberg] Univ Gothenburg, Inst Neurosci & Physiol, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [Miniscalco, Carmela; Johnels, Jakob Asberg] Univ Gothenburg, Inst Neurosci & Physiol, Div Speech & Language Pathol, Gothenburg, Sweden. [Rudling, Maja; Rastam, Maria] Lund Univ, Dept Clin Sci Lund Child & Adolescent Psychiat, S-22100 Lund, Sweden. [Johnels, Jakob Asberg] Univ Gothenburg, Dept Psychol, Gothenburg, Sweden. RP Miniscalco, C (reprint author), Gillberg Neuropsychiat Ctr, Kungsgatan 12, S-41119 Gothenburg, Sweden. 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PD MAY PY 2014 VL 49 IS 3 BP 369 EP 375 DI 10.1111/1460-6984.12085 PG 7 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AG0AZ UT WOS:000335078200009 PM 24684579 ER PT J AU Siu, AFY Zhou, Y AF Siu, Angela F. Y. Zhou, Ya TI Behavioral Assessment of the Dysexecutive Syndrome for Children An Examination of Clinical Utility for Children With Attention-Deficit Hyperactivity Disorder (ADHD) SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE executive function; ecological validity; Hong Kong; assessment; ADHD ID LATENT-VARIABLE ANALYSIS; PERFORMANCE-BASED MEASURES; AUTISM SPECTRUM DISORDERS; EXECUTIVE FUNCTION; RATING INVENTORY; DEFICIT/HYPERACTIVITY DISORDER; ECOLOGICAL VALIDITY; CONSTRUCT-VALIDITY; INTERFERENCE; SUBTYPES AB The present study evaluated the utility of the Behavioral Assessment of Dysexecutive Syndrome for Children for discerning differences in executive functioning between attention-deficit hyperactivity disorder (ADHD) children and normal controls and examined its associations with real-life executive function as rated by parent reports on the Dysexecutive Questionnaire for Children. Sixty-three children diagnosed with ADHD and 60 normal healthy peers were recruited for this study. All participants completed the Behavioral Assessment of Dysexecutive Syndrome for Children, while their parents completed the Dysexecutive Questionnaire for Children. Results revealed that the ADHD group exhibited significantly poorer performance than the controls on 3 subtests of the Behavioral Assessment of Dysexecutive Syndrome for Children (ie, Playing Cards Test, Water Test, and Zoo Map Test 2), as well as on the total Dysexecutive Questionnaire for Children. Significant correlation was found between the total Dysexecutive Questionnaire for Children and the 6-Part Test. Findings suggested that some subtests of the Behavioral Assessment of Dysexecutive Syndrome for Children were particularly useful for detecting real-life executive dysfunction in ADHD. Yet, further studies are needed to provide extended validity data. C1 [Siu, Angela F. 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Child Neurol. PD MAY PY 2014 VL 29 IS 5 BP 608 EP 616 DI 10.1177/0883073813516191 PG 9 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AG0FJ UT WOS:000335090400006 PM 24453147 ER PT J AU Marques, F Brito, MJ Conde, M Pinto, M Moreira, A AF Marques, Filipa Brito, Maria Joao Conde, Marta Pinto, Monica Moreira, Ana TI Autism Spectrum Disorder Secondary to Enterovirus Encephalitis SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE children; enterovirus; autism spectrum disorder; encephalitis ID HERPES-SIMPLEX ENCEPHALITIS; CENTRAL-NERVOUS-SYSTEM; PCR ASSAY; INFECTIONS; CHILDHOOD; MENINGITIS; DIAGNOSIS; SYMPTOMS; CHILDREN; COHORT AB Millions of children are infected by enteroviruses each year, usually exhibiting only mild symptoms. Nevertheless, these viruses are also associated with severe and life-threatening infections, such as meningitis and encephalitis. We describe a 32-month-old patient with enteroviral encephalitis confirmed by polymerase chain reaction in cerebrospinal fluid, with unfavorable clinical course with marked developmental regression, autistic features, persistent stereotypes and aphasia. She experienced slow clinical improvement, with mild residual neurologic and developmental deficits at follow-up. Viral central nervous system infections in early childhood have been associated with autism spectrum disorders but the underlying mechanisms are still poorly understood. This case report is significant in presenting a case of developmental regression with autistic features and loss of language improving on follow-up. To our knowledge, this is the first published report of enterovirus encephalitis leading to an autism spectrum disorder. C1 [Marques, Filipa; Brito, Maria Joao; Conde, Marta] Ctr Hosp Lisboa Cent EPE, Hosp Dona Estefania, Infect Dis Unit, P-1169045 Lisbon, Portugal. [Pinto, Monica] Ctr Hosp Lisboa Cent EPE, Hosp Dona Estefania, Child Dev Ctr, P-1169045 Lisbon, Portugal. [Moreira, Ana] Ctr Hosp Lisboa Cent EPE, Hosp Dona Estefania, Paediat Neurol Unit, P-1169045 Lisbon, Portugal. RP Marques, F (reprint author), Ctr Hosp Lisboa Cent EPE, Hosp Dona Estefania, Infect Dis Unit, Rua Jacinto Marto, P-1169045 Lisbon, Portugal. EM filipa3marques@gmail.com CR Acharya VZ, 2001, J CHILD NEUROL, V16, P864, DOI 10.1177/08830738010160111403 Atladottir HO, 2010, ARCH PEDIAT ADOL MED, V164, P470, DOI 10.1001/archpediatrics.2010.9 Chang L, 2007, NEW ENGL J MED, V356, P1226, DOI 10.1056/NEJMoa065954 Croen L. 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Child Neurol. PD MAY PY 2014 VL 29 IS 5 BP 708 EP 714 DI 10.1177/0883073813508314 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AG0FJ UT WOS:000335090400022 PM 24782421 ER PT J AU Puts, NAJ Wodka, EL Tommerdahl, M Mostofsky, SH Edden, RAE AF Puts, Nicolaas A. J. Wodka, Ericka L. Tommerdahl, Mark Mostofsky, Stewart H. Edden, Richard A. E. TI Impaired tactile processing in children with autism spectrum disorder SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE autism; inhibition; tactile; somatosensory; psychophysics ID GABA CONCENTRATION; CANDIDATE GENE; SENSITIVITY; ADAPTATION; DISRUPTION; GABRB3; ADULTS; DISCRIMINATION; INDIVIDUALS; PERCEPTION AB Impaired responses to tactile stimulation are a commonly reported symptom among children with autism spectrum disorder (ASD). Furthermore, impairments in filtering or habituation to tactile input have been described in ASD. This study measured different aspects of tactile processing to investigate atypical touch sensitivity in children with ASD, methodology that has not been previously used in this population. Sixty-seven typically developing children (TDC) and 32 children with ASD (ages 8-12) completed vibrotactile tasks assessing: reaction time (RT); static and dynamic detection threshold (DT); amplitude discrimination with and without single-site adaptation; frequency discrimination; and temporal order judgment (TOJ) with and without concurrent stimulation. Children with ASD showed raised static detection thresholds and an absence of the effect of a dynamically increasing subthreshold stimulus on static detection threshold. Children with ASD also showed poorer amplitude discrimination than TDC, as well as decreased adaptation. There were no significant differences in frequency discrimination or TOJ performance between the groups. Differences in the effect of dynamic stimulation on detection threshold suggest impaired feed-forward inhibition in autism, which may be linked to poor sensory filtering. Increased baseline amplitude discrimination thresholds in ASD suggest that lateral inhibitory connections are weaker in ASD, and an absence of the effect of adaptation suggests impaired modulation of lateral inhibitory connections in ASD, which may relate to aberrant habituation. These results suggest a functional deficit in the somatosensory inhibitory system in autism. Understanding the specific mechanisms underlying sensory symptoms in autism may allow for more specific therapeutic or drug targeting in the near future. C1 [Puts, Nicolaas A. J.; Edden, Richard A. E.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Puts, Nicolaas A. J.; Edden, Richard A. E.] Kennedy Krieger Inst, FM Kirby Ctr Funct Brain Imaging, Baltimore, MD USA. [Wodka, Ericka L.; Mostofsky, Stewart H.] Kennedy Krieger Inst, Lab Neurocognit & Imaging Res, Baltimore, MD USA. [Wodka, Ericka L.] Kennedy Krieger Inst, Ctr Autism & Related Disorders, Baltimore, MD USA. [Mostofsky, Stewart H.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Wodka, Ericka L.; Mostofsky, Stewart H.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Tommerdahl, Mark] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC USA. RP Puts, NAJ (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 600 N Wolfe St, Baltimore, MD 21287 USA. EM nputs1@jhmi.edu FU Autism Speaks Translational Postdoctoral Fellowship; Organization for Autism Research; National Institutes of Health [P41-EB-015909, R21-MH-098228, 2-R01-NS-048527-08, 2-R01-MH-078160-06A1]; Johns Hopkins University School of Medicine Institute for Clinical and Translational Research National Institutes of Health/ National Center for Research Resources Clinical and Translational Science Award Program [UL1-RR-025005] FX N. A. Puts is funded by an Autism Speaks Translational Postdoctoral Fellowship. E. L. Wodka is supported by the Organization for Autism Research. This work was further supported by National Institutes of Health Grants P41-EB-015909, R21-MH-098228, 2-R01-NS-048527-08, and 2-R01-MH-078160-06A1 and Johns Hopkins University School of Medicine Institute for Clinical and Translational Research National Institutes of Health/ National Center for Research Resources Clinical and Translational Science Award Program UL1-RR-025005. None of the funding bodies had influence on the acquisition or analysis of the data nor on the writing and submission of this article. 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Neurophysiol. PD MAY PY 2014 VL 111 IS 9 BP 1803 EP 1811 DI 10.1152/jn.00890.2013 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA AG9ZR UT WOS:000335779300009 PM 24523518 ER PT J AU Kim, YS Fombonne, E Koh, YJ Kim, SJ Cheon, KA Leventhal, BL AF Kim, Young Shin Fombonne, Eric Koh, Yun-Joo Kim, Soo-Jeong Cheon, Keun-Ah Leventhal, Bennett L. TI A Comparison of DSM-IV Pervasive Developmental Disorder and DSM-5 Autism Spectrum Disorder Prevalence in an Epidemiologic Sample SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ASD; SCD; DSM-IV; DSM-5; prevalence ID CRITERIA; CHILDREN AB Objective: Changes in autism diagnostic criteria found in DSM-5 may affect autism spectrum disorder (ASD) prevalence, research findings, diagnostic processes, and eligibility for clinical and other services. Using our published, total-population Korean prevalence data, we compute DSM-5 ASD and social communication disorder (SCD) prevalence and compare them with DSM-IV pervasive developmental disorder (PDD) prevalence estimates. We also describe individuals previously diagnosed with DSM-IV PDD when diagnoses change with DSM-5 criteria. Method: The target population was all children from 7 to 12 years of age in a South Korean community (N = 55,266), those in regular and special education schools, and a disability registry. We used the Autism Spectrum Screening Questionnaire for systematic, multi-informant screening. Parents of screen-positive children were offered comprehensive assessments using standardized diagnostic procedures, including the Autism Diagnostic Interview Revised and Autism Diagnostic Observation Schedule. Best-estimate clinical diagnoses were made using DSM-IV PDD and DSM-5 ASD and SCD criteria. Results: DSM-5 ASD estimated prevalence was 2.20% (95% confidence interval = 1.77-3.64). Combined DSM-5 ASD and SCD prevalence was virtually the same as DSM-IV PDD prevalence (2.64%). Most children with autistic disorder (99%), Asperger disorder (92%), and PDD-NOS (63%) met DSM-5 ASD criteria, whereas 1%, 8%, and 32%, respectively, met SCD criteria. All remaining children (2%) had other psychopathology, principally attention-deficit/hyperactivity disorder and anxiety disorder. Conclusion:. Our findings suggest that most individuals with a prior DSM-IV PDD meet DSM-5 diagnostic criteria for ASD and SCD. PDD, ASD or SCD; extant diagnostic criteria identify a large, clinically meaningful group of individuals and families who require evidence-based services. C1 [Kim, Young Shin] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Kim, Young Shin; Leventhal, Bennett L.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Kim, Young Shin; Cheon, Keun-Ah; Leventhal, Bennett L.] Yonsei Univ, Seoul 120749, South Korea. [Fombonne, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Koh, Yun-Joo] Korea Inst Childrens Social Dev Rudolph, Seoul, South Korea. [Kim, Soo-Jeong] Univ Washington, Seattle, WA 98195 USA. [Leventhal, Bennett L.] Univ Illinois, Chicago, IL USA. RP Leventhal, BL (reprint author), Nathan S Kline Inst Psychiat Res, 140 Old Orangeburg Rd,Bldg 35, Orangeburg, NY 10962 USA. FU Autism Speaks Pilot Research Grant; Brain Research Foundation; Simons Foundation [137032 M134793]; National Institute for Mental Health (NIMH) [5K01MH079317-02, K23MH082883]; National Institute of Environmental Health Sciences (NIEHS) [R01 ES021462-01]; Korean Health Technology Research and Development Project, Ministry of Health and Welfare [HI12C0021, HI12C0245-A120029]; Jean Young and Walden W. Shaw Foundation; Daniel X. and Mary Freedman Foundation; Dukyoung Foundation; [7996] FX This research was funded by an Autism Speaks Pilot Research Grant, and a Supplement Grant (7996), a Brain Research Foundation Research Grant, a Simons Foundation Autism Research Initiative Pilot Grant (137032 M134793), the National Institute for Mental Health (NIMH) Career Awards (5K01MH079317-02 [Y.S.K.] and K23MH082883 [S.J.K.]), the National Institute of Environmental Health Sciences (NIEHS) R01 Award (R01 ES021462-01), and the Korean Health Technology Research and Development Project, Ministry of Health and Welfare (HI 12C0021; HI12C0245-A120029).Additional funding was provided by the Jean Young and Walden W. Shaw Foundation, the Daniel X. and Mary Freedman Foundation, and the Dukyoung Foundation. CR American Psychiatric Association, 2013, DSM5 AM PSYCH ASS American Psychiatric Association, 2013, A05 SOC COMM [Anonymous], 2012, NY TIMES Baird G, 2006, LANCET, V368, P210, DOI 10.1016/S0140-6736(06)69041-7 Fombonne E, 1999, PSYCHOL MED, V29, P769, DOI 10.1017/S0033291799008508 Fombonne E, 2009, PEDIATR RES, V65, P591 Frazier TW, 2012, J AM ACAD CHILD PSY, V51, P28, DOI 10.1016/j.jaac.2011.09.021 Gibbs V, 2012, J AUTISM DEV DISORD, V42, P1750, DOI 10.1007/s10803-012-1560-6 Huerta M, 2012, AM J PSYCHIAT, V169, P1056, DOI 10.1176/appi.ajp.2012.12020276 Kelsey J. L., 1996, METHODS OBSERVATIONA Kim YS, 2011, AM J PSYCHIAT, V168, P904, DOI 10.1176/appi.ajp.2011.10101532 Mattila ML, 2011, J AM ACAD CHILD PSY, V50, P583, DOI 10.1016/j.jaac.2011.04.001 McPartland JC, 2012, J AM ACAD CHILD PSY, V51, P368, DOI 10.1016/j.jaac.2012.01.007 Taheri A, 2012, J AUTISM DEV DISORD, V42, P1810, DOI 10.1007/s10803-012-1599-4 NR 14 TC 2 Z9 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2014 VL 53 IS 5 BP 500 EP 508 DI 10.1016/j.jaac.2013.12.021 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AG0HJ UT WOS:000335096200004 PM 24745950 ER PT J AU Jordan, L AF Jordan, Lisa TI Kids in the Syndrome Mix of ADHD, LD, Autism Spectrum, Tourette's, Anxiety, and More! The One Stop Guide for Parents, Teachers, and Other Professionals, 2nd edition SO LIBRARY JOURNAL LA English DT Book Review C1 [Jordan, Lisa] Johnsen Cty Lib, Gardner, KS 66030 USA. RP Jordan, L (reprint author), Johnsen Cty Lib, Gardner, KS 66030 USA. CR KUTSCHER ML, 2014, KIDS SYNDROME MIX AD NR 1 TC 0 Z9 0 PU REED BUSINESS INFORMATION PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD MAY 1 PY 2014 VL 139 IS 8 BP 91 EP 91 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA AG3DN UT WOS:000335296100130 ER PT J AU Strickland, AD AF Strickland, Alan D. TI Prevention of cerebral palsy, autism spectrum disorder, and attention deficit - Hyperactivity disorder SO MEDICAL HYPOTHESES LA English DT Article ID FETAL HYPOXIA-ISCHEMIA; FATTY-ACID COMPOSITION; WHITE-MATTER; DEFICIT/HYPERACTIVITY DISORDER; DOCOSAHEXAENOIC ACID; NEONATAL-RATS; BRAIN; INFLAMMATION; MICROGLIA; DAMAGE AB This hypothesis states that cerebral palsy (CP), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) are all caused by an exaggerated central nervous system inflammatory response to a prenatal insult. This prenatal insult may be one or more episodes of ischemia-reperfusion, an infectious disease of the mother or the fetus, or other causes of maternal inflammation such as allergy or autoimmune disease. The resultant fetal inflammatory hyper-response injures susceptible neurons in the developing white matter of the brain in specific areas at specific gestational ages. The exaggerated neuroinflammatory response is theorized to occur between about 19 and 34 post-conception weeks for CP, about 32 and 40 weeks for ADHD, and about 36 and 48 weeks (i.e. 2 months after delivery) for ASD. The exaggerated inflammatory response is hypothesized to occur because present diets limit intake of effective antioxidants and omega-3 polyunsaturated fatty acids while increasing intake of omega-6 polyunsaturated fatty acids. Oxidation products of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) limit neuroinflammation while oxidation products of the omega-6 fatty acid arachidonic acid exacerbate inflammation. Preventative treatment should begin in all pregnant women during the first trimester and should include both DHA and an effective antioxidant for prevention of neuroinflammation. The suggested antioxidant would be N-acetylcysteine, though melatonin could be chosen instead. Combined DHA and NAC therapy is theorized to decrease the incidence of the three disorders by more than 75%. (C) 2014 Elsevier Ltd. All rights reserved. RP Strickland, AD (reprint author), 101 Waterlily, Lake Jackson, TX 77566 USA. 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Hypotheses PD MAY PY 2014 VL 82 IS 5 BP 522 EP 528 DI 10.1016/j.mehy.2014.02.003 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AG0KT UT WOS:000335105100004 PM 24581674 ER PT J AU Wen, W Wen, SW AF Wen, Wendy Wen, Shi Wu TI Expanding upon the 'extreme male brain' theory of autism as a common link between other major risk factors: A hypothesis SO MEDICAL HYPOTHESES LA English DT Article ID SEX-DIFFERENCES; EMPATHY QUOTIENT; AGGRESSION; MECHANISMS AB On average, males have a stronger preference for physical systems and machines over interpersonal interactions; they have lower average levels of cognitive empathy or social cognition than females; and they have higher rates of 'extreme' intelligence when it comes to abstract concepts such as those found in mathematics and sciences. All three traits are also commonly associated with individuals with an autism spectrum disorder or ASD; clearly, it is not coincidental that incidence rates of autism are reportedly four times higher in males than in females. The common link between the majority of risk factors assessed in this review (including technological advancements, advanced parental age, socioeconomic status, and genetic predispositions towards ASDs in families of scientists and engineers) can be traced to a specific hormone, testosterone. It was established that traits which are typically associated with males are also typically associated with ASDs as well as individuals with antisocial personality disorder, or APD. The key distinction between individuals who are considered to be 'autistic' as opposed to those who are considered 'sociopathic' lies in the difference between their empathy deficits: whereas those who are 'autistic' are said to lack cognitive empathy (the ability to identify and understand the thoughts and feelings of others and to respond to these with appropriate emotions), those who are 'sociopathic' are said to lack emotional empathy (which is responsible for inhibiting acts of physical aggression or violence). This would explain why autistic individuals can have elevated testosterone levels without becoming physically aggressive. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Wen, Wendy] Univ Ottawa, Dept Math & Stat, Fac Sci, Ottawa, ON K1H 8L6, Canada. [Wen, Shi Wu] Univ Ottawa, Dept Obstet & Gynecol, OMNI Res Grp, Ottawa, ON K1H 8L6, Canada. [Wen, Shi Wu] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. 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However, many children have difficulty learning symbolic matching, even though they may demonstrate generalized identity matching. The current study investigated whether training on symbolic MTS tasks in which the stimuli are physically dissimilar but members of familiar categories (i.e., thematic matching) can remediate an individual's difficulty learning symbolic MTS tasks involving non-representative stimuli. Three adolescent males diagnosed with autism spectrum disorder were first trained on symbolic MTS tasks with unfamiliar, non-representative form stimuli. Thematic matching was introduced after the participants failed to learn 0, 2 or 4 symbolic MTS tasks and before additional symbolic MTS tasks were introduced. After exposure to thematic matching, accuracy on symbolic MTS tasks with novel stimuli increased to above chance for all participants. For two participants, high accuracy (>90%) was achieved on a majority of these sessions. 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Autism Spectr. Disord. PD MAY PY 2014 VL 8 IS 5 BP 455 EP 462 DI 10.1016/j.rasd.2014.01.004 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200001 ER PT J AU Horlin, C Albrecht, MA Falkmer, M Leung, D Ordqvist, A Tan, T Lee, WL Falkmer, T AF Horlin, Chiara Albrecht, Matthew A. Falkmer, Marita Leung, Denise Ordqvist, Anna Tan, Tele Lee, Wee Lih Falkmer, Torbjorn TI Visual search strategies of children with and without autism spectrum disorders during an embedded figures task SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE ASD; Eye tracking; Embedded figures test; Visual search ID ASPERGER SYNDROME; SUPERIOR; PERFORMANCE; COHERENCE; ADULTS AB Individuals with ASD often demonstrate superior performance on embedded figures tasks (EFTs). We investigated visual scanning behaviour in children with ASD during an EFT in an attempt replicating a previous study examining differences in visual search behaviour. Twenty-three children with, and 31 children without an ASD were shown 16 items from the Figure-Ground subtest of the TVPS-3 while wearing an eye tracker. Children with ASD exhibited fewer fixations, and less time per fixation, on the target figure. Accuracy was similar between the two groups. There were no other noteworthy differences between children with and without ASD. Differences in visual scanning patterns in the presence of typical behavioural performance suggest that any purported differences in processing style may not be detrimental to cognitive performance and further refinement of the current methodology may lead to support for a purported advantageous cognitive style. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Horlin, Chiara; Falkmer, Marita; Leung, Denise; Falkmer, Torbjorn] Curtin Univ, CHIRI, Sch Occupat Therapy & Social Work, Perth, WA 6845, Australia. [Albrecht, Matthew A.] Curtin Univ, Sch Psychol & Speech Pathol, CHIRI, Perth, WA 6845, Australia. [Falkmer, Marita] Jonkoping Univ, Inst Disabil Res, CHILD Programme, Sch Educ & Commun, Jonkoping, Sweden. [Ordqvist, Anna; Falkmer, Torbjorn] Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci IMH, SE-58185 Linkoping, Sweden. [Ordqvist, Anna; Falkmer, Torbjorn] Pain & Rehabil Ctr, SE-58185 Linkoping, Sweden. [Tan, Tele] Curtin Univ, Dept Mech Engn, Perth, WA 6845, Australia. [Lee, Wee Lih] Curtin Univ, Dept Elect & Comp Engn, Perth, WA 6845, Australia. [Falkmer, Torbjorn] La Trobe Univ, Sch Occupat Therapy, Melbourne, Vic 3086, Australia. RP Falkmer, T (reprint author), Curtin Univ Technol, CHIRI, Sch Occupat Therapy & Social Work, Fac Hlth Sci, GPO Box U1987, Perth, WA 6845, Australia. EM T.Falkmer@curtin.edu.au CR Albrecht M. 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Autism Spectr. Disord. PD MAY PY 2014 VL 8 IS 5 BP 463 EP 471 DI 10.1016/j.rasd.2014.01.006 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200002 ER PT J AU Stasolla, F Perilli, V Damiani, R AF Stasolla, Fabrizio Perilli, Viviana Damiani, Rita TI Self monitoring to promote on-task behavior by two high functioning boys with autism spectrum disorders and symptoms of ADHD SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Self monitoring; Autism spectrum disorders; ADHD; Stereotypy; Indices of happiness; Social validation ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SCANNING KEYBOARD EMULATOR; MICROSWITCH-BASED PROGRAMS; DEVELOPMENTAL-DISABILITIES; MOTOR DISABILITIES; MULTIPLE DISABILITIES; YOUNG-CHILDREN; INTERVENTION; ENGAGEMENT; MANAGEMENT AB We assessed a self-monitoring procedure to promote on-task behavior in classroom by two high functioning boys with autism spectrum and attention deficit hyperactivity disorders.A second aim of the study was to reduce stereotyped behaviors for both boys. Finally, a third goal was to verify the effects of the intervention on the participant's mood. The study was conducted according to a non concurrent multiple baseline design across participants. Results show an increase of on-task behavior and indices of happiness during the intervention phase. Moreover, the stereotyped behaviors decreased during intervention phase for both boys. Participants maintained their performance during the maintenance phase, which occurred a month after the end of the intervention. The effectiveness of the rehabilitation program was confirmed by 72 university students involved in a social validation assessment as raters. Psychological and practical implications of the findings are discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Stasolla, Fabrizio] Lega del Filo dOro Res Ctr, Molfetta, Italy. [Perilli, Viviana] Lega del Filo dOro Res Ctr, Lesmo, Italy. [Damiani, Rita] Univ Bari, Dept Educ Sci, I-70121 Bari, Italy. 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Autism Spectr. Disord. PD MAY PY 2014 VL 8 IS 5 BP 472 EP 479 DI 10.1016/j.rasd.2014.01.007 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200003 ER PT J AU Daou, N Vener, SM Poulson, CL AF Daou, Nidal Vener, Susan M. Poulson, Claire L. TI Analysis of three components of affective behavior in children with autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Affective behavior; Applied behavior analysis; Autism; Emotion; Facial expression; Vocal intonation ID GENERALIZED IMITATION; SKILLS; EXPRESSION; YOUTH AB Affective behavior is a crucial ingredient for appropriate, sustainable social interactions. People with autism have deficits in social interaction that are apparent in nonverbal behavior. Few studies have applied behavioral procedures to increase appropriate affective responding in people with autism. This study adds to that literature by examining three components of affective behavior, thus reinforcing the notion that it is not only what the learner says (verbal responding), but also how she says it (vocal intonation); not only whether the learner makes eye contact with his conversation partner, but also how he presents himself (facial expression). A multiple-baseline design evaluated the effects of an affect-training program on the percentage of appropriate responding emitted by three children with autism. The program consisted of reinforcement, prompting, script-fading, and shaping procedures. The percentage of appropriate affective responding emitted by participants across categories increased systematically following treatment; so did performance on nonreinforced probes. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Daou, Nidal; Poulson, Claire L.] CUNY Queens Coll, Flushing, NY 11367 USA. [Daou, Nidal; Poulson, Claire L.] CUNY, Grad Ctr, New York, NY 10016 USA. 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PD MAY PY 2014 VL 8 IS 5 BP 480 EP 501 DI 10.1016/j.rasd.2014.01.005 PG 22 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200004 ER PT J AU Cervantes, PE Matson, JL Williams, LW Jang, JN AF Cervantes, Paige E. Matson, Johnny L. Williams, Lindsey W. Jang, Jina TI The effect of cognitive skills and autism spectrum disorder on stereotyped behaviors in infants and toddlers SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE ASD; Stereotypies; BISCUIT; BDI-2; Cognitive skills ID PERVASIVE DEVELOPMENTAL DISORDER; SELF-INJURIOUS-BEHAVIOR; INTELLECTUAL DISABILITY; CHALLENGING BEHAVIORS; REPETITIVE BEHAVIORS; VOCAL STEREOTYPY; MOTOR STEREOTYPIES; CHILDREN; ADULTS; AGGRESSION AB Stereotyped behaviors are prominent in both the ASD and ID populations; stereotypies can impede social skill acquisition, interfere with learning, and adversely affect an individual's quality of life. The current study explored the effect of cognitive skills and autism spectrum disorder (ASD) on the rate of stereotypies in 2019 children aged 17-39 months. Cognitive abilities were assessed using the cognitive developmental quotient (DQ) on the Battelle Developmental Inventory, Second Edition (BDI-2); two levels of cognitive skill were used: (1) low (cognitive DQ less than or equal to 70), and (2) typical (cognitive DQ greater than 70). Stereotypies were examined utilizing the Baby and Infant Screen for Children with aUtIsm Traits, Part 3 (BISCUIT-Part 3). Children with ASD were found to have greater rates of overall stereotyped behaviors compared to children with atypical development, regardless of cognitive level; however, children with ASD and typical cognitive ability evinced the highest rate of stereotypies. An examination of specific stereotyped behaviors (i.e., unusual play with objects, repeated and unusual vocalizations, repeated and unusual body movements) revealed disparate results. Research and clinical implications regarding these findings are discussed. (C) 2014 Elsevier Ltd. All rights reserved. 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PD MAY PY 2014 VL 8 IS 5 BP 502 EP 508 DI 10.1016/j.rasd.2014.01.008 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200005 ER PT J AU Van der Paelt, S Warreyn, P Roeyers, H AF Van der Paelt, Sara Warreyn, Petra Roeyers, Herbert TI Social-communicative abilities and language in preschoolers with autism spectrum disorders: Associations differ depending on language age SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Language development; Imitation; Joint attention; Pretend play; Social-communicative abilities ID JOINT ATTENTION; YOUNG-CHILDREN; INDIVIDUAL-DIFFERENCES; PRETEND PLAY; 2ND YEAR; IMITATION; ACQUISITION; TODDLERS; INFANTS; SKILLS AB The aim of this study was to look at the unique contributions of imitation, pretend play and joint attention to differences in receptive and expressive language. Associations between social-communicative and language abilities were assessed thoroughly in a large sample (n = 83) of preschoolers with ASD. We hypothesized that these associations are dependent of language age. Therefore the sample was divided in two subsamples based on either the receptive or expressive language age for each of the analyses. Results revealed that imitation, pretend play, response to joint attention and imperative and declarative joint attention, were all uniquely associated with language. However, these relationships were different for receptive and expressive language and they also differed depending on the language age of the children. While imitation and pretend play showed unique associations with language in children with a language age under 2 years old and children with a language age above 2 years old, joint attention abilities were only uniquely associated with language in children with the youngest language age. These findings lend support to the idea that social-communicative abilities are important intervention targets for children with ASD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Van der Paelt, Sara; Warreyn, Petra; Roeyers, Herbert] Univ Ghent, Dept Expt Clin & Hlth Psychol, Res Grp Dev Disorders, B-9000 Ghent, Belgium. RP Van der Paelt, S (reprint author), Univ Ghent, Dept Expt Clin & Hlth Psychol, Henri Dunantlaan 2, B-9000 Ghent, Belgium. 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PD MAY PY 2014 VL 8 IS 5 BP 518 EP 528 DI 10.1016/j.rasd.2014.01.010 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200007 ER PT J AU Lanovaz, MJ Rapp, JT Maciw, I Pregent-Pelletier, E Dorion, C Ferguson, S Saade, S AF Lanovaz, Marc J. Rapp, John T. Maciw, Isabella Pregent-Pelletier, Emilie Dorion, Catherine Ferguson, Stephanie Saade, Sabine TI Effects of multiple interventions for reducing vocal stereotypy: Developing a sequential intervention model SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Differential reinforcement; Intervention model; Music; Prompting; Stereotypy ID AUTISM SPECTRUM DISORDERS; RESPONSE INTERRUPTION; NONCONTINGENT REINFORCEMENT; DEVELOPMENTAL-DISABILITIES; AUTOMATIC REINFORCEMENT; CHILDREN; BEHAVIOR; STIMULATION; REDIRECTION; MUSIC AB Despite the availability of several interventions designed to reduce engagement in vocal stereotypy, few studies have compared two or more interventions together. Consequently, practitioners have limited amount of data to make informed decisions on whether an intervention may be more suitable than another to begin treating vocal stereotypy. The purpose of the study was to address this limitation by examining the direct and collateral effects of multiple interventions in 12 individuals with autism and other developmental disabilities in order to guide the development of a sequential intervention model. Using single-case experimental designs, we conducted a series of four experiments which showed that (a) noncontingent music generally produced more desirable outcomes than differential reinforcement of alternative behavior, (b) differential reinforcement of other behavior reduced vocal stereotypy in two participants for whom noncontingent music had failed to do so, (c) the addition of simple prompting procedures may enhance the effects of the interventions, and (d) the effects of noncontingent music may persist during sessions with extended durations. Based on these results, we propose a sequential intervention model to facilitate the initial and subsequent selection of an intervention most likely to reduce vocal stereotypy while producing desired collateral outcomes. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved. C1 [Lanovaz, Marc J.; Maciw, Isabella; Pregent-Pelletier, Emilie; Dorion, Catherine; Ferguson, Stephanie; Saade, Sabine] Univ Montreal, Ecole Psychoeduc, Montreal, PQ H3C 3J7, Canada. [Rapp, John T.] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. RP Lanovaz, MJ (reprint author), Univ Montreal, Ecole Psychoeduc, CP 6128,Succ Ctr Ville, Montreal, PQ H3C 3J7, Canada. 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Autism Spectr. Disord. PD MAY PY 2014 VL 8 IS 5 BP 529 EP 545 DI 10.1016/j.rasd.2014.01.009 PG 17 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200008 ER PT J AU Magiati, I Chan, JY Tan, WLJ Poon, KK AF Magiati, Iliana Chan, Jing Yi Tan, Wen-Li Julianne Poon, Kenneth K. TI Do non-referred young people with Autism Spectrum Disorders and their caregivers agree when reporting anxiety symptoms? A preliminary investigation using the Spence Children's Anxiety Scale SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Anxiety; Assessment; Screening; Agreement; Reliability ID PSYCHOMETRIC PROPERTIES; ASPERGER-SYNDROME; PSYCHIATRIC-DISORDERS; BEHAVIORAL-PROBLEMS; CONTROLLED-TRIAL; ADOLESCENTS; PARENT; YOUTH; SAMPLE; RELIABILITY AB Anxiety difficulties and disorders are common in children and youth people with Autism Spectrum Disorders (ASD), but only a few studies have specifically examined informant agreement in non-referred samples. The present study examined informant agreement between 38 Singaporean caregiver-child dyads using the Spence Children's Anxiety Scale Parent Version (SCAS-P) and the SCAS Child self-report (SCAS-C) respectively. The young people with ASD (mean age 12 years 10 months) completed the SCAS-C, while their caregivers completed the SCAS-P, the Scales of Independent Behavior-Revised and the Developmental Behavior Checklist. There was overall moderately good agreement between caregivers and children's reporting of anxiety symptoms. Intra-class correlations were highest in the Separation Anxiety, Generalized Anxiety and Physical Injury subscales. Fourteen of the 38 SCAS items, most of which described overt anxiety symptoms, showed strong or moderate inter-rater agreement. Higher severity of autism symptoms was associated with poorer agreement in the Generalized Anxiety, Panic and Obsessions/Compulsions SCAS subscales. These preliminary findings suggest that the SCAS may be a useful measure for reporting anxiety symptoms in terms of satisfactory agreement between caregivers and young people in non-referred settings. Implications for screening for anxiety in non-referred young people with ASD are also discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Magiati, Iliana; Chan, Jing Yi; Tan, Wen-Li Julianne] Natl Univ Singapore, Dept Psychol, Singapore 117570, Singapore. 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PD MAY PY 2014 VL 8 IS 5 BP 546 EP 558 DI 10.1016/j.rasd.2014.01.015 PG 13 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200009 ER PT J AU Albrecht, MA Foster, JK Joosten, A Falkmer, M Tang, J Leung, D Ordqvist, A Falkmer, T AF Albrecht, Matthew A. Foster, Jonathan K. Joosten, Annette Falkmer, Marita Tang, Julia Leung, Denise Ordqvist, Anna Falkmer, Torbjorn TI Visual search strategies during facial recognition in children with ASD SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Face recognition; Eye-tracking; Developmental; Visual search ID AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; ASPERGER SYNDROME; FACE RECOGNITION; COGNITIVE-STYLE; EYE-TRACKING; ABILITY AB Facial recognition is a complex skill necessary for successful human interpersonal and social interactions. Given that the most prevalent disorder of social interaction is autism spectrum disorder (ASD), a number of studies have investigated and found impaired facial recognition abilities in people with ASD. Further, this impairment may be critically involved in mediating the deficits in interpersonal and social interactions in people with ASD. We sought to address the question of whether face processing is impaired in children with ASD in the current study. While there were a number of differences in visual search behaviours between the 19 children with ASD and the 15 controls, this did not manifest in deficits in facial recognition accuracy. In addition, there were notable differences with respect to eye fixation behaviours and recognition accuracy in this study compared to the findings in a previous similar study conducted in adults with ASD. These differences suggest a performance enhancing developmental trajectory in facial processing in controls that may not be present in individuals with ASD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Albrecht, Matthew A.; Foster, Jonathan K.] Curtin Univ, Sch Psychol & Speech Pathol, Perth, WA 6845, Australia. [Foster, Jonathan K.] Dept WA, Neurosci Unit, Perth, WA, Australia. [Joosten, Annette; Falkmer, Marita; Tang, Julia; Leung, Denise; Ordqvist, Anna; Falkmer, Torbjorn] Curtin Univ, CHIRI, Sch Occupat Therapy & Social Work, Perth, WA 6845, Australia. [Falkmer, Marita] Jonkoping Univ, Inst Disabil Res, CHILD Programme, Sch Educ & Commun, Jonkoping, Sweden. [Falkmer, Torbjorn] Jonkoping Univ, Sch Hlth Sci, Dept Rehabil, Jonkoping, Sweden. [Falkmer, Torbjorn] Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci IMH, Linkoping, Sweden. [Falkmer, Torbjorn] Pain & Rehabil Ctr, Linkoping, Sweden. [Falkmer, Torbjorn] La Trobe Univ, Sch Occupat Therapy, Melbourne, Vic, Australia. 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L., 1967, EYE MOVEMENTS VISION, V2 NR 32 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD MAY PY 2014 VL 8 IS 5 BP 559 EP 569 DI 10.1016/j.rasd.2014.01.014 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200010 ER PT J AU Hong, ER Ganz, JB Gilliland, W Ninci, J AF Hong, Ee Rea Ganz, Jennifer B. Gilliland, Whitney Ninci, Jennifer TI Teaching caregivers to implement an augmentative and alternative communication intervention to an adult with ASD SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Adult with autism; Complex communication needs; Tap to Talk (TM) application; Primary caregivers; AAC implementation; Single-case research ID AUTISM SPECTRUM DISORDERS; PARTICIPANT CHARACTERISTICS; PSYCHOSOCIAL OUTCOMES; TREATMENT INTEGRITY; SPECIAL-EDUCATION; YOUNG-CHILDREN; FOLLOW-UP; LANGUAGE; INDIVIDUALS; PARADIGM AB Many researchers have investigated the effectiveness of augmentative and alternative communication (AAC) systems on improving communication skills of children with autism spectrum disorder (ASD) and communication complex needs (CCN); however, few studies included adults with ASD. Also, there is a lack of research on primary caregiver implemented interventions with high treatment fidelity although primary caregiver-implemented interventions have been used effectively with adults with ASD and their families. This study investigated the accuracy of primary caregivers' implementation of a tablet-computer based AAC system while they were providing instruction to an adult with ASD. Also, independent use of AAC system of the participant was examined. We implemented a multiple probe design across three instructional coaching steps to examine the accuracy of the caregivers' AAC implementation. One adult with autism and CCN and his four primary caregivers participated in this study, twice a week for seven weeks. Both visual and statistical analyses were utilized. 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PD MAY PY 2014 VL 8 IS 5 BP 570 EP 580 DI 10.1016/j.rasd.2014.01.012 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200011 ER PT J AU Bjorgaas, HM Elgen, I Ryland, HK Hysing, M AF Bjorgaas, H. M. Elgen, I. Ryland, H. K. Hysing, M. TI Autism spectrum symptoms in children with cerebral palsy: Prevalence and co-occurring conditions SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Cerebral palsy; Mental health; Psychiatric disorders; Peer problems ID SCHOOL-AGE-CHILDREN; SCREENING QUESTIONNAIRE; PSYCHOLOGICAL-PROBLEMS; PSYCHIATRIC-DISORDERS; BEHAVIORAL-PROBLEMS; PEER PROBLEMS; POPULATION; HEMIPLEGIA; ILLNESS; ADHD AB Purpose: To explore autism spectrum symptoms in children with cerebral palsy (CP), and the association between autism spectrum symptoms and medical and psychiatric comorbidity. Methodology: Parents of children with CP in a Norwegian population were interviewed with a child psychiatric diagnostic instrument, and completed the Autism Spectrum Screening Questionnaire (ASSQ). Medical and socio-demographic data were obtained. ASSQ mean scores were compared to the Bergen Child Study (BCS), both to healthy controls and to subgroups of children with chronic illness in general, and neurological disorders specifically. Results: Interviews and data collection were completed for 47 children, of whom 30 were boys, most had spastic CP, and were less severely affected by CP. Large effect sizes were found when comparing ASSQ mean scores in children with CP to children with chronic illnesses and normal controls. One in five children was ASSQ high scorers defined as a score above the 98th percentile of normal controls. A high rate of co-occurring psychiatric disorders, mainly AD/HD, was found in ASSQ high scorers. Conclusions: More attention should be given to autism spectrum symptoms in the regular follow-up of children with CP in an attempt to enhance social functioning. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Bjorgaas, H. M.] Stavanger Univ Hosp, Stavanger HF, Dept Pediat Habilitat, N-4068 Stavanger, Norway. [Bjorgaas, H. M.; Elgen, I.] Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway. [Elgen, I.] Haukeland Hosp, Dept Pediat, Child Habilitat Unit, N-5021 Bergen, Norway. [Ryland, H. K.] Haukeland Hosp, Dept Pediat Habilitat, N-5021 Bergen, Norway. [Hysing, M.] Uni Res, Uni Hlth, Reg Ctr Child & Youth Mental Hlth & Child Welf, Bergen, Norway. RP Bjorgaas, HM (reprint author), Stavanger Univ Hosp, Osterlide Barnehabilitering, Stavanger HF, POB 8100, N-4068 Stavanger, Norway. 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Autism Spectr. Disord. PD MAY PY 2014 VL 8 IS 5 BP 581 EP 588 DI 10.1016/j.rasd.2014.01.011 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200012 ER PT J AU Siller, M Swanson, MR Serlin, G Teachworth, AG AF Siller, Michael Swanson, Meghan R. Serlin, Gayle Teachworth, Ann G. TI Internal state language in the storybook narratives of children with and without autism spectrum disorder: Investigating relations to theory of mind abilities SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Narrative; Internal state language; Theory of mind ID DIAGNOSTIC OBSERVATION SCHEDULE; HIGH-FUNCTIONING CHILDREN; BELIEFS; ADULTS; COMPREHENSION; CHARACTERS; MEMORIES; DEFICITS; STORIES AB The current study examines narratives elicited using a wordless picture book, focusing on language used to describe the characters' thoughts and emotions (i.e., internal state language, ISL). The sample includes 21 children with autism spectrum disorder (ASD) and 24 typically developing controls, matched on children's gender, IQ as well as receptive and expressive vocabulary. This research had three major findings. First, despite equivalent performance on standardized language assessments, the volume of children's narratives (i.e., the number of utterances and words, the range of unique verbs and adjectives) was lower in children with ASD than in typically developing controls. Second, after controlling for narrative volume, the narratives of children with ASD were less likely to reference the characters' emotions than was the case for typically developing controls. Finally, our results revealed a specific association between children's use of emotion terms and their performance on a battery of experimental tasks evaluating children's Theory of Mind abilities. Implications for our understanding of narrative deficits in ASD as well as interventions that use narrative as a context for improving social comprehension are discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Siller, Michael; Swanson, Meghan R.; Serlin, Gayle] CUNY, Grad Ctr, New York, NY 10016 USA. 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Autism Spectr. Disord. PD MAY PY 2014 VL 8 IS 5 BP 589 EP 596 DI 10.1016/j.rasd.2014.02.002 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AG0LO UT WOS:000335107200013 ER PT J AU Matson, JL Cervantes, PE AF Matson, Johnny L. Cervantes, Paige E. TI Commonly studied comorbid psychopathologies among persons with autism spectrum disorder SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Review DE Autism; Comorbidity; Psychopathology; ADHD; Intellectual disability ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDER; DEFICIT HYPERACTIVITY DISORDER; INTELLECTUALLY DISABLED ADULTS; OPPOSITIONAL DEFIANT DISORDER; HIGH-FUNCTIONING AUTISM; CHILDREN ASD-CC; II DASH-II; PSYCHIATRIC-DISORDERS; ASPERGERS-DISORDER AB The study of comorbid psychopathology among persons with autism spectrum disorder (ASD) is picking up steam. The purpose of this paper was to review and describe important characteristics of existing studies. Among the current crop of papers, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) have been frequently evaluated. Groups studied have most frequently been children. Persons with ASD and normal intelligence quotient (IQ) scores have been studied more often than individuals with ASD and intellectual disability. Additional characteristics are discussed, and the implications of these data for future developments in the field are reviewed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Matson, Johnny L.; Cervantes, Paige E.] Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. RP Cervantes, PE (reprint author), Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. 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Dev. Disabil. PD MAY PY 2014 VL 35 IS 5 BP 952 EP 962 DI 10.1016/j.ridd.2014.02.012 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AF1MU UT WOS:000334478800003 PM 24629541 ER PT J AU Cederlund, M Miniscalco, C Gillberg, C AF Cederlund, Mats Miniscalco, Carmela Gillberg, Christopher TI Pre-schoolchildren with autism spectrum disorders are rarely macrocephalic: A population study SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Preschool children; ASD; Macrocephaly; Population study ID HEAD CIRCUMFERENCE; ASPERGER-SYNDROME; BRAIN OVERGROWTH; BIRTH-WEIGHT; BODY LENGTH; 1ST YEAR; LIFE; GROWTH; CHILDREN; PROGRAM AB Numerous clinical studies over the past decades have concluded that there is an association between autism spectrum disorders (ASD) and large head size. Lately, some studies have reported conflicting results. The present study was conducted with a view to assess the presence of macrocephaly in a community-representative group of pre-school children with ASD. The prevalence of ASD in this general population was 0.8%. Thirty-three children (5 girls, 28 boys) recruited after general population screening for ASD, and diagnosed with ASD (two-thirds not globally delayed) were assessed as regards growth parameters; height, weight, and head circumference (HC), at birth and at comprehensive medical-psychiatric diagnostic examinations at a mean age of 3 years. Macrocephaly in the present study was defined as HC above the 97th percentile, and >= 2 SD above recorded length/height. Only one of the 33 children (3%) had macrocephaly which is similar to the general population prevalence. Another 9% had a big but proportional head. None of the children were microcephalic. In this community-based study we found no evidence to support a strong link between a large head size and ASD. Conclusions must be guarded because of the relatively small number of ASD cases included. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Cederlund, Mats; Miniscalco, Carmela; Gillberg, Christopher] Univ Gothenburg, Sahlgrenska Acad, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. RP Gillberg, C (reprint author), Gillberg Neuropsychiat Ctr, Kungsgatan 12, S-41119 Gothenburg, Sweden. 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Dev. Disabil. PD MAY PY 2014 VL 35 IS 5 BP 992 EP 998 DI 10.1016/j.ridd.2014.02.006 PG 7 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AF1MU UT WOS:000334478800007 PM 24629539 ER PT J AU Franco, F Itakura, S Pomorska, K Abramowski, A Nikaido, K Dimitriou, D AF Franco, Fabia Itakura, Shoji Pomorska, Krystyna Abramowski, Anna Nikaido, Kozue Dimitriou, Dagmara TI Can children with autism read emotions from the eyes? The Eyes Test revisited SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE ASD; Emotion recognition; Eye-test; Developmental disorders; Theory of mind (TOM) ID HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; FACIAL EXPRESSIONS; SPECTRUM DISORDER; WILLIAMS-SYNDROME; SOCIAL COGNITION; MIND DEVELOPMENT; CROWD EVIDENCE; MENTAL STATES; FALSE BELIEF AB This study aimed to test two new, simplified tasks related to the eye-test, targeting children with autism spectrum disorder (ASD) and typically developing controls (TD). Test-I assessed the recognition of emotion/mental states with displays using one word and two eye-pictures, whereas Test-2 presented displays using two words and one eye-picture. Black and white photographs of children were used as materials. A cross-cultural study (Caucasian/East-Asian) with adults was initially carried out to verify generalizability across different ethnic groups. Cross-sectional trajectory analyses were used to compare emotion recognition from the eyes in the two tests. Trajectories were constructed linking performance on both tests either to chronological age or to different measures of mental age (receptive vocabulary based on the BPVS, CARS or ASQ for the ASD group). Performance improved with chronological age in both the ASD and TD groups of children. However, performance in Test-I was significantly superior in children with ASD, who showed delayed onset and slower rate of improvement than TO children in Test-2. In both the ASD and TO groups the lowest error rate was recorded for the item 'anger', suggesting that threat-detection cue mechanisms may be intact in autism. In general, all children showed good performance on our novel tests, thus making them good candidates for assessing younger children and those with lower general abilities. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Franco, Fabia; Nikaido, Kozue] Middlesex Univ, Sch Hlth & Educ, Dept Psychol, London NW4 4BT, England. [Itakura, Shoji] Kyoto Univ, Dept Psychol, Kyoto 6068501, Japan. [Pomorska, Krystyna] Univ Social Sci & Humanities, Warsaw, Poland. [Abramowski, Anna] City Univ London, London, England. [Dimitriou, Dagmara] Univ London, Inst Educ, Dept Psychol & Human Dev, London WC1N 1AZ, England. RP Franco, F (reprint author), Middlesex Univ, Sch Hlth & Educ, Dept Psychol, Town Hall, London NW4 4BT, England. 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Dev. Disabil. PD MAY PY 2014 VL 35 IS 5 BP 1015 EP 1026 DI 10.1016/j.ridd.2014.01.037 PG 12 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AF1MU UT WOS:000334478800009 PM 24636022 ER PT J AU Thurman, AJ McDuffie, A Hagerman, R Abbeduto, L AF Thurman, Angela John McDuffie, Andrea Hagerman, Randi Abbeduto, Leonard TI Psychiatric symptoms in boys with fragile X syndrome: A comparison with nonsyndromic autism spectrum disorder SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Fragile X syndrome; Autism spectrum disorder; Anxiety; Hyperactivity; Social avoidance; Psychiatric symptoms ID DEVELOPMENTAL DISORDERS; BEHAVIORAL-PHENOTYPE; PRESCHOOL-CHILDREN; ATTENTION; HYPERACTIVITY; INDIVIDUALS; MINOCYCLINE; DIAGNOSIS; ANXIETY; MALES AB In the present study, we examined the profile of psychiatric symptoms in boys with fragile X syndrome (FXS) using a parent report instrument. In addition, by comparing boys with FXS to boys with nonsyndromic autism spectrum disorder (ASD) utilizing multiple matching strategies, we examined between-group differences in the types of psychiatric symptoms observed and in the strength of their concurrent associations. Across all matching strategies, symptoms of manic/hyperactive behaviors and general anxiety were more frequently reported for boys with FXS than for boys with nonsyndromic ASD. Results also indicated a positive association between social avoidance and general anxiety in FXS that was stronger than that observed in nonsyndromic ASD across all matching strategies. Theoretical and treatment implications are discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Thurman, Angela John; McDuffie, Andrea; Hagerman, Randi; Abbeduto, Leonard] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Thurman, Angela John; McDuffie, Andrea; Abbeduto, Leonard] Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. 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PD MAY PY 2014 VL 35 IS 5 BP 1072 EP 1086 DI 10.1016/j.ridd.2014.01.032 PG 15 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AF1MU UT WOS:000334478800014 PM 24629733 ER PT J AU Hao, G Layton, TL Zou, XB Li, DY AF Hao, Grace Layton, Thomas L. Zou, Xiao-Bing Li, Dong-Yun TI Evaluating autism in a Chinese population: the Clinical Autism Diagnostic Scale SO WORLD JOURNAL OF PEDIATRICS LA English DT Article DE autism spectrum disorders; diagnosis; rating scale AB Background: The purpose of this study was to report on the psychometric measures and discriminatory function of a new diagnostic test for autism spectrum disorders, the Clinical Autism Diagnostic Scale (CADS). Methods: The CADS was used to test 216 children in the study, including 86 with low-functioning autism specturm disorders (ASD), 16 children with high-functioning ASD, 16 with pervasive developmental disorder, not otherwise specified, 7 with Asperger syndrome, 65 with typical development, 11 children with language impairments and 15 with intellectual disabilities. Ages ranged from 38-73 months. Behaviors for the groups were compared across seven domains. Results: The results indicated the instrument was reliable, valid, and successfully differentiated the different groups of children with and without autism. All ASD groups were found to display difficulties in the domains of sensory behaviors and stereotyped behaviors. The play and social domains were found to measure similar underlying concepts of behaviors, while the receptive language and expressive language domains were also found to measure similar underlying-language concepts. The group of children diagnosed as having low-functioning autism performed less well on all tested domains in the instrument than did the other three groups of children with ASD, and these other three groups each also presented unique patterns of behaviors and differed on individual domains. Conclusions: CADS is a reliable and valid test. It successfully differentiates the abilities of children with ASD at different levels of functioning. C1 [Hao, Grace] N Carolina Cent Univ, Dept Allied Profess, Durham, NC 27707 USA. [Layton, Thomas L.] T&T Commun Serv Inc, Durham, NC 27713 USA. [Zou, Xiao-Bing; Li, Dong-Yun] Sun Yet Sen Univ, Affiliated Hosp 3, Children Dev & Behav Ctr, Guangzhou 510630, Guangdong, Peoples R China. RP Hao, G (reprint author), N Carolina Cent Univ, Dept Allied Profess, 710 Cecil St, Durham, NC 27707 USA. EM jhao@nccu.edu CR Centeno J, 2003, ELL COMPANION REDUCI, P171 Huang AX, 2013, J AUTISM DEV DISORD, V43, P1991, DOI 10.1007/s10803-012-1722-6 Layton T, 2013, CLIN AUTISM DIAGNOST Le Couteur A., 2003, AUTISM DIAGNOSTIC IN Schopler E., 2005, PSYCHOEDUCATIONAL PR Van de Vijver F, 1996, EUR PSYCHOL, V1, P89, DOI 10.1027/1016-9040.1.2.89 NR 6 TC 0 Z9 0 PU ZHEJIANG UNIV SCH MEDICINE PI HANGZHOU PA CHILDRENS HOSPITAL, 57 ZHUGAN XIANG, HANGZHOU, 310003, PEOPLES R CHINA SN 1708-8569 EI 1867-0687 J9 WORLD J PEDIATR JI World Journal of Pediatrics PD MAY PY 2014 VL 10 IS 2 BP 160 EP 163 DI 10.1007/s12519-014-0466-0 PG 4 WC Pediatrics SC Pediatrics GA AG4CT UT WOS:000335367600011 PM 24599613 ER PT J AU Preller, KH Hulka, LM Vonmoos, M Jenni, D Baumgartner, MR Seifritz, E Dziobek, I Quednow, BB AF Preller, Katrin H. Hulka, Lea M. Vonmoos, Matthias Jenni, Daniela Baumgartner, Markus R. Seifritz, Erich Dziobek, Isabel Quednow, Boris B. TI Impaired emotional empathy and related social network deficits in cocaine users SO ADDICTION BIOLOGY LA English DT Article DE social network; Cocaine; theory of mind; empathy; criminal behavior; mentalizing ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; DRUG-USE; ADOLESCENT ALCOHOL; IMPULSE CONTROL; DEPENDENCE; MIND; ADULTS; QUESTIONNAIRE AB Chronic cocaine users consistently display neurochemical and functional alterations in brain areas involved in social cognition (e.g. medial and orbitofrontal cortex). Although social functioning plays a crucial role in the development and treatment of drug dependence, studies investigating social cognition in cocaine users are lacking. Therefore, we investigated mental perspective taking ('theory of mind') and emotional and cognitive empathy in recreational (RCU) and dependent (DCU) cocaine users. Furthermore, we related these measures to real-life indicators of social functioning. One-hundred cocaine users (69 RCU, 31 DCU) and 68 stimulant-naive healthy controls were tested with the Multifaceted Empathy Test (MET), Movie for the Assessment of Social Cognition (MASC) and Reading the Mind in the Eyes Test (RMET). The Social Network Questionnaire was conducted to assess social network size. Furthermore, participants provided information on committed criminal offenses. RCU and DCU showed less emotional empathy compared to controls (MET), whereas cognitive empathy was not impaired (MET, RMET). Additionally, DCU made more errors in mental perspective taking (MASC). Notably, cocaine users committed more criminal offenses and displayed a smaller social network and higher cocaine use was correlated with less social contacts. Diminished mental perspective taking was tentatively correlated with more intense cocaine use as well. Finally, younger age of onset of cocaine use was associated with more pronounced empathy impairment. In conclusion, social cognition impairments in cocaine users were related to real-life social functioning and should therefore be considered in therapy and prevention strategies. C1 [Preller, Katrin H.; Hulka, Lea M.; Vonmoos, Matthias; Jenni, Daniela; Seifritz, Erich; Quednow, Boris B.] Univ Hosp Psychiat, Dept Psychiat Psychotherapy & Psychosomat, CH-8032 Zurich, Switzerland. [Baumgartner, Markus R.] Univ Zurich, Ctr Forens Hairanalyt, Inst Forens Med, CH-8006 Zurich, Switzerland. [Dziobek, Isabel] Free Univ Berlin, Cluster Languages Emot, Berlin, Germany. [Quednow, Boris B.] Univ Zurich, Zurich Ctr Integrat Human Physiol, CH-8006 Zurich, Switzerland. RP Quednow, BB (reprint author), Univ Hosp Psychiat, Lenggstr 31, CH-8032 Zurich, Switzerland. EM preller@bli.uzh.ch; quednow@bli.uzh.ch RI Quednow, Boris/A-1666-2008 OI Quednow, Boris/0000-0001-7933-2865 FU Swiss National Science Foundation (SNSF) [PP00P1-123516, PP00P1_146326]; Olga Mayenfisch Foundation FX This work was supported by grants from the Swiss National Science Foundation (SNSF; PP00P1-123516 and PP00P1_146326) and the Olga Mayenfisch Foundation. Experimental design, data acquisition, statistical analyses and interpretation of the results were conducted without input from any pharmaceutical company or any other funding source. 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Biol. PD MAY PY 2014 VL 19 IS 3 BP 452 EP 466 DI 10.1111/adb.12070 PG 15 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA AF3FS UT WOS:000334597500014 PM 23800218 ER PT J AU Al-Kateb, H Khanna, G Filges, I Hauser, N Grange, DK Shen, J Smyser, CD Kulkarni, S Shinawi, M AF Al-Kateb, Hussam Khanna, Geetika Filges, Isabel Hauser, Natalie Grange, Dorothy K. Shen, Joseph Smyser, Christopher D. Kulkarni, Shashikant Shinawi, Marwan TI Scoliosis and Vertebral Anomalies: Additional Abnormal Phenotypes Associated with Chromosome 16p11.2 Rearrangement SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE 16p11; 2 rearrangement; scoliosis; vertebral anomalies; deletion; duplication; phenotype ID ADOLESCENT IDIOPATHIC SCOLIOSIS; CANDIDATE REGIONS; LOCUS; SUSCEPTIBILITY; GENES; IDENTIFICATION; MICRODELETION; DISORDERS; DOSAGE; AUTISM AB The typical chromosome 16p11.2 rearrangements are estimated to occur at a frequency of approximately 0.6% of all samples tested clinically and have been identified as a major cause of autism spectrum disorders, developmental delay, behavioral abnormalities, and seizures. Careful examination of patients with these rearrangements revealed association with abnormal head size, obesity, dysmorphism, and congenital abnormalities. In this report, we extend this list of phenotypic abnormalities to include scoliosis and vertebral anomalies. We present detailed characterization of phenotypic and radiological data of 10 new patients, nine with the 16p11.2 deletion and one with the duplication within the coordinates chr16:29,366,195 and 30,306,956 (hg19) with a minimal size of 555kb. We discuss the phenotypical and radiological findings in our patients and review 5 previously reported patients with 16p11.2 rearrangement and similar skeletal abnormalities. Our data suggest that patients with the recurrent 16p11.2 rearrangement have increased incidence of scoliosis and vertebral anomalies. However, additional studies are required to confirm this observation and to establish the incidence of these anomalies. We discuss the potential implications of our findings on the diagnosis, surveillance and genetic counseling of patients with 16p11.2 rearrangement. (c) 2014 Wiley Periodicals, Inc. C1 [Al-Kateb, Hussam; Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Khanna, Geetika] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Filges, Isabel] Univ British Columbia, Dept Med Genet, Childrens & Womens Hosp, Vancouver, BC, Canada. [Hauser, Natalie; Shen, Joseph] Childrens Hosp Cent Calif, Dept Med Genet & Metab, Madera, CA USA. [Grange, Dorothy K.; Shinawi, Marwan] Washington Univ, Sch Med, Dept Pediat Genet & Genom Med, St Louis, MO 63110 USA. [Smyser, Christopher D.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Smyser, Christopher D.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP Shinawi, M (reprint author), Washington Univ, Sch Med, Dept Pediat, Div Genet & Genom Med, One Childrens Pl,Northwest Tower, St Louis, MO 63110 USA. 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J. Med. Genet. A PD MAY PY 2014 VL 164 IS 5 BP 1118 EP 1126 DI 10.1002/ajmg.a.36401 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AE8YZ UT WOS:000334290300005 PM 24458548 ER PT J AU Talisa, VB Boyle, L Crafa, D Kaufmann, WE AF Talisa, Victor B. Boyle, Lia Crafa, Daina Kaufmann, Walter E. TI Autism and Anxiety in Males with Fragile X Syndrome: An Exploratory Analysis of Neurobehavioral Profiles from a Parent Survey SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE fragile X; autism; anxiety; survey ID SELF-INJURIOUS-BEHAVIOR; SPECTRUM DISORDER; CHILDREN; PREVALENCE; PHENOTYPE; SYMPTOMS; BOYS AB Although it is suspected that anxiety modifies the clinical presentation of autism in fragile X syndrome (FXS), neuropsychiatric co-morbidity profiles of these two disorders have not been extensively studied. The National Fragile X Survey was completed for 1,027 males with FXS, for whom yes/no information regarding the presence of several disorders is provided. Although the survey exhibited limited depth and lacked validation by standardized measures, this exploratory study was conducted to take advantage of the data as an opportunity for identifying future lines of inquiry. We addressed the following questions: (i) how do the co-morbidity profiles of FXS males with both autism and anxiety compare to those without anxiety?; (ii) do individuals with autism exhibit specific co-morbidity profiles compared to FXS males with anxiety only, or without either autism or anxiety?; (iii) how do co-morbidity profiles in children ages 3-11 differ from profiles of individuals >12 years? The group with autism and anxiety reported the highest prevalence of attention problems, hyperactivity/impulsivity, self-injurious behavior and aggressiveness. In addition, the lowest prevalence rates of these conditions were often observed in non-anxious groups regardless of autism status. Overall, this exploratory analysis generated several hypotheses for further study: (i) anxiety increases the severity of autism in FXS, particularly through additional behavioral abnormalities; (ii) some neuropsychiatric and behavioral conditions (i.e., attention problems, hyperactivity/impulsivity, aggressiveness) are primarily related to comorbid anxiety, not autism; (iii) prevalence of behavioral abnormalities increases with age. Future studies evaluating these hypotheses should incorporate validated neurobehavioral assessments, and control for cognitive level. (c) 2014 Wiley Periodicals, Inc. C1 [Talisa, Victor B.; Boyle, Lia; Crafa, Daina; Kaufmann, Walter E.] Kennedy Krieger Inst, Ctr Genet Disorders Cognit & Behav, Baltimore, MD USA. [Talisa, Victor B.; Boyle, Lia; Crafa, Daina; Kaufmann, Walter E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kaufmann, Walter E.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Kaufmann, Walter E.] Harvard Univ, Sch Med, Boston, MA USA. RP Kaufmann, WE (reprint author), Boston Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM walter.kaufmann@childrens.harvard.edu FU Centers for Disease Control and Prevention (CDC); Association for Prevention Teaching and Research (APTR) [U50/CCU300860, TS-1380]; NIH [HD 24061] FX Grant sponsor: Centers for Disease Control and Prevention (CDC) and the Association for Prevention Teaching and Research (APTR) Cooperative Agreement; Grant number: U50/CCU300860, Project TS-1380; Grant sponsor: NIH; Grant number: HD 24061. CR Arron K, 2011, J INTELL DISABIL RES, V55, P109, DOI 10.1111/j.1365-2788.2010.01337.x Bailey DB, 2008, AM J MED GENET A, V146A, P2060, DOI 10.1002/ajmg.a.32439 Bebbington A, 2008, NEUROLOGY, V70, P868, DOI 10.1212/01.wnl.0000304752.50773.ec Berry-Kravis E, 2010, AJIDD-AM J INTELLECT, V115, P461, DOI [10.1352/1944-7558-115.6.461, 10.1352/194475581156461] Boyle L, 2010, AM J MED GENET C, V154C, P469, DOI 10.1002/ajmg.c.30277 Budimirovic DB, 2006, AM J MED GENET A, V140A, P1814, DOI 10.1002/ajmg.a.31405 Cohen D, 2005, J AUTISM DEV DISORD, V35, P103, DOI 10.1007/s10803-004-1038-2 Cordeiro L, 2011, J NEURODEV DISORD, V3, P57, DOI 10.1007/s11689-010-9067-y Daniels A. 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J. Med. Genet. A PD MAY PY 2014 VL 164 IS 5 BP 1198 EP 1203 DI 10.1002/ajmg.a.36468 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AE8YZ UT WOS:000334290300017 PM 24664669 ER PT J AU Bartholdi, D Stray-Pedersen, A Azzarello-Burri, S Kibaek, M Kirchhoff, M Oneda, B Rodningen, O Schmitt-Mechelke, T Rauch, A Kjaergaard, S AF Bartholdi, Deborah Stray-Pedersen, Asbjorg Azzarello-Burri, Silvia Kibaek, Maria Kirchhoff, Maria Oneda, Beatrice Rodningen, Olaug Schmitt-Mechelke, Thomas Rauch, Anita Kjaergaard, Susanne TI A Newly Recognized 13q12.3 Microdeletion Syndrome Characterized by Intellectual Disability, Microcephaly, and Eczema/Atopic Dermatitis Encompassing the HMGB1 and KATNAL1 Genes SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE microdeletion 13q12; 3; KATNAL1; HMGB1; intellectual disability; microarray analysis ID PETERS PLUS SYNDROME; DE-NOVO MUTATIONS; DELETION; KATANIN; MICROTUBULES; PHENOTYPE; ANOMALIES; PATIENT; AUTISM AB Proximal deletions of the long arm of chromosome 13 have been reported only rarely. Here we present three unrelated patients with heterozygous, apparently de novo deletions encompassing 13q12.3. The patients present with moderate demonstrated or apparent intellectual disability, postnatal microcephaly, and eczema/atopic dermatitis as the predominant symptoms. In addition, they had pronounced feeding difficulties in early infancy. They displayed similar facial features such as malar flattening, a prominent nose with underdeveloped alae nasi, a smooth philtrum, and a thin vermillion of the upper lip. The proximal and distal breakpoints were clustered and the deletions spanned from 1.4 to 1.7Mb, comprising at least 11 RefSeq genes. However, heterozygous deletions partially overlapping those observed in the present patients have been described in healthy parents of patients with Peters-Plus syndrome, an autosomal recessive disorder caused by inactivation of the B3GALTL gene. We therefore propose that the critical region of the 13q12.3 microdeletion syndrome contains only three genes, namely, KATNAL1, HMGB1, and LINC00426, a non-protein coding RNA. The KATNAL1 protein belongs to a family of microtubule severing enzymes that have been implicated in CNS plasticity in experimental models, but little is known about its function in humans. The HMGB1 protein is an evolutionarily conserved chromatin-associated protein involved in many biologically important processes. In summary, we propose that microdeletion 13q12.3 represents a novel clinically recognizable condition and that the microtubule severing gene KATNAL1 and the chromatin-associated gene HMGB1 are candidate genes for intellectual disability inherited in an autosomal dominant pattern. (c) 2014 Wiley Periodicals, Inc. C1 [Bartholdi, Deborah; Azzarello-Burri, Silvia; Oneda, Beatrice; Rauch, Anita] Univ Zurich, Inst Med Genet, Zurich, Switzerland. [Stray-Pedersen, Asbjorg; Rodningen, Olaug] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway. [Stray-Pedersen, Asbjorg] Baylor Coll Med, Houston, TX 77030 USA. [Kibaek, Maria] Odense Univ Hosp, Dept Pediat, DK-5000 Odense, Denmark. [Kirchhoff, Maria; Kjaergaard, Susanne] Rigshosp, Dept Clin Genet, Univ Hosp Copenhagen, DK-2100 Copenhagen, Denmark. [Schmitt-Mechelke, Thomas] Childrens Hosp, Luzern, Switzerland. RP Bartholdi, D (reprint author), Klinikum Stuttgart, Inst Clin Genet, Bismarckstr 3, D-70176 Stuttgart, Germany. EM deborah.bartholdi@usb.ch RI Rauch, Anita/C-5568-2014 OI Rauch, Anita/0000-0003-2930-3163 FU Swiss National Science Foundation [SNF 320030_135669] FX Grant sponsor: Swiss National Science Foundation; Grant number: SNF 320030_135669. 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J. Med. Genet. A PD MAY PY 2014 VL 164 IS 5 BP 1277 EP 1283 DI 10.1002/ajmg.a.36439 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AE8YZ UT WOS:000334290300031 PM 24664804 ER PT J AU Grynszpan, O Weiss, PL Perez-Diaz, F Gal, E AF Grynszpan, Ouriel Weiss, Patrice L. (Tamar) Perez-Diaz, Fernando Gal, Eynat TI Innovative technology- based interventions for autism spectrum disorders: A meta- analysis SO AUTISM LA English DT Article DE autism spectrum disorders; computer; innovative technology; meta-analysis; remediation; robotics; systematic review; training; virtual reality ID COMPUTER-ASSISTED-INSTRUCTION; HIGH-FUNCTIONING AUTISM; COMPLEX EMOTION RECOGNITION; ASPERGER-SYNDROME; VIRTUAL-REALITY; SOCIAL-SKILLS; INTERACTIVE MULTIMEDIA; COMMUNICATION-SKILLS; ANIMATED TUTOR; CHILDREN AB This article reports the results of a meta-analysis of technology-based intervention studies for children with autism spectrum disorders. We conducted a systematic review of research that used a pre-post design to assess innovative technology interventions, including computer programs, virtual reality, and robotics. The selected studies provided interventions via a desktop computer, interactive DVD, shared active surface, and virtual reality. None employed robotics. The results provide evidence for the overall effectiveness of technology-based training. The overall mean effect size for posttests of controlled studies of children with autism spectrum disorders who received technology-based interventions was significantly different from zero and approached the medium magnitude, d = 0.47 (confidence interval: 0.08-0.86). The influence of age and IQ was not significant. Differences in training procedures are discussed in the light of the negative correlation that was found between the intervention durations and the studies' effect sizes. The results of this meta-analysis provide support for the continuing development, evaluation, and clinical usage of technology-based intervention for individuals with autism spectrum disorders. C1 [Grynszpan, Ouriel] Univ Paris 06, F-75252 Paris 05, France. [Grynszpan, Ouriel; Perez-Diaz, Fernando] CNRS, USR 3246, F-75700 Paris, France. [Weiss, Patrice L. (Tamar); Gal, Eynat] Univ Haifa, IL-31999 Haifa, Israel. RP Grynszpan, O (reprint author), Hop La Pitie Salpetriere, CNRS, Ctr Emot, USR 3246, Pavillon Clerambault,47 Blvd Hop, F-75013 Paris, France. 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TI Assessment of global functioning in adolescents with autism spectrum disorders: Utility of the Developmental Disability- Child Global Assessment Scale SO AUTISM LA English DT Article DE adolescents; autism; global functioning; treatment ID RANDOMIZED CONTROLLED-TRIAL; ANXIETY; INTERVENTION; INDIVIDUALS; CHALLENGES; ISSUES AB Assessment of global functioning is an important consideration in treatment outcome research; yet, there is little guidance on its evidence-based assessment for children with autism spectrum disorders. This study investigated the utility and validity of clinician-rated global functioning using the Developmental Disability-Child Global Assessment Scale in a sample of higher functioning adolescents with autism spectrum disorders and comorbid anxiety disorders enrolled in a randomized controlled trial (n = 30). Pretreatment Developmental Disability-Child Global Assessment Scale scores correlated with severity of autism spectrum disorders core symptoms (r = -.388, p = .034), pragmatic communication (r = .407, p = .032), and verbal ability (r = .449, p = .013) and did not correlate with severity of anxiety symptoms or with parent-reported adaptive behavior. Change in Developmental Disability-Child Global Assessment Scale scores during treatment was associated with autism spectrum disorders symptomatic improvement (r = .414, p = .040) and with improved general communication (r = .499, p = .013). Results support the importance of assessing global functioning in addition to symptom change and treatment response in clinical trials. C1 [White, Susan W.; Smith, Laura A.; Schry, Amie R.] Virginia Tech, Blacksburg, VA 24061 USA. RP White, SW (reprint author), Virginia Tech, Dept Psychol, 109 Williams Hall 0436, Blacksburg, VA 24061 USA. 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Fewer studies have examined whether changes in cognition are associated with changes in social functioning. This study examined whether cognitive gains among 192 students from 47 kindergarten-through-second-grade autism support classrooms participating in a year-long behavioral intervention study were associated with gains in social functioning. Children's gains in cognitive ability were modestly associated with independent assessors' and teachers' evaluations of social functioning but were not associated with changes in parent ratings. Observed social gains were not commensurate with gains in cognition, suggesting the need both for interventions that directly target social functioning and relevant field measures of social functioning. C1 [Locke, Jill; Xie, Ming; Mandell, David] Univ Penn, Philadelphia, PA 19104 USA. [Rotheram-Fuller, Erin] Temple Univ, Philadelphia, PA 19122 USA. [Harker, Colleen] Univ Washington, Seattle, WA 98195 USA. 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Curtin, Carol Anderson, Sarah E. Maslin, Melissa Lividini, Keith Bandini, Linda G. TI Comparison of sedentary behaviors between children with autism spectrum disorders and typically developing children SO AUTISM LA English DT Article DE autism spectrum disorders; body mass index; children; sedentary behavior; television viewing ID NUTRITION EXAMINATION SURVEY; PHYSICAL-ACTIVITY; SCREEN TIME; NATIONAL-HEALTH; WEIGHT STATUS; US CHILDREN; MEDIA USE; ADOLESCENTS; OBESITY; ADIPOSITY AB Time spent in sedentary behavior is largely due to time spent engaged with electronic screen media. Little is known about the extent to which sedentary behaviors for children with autism spectrum disorder differ from typically developing children. We used parental report to assess and compare time spent in sedentary behaviors for 53 children with autism spectrum disorder and 58 typically developing children aged 3-11 years. We also determined how sedentary behavior was related to child weight status (body mass index z-score). Overall, children with autism spectrum disorder spent an hour more in sedentary behaviors on weekdays compared to typically developing children (5.2 vs 4.2 h, p = 0.03), and most of this difference was due to screen time. The age- and sex-adjusted estimate of weekday total daily screen time was 1.6 h (typically developing) compared to 2.5 h (autism spectrum disorder, p = 0.004 for difference). A significant relationship between BMI z-score and total sedentary behavior time on weekend days was observed among young children with ASD, but not among TD children. The modest association between weekend sedentary behaviour time and BMI z-score among children with ASD suggests that sedentary behaiour is linked to relative weight status in these children. Further research is needed to confirm these findings and identify causal pathways. C1 [Must, Aviva; Phillips, Sarah M.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Curtin, Carol; Maslin, Melissa; Bandini, Linda G.] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. [Anderson, Sarah E.] Ohio State Univ, Columbus, OH 43210 USA. [Lividini, Keith] HarvestPlus Int Food Policy Res Inst, Washington, DC USA. RP Must, A (reprint author), Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, 136 Harrison Ave, Boston, MA 02111 USA. 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In Study 1, we examined the developmental sequence of social-communicative skills in 26 typically developing infants when they were 9 months old and reexamined them when they were 12 and 15 months old. The results indicated a reliable developmental sequence of social-communicative skills in infants with typical development. In Study 2, we explored the emergence sequence of social-communicative skills of 23 children with autism and 23 children with developmental delay between the ages of 2 and 4 years. The results demonstrated that the developmental sequence of social-communicative skills in young children with autism and children with developmental delays was different. C1 [Wu, Chin-Chin] Kaohsiung Med Univ, Dept Psychol, Kaohsiung, Taiwan. [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. 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Souchay, Celine TI Metacognitive judgments- of- learning in adolescents with autism spectrum disorder SO AUTISM LA English DT Review DE autism; judgment-of-learning; memory; metamemory ID HIGH-FUNCTIONING AUTISM; STUDY-TIME ALLOCATION; ASPERGERS-SYNDROME; AUTOBIOGRAPHICAL MEMORY; UNANSWERABLE QUESTIONS; ACCESSIBILITY MODEL; CHILDRENS KNOWLEDGE; ALZHEIMERS-DISEASE; OLDER-ADULTS; FREE-RECALL AB This study investigated metacognitive monitoring abilities in adolescents with autism spectrum disorder in two experiments using the judgment-of-learning paradigm. Participants were asked to predict their future recall of unrelated word pairs during the learning phase. Experiment 1 compared judgments-of-learning made immediately after learning and judgments-of-learning made after a delay. We found that both groups overestimated their memory performance but that overall there were no group differences in judgment-of-learning accuracy. 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Our aim was to investigate the hypothesis that this abnormal behavioral repetition results from a tendency to over-rely on habits at the expense of flexible, goal-directed action. Twenty-four children with autism spectrum disorders and 24 age- and gender-matched controls (8-12 years) initially learned to give specific responses to different pictorial stimuli in order to gain valuable outcomes. Subsequently, in the slips-of-action test, some of these outcomes were no longer valuable. Children needed to refrain from responding when stimuli were shown that signaled the availability of those outcomes while continuing to respond for the still-valuable outcomes. Reliance on habits should lead to slips of action toward no longer valuable outcomes. Therefore, the children's ability to respond selectively for still-valuable outcomes provides a measure of relative habitual versus goal-directed control. Two additional tasks were included to control for general task characteristics (i.e. working memory and inhibition). Children with autism spectrum disorders learned equally well as controls and were not impaired at flexibly adjusting their behavior to devaluation of the outcomes or stimuli. We found no evidence for a disruption in the balance between goal-directed and habitual behavioral control in children with autism spectrum disorders. C1 [Geurts, Hilde M.; de Wit, Sanne] Univ Amsterdam, Dept Psychol, NL-1018 XA Amsterdam, Netherlands. [Geurts, Hilde M.; de Wit, Sanne] Univ Amsterdam, Cognit Sci Ctr Amsterdam, NL-1018 XA Amsterdam, Netherlands. [Geurts, Hilde M.] Autism Clin, Oosterbeek, Netherlands. [Geurts, Hilde M.] Dutch Autism & ADHD Res Ctr dArc, Amsterdam, Netherlands. RP Geurts, HM (reprint author), Univ Amsterdam, Dept Brain & Cognit, Weesperpl 4, NL-1018 XA Amsterdam, Netherlands. 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Anderson, Connie M. Law, Paul TI Risk factors for bullying among children with autism spectrum disorders SO AUTISM LA English DT Article DE autism spectrum disorder; bullying; schools; special needs ID LEARNING-DISABILITIES; PEER VICTIMIZATION; PSYCHOSOCIAL ADJUSTMENT; PSYCHIATRIC-DISORDERS; ASPERGER-SYNDROME; MIDDLE SCHOOL; SELF-ESTEEM; PREVALENCE; INCLUSION; STUDENTS AB Although children with disabilities have been found to be at an increased risk of bullying, there are limited studies investigating predictors of bullying involvement in children with autism spectrum disorders. The current study presents findings from 1221 parents of children diagnosed with autism spectrum disorder who were selected from a national web-based registry. Parents completed a survey dedicated to the school and bullying experiences of their child, and multivariate logistic regression analyses were conducted to identify child and school risk factors for involvement as victim, bully, or bully-victim. Additional analyses examined the risk of bullying involvement based on the amount of time spent in general education classrooms. Children diagnosed with Asperger's disorder, attending a public school or a school with a general education population, were at the greatest risk of being victimized in the past month. Children with comorbid conditions and a high level of autistic traits were the most likely to be victims, bullies, and bully-victims. Finally, children in full inclusion classrooms were more likely to be victimized than those who spend the majority of their time in special education settings. Future research studies should be invested in finding appropriate supports for children with autism spectrum disorder placed in inclusive settings. C1 [Zablotsky, Benjamin; Bradshaw, Catherine P.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Anderson, Connie M.] Towson Univ, Baltimore, MD USA. [Law, Paul] Kennedy Krieger Inst, Baltimore, MD USA. 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Baron-Cohen, Simon TI Sensory over- responsivity in adults with autism spectrum conditions SO AUTISM LA English DT Article DE autism spectrum conditions; autistic traits; Sensory Over-Responsivity Scale ID QUOTIENT AQ; CHILDRENS VERSION; OVER-RESPONSIVITY; ASPERGER-SYNDROME; DISORDERS; PROFILE; PATTERNS; MODULATION; VALIDITY AB Anecdotal reports and empirical evidence suggest that sensory processing issues are a key feature of autism spectrum conditions. This study set out to investigate whether adults with autism spectrum conditions report more sensory over-responsivity than adults without autism spectrum conditions. Another goal of the study was to identify whether autistic traits in adults with and without autism spectrum conditions were associated with sensory over-responsivity. Adults with (n = 221) and without (n = 181) autism spectrum conditions participated in an online survey. The Autism Spectrum Quotient, the Raven Matrices and the Sensory Processing Scale were used to characterize the sample. Adults with autism spectrum conditions reported more sensory over-responsivity than control participants across various sensory domains (visual, auditory, tactile, olfactory, gustatory and proprioceptive). Sensory over-responsivity correlated positively with autistic traits (Autism Spectrum Quotient) at a significant level across groups and within groups. Adults with autism spectrum conditions experience sensory over-responsivity to daily sensory stimuli to a high degree. A positive relationship exists between sensory over-responsivity and autistic traits. Understanding sensory over-responsivity and ways of measuring it in adults with autism spectrum conditions has implications for research and clinical settings. C1 [Tavassoli, Teresa; Baron-Cohen, Simon] Univ Cambridge, Cambridge CB2 1TN, England. [Tavassoli, Teresa] Icahn Sch Med Mt Sinai, Seaver Autism Ctr, New York, NY 10129 USA. [Miller, Lucy J.; Schoen, Sarah A.] Sensory Therapies & Res STAR Ctr, Greenwood Village, CO 80111 USA. [Miller, Lucy J.; Schoen, Sarah A.; Nielsen, Darci M.] Sensory Proc Disorder Fdn, Greenwood Village, CO USA. [Miller, Lucy J.] Univ Colorado Denver, Denver, CO USA. [Miller, Lucy J.; Schoen, Sarah A.] Rocky Mt Univ Hlth Profess, Provo, UT 84606 USA. RP Tavassoli, T (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr, 1428 Madison Ave, New York, NY 10129 USA. 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The sample included 70 families of young children with autism spectrum disorders. All parents were enrolled in a short education program, providing them with basic information and resources on advocating for a young child with autism spectrum disorders (Parent Advocacy Coaching). Longitudinal change in children's intervention program in the community was evaluated over a period of about 27 months, starting 12 months prior to enrollment in Parent Advocacy Coaching. Results revealed large individual differences in the intensity of children's individual and school-based services. Despite this variability, only two child characteristics (age, gender) emerged as independent predictors. In contrast, the intensity of children's intervention programs was independently predicted by a broad range of demographic characteristics, including parental education, child ethnicity and race, and family composition. Finally, even after child characteristics and family demographics were statistically controlled, results revealed associations between specific parental cognitions (parenting efficacy, understanding of child development) and the subsequent rate of change in the intensity of children's intervention programs. Implications for improving educational programs that aim to enhance parent advocacy are discussed. C1 [Siller, Michael; Reyes, Nuri; Hutman, Ted; Sigman, Marian] Univ Calif Los Angeles, Los Angeles, CA USA. [Siller, Michael; Hotez, Emily] CUNY, New York, NY USA. [Reyes, Nuri] Virginia Tech, Nashville, TN USA. RP Siller, M (reprint author), CUNY Hunter Coll, Dept Psychol, RM 611 HN,695 Pk Ave, New York, NY 10065 USA. 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TI Adaptation of the " ten questions" to screen for autism and other neurodevelopmental disorders in Uganda SO AUTISM LA English DT Article DE autism spectrum disorder screening and assessment; developing countries; low- and middle-income countries; neurodevelopmental disorder screening and assessment; Uganda ID CHILDHOOD DISABILITY; CHILDREN; PREVALENCE; VALIDITY; EPILEPSY; JAMAICA; RELIABILITY; IMPAIRMENT; BANGLADESH; COUNTRIES AB Neurodevelopmental disorders are recognized to be relatively common in developing countries but little data exist for planning effective prevention and intervention strategies. In particular, data on autism spectrum disorders are lacking. For application in Uganda, we developed a 23-question screener (23Q) that includes the Ten Questions screener and additional questions on autism spectrum disorder behaviors. We then conducted household screening of 1169 children, 2-9 years of age, followed by clinical assessment of children who screened positive and a sample of those who screened negative to evaluate the validity of the screener. We found that 320 children (27% of the total) screened positive and 68 children received a clinical diagnosis of one or more moderate to severe neurodevelopmental disorders (autism spectrum disorder; cerebral palsy; epilepsy; cognitive, speech and language, hearing, or vision impairment), including 8 children with autism spectrum disorders. Prevalence and validity of the screener were evaluated under different statistical assumptions. Sensitivity of the 23Q ranged from 0.55 to 0.80 and prevalence for 1 neurodevelopmental disorders from 7.7/100 children to 12.8/100 children depending on which assumptions were used. The combination of screening positive on both autism spectrum disorders and Ten Questions items was modestly successful in identifying a subgroup of children at especially high risk of autism spectrum disorders. We recommend that autism spectrum disorders and related behavioral disorders be included in studies of neurodevelopmental disorders in low-resource settings to obtain essential data for planning local and global public health responses. C1 [Kakooza-Mwesige, Angelina; Ssebyala, Keron; Karamagi, Charles; Kiguli, Sarah] Makerere Univ, Mulago Natl Referral Hosp, Kampala, Uganda. [Smith, Karen; Anderson, Meredith C.; Smith, Daniel; Grether, Judith K.] Sequoia Fdn, USA Kaiser Permanente Div Res, Berkeley, CA 94703 USA. [Croen, Lisa A.] St Louis Univ, Sch Publ Hlth & Social Justice, St Louis, MO 63103 USA. [Trevathan, Edwin] Univ Calif Davis, Davis, CA 95616 USA. [Hansen, Robin] Sequoia Fdn, Berkeley, CA 94703 USA. 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Hume, Kara A. TI Observational learning by individuals with autism: A review of teaching strategies SO AUTISM LA English DT Article DE autism; group instruction; modeling; observational learning ID SMALL-GROUP INSTRUCTION; SPECTRUM DISORDERS; REINFORCEMENT CONTINGENCIES; DEVELOPMENTAL-DISABILITIES; PRESCHOOL-CHILDREN; IN-VIVO; BEHAVIOR; SKILLS; ACQUISITION; STUDENTS AB Observational learning is the process used to explain the acquisition of novel behaviors or performance of previously acquired behaviors under novel conditions after observing the behavior of another person and the consequences that follow the behavior. Many learners with autism do not attend to environmental stimuli at a level sufficient to learn a range of prosocial behaviors through observation of others. Modeling, group or dyadic instruction, and explicit observation training can improve the extent to which individuals with autism learn through observation. 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Gantman, Alexander Ellingsen, Ruth Frankel, Fred Dillon, Ashley R. TI Predicting treatment success in social skills training for adolescents with autism spectrum disorders: The UCLA Program for the Education and Enrichment of Relational Skills SO AUTISM LA English DT Article DE adolescents; autism spectrum disorders; friendship; predictors; Program for the Education and Enrichment of Relational Skills; social skills ID ASPERGER-SYNDROME; CHILDREN AB This study seeks to examine the predictors of positive social skills outcomes from the University of California, Los Angeles Program for the Education and Enrichment of Relational Skills, an evidence-based parent-assisted social skills program for high-functioning middle school and high school adolescents with autism spectrum disorders. 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Stigler, Kimberly A. Szymanski, Ludwik King, Bryan H. Carlisle, L. Lee Cook, Edwin H., Jr. Pruett, John R., Jr. CA Amer Acad Child Adolescent TI Training of child and adolescent psychiatry fellows in autism and intellectual disability SO AUTISM LA English DT Article DE autism; intellectual disability; education; fellowship training ID PSYCHOTROPIC MEDICATION USE; SPECTRUM DISORDERS AB Patients with autism spectrum disorders and intellectual disability can be clinically complex and often have limited access to psychiatric care. Because little is known about post-graduate clinical education in autism spectrum disorder and intellectual disability, we surveyed training directors of child and adolescent psychiatry fellowship programs. On average, child and adolescent psychiatry directors reported lectures of 3 and 4 h per year in autism spectrum disorder and intellectual disability, respectively. Training directors commonly reported that trainees see 1-5 patients with autism spectrum disorder or intellectual disability per year for outpatient pharmacological management and inpatient treatment. Overall, 43% of directors endorsed the need for additional resources for training in autism spectrum disorder and intellectual disability, which, coupled with low didactic and clinical exposure, suggests that current training is inadequate. C1 [Marrus, Natasha; Pruett, John R., Jr.] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Nashville, TN USA. [Hellings, Jessica A.] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. [Stigler, Kimberly A.] Indiana Univ, Sch Med, Bloomington, IN 47405 USA. [Szymanski, Ludwik] Boston Childrens Hosp, Boston, MA USA. [King, Bryan H.; Carlisle, L. Lee] Univ Washington, Sch Med, Seattle, WA 98195 USA. [King, Bryan H.; Carlisle, L. Lee] Seattle Childrens Hosp, Seattle, WA USA. 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TI The role of microbiome in central nervous system disorders SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Review DE Microbiome; Central nervous system; Gut-brain axis; Neuro-immune disorders; Neuro-psychiatric disorders ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; IRRITABLE-BOWEL-SYNDROME; ANXIETY-LIKE BEHAVIOR; REGULATORY T-CELLS; POSTMYOCARDIAL INFARCTION DEPRESSION; PROBIOTIC BIFIDOBACTERIUM-INFANTIS; INDUCED VISCERAL HYPERSENSITIVITY; EXACERBATE NEUROLOGICAL SYMPTOMS; AUTISM SPECTRUM DISORDER; GUILLAIN-BARRE-SYNDROME AB Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome-gut-brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome-CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kasper, Lloyd H.] Dartmouth Coll, Geisel Sch Med, Dept Microbiol & Immunol, Hanover, NH 03755 USA. Dartmouth Coll, Geisel Sch Med, Dept Med, Hanover, NH 03755 USA. RP Kasper, LH (reprint author), Dartmouth Coll, Geisel Sch Med, Dept Microbiol & Immunol, Hanover, NH 03755 USA. 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Immun. PD MAY PY 2014 VL 38 BP 1 EP 12 DI 10.1016/j.bbi.2013.12.015 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA AF8RU UT WOS:000334984100001 PM 24370461 ER PT J AU Piras, IS Haapanen, L Napolioni, V Sacco, R Van de Water, J Persico, AM AF Piras, I. S. Haapanen, L. Napolioni, V. Sacco, R. Van de Water, J. Persico, A. M. TI Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with Autism Spectrum Disorder SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Autism; Autism Spectrum Disorder; Autoantibodies; Autoimmunity; Cerebellum; Cognitive impairment; Language development; Macrocephaly; Sleep/wake cycle ID PRINCIPAL PATHOGENETIC COMPONENTS; MATERNAL AUTOANTIBODIES; IMMUNE DYSFUNCTION; BRAIN; CEREBELLUM; AUTOIMMUNITY; NARCOLEPSY; PROTEINS; PLASMA; SYSTEM AB Circulating 45 and 62 kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73 kDa maternal antibodies (mAb) targeting the fetal brain were previously correlated with broad autism spectrum, irritability, abnormal brain enlargement and impaired expressive language. The present study aims towards clinically characterizing individuals with brain-targeted IgG and/or exposed to maternal antibrain antibodies in a large sample of Italian autistic children (N = 355), their unaffected siblings (N = 142) and mothers (N = 333). The presence of patient- and mother-produced anti-brain antibodies does not confer increased risk of autism within the same sibship. However, the 45 and 62 kDa antibodies are correlated with autism severity: the 45 kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62 kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P < 0.05). On the other hand, maternal 37, 39 and 73 kDa antibrain antibodies, either alone or in combination, are correlated with impaired verbal and non-verbal language development, neurodevelopmental delay and sleep/wake cycle disturbances in their autistic children (P < 0.05). Presence of the 62 kDa autoAb in the child is significantly associated with presence of the 39 and/or 73 kDa antibodies in his/her mother. Our results confirm and extend previous observations in an ethnically distinct sample, providing further evidence of a pathomorphic role for antibrain antibodies in autism while demonstrating their familial clustering. (C) 2014 Elsevier Inc. All rights reserved. C1 [Piras, I. S.; Napolioni, V.; Sacco, R.; Persico, A. M.] Univ Campus Biomed, Lab Mol Psychiat & Neurogenet, Unit Child & Adolescent NeuroPsychiat, Rome, Italy. [Haapanen, L.; Van de Water, J.] Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA. [Haapanen, L.; Van de Water, J.] Univ Calif Davis, Davis MIND Inst, Davis, CA 95616 USA. [Haapanen, L.; Van de Water, J.] Univ Calif Davis, Childrens Ctr Environm Hlth, Davis, CA 95616 USA. [Sacco, R.; Persico, A. M.] Fdn Santa Lucia, IRCCS, Dept Expt Neurosci, Rome, Italy. [Persico, A. M.] Mafalda Luce Ctr Pervas Dev Disorders, Milan, Italy. RP Persico, AM (reprint author), Univ Campus Biomed, Lab Mol Psychiat & Neurogenet, Unit Child & Adolescent NeuroPsychiat, Via Alvaro Portillo 21, Rome, Italy. EM a.persico@unicampus.it FU Italian Ministry for University, Scientific Research and Technology (PRIN) [2006058195, 2008BACT54_002]; Italian Ministry of Health [RFPS-2007-5-640174, RF-2011-02350537, CCM2012-Progetto NIDA]; Fondazione Gaetano e Mafalda Luce (Milan, Italy); Autism Aid ONLUS (Naples, Italy); Autism Speaks (Princeton, NJ); Autism Research Institute (San Diego, CA); Innovative Medicines Initiative Joint Undertaking (EU-AIMS) [115300]; NIEHS [1 P01 ES11269-01, 1 R01-ES015359]; U.S. Environmental Protection Agency (U.S.EPA) through the Science to Achieve Results (STAR) program [R829388]; UC Davis M.I.N.D. Institute FX The Authors wish to thank all the patients and families who participated in this study. This work was supported by the Italian Ministry for University, Scientific Research and Technology (PRIN no. 2006058195 and no. 2008BACT54_002), the Italian Ministry of Health (RFPS-2007-5-640174, RF-2011-02350537 and CCM2012-Progetto NIDA), the Fondazione Gaetano e Mafalda Luce (Milan, Italy), Autism Aid ONLUS (Naples, Italy), Autism Speaks (Princeton, NJ), the Autism Research Institute (San Diego, CA), and the Innovative Medicines Initiative Joint Undertaking (EU-AIMS, no. 115300), NIEHS 1 P01 ES11269-01, the U.S. Environmental Protection Agency (U.S.EPA) through the Science to Achieve Results (STAR) program (Grant R829388), NIEHS 1 R01-ES015359, the UC Davis M.I.N.D. Institute. 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Immun. PD MAY PY 2014 VL 38 BP 91 EP 99 DI 10.1016/j.bbi.2013.12.020 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA AF8RU UT WOS:000334984100010 PM 24389156 ER PT J AU Onore, CE Schwartzer, JJ Careaga, M Berman, RF Ashwood, P AF Onore, Charity E. Schwartzer, Jared J. Careaga, Milo Berman, Robert F. Ashwood, Paul TI Maternal immune activation leads to activated inflammatory macrophages in offspring SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE MIA; Maternal; Immune activation; Macrophage; M1; M2; Mouse; Autism; Behavior; Inflammation ID AUTISM SPECTRUM DISORDERS; T-CELLS; DENDRITIC RETRACTION; CONGENITAL-RUBELLA; NEONATAL MICE; RETT-SYNDROME; POLARIZATION; INFECTION; SCHIZOPHRENIA; BRAIN AB Several epidemiological studies have shown an association between infection or inflammation during pregnancy and increased risk of autism in the child. In addition, animal models have illustrated that maternal inflammation during gestation can cause autism-relevant behaviors in the offspring; so called maternal immune activation (MIA) models. More recently, permanent changes in T cell cytokine responses were reported in children with autism and in offspring of MIA mice; however, the cytokine responses of other immune cell populations have not been thoroughly investigated in these MIA models. Similar to changes in T cell function, we hypothesized that following MIA, offspring will have long-term changes in macrophage function. To test this theory, we utilized the poly (I:C) MIA mouse model in C57BL/6J mice and examined macrophage cytokine production in adult offspring. Pregnant dams were given either a single injection of 20 mg/kg polyinosinic-polycytidylic acid, poly (I:C), or saline delivered intraperitoneally on gestational day 12.5. When offspring of poly (I:C) treated dams reached 10 weeks of age, femurs were collected and bone marrow-derived macrophages were generated. Cytokine production was measured in bone marrow-derived macrophages incubated for 24 h in either growth media alone, LPS, IL-4/LPS, or IFN-gamma/LPS. Following stimulation with LPS alone, or the combination of IFN-gamma/LPS, macrophages from offspring of poly (I:C) treated dams produced higher levels of IL-12(p40) (p < 0.04) suggesting an increased M1 polarization. In addition, even without the presence of a polarizing cytokine or LPS stimulus, macrophages from offspring of poly (I:C) treated dams exhibited a higher production of CCL3 (p = 0.05). Moreover, CCL3 levels were further increased when stimulated with LPS, or polarized with either IL-4/LPS or IFN-gamma/LPS (p < 0.05) suggesting a general increase in production of this chemokine. Collectively, these data suggest that MIA can produce lasting changes in macrophage function that are sustained into adulthood. (C) 2014 Published by Elsevier Inc. C1 [Onore, Charity E.; Careaga, Milo; Ashwood, Paul] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Onore, Charity E.; Schwartzer, Jared J.; Careaga, Milo; Berman, Robert F.; Ashwood, Paul] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Schwartzer, Jared J.; Berman, Robert F.] Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. [Berman, Robert F.] Univ Calif Davis, Dept Neurol Surg, Davis, CA 95616 USA. [Schwartzer, Jared J.] Mt Holyoke Coll, Dept Psychol & Educ, S Hadley, MA 01075 USA. RP Ashwood, P (reprint author), MIND Inst, 2825 50th St, Sacramento, CA 95817 USA. EM pashwood@ucdavis.edu FU NIH [T32MH073124]; Jane Botsford Johnson Foundation; Peter Emch Foundation; Barbara and Michael Bass Foundation; Brain & Behavior Research Foundation; Autism Research Institute FX This work was supported by NIH T32MH073124, Jane Botsford Johnson Foundation, Peter Emch Foundation, Barbara and Michael Bass Foundation, the Brain & Behavior Research Foundation (formerly known as National Alliance for Research on Schizophrenia and Depression) and the Autism Research Institute. This research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 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The present research first investigated the relationship of autism traits with trait emotional intelligence and empathy in a sample of 163 adults aged between 18 and 51years (44% male). It then examined performance on a set of tasks assessing social cognition and cognitive flexibility in 69 participants with either high or low scores on ASD traits. Results confirm that there is pronounced variation within the general population relating to ASD traits, which reflect similar (though less severe) social-cognitive and emotional features to those observed in ASDs. C1 [Goekcen, Elif; Petrides, Konstantinos V.] UCL, London Psychometr Lab, London WC1E 6BT, England. [Hudry, Kristelle] La Trobe Univ, Sch Psychol Sci, Olga Tennison Autism Res Ctr, Bundoora, Vic 3086, Australia. [Frederickson, Norah] UCL, Res Dept Clin Educ & Hlth Psychol, London WC1E 6BT, England. [Smillie, Luke D.] Univ Melbourne, Melbourne Sch Psychol Sci, Melbourne, Vic 3010, Australia. 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First, we discuss the technology of genome and exome sequencing, including the different next-generation platforms and exome enrichment technologies. Second, we survey the pioneering centers and discoveries for rare diseases, including few of the research institutions that have contributed to the field, as well as an overview survey of different types of rare diseases that have had new discoveries due to next-generation sequencing. Third, we discuss the obstacles and challenges that allow for clinical implementation, including returning of results, informed consent and privacy. Last, we discuss possible outlook as clinical genomics receives wider adoption, as third-generation sequencing is coming onto the horizon, and some needs in informatics and software to further advance the field. C1 [Danielsson, Krissi; Mun, Liew Jun; Lordemann, Amanda; Mao, Jimmy; Lin, Cheng-Ho Jimmy] Rare Genom Inst, St Louis, MO 63108 USA. 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Mol. Diagn. PD MAY PY 2014 VL 14 IS 4 BP 469 EP 487 DI 10.1586/14737159.2014.904749 PG 19 WC Pathology SC Pathology GA AF3FW UT WOS:000334597900008 PM 24702023 ER PT J AU Xue, J Ooh, J Magiati, I AF Xue, J. Ooh, J. Magiati, I. TI Family functioning in Asian families raising children with autism spectrum disorders: the role of capabilities and positive meanings SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE reframing; coping; stressors; family functioning; autism spectrum disorders; adjustment ID DOUBLE ABCX MODEL; COPING STRATEGIES; BEHAVIOR PROBLEMS; INTELLECTUAL DISABILITY; PARENTING STRESS; DOWN-SYNDROME; HONG-KONG; MOTHERS; IMPACT; WELL AB Background There has been increasing interest in exploring the factors contributing to successful adaptation and family functioning in ethnically and culturally diverse families who raise children with autism spectrum disorders (ASD), in order to inform more appropriate strength-based family support services. This pilot study used the Family Adjustment and Adaptation Response (FAAR) model as a theoretical framework to investigate the role of families' capabilities (coping strategies and resources of support) and positive meanings in raising a child with ASD in family functioning in an Asian context. Methods Sixty-five Singaporean parents of 3- to 11-year-old children with ASD completed a series of questionnaires on demands, coping strategies, social support, positive meanings and family functioning. Results Families reported a number of helpful coping strategies. Coping through family integration/optimism was most helpful, followed by understanding the condition and by developing esteem and psychological stability. Reported capabilities, but not positive meanings, mediated the relationship between demands and family functioning. Conclusion The findings are discussed in relation to existing literature, possible specific cultural issues, and the strengths and limitations of the study. Implications for supporting families of children with ASD in different social and cultural contexts are also discussed. C1 [Xue, J.; Magiati, I.] Natl Univ Singapore, Singapore 117570, Singapore. [Ooh, J.] Natl Univ Singapore Hosp, Singapore 117548, Singapore. RP Magiati, I (reprint author), Natl Univ Singapore, AS4 02-24,9 ARTS LINK, Singapore 117570, Singapore. 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PD MAY PY 2014 VL 58 IS 5 BP 406 EP 420 DI 10.1111/jir.12034 PG 15 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA AE7KU UT WOS:000334177500002 PM 23510076 ER PT J AU Pozo, P Sarria, E Brioso, A AF Pozo, P. Sarria, E. Brioso, A. TI Family quality of life and psychological well-being in parents of children with autism spectrum disorders: a double ABCX model SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE coping strategies; family quality of life; autism spectrum disorders; double ABCX model; psychological well-being; sense of coherence ID SCHOOL-AGE-CHILDREN; DEVELOPMENTAL-DISABILITIES; MENTAL-RETARDATION; COPING STRATEGIES; BEHAVIOR-PROBLEMS; YOUNG-CHILDREN; POSITIVE PERCEPTIONS; PRESCHOOL-CHILDREN; COHERENCE SCALE; SOCIAL SUPPORT AB Background This study examined family quality of life (FQOL) and psychological well-being from a multidimensional perspective. The proposed model was based on the double ABCX model, with severity of the disorder, behaviour problems, social support, sense of coherence (SOC) and coping strategies as components. Method One hundred and eighteen parents (59 mothers and 59 fathers) with a child diagnosed with autism spectrum disorders (ASD) participated in the study. Separate path analyses were performed to evaluate models of FQOL and psychological well-being for mothers and fathers. Results In all models, behaviour problems had a negative indirect effect on adaptation (FQOL and psychological well-being) through SOC. For both mothers and fathers, the severity of the disorder and social support played significant roles in FQOL models. Coping strategies were related with adaptation, active avoidance coping with FQOL for fathers and positive and problem-focused coping with psychological well-being for mothers. Conclusions The results of this study highlight the value of the multidimensional approach. The specific patterns of results for mothers and fathers contribute to comprehension of the psychological adaptation of parents. Findings could be taken into account in interventions with families. 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Intell. Disabil. Res. PD MAY PY 2014 VL 58 IS 5 BP 442 EP 458 DI 10.1111/jir.12042 PG 17 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA AE7KU UT WOS:000334177500005 PM 23600450 ER PT J AU Gillespie-Smith, K Riby, DM Hancock, PJB Doherty-Sneddon, G AF Gillespie-Smith, K. Riby, D. M. Hancock, P. J. B. Doherty-Sneddon, G. TI Children with autism spectrum disorder (ASD) attend typically to faces and objects presented within their picture communication systems SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE eye-tracking; cognitive behaviour; communication; autism spectrum disorder ID WILLIAMS-SYNDROME; BEHAVIOR; LOOKING; PECS AB Background Children with autism spectrum disorder (ASD) may require interventions for communication difficulties. One type of intervention is picture communication symbols which are proposed to improve comprehension of linguistic input for children with ASD. However, atypical attention to faces and objects is widely reported across the autism spectrum for several types of stimuli. Method In this study we used eye-tracking methodology to explore fixation duration and time taken to fixate on the object and face areas within picture communication symbols. Twenty-one children with ASD were compared with typically developing matched groups. Results Children with ASD were shown to have similar fixation patterns on face and object areas compared with typically developing matched groups. Conclusions It is proposed that children with ASD attend to the images in a manner that does not differentiate them from typically developing individuals. Therefore children with and without autism have the same opportunity to encode the available information. We discuss what this may imply for interventions using picture symbols. C1 [Gillespie-Smith, K.; Hancock, P. J. B.] Univ Stirling, Dept Psychol, Sch Nat Sci, Stirling FK9 4LA, Scotland. [Riby, D. M.] Newcastle Univ, Sch Psychol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Doherty-Sneddon, G.] Northumbria Univ, Sch Life Sci, Dept Psychol, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England. RP Gillespie-Smith, K (reprint author), Univ Edinburgh, Dept Philosophy Psychol & Language, Edinburgh EH8 9JZ, Midlothian, Scotland. EM Karri.Gillespie-Smith@ed.ac.uk RI Hancock, Peter/A-4633-2009 OI Hancock, Peter/0000-0001-6025-7068 CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT BARONCOHEN S, 1996, BRIT J PSYCHIAT, V168, P158, DOI DOI 10.1192/BJP.168.2.158 Bondy A. 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C., 1990, RAVENS COLOURED PROG Riby D, 2009, J INTELL DISABIL RES, V53, P169, DOI 10.1111/j.1365-2788.2008.01142.x Riby DM, 2008, NEUROPSYCHOLOGIA, V46, P2855, DOI 10.1016/j.neuropsychologia.2008.05.003 Rutter M., 2003, SOCIAL COMMUNICATION Schopler E., 1998, CHILDHOOD AUTISM RAT Speer LL, 2007, AUTISM, V11, P265, DOI 10.1177/1362361307076925 Swettenham J, 1998, J CHILD PSYCHOL PSYC, V39, P747, DOI 10.1017/S0021963098002595 Tincani M., 2004, FOCUS AUTISM OTHER D, V19, P162 Trepagnier C, 2002, CYBERPSYCHOL BEHAV, V5, P213, DOI 10.1089/109493102760147204 van der Geest JN, 2002, J AUTISM DEV DISORD, V32, P69, DOI 10.1023/A:1014832420206 Volkmar FR, 2004, J CHILD PSYCHOL PSYC, V45, P135, DOI 10.1046/j.0021-9630.2003.00317.x Yoder P, 2006, J CONSULT CLIN PSYCH, V74, P426, DOI 10.1037/0022-006X.74.3.426 NR 35 TC 2 Z9 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-2633 EI 1365-2788 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD MAY PY 2014 VL 58 IS 5 BP 459 EP 470 DI 10.1111/jir.12043 PG 12 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA AE7KU UT WOS:000334177500006 PM 23600472 ER PT J AU Ly, AR Goldberg, WA AF Ly, A. R. Goldberg, W. A. TI New measure for fathers of children with developmental challenges SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE developmental disabilities; fathering; autism; parenting measures; scale development; developmental challenges ID PARENTING STRESS; DISABILITIES; MOTHERS; AUTISM; INVOLVEMENT; FAMILIES; SYSTEMS; PARTICIPATION AB Background There is a relative lack of measures tailored to the study of fathers of children with developmental challenges (DCs). The goal of the current study was to create and validate a brief measure designed to capture the perceptions and experiences of these fathers. The Fathers of Children with Developmental Challenges (FCDC) questionnaire was designed to assess fathers' perceptions of the supports for, and challenges to, their efforts to be involved in the rearing of their children. Method Participants were 101 fathers of children with DCs who completed an online survey. Scale validation included tests to determine reliability, validity and factor structure. Used to establish validity were measures of parenting stress, parenting commitment, parent personality and child social-communicative skills. Results Analyses indicated that the FCDC is reliable (alpha = 0.89), demonstrates content validity, construct validity and acts in theoretically expected ways. Factor analysis on the 20-item measure yielded two sub-scales: (1) impact on parenting, and (2) involvement with child intervention. Conclusions The FCDC fills a gap in the literature by offering an easy-to-administer self-report measure of fathers' perceptions of supports for, and barriers to, their involvement with their children with DCs. The FCDC could assist professionals in delivering support services specifically for fathers of children with DCs. C1 [Ly, A. R.] Univ Delaware, Newark, DE 19716 USA. [Goldberg, W. A.] Univ Calif Irvine, Irvine, CA USA. RP Ly, AR (reprint author), Univ Delaware, 108 Wolf Hall, Newark, DE 19716 USA. EM aly@psych.udel.edu CR Abidin R. R, 1995, MANUAL PARENTING STR Altiere M. 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H., 2010, ROLE FATHER CHILD DE, P58 Pleck JH, 2007, APPL DEV SCI, V11, P196 Pleck JH, 2012, PARENT-SCI PRACT, V12, P243, DOI 10.1080/15295192.2012.683365 Rutter M., 2003, SOCIAL COMMUNICATION Saloviita T, 2003, J INTELL DISABIL RES, V47, P300, DOI 10.1046/j.1365-2788.2003.00492.x Schieve LA, 2007, PEDIATRICS, V119, pS114, DOI 10.1542/peds.2006-2089Q Towers C., 2006, RECOGNISING FATHERS Trochim W., 2007, RES METHODS KNOWLEDG Turbiville VP, 2001, TOP EARLY CHILD SPEC, V21, P223, DOI 10.1177/027112140102100403 von Klitzing K, 2011, FAMILY SCI, V2, P156, DOI [10.1080/19424620.2011.657831, DOI 10.1080/19424620.2011.657831.] West S, 2000, JUST SHADOW REV SUPP NR 48 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-2633 EI 1365-2788 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD MAY PY 2014 VL 58 IS 5 BP 471 EP 484 DI 10.1111/jir.12044 PG 14 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA AE7KU UT WOS:000334177500007 PM 23627678 ER PT J AU Jung, JY DeLuca, TF Nelson, TH Wall, DP AF Jung, Jae-Yoon DeLuca, Todd F. Nelson, Tristan H. Wall, Dennis P. TI A literature search tool for intelligent extraction of disease-associated genes SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID HUMAN GENOME EPIDEMIOLOGY; BIPOLAR DISORDER; MULTIPLE-SCLEROSIS; CANDIDATE GENES; AUTISM; NORMALIZATION; EXPRESSION; MUTATIONS; MODELS; TEXT AB Objective To extract disorder-associated genes from the scientific literature in PubMed with greater sensitivity for literature-based support than existing methods. Methods We developed a PubMed query to retrieve disorder-related, original research articles. Then we applied a rule-based text-mining algorithm with keyword matching to extract target disorders, genes with significant results, and the type of study described by the article. Results We compared our resulting candidate disorder genes and supporting references with existing databases. We demonstrated that our candidate gene set covers nearly all genes in manually curated databases, and that the references supporting the disorder-gene link are more extensive and accurate than other general purpose gene-to-disorder association databases. Conclusions We implemented a novel publication search tool to find target articles, specifically focused on links between disorders and genotypes. Through comparison against gold-standard manually updated gene-disorder databases and comparison with automated databases of similar functionality we show that our tool can search through the entirety of PubMed to extract the main gene findings for human diseases rapidly and accurately. C1 [Jung, Jae-Yoon; DeLuca, Todd F.; Wall, Dennis P.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Nelson, Tristan H.; Wall, Dennis P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Wall, DP (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. EM dpwall@hms.harvard.edu FU National Science Foundation [0543480, 0640809]; National Institutes of Health [LM009261] FX This work was supported by the National Science Foundation grant nos 0543480 and 0640809 to DPW; and the National Institutes of Health grant no. LM009261 to DPW. 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TI High rate of disease-related copy number variations in childhood onset schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE CNV; genetics; neurodevelopment; schizophrenia ID AUTISM SPECTRUM DISORDERS; HIDDEN-MARKOV MODEL; SNP GENOTYPING DATA; RECURRENT MICRODELETIONS; DEVELOPMENTAL DELAY; INCREASE RISK; DOUBLE-BLIND; DELETIONS; VARIANTS; 16P11.2 AB Copy number variants (CNVs) are risk factors in neurodevelopmental disorders, including autism, epilepsy, intellectual disability (ID) and schizophrenia. Childhood onset schizophrenia (COS), defined as onset before the age of 13 years, is a rare and severe form of the disorder, with more striking array of prepsychotic developmental disorders and abnormalities in brain development. Because of the well-known phenotypic variability associated with pathogenic CNVs, we conducted whole genome genotyping to detect CNVs and then focused on a group of 46 rare CNVs that had well-documented risk for adult onset schizophrenia (AOS), autism, epilepsy and/or ID. We evaluated 126 COS probands, 69 of which also had a healthy full sibling. When COS probands were compared with their matched related controls, significantly more affected individuals carried disease-related CNVs (P = 0.017). Moreover, COS probands showed a higher rate than that found in AOS probands (P < 0.0001). A total of 15 (11.9%) subjects exhibited at least one such CNV and four of these subjects (26.7%) had two. Five of 15 (4.0% of the sample) had a 2.5-3Mb deletion mapping to 22q11.2, a rate higher than that reported for adult onset (0.3-1%) (P < 0.001) or autism spectrum disorder and, indeed, the highest rate reported for any clinical population to date. For one COS subject, a duplication found at 22q13.3 had previously only been associated with autism, and for four patients CNVs at 8q11.2, 10q22.3, 16p11.2 and 17q21.3 had only previously been associated with ID. Taken together, these findings support the well-known pleiotropic effects of these CNVs suggesting shared abnormalities early in brain development. Clinically, broad CNV-based population screening is needed to assess their overall clinical burden. C1 [Ahn, K.; Gotay, N.; Andersen, T. M.; Anvari, A. A.; Gochman, P.; Lee, Y.; Rapoport, J. L.] NIMH, Childhood Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Sanders, S.; State, M. W.] Yale Univ, Sch Med, Dept Genet, Program Neurogenet,Child Study Ctr,Dept Psychiat, New Haven, CT 06510 USA. [Guha, S.; Lencz, T.] Zucker Hillside Hosp, Glen Oaks, NY USA. [Darvasi, A.] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. [Glessner, J. 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Psychiatr. PD MAY PY 2014 VL 19 IS 5 BP 568 EP 572 DI 10.1038/mp.2013.59 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AF7VY UT WOS:000334924300009 PM 23689535 ER PT J AU Jones, B AF Jones, Bryony TI HUMAN GENETICS Autism - clues from brains and protein domains SO NATURE REVIEWS GENETICS LA English DT Editorial Material CR Davis JM, 2014, PLOS GENET, V10, DOI 10.1371/journal.pgen.1004241 Stoner R, 2014, NEW ENGL J MED, V370, P1209, DOI 10.1056/NEJMoa1307491 NR 2 TC 0 Z9 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 EI 1471-0064 J9 NAT REV GENET JI Nat. Rev. Genet. PD MAY PY 2014 VL 15 IS 5 BP 287 EP 287 DI 10.1038/nrg3715 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA AF3GM UT WOS:000334599700001 PM 24709752 ER PT J AU Sham, PC Purcell, SM AF Sham, Pak C. Purcell, Shaun M. TI STUDY DESIGNS Statistical power and significance testing in large-scale genetic studies SO NATURE REVIEWS GENETICS LA English DT Review ID GENOME-WIDE ASSOCIATION; AUTISM SPECTRUM DISORDERS; SAMPLE-SIZE REQUIREMENTS; MONTE-CARLO PROCEDURES; EMPIRICAL P-VALUES; RARE VARIANTS; COMPLEX TRAITS; QUANTITATIVE TRAITS; SEQUENCE DATA; ENVIRONMENT INTERACTION AB Significance testing was developed as an objective method for summarizing statistical evidence for a hypothesis. It has been widely adopted in genetic studies, including genome-wide association studies and, more recently, exome sequencing studies. However, significance testing in both genome-wide and exome-wide studies must adopt stringent significance thresholds to allow multiple testing, and it is useful only when studies have adequate statistical power, which depends on the characteristics of the phenotype and the putative genetic variant, as well as the study design. 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TI Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families SO NEUROGENETICS LA English DT Article DE Autism; Copy number variant; Genomic; Gephyrin; Synapse ID LINKED MENTAL-RETARDATION; DEVELOPMENTAL DELAY; EXONIC DELETIONS; DE-NOVO; MUTATIONS; SCHIZOPHRENIA; OBESITY; REGION; SHANK3; DUPLICATIONS AB Autism or autism spectrum disorder (ASD) is a range of neurodevelopmental disorders starting in early childhood and is characterized by impairments in communication and reciprocal social interaction and presence of restricted and repetitive patterns of behavior. The contribution of genetic factors to autism is clear in twin and family studies. It is apparent that, overall, ASD is a complex non-Mendelian disorder. Recent studies suggest that copy number variations (CNVs) play a significant role in the etiology of ASD. For the current work, we recruited 245 family members from 73 ASD families from Styria, Austria. The DNA from probands was genotyped with Affymetrix single nucleotide polymorphism (SNP) 6.0 microarrays to screen for CNVs in their genomes. Analysis of the microarray data was performed using three different algorithms, and a list of stringent calls was compared to existing CNV data from over 2,357 controls of European ancestry. For stringent calls not present in controls, quantitative real-time PCR (qRT-PCR) was used to validate the CNVs in the probands and in their family members. Twenty-two CNVs were validated from this set (five of which are apparently de novo), many of which appear likely to disrupt genes that may be considered as good candidates for neuropsychiatric disorders, including DLG2, S100B, ARX, DIP2A, HPCAL1, and GPHN. Several others disrupt genes that have previously been implicated in autism, such as BDNF, AUTS2, DPP6, and C18orf22, and our data add to the growing evidence of their involvement in ASD. C1 [Egger, Gerald; Noor, Abdul; Mahmood, Huda; Boright, Oliver; Mikhailov, Anna; Vincent, John B.] CAMH, Neurogenet Sect, Campbell Family Brain Res Inst, Toronto, ON M5T 1R8, Canada. [Egger, Gerald; Roetzer, Katharina M.; Schwarzbraun, Thomas; Windpassinger, Christian; Petek, Erwin] Med Univ Graz, Inst Human Genet, Graz, Austria. [Noor, Abdul] Hosp Sick Children, Dept Pediat & Lab Med, Toronto, ON M5G 1X8, Canada. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. [Kaschnitz, Wolfgang] Med Univ Graz, Univ Clin Child & Adolescent Med, Graz, Austria. [Vincent, John B.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Vincent, John B.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. RP Vincent, JB (reprint author), CAMH, Neurogenet Sect, Campbell Family Brain Res Inst, R-30,250 Coll St, Toronto, ON M5T 1R8, Canada. EM john_vincent@camh.net RI Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU Genome Canada; Ontario Genomics Institute; ONB Jubilaumsfonds [13226]; NeuroDevNet; Wellcome Trust FX We thank the patients and their families for participating in this study. This work was supported by grants from Genome Canada and the Ontario Genomics Institute, and ONB Jubilaumsfonds (Project Number 13226). A. C. L. holds a NeuroDevNet doctoral fellowship. S. W. S. holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children. This study makes use of data generated by the DECIPHER and ISCA (www.iscaconsortium.org) consortia. A full list of centers contributing to the generation of the DECIPHER data is available from http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Funding for the DECIPHER project was provided by the Wellcome Trust. 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Joseph, Lisa A. Farmer, Cristan A. Luckenbaugh, David A. Lougee, Lorraine C. Zarate, Carlos A., Jr. Swedo, Susan E. TI 12-Week, Placebo-Controlled Trial of Add-on Riluzole in the Treatment of Childhood-Onset Obsessive-Compulsive Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE mood/anxiety/stress disorders; psychiatry and behavioral sciences; clinical pharmacology/clinical trials; psychopharmacology; riluzole; obsessive-compulsive disorder ID OF-THE-LITERATURE; AUTISTIC DISORDER; CHILDREN; ADOLESCENTS; METAANALYSIS; RELIABILITY; VALIDITY; SCALE; PHARMACOTHERAPY; SCHEDULE AB Many children with childhood-onset obsessive compulsive disorder (OCD) fail to respond adequately to standard therapies. Evidence from preclinical and clinical studies suggests that the glutamatergic neurotransmitter system might be an alternative treatment target. This study examined the efficacy of riluzole, a glutamatergic modulator, as an adjunctive therapy for children with treatment-resistant OCD. In a 12-week, double-blind, placebo-controlled study, 60 treatment-resistant children and adolescents (mean age=14.5 +/- 2.4 years), with moderate to severe OCD (mean Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)=28.2 +/- 3.7), 17 of whom also had concomitant autism spectrum disorder, were randomized to receive riluzole (final dose of 100 mg/day) or placebo in addition to the existing treatment regimen. Fifty-nine subjects completed the randomized trial. Primary outcome measures were changes on the CY-BOCS, the Clinical Global Impressions Scale, and the Children's Global Assessment Scale. Riluzole was fairly well tolerated, although it was associated with one case of pancreatitis and five instances of slight increases in transaminases. All subjects showed significant reductions in CY-BOCS scores during treatment; however, there was no significant difference between placebo and riluzole on any of the primary or secondary outcome measures. The study failed to demonstrate superiority of riluzole over placebo as an adjunctive treatment for children with childhood-onset OCD. However, future studies may show benefits for less treatment-refractory children with fewer concomitant medications. C1 [Grant, Paul J.; Joseph, Lisa A.; Farmer, Cristan A.; Lougee, Lorraine C.; Swedo, Susan E.] NIMH, Pediat & Dev Neurosci Branch, NIH, Bethesda, MD 20892 USA. [Luckenbaugh, David A.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. RP Swedo, SE (reprint author), NIMH, Pediat & Dev Neurosci Branch, NIH, 10 Ctr Dr MSC 1255,Bldg 10,Room 1C250, Bethesda, MD 20892 USA. 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M. Bavelaar, Bas M. da Silva, Sofia Lopes Korte, Sijmen Mechiel Olivier, Berend Garssen, Johan Kraneveld, Aletta D. TI Food allergy and food-based therapies in neurodevelopmental disorders SO PEDIATRIC ALLERGY AND IMMUNOLOGY LA English DT Review DE attention deficit hyperactivity disorder; autism spectrum disorder; food allergy; food-based therapy; gut-brain axis; neurodevelopment ID AUTISM SPECTRUM DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; IRRITABLE-BOWEL-SYNDROME; POLYUNSATURATED FATTY-ACIDS; TUBEROUS SCLEROSIS COMPLEX; PRENATAL IMMUNE ACTIVATION; CELIAC-DISEASE; MAST-CELLS; GASTROINTESTINAL SYMPTOMS AB Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders which occur in childhood and may persist into adulthood. Although the etiology of these disorders is largely unknown, genetic and environmental factors are thought to play a role in the development of ASD and ADHD. Allergic immune reactions, in prenatal and postnatal phases, are examples of these environmental factors, and adverse reactions to foods are reported in these children. In this review, we address the clinical and preclinical findings of (food) allergy in ASD and ADHD and suggest possible underlying mechanisms. Furthermore, opportunities for nutritional interventions in neurodevelopmental disorders are provided. C1 [de Theije, Caroline G. M.; Bavelaar, Bas M.; Korte, Sijmen Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Fac Sci, Div Pharmacol, Utrecht, Netherlands. [da Silva, Sofia Lopes; Garssen, Johan] Nutricia Res, Utrecht, Netherlands. [Korte, Sijmen Mechiel; Olivier, Berend] Univ Med Ctr Utrecht, UMC Utrecht Brain Ctr Rudolf Magnus, Utrecht, Netherlands. RP de Theije, CGM (reprint author), Univ Weg 99, NL-3584 CG Utrecht, Netherlands. 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Allergy Immunol. PD MAY PY 2014 VL 25 IS 3 BP 218 EP 226 DI 10.1111/pai.12149 PG 9 WC Allergy; Immunology; Pediatrics SC Allergy; Immunology; Pediatrics GA AF4NX UT WOS:000334691100003 PM 24236934 ER PT J AU Janeslatt, G Kottorp, A Granlund, M AF Janeslatt, Gunnel Kottorp, Anders Granlund, Mats TI Evaluating intervention using time aids in children with disabilities SO SCANDINAVIAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE assistive devices; child; intervention; time management; time perception ID PROCESSING ABILITY; ASSISTIVE TECHNOLOGY; DEVELOPMENTAL-DISABILITIES; MAINSTREAM SCHOOLS; CONTROLLED-TRIAL; RASCH ANALYSIS; ADHD; MANAGEMENT; STUDENTS; AUTISM AB Objective: The aim of this study was to evaluate complex intervention using time aids for children with intellectual and developmental disabilities who exhibit limitations in daily time management. Methods: Participating children (n = 47) (F17/M30) were aged 6-11 with ADHD, autism spectrum disorders, mild or moderate intellectual disability, spina bifida, and cerebral palsy. This study used a Randomized Block and Waiting List control group design, with 25 children allocated to control and 22 to intervention group. In total 10 children (21.3%), five from each group, dropped out, leaving 37 children in the data analysis. Results: Children in both groups gained significantly in time-processing ability between the first and second data collection, but the children in the intervention group improved time-processing ability significantly more than controls. The control group also displayed significant changes after receiving intervention between the second and third data collection. The intervention had a large effect (ES Cohen's d = 0.81) on time-processing ability and a medium effect (ES Cohen's d = 0.68) on managing one's time. Conclusions: This study provides preliminary evidence that time-processing ability and managing one's time can be improved by intervention using time aids in children with intellectual and developmental disabilities, supporting the need to consider time aids in intervention in these children. C1 [Janeslatt, Gunnel] Uppsala Univ, Dept Publ Hlth & Caring Sci Disabil & Habilitat, Uppsala, Sweden. [Janeslatt, Gunnel] Ctr Clin Res Dalarna, SE-79182 Falun, Sweden. [Kottorp, Anders] Karolinska Inst, Dept NVS, Div Occupat Therapy, Huddinge, Sweden. [Kottorp, Anders] Zurich Univ Appl Sci, Inst Occupat Therapy, Zurich, Switzerland. [Janeslatt, Gunnel; Granlund, Mats] Jonkoping Univ, Sch Hlth Sci, CHILD, Jonkoping, Sweden. RP Janeslatt, G (reprint author), Ctr Clin Res Dalarna, Nissers Vag 3, SE-79182 Falun, Sweden. EM gunnel.janeslatt@ltdalarna.se FU Clas Groschinskys Minnesfond; Centre for Clinical Research in Dalarna; Stiftelsen Sunnerdahls Handikappfond FX First, the authors would like to thank all 47 participating children and their families. The funding from Clas Groschinskys Minnesfond and Centre for Clinical Research in Dalarna supported the education of the OTs and teachers helping out in this study, including collecting data. The authors are also grateful to Nilbild AB for allowing the use of their pictures in KaTid. Thanks are also offered to Specialpedagogiska Institutet, SIH Laromedel, Umea for permission to use photos and two painted pictures originating from "Bildbanken", with design, sample, and photo by Manne Liden. The funding from Stiftelsen Sunnerdahls Handikappfond and Center for Clinical Research in Dalarna made the research possible. 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Bull. PD MAY PY 2014 VL 40 IS 3 BP 492 EP 496 DI 10.1093/schbul/sbu042 PG 5 WC Psychiatry SC Psychiatry GA AF5JW UT WOS:000334750800004 PM 24674812 ER PT J AU Chung, YS Barch, D Strube, M AF Chung, Yu Sun Barch, Deanna Strube, Michael TI A Meta-Analysis of Mentalizing Impairments in Adults With Schizophrenia and Autism Spectrum Disorder SO SCHIZOPHRENIA BULLETIN LA English DT Article DE mentalizing; schizophrenia; autism; social cognition ID HIGH-FUNCTIONING AUTISM; UNAFFECTED 1ST-DEGREE RELATIVES; NORMALLY DEVELOPING-CHILDREN; ASPERGER-SYNDROME; SOCIAL COGNITION; JOINT ATTENTION; LONGITUDINAL ASSOCIATIONS; EXECUTIVE FUNCTION; BIPOLAR DISORDER; FALSE BELIEF AB Mentalizing has been examined both in autism spectrum disorder (ASD) and schizophrenia (SCZ) primarily by either cognitive-linguistic (referred to as verbal) or emotion recognition from eyes (referred to as visual) mentalizing tasks. Each type of task is thought to measure different aspects of mentalizing. 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Bull. PD MAY PY 2014 VL 40 IS 3 BP 602 EP 616 DI 10.1093/schbul/sbt048 PG 15 WC Psychiatry SC Psychiatry GA AF5JW UT WOS:000334750800019 PM 23686020 ER PT J AU Johnson, S Hollis, C Marlow, N Simms, V Wolke, D AF Johnson, Samantha Hollis, Chris Marlow, Neil Simms, Victoria Wolke, Dieter TI Screening for childhood mental health disorders using the Strengths and Difficulties Questionnaire: the validity of multi-informant reports SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID LOW-BIRTH-WEIGHT; PSYCHIATRIC-DISORDERS; BEHAVIORAL OUTCOMES; CHILDREN BORN; ADOLESCENTS; PRETERM; SYMPTOMS; AGE; PSYCHOPATHOLOGY; PREVALENCE AB Aim This study investigated the diagnostic accuracy of the Strengths and Difficulties Questionnaire (SDQ) in a population of children born extremely preterm (<26wks gestation). Method Parents and teachers of 219 extremely preterm children (118 females, 101 males; age 11y) were asked to complete the SDQ to screen for psychological problems. Multi-informant ratings were aggregated using two methods: combined (parent or teacher rated the child with problems) and pervasive (parent and teacher rated the child with problems). Psychiatric diagnoses were assigned using the Development and Well-Being Assessment. Results Pervasive ratings had the greatest diagnostic accuracy for emotional disorders (89%), conduct disorders (94%), attention-deficit-hyperactivity disorder (ADHD; 90%), and autism spectrum disorders (ASDs; 94%), but were associated with low sensitivity (<= 50%). For clinical use, combined ratings were best for detecting emotional disorders (sensitivity 77%, specificity 75%), conduct disorders (83%, 88%), and ADHD (85%, 72%). Parent ratings were best for ASDs (93%, 66%). Teacher ratings significantly improved prediction over parent ratings alone for conduct disorders ( increment chi(2)=9.3, p=0.002) and ADHD ( increment chi(2)=24.1, p<0.001) only. Interpretation Multi-informant data are preferable for assessing most mental health outcomes using the SDQ. As an outcome measure, pervasive ratings have the best predictive accuracy. For screening, combined ratings are best for detecting ADHD and emotional and conduct disorders. For ASDs, parent ratings were best. C1 [Johnson, Samantha; Simms, Victoria] Univ Leicester, Dept Hlth Sci, Leicester LE1 6TP, Leics, England. [Hollis, Chris] Univ Nottingham, Sch Med, Div Psychiat & Appl Psychol, Nottingham, England. [Marlow, Neil] UCL, Res Dept Acad Neonatol, Inst Womens Hlth, London, England. [Wolke, Dieter] Univ Warwick, Dept Psychol, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Wolke, Dieter] Univ Warwick, Hlth Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. RP Johnson, S (reprint author), Univ Leicester, Dept Hlth Sci, 22-28 Princess Rd West, Leicester LE1 6TP, Leics, England. EM sjj19@le.ac.uk RI Marlow, Neil/D-2918-2009 OI Marlow, Neil/0000-0001-5890-2953 FU Medical Research Council, UK; Department of Health's NIHR Biomedical Research Centres funding scheme at UCLH/UCL; Action Medical Research project grant FX This study was funded by the Medical Research Council, UK. Neil Marlow receives a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme at UCLH/UCL. Victoria Simms's post was funded by an Action Medical Research project grant. We are indebted to the schools and teachers who supported assessments and completed questionnaires for this study, and to the children and parents for their continued participation in the EPICure Studies. EPICure co-investigators were Neil Marlow (UCL; Chief Investigator), Kate Costeloe (London), Enid Hennessy (London), Janet Stocks (London), and Elizabeth Draper (Leicester). The 11-year Developmental Group also comprised Neil Marlow (UCL), Samantha Johnson (Leicester), Dieter Wolke (Warwick), Chris Hollis (Nottingham), and Enid Hennessy (London). Heather Palmer was the study manager. 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Med. Child Neurol. PD MAY PY 2014 VL 56 IS 5 BP 453 EP 459 DI 10.1111/dmcn.12360 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AE7DG UT WOS:000334156300012 PM 24410039 ER PT J AU Ware, TL Earl, J Salomons, GS Struys, EA Peters, HL Howell, KB Pitt, JJ Freeman, JL AF Ware, Tyson L. Earl, John Salomons, Gajja S. Struys, Eduard A. Peters, Heidi L. Howell, Katherine B. Pitt, James J. Freeman, Jeremy L. TI Typical and atypical phenotypes of PNPO deficiency with elevated CSF and plasma pyridoxamine on treatment SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID NEONATAL EPILEPTIC ENCEPHALOPATHY; PYRIDOXINE; OXIDASE; METABOLISM; SEIZURES AB Pyridox(am)ine phosphate oxidase (PNPO) deficiency causes severe early infantile epileptic encephalopathy and has been characterized as responding to pyridoxal-5 '-phosphate but not to pyridoxine. Two males with PNPO deficiency and novel PNPO mutations are reported and their clinical, metabolic, and video-electroencephalographic (EEG) findings described. The first child showed electro-clinical responses to pyridoxine and deterioration when pyridoxine was withheld. At last review, he has well-controlled epilepsy with pyridoxal-5 '-phosphate monotherapy and an autism spectrum disorder. The second child had a perinatal middle cerebral artery infarct and a myoclonic encephalopathy. He failed to respond to pyridoxine but responded well to pyridoxal-5 '-phosphate. At the age of 21months he has global developmental delay and hemiparesis but is seizure-free with pyridoxal-5 '-phosphate monotherapy. Plasma and cerebrospinal fluid pyridoxamine levels were increased in both children during treatment with pyridoxine or pyridoxal-5 '-phosphate. These observations indicate that differential responses to pyridoxine and pyridoxal-5 '-phosphate treatment cannot be relied upon to diagnose PNPO deficiency. C1 [Ware, Tyson L.; Howell, Katherine B.; Freeman, Jeremy L.] Royal Childrens Hosp, Dept Neurol, Melbourne, Vic, Australia. [Earl, John] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia. [Salomons, Gajja S.; Struys, Eduard A.] Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Metab Unit, Amsterdam, Netherlands. [Peters, Heidi L.] Royal Childrens Hosp, Dept Metab Genet, Melbourne, Vic, Australia. [Pitt, James J.] Murdoch Childrens Res Inst, Victorian Clin Genet Serv, Melbourne, Vic, Australia. RP Freeman, JL (reprint author), Royal Childrens Hosp, Dept Neurol, 50 Flemington Rd, Parkville, Vic 3052, Australia. EM jeremy.freeman@rch.org.au FU Victorian Government's Operational Infrastructure Support Program FX The authors wish to thank Avantika Mishra for amino acid analysis and Trent Burgess for providing the single nucleotide polymorphism microarray results. Portions of this work were supported by the Victorian Government's Operational Infrastructure Support Program. The authors have stated that they had no interests which might be perceived as posing a conflict or bias. CR Bagci S, 2008, ARCH DIS CHILD-FETAL, V93, pF151, DOI 10.1136/adc.2006.115162 Baxter P, 2001, DEV MED CHILD NEUROL, V43, P416, DOI 10.1017/S0012162201000779 Brautigam C, 2002, NEUROPEDIATRICS, V33, P113, DOI 10.1055/s-2002-33673 Clayton PT, 2003, LANCET, V361, P1614, DOI 10.1016/S0140-6736(03)13312-0 di Salvo ML, 2002, J MOL BIOL, V315, P385, DOI 10.1006/jmbi.2001.5254 Footitt EJ, 2013, J INHERIT METAB DIS, V36, P139, DOI 10.1007/s10545-012-9493-y HUNT AD, 1954, PEDIATRICS, V13, P140 Khayat M, 2008, MOL GENET METAB, V94, P431, DOI 10.1016/j.ymgme.2008.04.008 Kuo MF, 2002, PEDIATR NEUROL, V26, P146, DOI 10.1016/S0887-8994(01)00357-5 Mills PB, 2005, HUM MOL GENET, V14, P1077, DOI 10.1093/hmg/ddi120 Musayev FN, 2009, J BIOL CHEM, V284, P30949, DOI 10.1074/jbc.M109.038372 Pearl PL, 2013, JIMD REP, V9, P139, DOI 10.1007/8904_2012_194 Ruiz A, 2008, MOL GENET METAB, V93, P216, DOI 10.1016/j.ymgme.2007.10.003 Schmitt B, 2010, DEV MED CHILD NEUROL, V52, pe133, DOI 10.1111/j.1469-8749.2010.03660.x NR 14 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1622 EI 1469-8749 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD MAY PY 2014 VL 56 IS 5 BP 498 EP 502 DI 10.1111/dmcn.12346 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AE7DG UT WOS:000334156300018 PM 24266778 ER PT J AU Davidson, C Greenwood, N Stansfield, A Wright, S AF Davidson, Conor Greenwood, Nick Stansfield, Alison Wright, Stephen TI Prevalence of Asperger syndrome among patients of an Early Intervention in Psychosis team SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Article DE Asperger syndrome; autism; early intervention; psychosis; schizophrenia ID AUTISM SPECTRUM DISORDERS; DIAGNOSTIC-CRITERIA; SCHIZOPHRENIA; COMORBIDITY; ADULTS AB BackgroundThere is a lack of systematic studies into comorbidity of Asperger syndrome and psychosis. AimTo determine the prevalence of Asperger syndrome among patients of an early intervention in psychosis service. MethodsThis study was a cross-sectional survey consisting of three phases: screening, case note review and diagnostic interviews. All patients on caseload (n=197) were screened using the Autism Spectrum Disorder in Adults Screening Questionnaire. The case notes of patients screened positive were then reviewed for information relevant to Asperger syndrome. Those suspected of having Asperger syndrome were invited for a diagnostic interview. ResultsThirty patients were screened positive. Three of them already had a diagnosis of Asperger syndrome made by child and adolescent mental health services. After case note review, 13 patients were invited to interview. Four did not take part, so nine were interviewed. At interview, four were diagnosed with Asperger syndrome. In total, seven patients had Asperger syndrome. Thus, the prevalence rate in this population is at least 3.6%. ConclusionsThe results suggest that the prevalence of Asperger syndrome in first-episode psychosis is considerably higher than that in the general population. Clinicians working in early intervention teams need to be alert to the possibility of Asperger syndrome when assessing patients. C1 [Davidson, Conor; Greenwood, Nick; Wright, Stephen] Aspire, Leeds Early Intervent Psychosis Serv, Leeds LS85LJ, W Yorkshire, England. [Davidson, Conor; Stansfield, Alison; Wright, Stephen] Leeds & York Partnerships NHS Fdn Trust, Leeds, W Yorkshire, England. [Davidson, Conor] Univ Leeds, Leeds, W Yorkshire, England. RP Davidson, C (reprint author), Aspire, Leeds Early Intervent Psychosis Serv, Bank House,Roundhay Rd, Leeds LS85LJ, W Yorkshire, England. EM conor.davidson@nhs.net CR [Anonymous], 2006, PSYCH SERV AD AD ASP, P19 (APA) APA, 2000, DIAGN STAT MAN MENT Arrasate-Gil M, 2011, ACTAS ESP PSIQUIATRI, V39, P140 Attwood T., 2008, COMPLETE GUIDE ASPER Burbach JPH, 2009, TRENDS NEUROSCI, V32, P69, DOI 10.1016/j.tins.2008.11.002 del Real A, 2010, EARLY INTERV PSYCHIA, V4, P93, DOI 10.1111/j.1751-7893.2009.00153.x Dossetor David R, 2007, Clin Child Psychol Psychiatry, V12, P537, DOI 10.1177/1359104507078476 Fraser R, 2012, EARLY INTERV PSYCHIA, V6, P83, DOI 10.1111/j.1751-7893.2011.00288.x Ghaziuddin M, 1998, J INTELL DISABIL RES, V42, P279 Gillberg C., 2000, AUTISM, V4, P11, DOI 10.1177/1362361300004001002 Gillberg C., 1998, ASPERGER SYNDROME HI, P79 Hare DJ, 2006, AUTISM, V10, P428, DOI 10.1177/1362361306065625 Hofvander B., 2009, BMC PSYCHIATRY, V9, P1, DOI DOI 10.1186/1471-244X-9-35 Kanner L, 1943, NERV CHILD, V2, P217 KOLVIN I, 1971, BRIT J PSYCHIAT, V118, P381, DOI 10.1192/bjp.118.545.381 Lugnegard T, 2011, RES DEV DISABIL, V32, P1910, DOI 10.1016/j.ridd.2011.03.025 Mattila ML, 2010, J AUTISM DEV DISORD, V40, P1080, DOI 10.1007/s10803-010-0958-2 Mattila ML, 2007, J AM ACAD CHILD PSY, V46, P636, DOI 10.1097/chi.0b013e318033ff42 NHS Information Centre, 2012, EST PREV AUT SPECTR Nylander L, 2001, ACTA PSYCHIAT SCAND, V103, P428, DOI 10.1034/j.1600-0447.2001.00175.x PARNAS J, 1991, COMPR PSYCHIAT, V32, P7, DOI 10.1016/0010-440X(91)90065-K Parnas J, 2011, SCHIZOPHRENIA BULL, V37, P1121, DOI 10.1093/schbul/sbr081 Stahlberg O, 2004, J NEURAL TRANSM, V111, P891, DOI 10.1007/s00702-004-0115-1 St Clair D, 2009, SCHIZOPHRENIA BULL, V35, P9, DOI 10.1093/schbul/sbn147 Tantam D, 2009, BRIT MED BULL, V89, P41, DOI 10.1093/bmb/ldp006 Toal F, 2009, BRIT J PSYCHIAT, V194, P418, DOI 10.1192/bjp.bp.107.049007 Witwer AN, 2008, J AUTISM DEV DISORD, V38, P1611, DOI 10.1007/s10803-008-0541-2 NR 27 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD MAY PY 2014 VL 8 IS 2 BP 138 EP 146 DI 10.1111/eip.12039 PG 9 WC Psychiatry SC Psychiatry GA AE9RG UT WOS:000334345800006 PM 23472601 ER PT J AU Thabet, EM AF Thabet, Elsaeid M. TI Ocular vestibular evoked myogenic potentials n10 response in autism spectrum disorders children with auditory hypersensitivity: an indicator of semicircular canal dehiscence SO EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY LA English DT Article DE Autism spectrum disorders; Auditory hypersensitivity; oVEMP; Superior canal dehiscence ID BONE-CONDUCTED VIBRATION; COMPUTED-TOMOGRAPHY; VESTIBULOOCULAR REFLEX; FZ AB Sensitivity to sound is one of the most commonly reported challenges in ASD. No compelling evidence shows that hearing of ASD individuals differs physiologically from normal peers. Superior semicircular canal dehiscence was found to be more common in ASD children with auditory hypersensitivity (29 %) by means of high-resolution CT scan than the reported (14 %) in normal pediatric population by other investigators. The increased prevalence of radiographic dehiscence might be due to inability of CT scan to visualize immature bone. We wished to determine whether ocular vestibular evoked myogenic potentials in ASD children with auditory hypersensitivity produces similar responses to those obtained in adult superior canal dehiscence, and whether it could help differentiate radiographic dehiscence due to bone immaturity from true canal dehiscence syndrome. A prospective study on 14 ASD children complaining of auditory hypersensitivity served as the study group. 15 ASD children without auditory hypersensitivity, age and gender matched, served as a control group. oVEMP and high-resolution CT scan of petrous and temporal bone were performed to all participants. Mean amplitude of n10 was 1.83 +/- A 0.11 and 1.79 +/- A 0.09 mu V in the control group with mean peak latency of 9.79 +/- A 0.42 and 9.77 +/- A 0.30 ms for the right and left ears, respectively. Asymmetry ratio was 2.04 +/- A 1.37. In the study group, the mean amplitude of n10 was 2.07 +/- A 0.46 and 1.89 +/- A 0.30 mu V, with mean peak latency of 9.52 +/- A 0.33 and 9.59 +/- A 0.21 ms for the right and left ears, respectively, with asymmetry 5.23 +/- A 6.93 %. No statistically significant difference was observed for the studied parameters. In the study group, the number of ears showing an augmented amplitude (> 2SD) of n10 was (N = 5). Furthermore, the study group demonstrated a radiographic SSCD in 6 ears. n10 was normal in the control group while radiographic SSCD was observed in 3 of them. Conclusion: oVEMPs show diagnostic ability in differentiating ASD children complaining of auditory hypersensitivity due to superior canal dehiscence from those with radiographic dehiscence only due to bone immaturity or atypical cortical development. C1 Mansoura Univ, ENT HNS Dept, Audiol Unit, Mansoura, Egypt. RP Thabet, EM (reprint author), Mansoura Univ, ENT HNS Dept, Audiol Unit, Mansoura, Egypt. 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Arch. Oto-Rhino-Laryn. PD MAY PY 2014 VL 271 IS 5 BP 1283 EP 1288 DI 10.1007/s00405-013-2736-1 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA AF0NB UT WOS:000334410200060 PM 24100882 ER PT J AU Scherff, A Taylor, M Eley, TC Happe, F Charman, T Ronald, A AF Scherff, Aline Taylor, Mark Eley, Thalia C. Happe, Francesca Charman, Tony Ronald, Angelica TI What Causes Internalising Traits and Autistic Traits to Co-occur in Adolescence? A Community-Based Twin Study SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE Adolescence; Autistic disorder; Comorbidity; Genetics; Internalising disorders ID SPECTRUM QUOTIENT AQ; DIFFICULTIES QUESTIONNAIRE; GENERAL-POPULATION; DISORDERS; CHILDREN; STRENGTHS; ASSOCIATION; DEPRESSION; VALIDITY; ANXIETY AB Autism shows a high degree of comorbidity with anxiety disorders. Adolescence is a time of increased stress and vulnerability to internalising problems. This study addresses for the first time the degree of genetic and environmental overlap between autistic traits (total measure and subscales) and internalising traits in a community-based adolescent twin sample. Parents of 12-14-year-old twins (N = 3,232 pairs; 3,460 males, 3,004 females) reported on the twins' internalising and autistic traits. Autistic trait subscales were created using principal component analysis. Bivariate twin model-fitting was conducted. Autistic and internalising traits correlated moderately (r = 0.30). Genetic influences on individual traits were substantial but genetic overlap between traits was moderate (genetic correlation: males = 0.30, females = 0.12). Shared environmental influences were low for internalising traits and moderate for autistic traits, and showed considerable overlap (shared environmental correlation: males = 0.53, females = 1). Nonshared environmental influences were moderate for internalising traits and low for autistic traits and showed low overlap. A multiple component solution was found for autistic traits and of the derived subscales, autistic-like 'Social Unease' showed the most phenotypic and genetic overlap with internalising traits. C1 [Scherff, Aline; Ronald, Angelica] Univ London, Ctr Brain & Cognit Dev, Dept Psychol Sci, London WC1E 7JL, England. [Taylor, Mark] Univ London, Ctr Res Autism & Educ, Dept Psychol & Human Dev, Inst Educ, London WC1E 7JL, England. [Eley, Thalia C.; Happe, Francesca] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Charman, Tony] Kings Coll London, Dept Psychol, Inst Psychiat, London WC2R 2LS, England. RP Scherff, A (reprint author), Univ London, Ctr Brain & Cognit Dev, Dept Psychol Sci, 32 Torrington Sq, London WC1E 7JL, England. 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Abnorm. Child Psychol. PD MAY PY 2014 VL 42 IS 4 BP 601 EP 610 DI 10.1007/s10802-013-9796-y PG 10 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA AE8TI UT WOS:000334274500008 PM 23975079 ER PT J AU Imaizumi, Y Okano, H AF Imaizumi, Yoichi Okano, Hideyuki TI Modeling human neurological disorders with induced pluripotent stem cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE human disease model; induced pluripotent stem cells; neurological disorders; Parkinson's disease ID MIDBRAIN DOPAMINERGIC-NEURONS; FAMILIAL ALZHEIMERS-DISEASE; MUSCULAR-ATROPHY PATIENT; IPSC-DERIVED NEURONS; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; OXIDATIVE STRESS; GENE-EXPRESSION; FUNCTIONAL-NEURONS; HUMAN FIBROBLASTS AB Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. C1 [Imaizumi, Yoichi; Okano, Hideyuki] Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan. [Imaizumi, Yoichi] Eisai & Co Ltd, Next Generat Syst CFU, Ibaraki, Japan. RP Okano, H (reprint author), Keio Univ, Sch Med, Dept Physiol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. EM hidokano@a2.keio.jp RI Okano, Hideyuki/J-5973-2013 FU Program for Intractable Disease Research utilizing disease-specific iPS Cells from the Japan Science and Technology Agency (JST) FX We thank all of the members of the Okano laboratory for their encouragement and support. This study was supported by the Program for Intractable Disease Research utilizing disease-specific iPS Cells from the Japan Science and Technology Agency (JST) to H.O. Dr H. Okano is a scientific consultant for San Bio, Inc., Eisai Co., Ltd, and Daiichi Sankyo Co., Ltd. Dr Y. Imaizumi is currently employed by Eisai Co., Ltd. The authors have no conflict of interest to declare. 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Treatments including behavioural interventions, established and emergent medication, and complementary and alternative therapies are discussed. The key role of paediatricians as both individual child and family care providers and advocates, as well as agents of service reform in Australia, is evident. Much still needs to be done. C1 [Williams, Katrina] Royal Childrens Hosp, Melbourne, Vic, Australia. [Williams, Katrina] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Williams, Katrina] Univ Melbourne, Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Prior, Margot] Univ Melbourne, Melbourne, Vic, Australia. [Bartak, Lawrence] Monash Univ, Fac Educ, Melbourne, Vic 3004, Australia. [Woolfenden, Susan] Sydney Childrens Hosp Network, Randwick, NSW, Australia. [Roberts, Jacqueline] Griffith Univ, Autism Ctr Excellence, Brisbane, Qld 4111, Australia. [Rodger, Sylvia] Univ Queensland, Sch Hlth & Rehabil Sci, Brisbane, Qld, Australia. RP Williams, K (reprint author), Royal Childrens Hosp, Flemington Rd, Parkville, Vic 3052, Australia. 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Paediatr. Child Health PD MAY PY 2014 VL 50 IS 5 BP 341 EP 346 DI 10.1111/jpc.12456 PG 6 WC Pediatrics SC Pediatrics GA AF1EI UT WOS:000334456800003 PM 24422663 ER PT J AU Sidrak, S Yoong, T Woolfenden, S AF Sidrak, Samuel Yoong, Terence Woolfenden, Susan TI Iron deficiency in children with global developmental delay and autism spectrum disorder SO JOURNAL OF PAEDIATRICS AND CHILD HEALTH LA English DT Article DE pervasive developmental disorder; child; autistic disorder; iron deficiency; Australia; anaemia ID PRESCHOOL-CHILDREN; YOUNG-CHILDREN; PREVALENCE; ANEMIA; CHILDHOOD; DIAGNOSIS; INFANTS; SUPPLEMENTATION; PREVENTION; AUSTRALIA AB Aim To investigate the prevalence of and risk factors for iron deficiency in children with global developmental delay and/or autism spectrum disorder (ASD). Method A retrospective review was conducted of the files of children referred to community paediatric clinics in South West Sydney from May 2009 to July 2011 who were diagnosed with global developmental delay and/or ASD. Data were extracted on iron studies and potential risk factors. Data were analysed using Pearson's divided by(2)-test and Fisher's exact test. Results Subjects included 122 children. The prevalence of iron depletion was 2.5% (95% CI 0.5-7.0%); that of iron deficiency was 6.6% (95% CI 2.9-12.5%), and that of iron deficiency anaemia was 4.1% (95% CI 1.3-9.3%). In children with global developmental delay without ASD, the prevalence of iron depletion was 1.8% (95% CI 0-9.7%), that of iron deficiency 5.5% (95% CI 1.1-15.1%) and that of iron deficiency anaemia 5.5% (95% CI 1.1-15.1%). In children with ASD with or without global developmental delay, the prevalence of iron depletion was 3.0% (95% CI 0.4-10.4%), that of iron deficiency 7.5% (95% CI 2.5-16.6%) and that of iron deficiency anaemia 3.0% (95% CI 0.4-10.4%). Univariate analysis demonstrated three significant potential risk factors for iron depletion, iron deficiency and iron deficiency anaemia: problems sucking, swallowing or chewing (P = 0.002); poor eating behaviour (P = 0.008); and inadequate amounts of meat, chicken, eggs or fish (P = 0.002). Conclusion Iron deficiency and iron deficiency anaemia were more common in this clinical sample of children with global developmental delay and/or ASD than in the general population. C1 [Sidrak, Samuel; Yoong, Terence] Sydney & South Western Sydney Local Hlth Dist, Dept Community Paediat, Sydney, NSW, Australia. [Woolfenden, Susan] Sydney Childrens Hosp, Sydney Childrens Community Hlth Ctr, Sydney, NSW, Australia. RP Yoong, T (reprint author), Sydney & South Western Sydney Local Hlth Dist, Dept Community Paediat, Level 3,Hlth Serv Bldg,Cnr Campbell & Goulburn St, Liverpool, NSW 2170, Australia. 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TI Psychometric Properties of the Resourcefulness Scale Among Caregivers of Persons With Autism Spectrum Disorder SO WESTERN JOURNAL OF NURSING RESEARCH LA English DT Article DE population focus behavior/symptom focus; caregivers; clinical focus; mental health; instrument development ID DEPRESSIVE SYMPTOMS; SOCIAL SUPPORT; CHILDREN; MOTHERS; BURDEN; WOMEN; SCHEDULE; STRESS; ELDERS; HEALTH AB Caregiving for children with autism spectrum disorder (ASD) can be very costly to caregivers' well-being. Resourcefulness interventions have shown increases in positive health outcomes. However, before delivering the intervention, there should be a reliable and a valid measure to test resourcefulness. The psychometric properties of the Resourcefulness Scale (RS) have not been examined among ASD caregivers. This study examined the psychometrics of the 28-item RS in a convenience sample of 204 ASD caregivers. A Cronbach's alpha of .91 showed the internal consistency of the RS. Construct validity was supported by the emergence of two dimensions of resourcefulness (personal and social) in a confirmatory factor analysis and by substantial intercorrelations between the two subscales (r = .48, p < .001). Findings suggested the reliability and validity of RS among ASD caregivers, which is a necessary step toward implementing resourcefulness interventions to help ASD caregivers to deal with their stress and improve their quality of life. C1 [Bekhet, Abir K.] Marquette Univ, Coll Nursing, Milwaukee, WI 53233 USA. [Zauszniewski, Jaclene A.] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Bekhet, AK (reprint author), Marquette Univ, Coll Nursing, Clark Hall,530 N 16th St, Milwaukee, WI 53233 USA. EM abir.bekhet@marquette.edu FU American Psychiatric Nurses Foundation (APNF) [74614]; Marquette University FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The parent studies are funded by the American Psychiatric Nurses Foundation (APNF) Grant 74614 and by the Way Klinger Young Scholar Award from Marquette University. Both grants were awarded to the principal investigator (Dr. Abir K. Bekhet). 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We investigated the extent to which patterns of attention to social stimuli would differentiate early and late language onset groups. Children with ASD (mean age = 10 years) differing on language onset timing (late/normal) and a typically developing comparison group completed a task in which visual attention to interacting and noninteracting human figures was mapped using eye tracking. Correlations on visual attention data and results from tests measuring current social and language ability were conducted. Patterns of visual attention did not distinguish typically developing children and ASD children with normal language onset. Children with ASD and late language onset showed significantly reduced attention to salient social stimuli. Associations between current language ability and social attention were observed. Delay in language onset is associated with current language skills as well as with specific eye-tracking patterns. 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PD MAY PY 2014 VL 26 IS 2 BP 529 EP 537 DI 10.1017/S0954579414000108 PG 9 WC Psychology, Developmental SC Psychology GA AE5RS UT WOS:000334047100017 PM 24622054 ER PT J AU Cauda, F Costa, T Palermo, S D'Agata, F Diano, M Bianco, F Duca, S Keller, R AF Cauda, Franco Costa, Tommaso Palermo, Sara D'Agata, Federico Diano, Matteo Bianco, Francesca Duca, Sergio Keller, Roberto TI Concordance of white matter and gray matter abnormalities in autism spectrum disorders: A voxel-based meta-analysis study SO HUMAN BRAIN MAPPING LA English DT Article DE DTI; white matter changes; VBM; gray matter changes; ALE meta-analysis; autism spectrum disorder ID HIGH-FUNCTIONING AUTISM; LIKELIHOOD ESTIMATION METAANALYSIS; OBSESSIVE-COMPULSIVE DISORDER; MIRROR-NEURON SYSTEM; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; CORTICAL THICKNESS; ASPERGERS-SYNDROME; HUMAN BRAIN; FRACTIONAL ANISOTROPY AB There are at least two fundamental unanswered questions in the literature on autism spectrum disorders (ASD): Are abnormalities in white (WM) and gray matter (GM) consistent with one another? Are WM morphometric alterations consistent with alterations in the GM of regions connected by these abnormal WM bundles and vice versa? The aim of this work is to bridge this gap. After selecting voxel-based morphometry and diffusion tensor imaging studies comparing autistic and normally developing groups of subjects, we conducted an activation likelihood estimation (ALE) meta-analysis to estimate consistent brain alterations in ASD. Multidimensional scaling was used to test the similarity of the results. The ALE results were then analyzed to identify the regions of concordance between GM and WM areas. We found statistically significant topological relationships between GM and WM abnormalities in ASD. The most numerous were negative concordances, found bilaterally but with a higher prevalence in the right hemisphere. Positive concordances were found in the left hemisphere. Discordances reflected the spatial distribution of negative concordances. Thus, a different hemispheric contribution emerged, possibly related to pathogenetic factors affecting the right hemisphere during early developmental stages. Besides, WM fiber tracts linking the brain structures involved in social cognition showed abnormalities, and most of them had a negative concordance with the connected GM regions. We interpreted the results in terms of altered brain networks and their role in the pervasive symptoms dramatically impairing communication and social skills in ASD patients. Hum Brain Mapp 35:2073-2098, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Cauda, Franco; D'Agata, Federico; Diano, Matteo; Duca, Sergio] Koelliker Hosp, CCS fMRI, Turin, Italy. [Cauda, Franco; Costa, Tommaso; Palermo, Sara; D'Agata, Federico; Diano, Matteo] Univ Turin, Dept Psychol, I-10123 Turin, Italy. [Bianco, Francesca; Keller, Roberto] ASL To2, Adult Autism Ctr, Turin, Italy. RP Cauda, F (reprint author), Univ Turin, Dept Psychol, Via Po 14, I-10123 Turin, Italy. 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Brain Mapp. PD MAY PY 2014 VL 35 IS 5 BP 2073 EP 2098 DI 10.1002/hbm.22313 PG 26 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AE5FB UT WOS:000334012100021 PM 23894001 ER PT J AU Pride, NA Korgaonkar, MS Barton, B Payne, JM Vucic, S North, KN AF Pride, Natalie A. Korgaonkar, Mayuresh S. Barton, Belinda Payne, Jonathan M. Vucic, Steve North, Kathryn N. TI The genetic and neuroanatomical basis of social dysfunction: Lessons from neurofibromatosis type 1 SO HUMAN BRAIN MAPPING LA English DT Article DE social cognition; voxel-based morphometry; neurofibromatosis 1; emotion perception; theory of mind ID SUPERIOR TEMPORAL SULCUS; BRAIN ABNORMALITIES; FACIAL EXPRESSIONS; FACE PERCEPTION; HUMAN AMYGDALA; CHILDREN; AUTISM; COGNITION; GYRUS; ADOLESCENTS AB Neurofibromatosis type 1 (NF1) is a common genetic condition associated with cognitive and social dysfunction as well as abnormal brain structure. The pathophysiology underlying social dysfunction in NF1 is poorly understood. Here, we investigate for the first time whether there is a broad deficit of social cognition in NF1 and explore the neural correlates for these deficits. Twenty-nine adults with NF1 and 30 controls were administered an ecologically based test of social cognition, The Awareness of Social Inference Test (TASIT), to identify deficits in emotion recognition and sarcasm detection. We employed voxel-based morphometry in a subset of NF1 patients (n = 16) and 16 additional controls to examine the neural correlates of these deficits. Results indicated that adults with NF1 were impaired in their ability to understand paradoxical sarcasm and their capacity to recognize emotion, particularly anger. TASIT performance was not associated with measures of attention, visuospatial skills or executive function. Relative to controls, gray matter (GM) volume within the right superior temporal gyrus (STG) was decreased, after controlling for total brain volume. Decreased volume in this region was significantly associated with social cognitive deficits in adults with NF1. We conclude that patients with NF1 are at high risk for a social cognitive deficit and provide evidence for a neuroanatomical basis for this deficit; GM volumetric reductions in the right STG. These findings improve our understanding of the nature of social interaction impairments in NF1 and add to the growing body of literature indicating the STG as a critical brain region for social cognition. Hum Brain Mapp 35:2372-2382, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Pride, Natalie A.; Payne, Jonathan M.; North, Kathryn N.] Sydney Childrens Hosp Network, Inst Neurosci & Muscle Res, Westmead, NSW 2145, Australia. [Pride, Natalie A.; Barton, Belinda; Payne, Jonathan M.; North, Kathryn N.] Univ Sydney, Discipline Paediat & Child Hlth, Fac Med, Sydney, NSW 2006, Australia. [Korgaonkar, Mayuresh S.] Westmead Millennium Inst, Brain Dynam Ctr, Sydney, NSW, Australia. [Korgaonkar, Mayuresh S.] Univ Sydney, Sch Med, Sydney, NSW 2006, Australia. [Korgaonkar, Mayuresh S.] Univ Sydney, Westmead Hosp, Discipline Psychiat, Med Sch Western, Sydney, NSW 2006, Australia. [Barton, Belinda] Sydney Childrens Hosp Network, Childrens Hosp Educ Res Inst, Sydney, NSW, Australia. [Vucic, Steve] Univ Sydney, Western Clin Sch, Sydney, NSW 2006, Australia. [North, Kathryn N.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia. RP North, KN (reprint author), Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia. 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Brain Mapp. PD MAY PY 2014 VL 35 IS 5 BP 2372 EP 2382 DI 10.1002/hbm.22334 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AE5FB UT WOS:000334012100041 PM 23881898 ER PT J AU Limeres, J Martinez, F Feijoo, JF Ramos, I Linares, A Diz, P AF Limeres, J. Martinez, F. Feijoo, J. F. Ramos, I. Linares, A. Diz, P. TI A new indicator of the oral hygiene habits of disabled persons: relevance of the carer's personal appearance and interest in oral health SO INTERNATIONAL JOURNAL OF DENTAL HYGIENE LA English DT Article DE oral hygiene habits; motivation; disability; dental hygiene ID CHILDREN; ATTITUDES; PARENTS; AUTISM; DISABILITIES; KNOWLEDGE; BEHAVIOR; ADULTS AB Objective To investigate whether there is a relationship between the oral hygiene habits of individuals with severe disability the carer's personal appearance and interest in oral health. Patients and methods The study group was formed of 60 disabled persons and their respective carers who came for the first time to consultation in the Special-Needs Dentistry Unit of the University of Santiago de Compostela, Spain. All the carers answered a standardised questionnaire of 28 questions divided into four sections: disabled individual's demographic data, disabled individual's general medical details, social aspects of the carer (personal appearance of the carer and interest in oral health), and disabled individual's oral hygiene habits. The personal appearance of the carers and their interest in the disabled individual's oral health were evaluated using independent scales designed specifically for the study, with five binary items in each scale. Results The carer's personal appearance and interest in the disabled individual's oral health showed a statistically significant relationship with the individual's oral hygiene habits, particularly with respect to the frequency and duration of toothbrushing, need for physical restraint during toothbrushing, use of a manual toothbrush and use of toothpaste. Conclusions The carer's personal appearance and interest in the disabled individual's oral health are good indicators of the oral hygiene habits of an individual with severe disability. Consideration should be given to the inclusion of these aspects as a complementary element of the dental record. C1 [Limeres, J.; Martinez, F.; Feijoo, J. F.; Ramos, I.; Linares, A.; Diz, P.] Univ Santiago de Compostela, Sch Med & Dent, Grp Invest Odontol Med Quirurg OMEQUI, Santiago De Compostela 15782, A Coruna, Spain. RP Limeres, J (reprint author), Univ Santiago de Compostela, Sch Med & Dent, Grp Invest Odontol Med Quirurg OMEQUI, C Entrerrios Sn, Santiago De Compostela 15782, A Coruna, Spain. 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J. Dent. Hyg. PD MAY PY 2014 VL 12 IS 2 BP 121 EP 126 DI 10.1111/idh.12033 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AE4BG UT WOS:000333922500009 PM 23730898 ER PT J AU Hampshire, PK Butera, GD Dustin, TJ AF Hampshire, Patricia Korzekwa Butera, Gretchen D. Dustin, Timothy J. TI Promoting Homework Independence for Students With Autism Spectrum Disorders SO INTERVENTION IN SCHOOL AND CLINIC LA English DT Article DE disabilities; parents; family/families; autism; involvement; partnerships with professionals; self-management/regulation ID SELF-MANAGEMENT; CHILDREN; INVOLVEMENT; PERFORMANCE; PREFERENCE; ATTENTION; ACCURACY; BEHAVIOR AB For students with autism, homework time may be especially challenging due to problems in self-organization and difficulties generalizing skills from one setting to another. Although often problematic, homework can provide a valuable context for teaching organizational skills that become essential as students become more independent. By learning to self-manage, students develop a set of skills necessary for self-determination. This article describes the process for developing an intervention plan for students who may be struggling to complete homework successfully. C1 [Hampshire, Patricia Korzekwa] Boise State Univ, Boise, ID 83725 USA. [Butera, Gretchen D.] Indiana Univ, Bloomington, IN USA. [Dustin, Timothy J.] St Josephs Orphanage Villa Acad, Cincinnati, OH USA. RP Hampshire, PK (reprint author), Boise State Univ, Dept Special Educ & Early Childhood Studies, MS 1725, Boise, ID 83725 USA. 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Sch. Clin. PD MAY PY 2014 VL 49 IS 5 BP 290 EP 297 DI 10.1177/1053451213513955 PG 8 WC Education, Special SC Education & Educational Research GA AE5KQ UT WOS:000334028300004 ER PT J AU Larsson, H Sariaslan, A Langstrom, N D'Onofrio, B Lichtenstein, P AF Larsson, Henrik Sariaslan, Amir Langstroem, Niklas D'Onofrio, Brian Lichtenstein, Paul TI Family income in early childhood and subsequent attention deficit/hyperactivity disorder: a quasi-experimental study SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE causality; family income; ADHD; quasi-experimental approaches; childhood ID DEFICIT HYPERACTIVITY DISORDER; TELEPHONE INTERVIEW; BEHAVIOR PROBLEMS; AUTISM-TICS; DSM-IV; A-TAC; ADHD; ADVERSITY; ASSOCIATION; CHILDREN AB Background Studies have found negative associations between socioeconomic position and attention deficit/hyperactivity disorder (ADHD), but it remains unclear if this association is causal.The aim of this study was to determine the extent to which the association between family income in early childhood and subsequent ADHD depends on measured and unmeasured selection factors. Methods A total of 811,803 individuals born in Sweden between 1992 and 2000 were included in this nationwide population-based cohort study. Diagnosis of ADHD was assessed via the Swedish national Patient Register and the Swedish Prescribed Drug Register. Annual family income during offspring's first 5years in life was collected prospectively from the Swedish Integrated Database for Labour Market Research and divided into quartiles by (lower) family disposable income. We predicted ADHD from family income while controlling for covariates and also comparing differently exposed cousins and siblings to control for unmeasured familial confounding. Results The crude analyses suggested that children exposed to lower income levels were at increased risk for ADHD (HRQuartile1=2.52; 95% CI, 2.42-2.63; HRQuartile2=1.52; 95% CI, 1.45-1.58; HRQuartile3=1.20; 95% CI, 1.14-1.15). This dose-dependent association decreased after adjustment for measured covariates (HRQuartile1=2.09; 95% CI, 2.00-2.19; HRQuartile2=1.36; 95% CI, 1.30-1.42; HRQuartile3=1.13; 95% CI, 1.08-1.18). Although the association was attenuated in cousin comparisons (HRQuartile1=1.61; 95% CI, 1.40-1.84; HRQuartile2=1.28; 95% CI, 1.12-1.45; HRQuartile3=1.14; 95% CI, 1.01-1.28) and sibling comparison models (HRQuartile1=1.37; 95% CI, 1.07-1.75; HRQuartile2=1.37; 95% CI, 1.12-1.68; HRQuartile3=1.23; 95% CI, 1.04-1.45), it remained statistically significant across all levels of decreased disposable family income. Conclusions Our results indicated that low family income in early childhood was associated with increased likelihood of ADHD. The link remained even after controlling for unmeasured selection factors, highlighting family income in early childhood as a marker of causal factors for ADHD. C1 [Larsson, Henrik; Sariaslan, Amir; Langstroem, Niklas; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [D'Onofrio, Brian] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. RP Larsson, H (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, SE-17177 Stockholm, Sweden. 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Child Psychol. Psychiatry PD MAY PY 2014 VL 55 IS 5 BP 428 EP 435 DI 10.1111/jcpp.12140 PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AE2QA UT WOS:000333816800003 PM 24111650 ER PT J AU Anderson, DK Liang, JW Lord, C AF Anderson, Deborah K. Liang, Jessie W. Lord, Catherine TI Predicting young adult outcome among more and less cognitively able individuals with autism spectrum disorders SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Very Positive Outcome; ASD; longitudinal; Autism; adult outcome ID DIAGNOSTIC-OBSERVATION-SCHEDULE; REVISED ALGORITHMS; FOLLOW-UP; CHILDREN; ABILITIES; ADOLESCENCE; CHILDHOOD; PATTERNS; AVERAGE; GROWTH AB Background The range of outcomes for young adults with Autism Spectrum Disorders (ASD) and the early childhood factors associated with this diversity have implications for clinicians and scientists. Methods This prospective study provided a unique opportunity to predict outcome 17years later for a relatively large sample of children diagnosed with ASD at 2 years old. Diagnostic and psychometric instruments were administered between 2 and 19 with data from 2, 3, and 19 included in this study. Clinicians administered tests without knowledge of previous assessments whenever possible. Caregivers provided additional information through questionnaires. Results Significant intellectual disabilities at 19 were predicted by age 2 about 85% of the time from VIQ and NVIQ scores together, though prediction of young adult outcome for youths with average or higher intelligence was more complex. By 19, 9% of participants had largely overcome core difficulties associated with ASD and no longer retained a diagnosis. These youths with Very Positive Outcomes were more likely to have participated in treatment and had a greater reduction in repetitive behaviors between age 2 and 3 compared to other Cognitively Able youths (VIQ >= 70) with ASD. Very Positive Outcome youths did not differ phenotypically from Cognitively Able ASD individuals at 2 but both groups differed from Cognitively Less Able individuals (VIQ <70). Conclusion Those most at risk for intellectual disabilities and ASD can be reliably identified at an early age to receive comprehensive treatment. Findings also suggest that some cognitively able children with ASD who participate in early intervention have very positive outcomes, although replication with randomized, larger samples is needed. In order to improve understanding of very positive outcomes in ASD, future research will need to identify how variations in child characteristics and environmental factors contribute to the nature and timing of growth across individuals and areas of development. C1 [Anderson, Deborah K.; Lord, Catherine] Weill Cornell Med Coll, CADB, White Plains, NY USA. [Liang, Jessie W.] Univ Denver, Grad Sch Social Work, Denver, CO USA. RP Anderson, DK (reprint author), Univ Michagan, Ctr Comprehens Canc, Clin Trials Complex,North Campus Res Complex, Ann Arbor, MI 48109 USA. EM debcarl87@gmail.com FU National Institute of Mental Health [MH081873]; National Institute of Child Health and Human Development [U 19 HD 035482]; Autism Speaks FX This work was supported by grants from the National Institute of Mental Health (MH081873), the National Institute of Child Health and Human Development (U 19 HD 035482), and Autism Speaks (dated 11 January 2008) to C. L. The funding sources played no role in the writing of the manuscript or the decision to submit it for publication, including study design, recruitment of the sample, or the collection, analysis and interpretation of the data. The authors were not paid by a pharmaceutical company to write this article. The authors had full access to all of the data in the study as well as the final responsibility for the decision to submit for publication. 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Psychiatry PD MAY PY 2014 VL 55 IS 5 BP 485 EP 494 DI 10.1111/jcpp.12178 PG 10 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AE2QA UT WOS:000333816800010 PM 24313878 ER PT J AU Mok, PLH Pickles, A Durkin, K Conti-Ramsden, G AF Mok, Pearl L. H. Pickles, Andrew Durkin, Kevin Conti-Ramsden, Gina TI Longitudinal trajectories of peer relations in children with specific language impairment SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE peer relations; developmental trajectories; prosocial behaviour; pragmatic language impairment; autistic symptomatology; Specific language impairment ID RANDOMIZED CONTROLLED-TRIAL; AUTISM SPECTRUM DISORDER; SOCIAL-BEHAVIOR; SLI; ADOLESCENTS; HISTORY; DIFFICULTIES; QUESTIONNAIRE; PREVALENCE; OUTCOMES AB Background Peer relations is a vulnerable area of functioning in children with specific language impairment (SLI), but little is known about the developmental trajectories of individuals. Methods Peer problems were investigated over a 9-year period (from 7 to 16years of age) in 171 children with a history of SLI. Discrete factor growth modelling was used to chart developmental trajectories. Multinomial logistic regression analysis was conducted to investigate factors associated with group membership. Results Four distinct developmental trajectories were identified: low-level/no problems in peer relations (22.2% of participants), childhood-limited problems (12.3%), childhood-onset persistent problems (39.2%) and adolescent-onset problems (26.3%). Risk of poor trajectories of peer relations was greater for those children with pragmatic language difficulties. Prosocial behaviour was the factor most strongly associated with trajectory group membership. Overall, the more prosocial children with better pragmatic language skills and lower levels of emotional problems had less difficulty in developing peer relations. Conclusions Analysis of developmental trajectories enriches our understanding of social development. A sizeable minority in the present sample sustained positive relations through childhood and adolescence, and others overcame early difficulties to achieve low levels of problems by their early teens; the majority, however, showed childhood-onset persistent or adolescent-onset problems. C1 [Mok, Pearl L. H.; Conti-Ramsden, Gina] Univ Manchester, Manchester M13 9PL, Lancs, England. [Pickles, Andrew] Kings Coll London, London WC2R 2LS, England. [Durkin, Kevin] Univ Strathclyde, Glasgow, Lanark, Scotland. RP Conti-Ramsden, G (reprint author), Univ Manchester, Sch Psychol Sci, Ellen Wilkinson Bldg,Oxford Rd, Manchester M13 9PL, Lancs, England. EM gina.conti-ramsden@manchester.ac.uk RI Pickles, Andrew/A-9625-2011 OI Pickles, Andrew/0000-0003-1283-0346 FU Economic and Social Research Council [RES-062-23-2745]; Nuffield Foundation [AT251[OD], DIR/28, EDU 8366, EDU 32083]; Wellcome Trust [060774]; Medical Research Council [G0802307] FX The authors acknowledge the support of the Economic and Social Research Council (grant RES-062-23-2745). We also acknowledge the support of the Nuffield Foundation for grants AT251[OD], DIR/28, EDU 8366 and EDU 32083 and the Wellcome Trust for grant 060774 which supported the data collection. A. P. additionally received funding from the Medical Research Council (G0802307). The authors have declared that they have no competing or potential conflicts of interest. The authors thank all the families that have participated in the study and the research assistants who helped with data gathering. CR Achenbach T. 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Child Psychol. Psychiatry PD MAY PY 2014 VL 55 IS 5 BP 516 EP 527 DI 10.1111/jcpp.12190 PG 12 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AE2QA UT WOS:000333816800013 PM 24410167 ER PT J AU Gatto, CL Pereira, D Broadie, K AF Gatto, Cheryl L. Pereira, Daniel Broadie, Kendal TI GABAergic circuit dysfunction in the Drosophila Fragile X syndrome model SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Fragile X mental retardation protein (FMRP); Mushroom Body; Glutamic acid decarboxylase; Synapse; Calcium signaling; Associative learning ID MENTAL-RETARDATION PROTEIN; LONG-TERM-MEMORY; MUSHROOM BODY NEURONS; KNOCKOUT MOUSE MODEL; CELL MARKER MARCM; GABA(A) RECEPTOR; ADULT DROSOPHILA; TEMPORAL REQUIREMENTS; SIGNALING COMPONENTS; SYNAPTIC STRUCTURE AB Fragile X syndrome (FXS), caused by loss of FMR1 gene function, is the most common heritable cause of intellectual disability and autism spectrum disorders. The FMR1 protein (FMRP) translational regulator mediates activity-dependent control of synapses. In addition to the metabotropic glutamate receptor (mGluR) hyperexcitation FXS theory, the GABA theory postulates that hypoinhibition is causative for disease state symptoms. Here, we use the Drosophila FXS model to assay central brain GABAergic circuitry, especially within the Mushroom Body (MB) learning center. All 3 GABA(A) receptor (GABA(A)R) subunits are reportedly downregulated in dfmr1 null brains. We demonstrate parallel downregulation of glutamic acid decarboxylase (GAD), the rate-limiting GABA synthesis enzyme, although GABAergic cell numbers appear unaffected. Mosaic analysis with a repressible cell marker (MARCM) single-cell clonal studies show that dfmr1 null GABAergic neurons innervating the MB calyx display altered architectural development, with early underdevelopment followed by later overelaboration. In addition, a new class of extra-calyx terminating GABAergic neurons is shown to include MB intrinsic alpha/beta Kenyon Cells (KCs), revealing a novel level of MB inhibitory regulation. Functionally, dfmr1 null GABAergic neurons exhibit elevated calcium signaling and altered kinetics in response to acute depolarization. latest the role of these GABAergic changes, we attempted to pharmacologically restore GABAergic signaling and assay effects on the compromised MB-dependent olfactory learning in dfmr1 mutants, but found no improvement Our results show that GABAergic circuit structure and function are impaired in the FXS disease state, but that correction of hypoinhibition alone is not sufficient to rescue a behavioral learning impairment (C) 2014 Elsevier Inc. All rights reserved. C1 Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Kennedy Ctr Res Human Dev, Nashville, TN 37203 USA. RP Broadie, K (reprint author), 6270A MRB 3,465 21st Ave South,PMB 35-1634, Nashville, TN 37232 USA. EM kendal.broadie@vanderbilt.edu FU NIH [R01 MH084989] FX We are grateful to Terry Page for expert guidance in olfactory learning experiments. We thank generous donors of key reagents: dfmr12 from Thomas Dockendorff (University of Tennessee, Knoxville, TN), GAD-Gal4 from Gero Misenbock (University of Oxford, Oxford, UK), and anti-GAD from F. Rob Jackson (Tufts University, Boston, MA). We also thank Broadie Lab members, especially Caleb Doll, Neil Dani, William Parkinson, and Emma Rushton for insightful discussions on the study and critical feedback during manuscript preparation, He Zhu for assistance with time-lapse data management and Eriny Hanna for continued experimental interest. This work was supported by the NIH R01 MH084989 to K.B. 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Dis. PD MAY PY 2014 VL 65 BP 142 EP 159 DI 10.1016/j.nbd.2014.01.008 PG 18 WC Neurosciences SC Neurosciences & Neurology GA AD8WL UT WOS:000333546300014 PM 24423648 ER PT J AU Stenberg, N Bresnahan, M Gunnes, N Hirtz, D Hornig, M Lie, KK Lipkin, WI Lord, C Magnus, P Reichborn-Kjennerud, T Schjolberg, S Suren, P Susser, E Svendsen, BK von Tetzchner, S Oyen, AS Stoltenberg, C AF Stenberg, Nina Bresnahan, Michaeline Gunnes, Nina Hirtz, Deborah Hornig, Mady Lie, Kari Kveim Lipkin, W. Ian Lord, Catherine Magnus, Per Reichborn-Kjennerud, Ted Schjolberg, Synnve Suren, Pal Susser, Ezra Svendsen, Britt Kveim von Tetzchner, Stephen Oyen, Anne-Siri Stoltenberg, Camilla TI Identifying Children with Autism Spectrum Disorder at 18 Months in a General Population Sample SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE Norwegian Mother and Child Cohort Study; early identification; Autism Birth Cohort Study; longitudinal studies; M-CHAT; autism spectrum disorders ID PERVASIVE DEVELOPMENTAL DISORDERS; MODIFIED CHECKLIST; SCREENING INSTRUMENT; EARLY RECOGNITION; TODDLERS; AGE; DIAGNOSIS; COHORT; 1ST; SIGNS AB Background Previous research on clinical and high-risk samples suggests that signs of autism spectrum disorder (ASD) can be detected between 1 and 2 years of age. We investigated signs of ASD at 18 months in a population-based sample and the association with later ASD diagnosis. Methods The study sample includes 52 026 children born 2003 through 2008 and is a subset of children that participated in the Norwegian Mother and Child Cohort (MoBa), a population-based longitudinal study, and the Autism Birth Cohort (ABC), a sub-study on ASD. Parents completed all 23 items from the Modified Checklist for Autism in Toddlers (M-CHAT) at 18 months. Results The M-CHAT 6-critical-item criterion and the 23-item criterion had a specificity of 97.9% and 92.7% and a sensitivity of 20.8% and 34.1%, respectively. In the 173 children diagnosed with ASD to date, 60 children (34.7%) scored above the cut-off on either of the screening criteria. The items with the highest likelihood ratios were 'interest in other children', 'show objects to others' and 'response to name'. Conclusion Even though one-third of the children who later received an ASD diagnosis were identified through M-CHAT items, the majority scored below cut-off on the screening criteria at 18 months. The results imply that it might not be possible to detect all children with ASD at this age. C1 [Stenberg, Nina; Gunnes, Nina; Lie, Kari Kveim; Magnus, Per; Reichborn-Kjennerud, Ted; Schjolberg, Synnve; Suren, Pal; Oyen, Anne-Siri; Stoltenberg, Camilla] Norwegian Inst Publ Hlth, N-0403 Oslo, Norway. [Bresnahan, Michaeline; Hornig, Mady; Lipkin, W. Ian; Susser, Ezra] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [von Tetzchner, Stephen] Univ Oslo, Inst Psychol, Oslo, Norway. [Susser, Ezra] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Hornig, Mady; Lipkin, W. Ian] Columbia Univ, Ctr Infect & Immun, New York, NY USA. [Svendsen, Britt Kveim; Oyen, Anne-Siri] Lovisenberg Hosp, Nic Waals Inst, Oslo, Norway. [Hirtz, Deborah] NINDS, NIH, Bethesda, MD 20892 USA. [Lord, Catherine] New York Presbyterian Hosp, Weill Cornell Med Coll, Inst Brain Dev, New York, NY USA. [Lord, Catherine] Columbia Univ, Med Ctr, New York, NY USA. [Stoltenberg, Camilla] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. [Reichborn-Kjennerud, Ted] Univ Oslo, Inst Psychiat, Oslo, Norway. RP Stenberg, N (reprint author), Norwegian Inst Publ Hlth, POB 4404 Nydalen, N-0403 Oslo, Norway. EM nist@fhi.no FU Norwegian Ministry of Health and Care Services; Norwegian Ministry of Education and Research; Research Council of Norway/FUGE [151918]; National Institute of Neurological Disorders and Stroke (NIH/NINDS), Bethesda, MD, USA [NS47537]; National Institute of Environmental Health Sciences (NIH/NIEHS), Research Triangle Park, NC, USA [NO-ES-75558]; National Institute of Neurological Disorders and Stroke, (NIH/NINDS), Bethesda, MD, USA [NS47537]; Norwegian Research Council [196452] FX The authors would like to acknowledge and thank all participating families. The Norwegian Mother and Child Cohort Study is funded by the Norwegian Ministry of Health and Care Services, the Norwegian Ministry of Education and Research, the Research Council of Norway/FUGE (grant no. 151918), the National Institute of Neurological Disorders and Stroke (NIH/NINDS), Bethesda, MD, USA (grant no. NS47537) and the National Institute of Environmental Health Sciences (NIH/NIEHS), Research Triangle Park, NC, USA (contract no. NO-ES-75558). The Autism Birth Cohort study is funded by the National Institute of Neurological Disorders and Stroke, (NIH/NINDS), Bethesda, MD, USA (grant no. NS47537). The present study was supported by a grant from the Norwegian Research Council (grant no. 196452). 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Perinat. Epidemiol. PD MAY PY 2014 VL 28 IS 3 BP 255 EP 262 DI 10.1111/ppe.12114 PG 8 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA AE2KH UT WOS:000333801300009 PM 24547686 ER PT J AU Ikeda, E Hinckson, E Krageloh, C AF Ikeda, Erika Hinckson, Erica Kraegeloh, Chris TI Assessment of quality of life in children and youth with autism spectrum disorder: a critical review SO QUALITY OF LIFE RESEARCH LA English DT Review DE Adolescents; Autism; Health-related quality of life; Paediatric; Self-report; Social Functioning ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; HIGH-FUNCTIONING AUTISM; HEALTH UTILITIES INDEX; ASPERGER-SYNDROME; ADOLESCENTS; RELIABILITY; QUESTIONNAIRE; METAANALYSIS; INSTRUMENTS; CHALLENGES AB To review the use of quality of life (QOL) measures utilised in children and youth with autism spectrum disorder (ASD). Relevant articles were identified through database searches using MEDLINE, CINAHL Plus with Full Text and SPORTDiscus with Full Text via EBSCO Health Database, PsycINFO and ProQuest Health and Medicine (from 2000 to May 2013). Original research articles were included that measured QOL in children and youth with ASD aged 5-20 years. Searches were limited to articles from peer-reviewed journals, in English or German, and those available in full text. The search identified 1,165 titles and 13 met the inclusion criteria. The review identified a number of QOL measures used in children and youth with ASD, with the most common one being the Pediatric Quality of Life Inventory (TM) (PedsQL). QOL measures using self-reports were uncommon, and the reliability and validity of QOL measures were not sufficiently reported for this population. Large discrepancies in QOL scores were found between self-reports and proxy-reports. Despite the differences in study design and methodological quality, there was consistency in the results among studies; children and youth with ASD provided lower QOL scores, particularly for social domains, compared to their healthy counterparts. The PedsQL is likely to be an appropriate QOL measure for use in children and youth with ASD. Future research should focus on examining the appropriateness, reliability and validity of QOL self-reports for use in this population. C1 [Ikeda, Erika; Hinckson, Erica; Kraegeloh, Chris] Auckland Univ Technol, Fac Hlth & Environm Sci, Auckland 1142, New Zealand. RP Hinckson, E (reprint author), Auckland Univ Technol, Fac Hlth & Environm Sci, Private Bag 92006, Auckland 1142, New Zealand. 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Life Res. PD MAY PY 2014 VL 23 IS 4 BP 1069 EP 1085 DI 10.1007/s11136-013-0591-6 PG 17 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AD6SK UT WOS:000333391000005 PM 24310317 ER PT J AU Wood, BK Drogan, RR Janney, DM AF Wood, Brenna K. Drogan, Robin R. Janney, Donna M. TI Early Childhood Practitioner Involvement in Functional Behavioral Assessment and Function-Based Interventions: A Literature Review SO TOPICS IN EARLY CHILDHOOD SPECIAL EDUCATION LA English DT Article DE functional behavioral assessment; function-based interventions; early childhood; challenging behavior; teacher involvement ID CHALLENGING BEHAVIOR; TREATMENT INTEGRITY; YOUNG-CHILDREN; EXTINCTION; KNOWLEDGE; SETTINGS; AUTISM; FUTURE AB Reviewers analyzed studies published from 1990 to 2012 to determine early childhood practitioner involvement in functional behavioral assessment (FBA) and function-based behavioral intervention plans (BIP) for children with challenging behavior, age 6 and younger. Coding of 30 studies included practitioner involvement in FBA and BIP processes, training received to conduct FBAs and implement BIPs, and social validity and treatment integrity data. Findings indicate that early childhood practitioners had a limited role in FBAs and BIPs. Practitioner training occurred more often for the BIP than for the FBA. Approximately one fourth of the studies included a description of practitioners in a collaborative role with researchers during the FBA, and approximately one-half during the BIP process, even though practitioners implemented the BIP in the majority of studies reviewed. More than one half of the studies included social validity and/or treatment integrity measures. C1 [Wood, Brenna K.; Drogan, Robin R.] Lehigh Univ, Bethlehem, PA 18015 USA. [Janney, Donna M.] Towson Univ, Towson, MD USA. RP Wood, BK (reprint author), Lehigh Univ, Dept Educ & Human Serv, 111 Res Dr, Bethlehem, PA 18015 USA. EM bkw209@lehigh.edu CR Bambara L., 2005, INDIVIDUALIZED SUPPO Blakeslee T., 1994, J BEHAV ED, V4, P397, DOI 10.1007/BF01539541 Children's Defense Fund, 2013, FULL DAY KIND STAT Conroy MA, 2005, TOP EARLY CHILD SPEC, V25, P157, DOI 10.1177/02711214050250030301 Deaver CM, 2001, J APPL BEHAV ANAL, V34, P535, DOI 10.1901/jaba.2001.34-535 Derby KM, 1997, J APPL BEHAV ANAL, V30, P507, DOI 10.1901/jaba.1997.30-507 Dunlap G., 2010, PREVENT TEACH REINFO Dunlap G, 2006, BEHAV DISORDERS, V32, P29 Dunlap G, 2011, J EARLY INTERVENTION, V33, P333, DOI 10.1177/1053815111429971 Ellis J. C., 1999, ED TREATMENT CHILDRE, V22, P291 Fox L., 2001, J POSIT BEHAV INTERV, V3, P251, DOI 10.1177/109830070100300406 Gilliam W. S., 2005, PREKINDERGARTENERS L GRESHAM FM, 1993, SCHOOL PSYCHOL REV, V22, P254 GRESHAM FM, 1993, J APPL BEHAV ANAL, V26, P257, DOI 10.1901/jaba.1993.26-257 Hemmeter M. L., 2006, ANN POL MAK SUMM CTR HORNER RH, 1994, J APPL BEHAV ANAL, V27, P401, DOI 10.1901/jaba.1994.27-401 Kazdin A. 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TI Parent Implementation of Function-Based Intervention to Reduce Children's Challenging Behavior: A Literature Review SO TOPICS IN EARLY CHILDHOOD SPECIAL EDUCATION LA English DT Article DE collaboration; families; challenging behaviors; intervention strategies ID YOUNG-CHILDREN; SOCIAL COMPETENCE; SUPPORT; AUTISM; MODEL; PERSPECTIVES; PREVENTION; TODDLERS; STUDENTS AB The purpose of this literature review was to analyze the research on parent-implemented functional assessment (FA)-based interventions for reducing children's challenging behaviors. Thirteen studies met the review inclusion criteria. These studies were analyzed across independent variables, types of parent coaching and support provided, measurement of implementation and intervention fidelity, child dependent variables, social validity, and study rigor. Overall, the evidence provide some support that parents can be trained to implement FA-based interventions with follow-up coaching and support, and these interventions reduce children's challenging behaviors and increase children's use of appropriate behaviors. However, inadequacies in study rigor and reporting of the implementation and intervention fidelity limit interpretations. Implications for practice and future research are discussed. C1 [Fettig, Angel] Univ Massachusetts, Boston, MA 02125 USA. [Barton, Erin E.] Vanderbilt Univ, Nashville, TN 37235 USA. RP Fettig, A (reprint author), Univ Massachusetts, Dept Curriculum & Instruct, 100 Morrissey Blvd, Boston, MA 02125 USA. EM angel.fettig@umb.edu CR Albin R. W., 1996, POSITIVE BEHAV SUPPO, P81 Barton E. E., 2013, J EARLY INTERVENTION Barton E. 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PD MAY PY 2014 VL 34 IS 1 BP 49 EP 61 DI 10.1177/0271121413513037 PG 13 WC Education, Special SC Education & Educational Research GA AE2PZ UT WOS:000333816700005 ER PT J AU Fu, RR Wang, H AF Fu, Rongrong Wang, Hong TI DETECTION OF DRIVING FATIGUE BY USING NONCONTACT EMG AND ECG SIGNALS MEASUREMENT SYSTEM SO INTERNATIONAL JOURNAL OF NEURAL SYSTEMS LA English DT Article DE Driver fatigue; sensor; EMG; ECG; Mahalanobis distance ID INDEPENDENT COMPONENT ANALYSIS; FUNCTION NEURAL-NETWORK; EEG-BASED DIAGNOSIS; FUZZY SYNCHRONIZATION LIKELIHOOD; WAVELET-CHAOS METHODOLOGY; AUTISM SPECTRUM DISORDER; WORK ZONE CAPACITY; INCIDENT-DETECTION; SEIZURE DETECTION; DRIVER FATIGUE AB Driver fatigue can be detected by constructing a discriminant mode using some features obtained from physiological signals. There exist two major challenges of this kind of methods. One is how to collect physiological signals from subjects while they are driving without any interruption. The other is to find features of physiological signals that are of corresponding change with the loss of attention caused by driver fatigue. Driving fatigue is detected based on the study of surface electromyography (EMG) and electrocardiograph (ECG) during the driving period. The noncontact data acquisition system was used to collect physiological signals from the biceps femoris of each subject to tackle the first challenge. Fast independent component analysis (FastICA) and digital filter were utilized to process the original signals. Based on the statistical analysis results given by Kolmogorov-Smirnov Z test, the peak factor of EMG (p < 0.001) and the maximum of the cross-relation curve of EMG and ECG (p < 0.001) were selected as the combined characteristic to detect fatigue of drivers. The discriminant criterion of fatigue was obtained from the training samples by using Mahalanobis distance, and then the average classification accuracy was given by 10-fold cross-validation. The results showed that the method proposed in this paper can give well performance in distinguishing the normal state and fatigue state. The noncontact, onboard vehicle drivers' fatigue detection system was developed to reduce fatigue-related risks. C1 [Fu, Rongrong; Wang, Hong] Northeastern Univ, Sch Mech Engn & Automat, Lab Biomechatron Engn, Shenyang 110189, Peoples R China. RP Wang, H (reprint author), Northeastern Univ, Sch Mech Engn & Automat, Lab Biomechatron Engn, Shenyang 110189, Peoples R China. EM hgwang@mail.neu.edu.cn FU Natural Science Foundation of China [61071057]; Fundamental Research Funds for the Central Universities of China [N100603003] FX This work was supported by Natural Science Foundation of China (Project No. 61071057) and Fundamental Research Funds for the Central Universities of China (Project No. N100603003). The author would like to thank Dr. Shalini Puwar, Dr. Wenbo Zhao and Dr. Morteza Delgir for helpful discussions about the manuscript. In addition, the authors would like to thank the reviewers and the editor, whose inputs significantly improved this manuscript. 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PD MAY PY 2014 VL 24 IS 3 AR 1450006 DI 10.1142/S0129065714500063 PG 15 WC Computer Science, Artificial Intelligence SC Computer Science GA AB8LE UT WOS:000332040900005 PM 24552510 ER PT J AU Owen, JP Chang, YS Pojman, NJ Bukshpun, P Wakahiro, MLJ Marco, EJ Berman, JI Spiro, JE Chung, WK Buckner, RL Roberts, TPL Nagarajan, SS Sherr, EH Mukherjee, P AF Owen, Julia P. Chang, Yi Shin Pojman, Nicholas J. Bukshpun, Polina Wakahiro, Mari L. J. Marco, Elysa J. Berman, Jeffrey I. Spiro, John E. Chung, Wendy K. Buckner, Randy L. Roberts, Timothy P. L. Nagarajan, Srikantan S. Sherr, Elliott H. Mukherjee, Pratik CA Simons VIP Consortium TI Aberrant White Matter Microstructure in Children with 16p11.2 Deletions SO JOURNAL OF NEUROSCIENCE LA English DT Article DE autism; copy number variants; diffusion tensor imaging; genetics; magnetic resonance imaging; neurodevelopmental disorders ID AUTISM SPECTRUM DISORDER; BRAIN MATURATION; DIFFUSION; PHENOTYPES; DOSAGE AB Copy number variants (CNVs) of the chromosomal locus 16p11.2, consisting of either deletions or duplications, have been implicated in autism, schizophrenia, epilepsy, and other neuropsychiatric disorders. Since abnormal white matter microstructure can be seen in these more broadly defined clinical disorders, we used diffusion magnetic resonance imaging and tract-based spatial statistics to investigate white matter microstructural integrity in human children with 16p11.2 deletions. We show that deletion carriers, compared with typically developing matched controls, have increased axial diffusivity (AD) in many major central white matter tracts, including the anterior corpus callosum as well as bilateral internal and external capsules. Higher AD correlated with lower nonverbal IQ in the deletion carriers, but not controls. Increases in fractional anisotropy and mean diffusivity were also found in some of the same tracts with elevated AD. Closer examination with neurite orientation dispersion and density imaging revealed that fiber orientation dispersion was decreased in some central white matter tracts. Notably, these alterations of white matter are unlike microstructural differences reported for any other neurodevelopmental disorders, including autism spectrum disorders that have phenotypic overlap with the deletion carriers. These findings suggest that deletion of the 16p11.2 locus is associated with a unique widespread pattern of aberrant white matter microstructure that may underlie the impaired cognition characteristic of this CNV. C1 [Owen, Julia P.; Chang, Yi Shin; Nagarajan, Srikantan S.; Mukherjee, Pratik] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94107 USA. [Owen, Julia P.; Nagarajan, Srikantan S.; Mukherjee, Pratik] Univ Calif San Francisco, Bioengn Program, San Francisco, CA 94158 USA. [Pojman, Nicholas J.; Bukshpun, Polina; Wakahiro, Mari L. J.; Marco, Elysa J.; Sherr, Elliott H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. [Berman, Jeffrey I.; Roberts, Timothy P. L.] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [Spiro, John E.] Simons Fdn, New York, NY 10010 USA. [Chung, Wendy K.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10032 USA. [Chung, Wendy K.] Columbia Univ, Dept Med, Med Ctr, New York, NY 10032 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. RP Mukherjee, P (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, Ctr Mol & Funct Imaging, UCSF Box 0946,185 Berry St,Suite 350, San Francisco, CA 94107 USA. EM pratik.mukherjee@ucsf.edu FU Simons Foundation [Simons Foundation Autism Research Initiative (SFARI)] [220843] FX This work was supported by a grant from the Simons Foundation [Simons Foundation Autism Research Initiative (SFARI) Award # 220843 to E.H.S.]. We are grateful to all of the families at the participating Simons Variation in Individuals Project (Simons VIP) sites, as well as the Simons VIP working group (Simons VIP Consortium, 2012). We appreciate obtaining access to phenotypic data on SFARI Base. 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Neurosci. PD APR 30 PY 2014 VL 34 IS 18 BP 6214 EP 6223 DI 10.1523/JNEUROSCI.4495-13.2014 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AH2AA UT WOS:000335921900011 PM 24790192 ER PT J AU Nakajima, M Nishikawa, C Miyasaka, Y Kikkawa, Y Mori, H Tsuruta, M Okuyama, S Furukawa, Y AF Nakajima, Mitsunari Nishikawa, Chisa Miyasaka, Yuki Kikkawa, Yoshiaki Mori, Hisamichi Tsuruta, Momoko Okuyama, Satoshi Furukawa, Yoshiko TI Dilation of the inferior colliculus and hypersensitivity to sound in Wnt1-cre and Wnt1-GAL4 double-transgenic mice SO NEUROSCIENCE LETTERS LA English DT Article DE Animal model; Wnt1-cre; Psychiatric disorder ID WILLIAMS-SYNDROME; CRE RECOMBINASE; NEURAL CREST; HEARING-LOSS; ABNORMALITIES; BEHAVIOR; AUTISM AB The processing of sound information is mediated by the cochlea and the central auditory system. Among the central auditory system, the inferior colliculus (IC) has leading roles in the acoustic processing. In a previous study, we demonstrated psychiatric disorder-related behavioral abnormalities in a genetically modified animal of Wnt1-cre and Wnt1-GAL4 double-transgenic (dTg) mouse. Here we report an abnormal morphology of the IC and dysacusis in the dTg mice. The IC in the brain of the dTg mice is dilated in appearance and histologic analysis revealed a high cell-density in the IC. Also, the dTg mice showed high scores in a startle response test using a click box that emits a 20-kHz sound. Auditory brainstem response (ABR) test revealed lower ABR thresholds of the dTg mice at a test-stimulus frequency of 32 kHz, but not at 4-16 kHz. These findings suggest that the dTg mice could be a useful animal model for studying the physiologic function of the IC and the pathophysiology of psychiatric disorder-related dysacusis. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Nakajima, Mitsunari; Nishikawa, Chisa; Mori, Hisamichi; Tsuruta, Momoko; Okuyama, Satoshi; Furukawa, Yoshiko] Matsuyama Univ, Coll Pharmaceut Sci, Sch Clin Pharm, Dept Pharmaceut Pharmacol, Matsuyama, Ehime 7908578, Japan. [Miyasaka, Yuki; Kikkawa, Yoshiaki] Tokyo Metropolitan Inst Med Sci, Mammalian Genet Project, Setagaya Ku, Tokyo 1568506, Japan. [Miyasaka, Yuki] Niigata Univ, Grad Sch Med & Dent Sci, Niigata 9518510, Japan. RP Nakajima, M (reprint author), Matsuyama Univ, Coll Pharmaceut Sci, Sch Clin Pharm, Dept Pharmaceut Pharmacol, 4-2 Bunkyo Cho, Matsuyama, Ehime 7908578, Japan. EM mnakajim@cc.matsuyama-u.ac.jp FU JSPS KAKENHI Grant [25461567] FX We thank K. Kamiya and K. Ikeda in Juntendo University School of Medicine for helpful discussion. This work was supported by JSPS KAKENHI Grant number 25461567. The authors declare no competing financial interests. Author contributions: M.N., Y.K., and Y.F. designed the research; C.N., Y.M., H.M., M.T., and S.O. performed the research; M.N., Y.K., and Y.F. wrote the manuscript. 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Klei, Lambertus Neale, Benjamin M. Franjic, Daniel Daly, Mark J. Lifton, Richard P. De Camilli, Pietro Zhao, Hongyu Sestan, Nenad State, Matthew W. TI Rare deleterious mutations of the gene EFR3A in autism spectrum disorders SO MOLECULAR AUTISM LA English DT Article DE Autism spectrum disorder; Genetics; Rare variants; EFR3A; Synapse; Phosphoinositide metabolism ID DE-NOVO MUTATIONS; PLASMA-MEMBRANE; TUBEROUS-SCLEROSIS; ROLLING BLACKOUT; EVOLUTION; IDENTITY; COMPLEX; IMPACT; REGION; EXOMES AB Background: Whole-exome sequencing studies in autism spectrum disorder (ASD) have identified de novo mutations in novel candidate genes, including the synaptic gene Eighty-five Requiring 3A (EFR3A). EFR3A is a critical component of a protein complex required for the synthesis of the phosphoinositide PtdIns4P, which has a variety of functions at the neural synapse. We hypothesized that deleterious mutations in EFR3A would be significantly associated with ASD. Methods: We conducted a large case/control association study by deep resequencing and analysis of whole-exome data for coding and splice site variants in EFR3A. We determined the potential impact of these variants on protein structure and function by a variety of conservation measures and analysis of the Saccharomyces cerevisiae Efr3 crystal structure. We also analyzed the expression pattern of EFR3A in human brain tissue. Results: Rare nonsynonymous mutations in EFR3A were more common among cases (16 / 2,196 = 0.73%) than matched controls (12 / 3,389 = 0.35%) and were statistically more common at conserved nucleotides based on an experiment-wide significance threshold (P = 0.0077, permutation test). Crystal structure analysis revealed that mutations likely to be deleterious were also statistically more common in cases than controls (P = 0.017, Fisher exact test). Furthermore, EFR3A is expressed in cortical neurons, including pyramidal neurons, during human fetal brain development in a pattern consistent with ASD-related genes, and it is strongly co-expressed (P < 2.2 x 10-16, Wilcoxon test) with a module of genes significantly associated with ASD. Conclusions: Rare deleterious mutations in EFR3A were found to be associated with ASD using an experiment-wide significance threshold. Synaptic phosphoinositide metabolism has been strongly implicated in syndromic forms of ASD. These data for EFR3A strengthen the evidence for the involvement of this pathway in idiopathic autism. C1 [Gupta, Abha R.] Yale Sch Med, Dept Pediat, New Haven, CT 06520 USA. [Gupta, Abha R.; Fernandez, Thomas V.] Yale Sch Med, Ctr Child Study, New Haven, CT 06520 USA. [Pirruccello, Michelle] Scholar Rock LLC, Cambridge, MA 02142 USA. [Cheng, Feng; Kang, Hyo Jung; Franjic, Daniel; Sestan, Nenad] Yale Sch Med, Kavli Inst Neurosci, Dept Neurobiol, New Haven, CT 06520 USA. [Cheng, Feng] Univ S Florida, Coll Pharm, Tampa, FL 33612 USA. [Kang, Hyo Jung] Chung Ang Univ, Dept Life Sci, Seoul 156756, South Korea. [Fernandez, Thomas V.] Yale Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Baskin, Jeremy M.; De Camilli, Pietro] Yale Sch Med, Howard Hughes Med Inst, Dept Cell Biol, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT 06520 USA. [Choi, Murim; Lifton, Richard P.] Yale Sch Med, Howard Hughes Med Inst, Dept Genet, New Haven, CT 06520 USA. [Liu, Li] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Ercan-Sencicek, Adife Gulhan] Yale Sch Med, Ctr Child Study, Program Neurogenet, New Haven, CT 06520 USA. [Murdoch, John D.] Yale Sch Med, Ctr Child Study, Dept Genet, Dept Psychiat,Program Neurogenet, New Haven, CT 06520 USA. [Klei, Lambertus] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Neale, Benjamin M.; Daly, Mark J.] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Zhao, Hongyu] Yale Sch Med, Dept Biostat, New Haven, CT 06520 USA. [Zhao, Hongyu] Yale Sch Med, Dept Genet, New Haven, CT 06520 USA. [State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Gupta, AR (reprint author), Yale Sch Med, Dept Pediat, New Haven, CT 06520 USA. EM abha.gupta@yale.edu; matthew.state@ucsf.edu RI Liu, Li/G-1897-2015 FU National Institutes of Health [K08MH087639, K99HL11134001, R01MH089208, R37NS036251, R01GM59507, U01MH081896, R01MH081754-04, RC2MH089956]; Jane Coffin Childs Fund; Howard Hughes Medical Institute; James S McDonnell Foundation Scholar Award; Simons Foundation FX We are very grateful to all of the families participating in the cohorts described in this paper. We thank the members of the AASC for whole-exome sequencing data and Weizhen Ji for providing the NE control samples. We greatly appreciate the expertise of Karin Reinisch and Xudong Wu in analyzing the EFR3A human mutations using their Efr3 crystal structure. We thank Bernie Devlin, Kenneth Kidd, and Ellen J Hoffman for helpful discussions and Gordon T Ober, Michael F Walker, Nicholas M DiLullo and Cynthia A Zerillo for technical assistance. This work was supported by the National Institutes of Health (grants K08MH087639 to ARG, K99HL11134001 to MC, R01MH089208 to MJD, R37NS036251 to PDC, R01GM59507 to HZ, U01MH081896 to NS, R01MH081754-04 and RC2MH089956 to MWS), the Jane Coffin Childs Fund (JMB), the Howard Hughes Medical Institute (RPL), the James S McDonnell Foundation Scholar Award (NS) and the Simons Foundation (PDC and MWS). 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Hum. Neurosci. PD APR 29 PY 2014 VL 8 AR 268 DI 10.3389/fnhum.2014.00268 PG 8 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AH4JG UT WOS:000336092600001 PM 24808851 ER PT J AU Puscian, A Leski, S Gorkiewicz, T Meyza, K Lipp, HP Knapska, E AF Puscian, Alicja Leski, Szymon Gorkiewicz, Tomasz Meyza, Ksenia Lipp, Hans-Peter Knapska, Ewelina TI A novel automated behavioral test battery assessing cognitive rigidity in two genetic mouse models of autism SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE autism; perseveration; cognitive rigidity; valproate mouse model; IntelliCages; automatic behavioral tests ID CIRCADIAN-RHYTHM; HISTONE DEACETYLASE; SODIUM VALPROATE; ANIMAL-MODEL; MICE; MELATONIN; CHILDREN; EXPOSURE; DEFICITS; CORTEX AB Repetitive behaviors are a key feature of many pervasive developmental disorders, such as autism. As a heterogeneous group of symptoms, repetitive behaviors are conceptualized into two main subgroups: sensory/motor (lower-order) and cognitive rigidity (higher-order). Although lower-order repetitive behaviors are measured in mouse models in several paradigms, so far there have been no high-throughput tests directly measuring cognitive rigidity. We describe a novel approach for monitoring repetitive behaviors during reversal learning in mice in the automated IntelliCage system. During the reward-motivated place preference reversal learning, designed to assess cognitive abilities of mice, visits to the previously rewarded places were recorded to measure cognitive flexibility. Thereafter, emotional flexibility was assessed by measuring conditioned fear extinction. Additionally, to look for neuronal correlates of cognitive impairments, we measured CA3-CA1 hippocampal long term potentiation (LIP). To standardize the designed tests we used C57BL/6 and BALB/c mice, representing two genetic backgrounds, for induction of autism by prenatal exposure to the sodium valproate. We found impairments of place learning related to perseveration and no LIP impairments in C57BL/6 valproate-treated mice. In contrast, BALB/c valproate-treated mice displayed severe deficits of place learning not associated with perseverative behaviors and accompanied by hippocampal LIP impairments. Alterations of cognitive flexibility observed in C57BL/6 valproate-treated mice were related to neither restricted exploration pattern nor to emotional flexibility. Altogether, we showed that the designed tests of cognitive performance and perseverative behaviors are efficient and highly replicable. Moreover, the results suggest that genetic background is crucial for the behavioral effects of prenatal valproate treatment. C1 [Puscian, Alicja; Leski, Szymon; Gorkiewicz, Tomasz; Meyza, Ksenia; Knapska, Ewelina] M Nencki Inst Expt Biol, Dept Neurophysiol, PL-02093 Warsaw, Poland. [Lipp, Hans-Peter] Univ Zurich, Inst Anat, Div Funct Neuroanat, Zurich, Switzerland. [Lipp, Hans-Peter] Kwazulu Natal Univ, Dept Physiol, Sch Lab Med, Durban, South Africa. RP Knapska, E (reprint author), Nencki Inst Expt Biol PAS, Neurobiol Emot Lab, Dept Neurophysiol, Pasteur 3, PL-02093 Warsaw, Poland. EM e.knapska@nencki.gov.pl FU Switzerland through the Swiss Contribution to the enlarged European Union [PSPB-210/2010]; Foundation for Polish Science [HOMING PLUS/2012-6/6] FX This work was supported by a grant from Switzerland through the Swiss Contribution to the enlarged European Union (PSPB-210/2010 to Ewelina Knapska and Hans-Peter Lipp) and Ksenia Meyza was supported by the Foundation for Polish Science (HOMING PLUS/2012-6/6). We are thankful to Leszek Kaczmarek for critical reading the previous version of the manuscript and Agata Romanowska-Lasek for excellent technical assistance. 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The identification of autism biomarkers in patients with different degrees of clinical presentation (i.e., mild, moderate and severe) will give greater insight into the pathogenesis of this disease and will enable effective early diagnostic strategies and treatments for this disorder. Methods: In this study, the concentration of two toxic heavy metals, lead (Pb) and mercury (Hg), were measured in red blood cells, while glutathione-s-transferase (GST) and vitamin E, as enzymatic and non-enzymatic antioxidants, respectively, were measured in the plasma of subgroups of autistic patients with different Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS) scores. The results were compared to age- and gender-matched healthy controls. Results: The obtained data showed that the patients with autism spectrum disorder had significantly higher Pb and Hg levels and lower GST activity and vitamin E concentrations compared with the controls. The levels of heavy metals (Hg and Pb), GST and vitamin E were correlated with the severity of the social and cognitive impairment measures (SRS and CARS). Receiver Operating Characteristics (ROC) analysis and predictiveness curves indicated that the four parameters show satisfactory sensitivity, very high specificity and excellent predictiveness. Multiple regression analyses confirmed that higher levels of Hg and Pb, together with lower levels of GST and vitamin E, can be used to predict social and cognitive impairment in patients with autism spectrum disorders. Conclusion: This study confirms earlier studies that implicate toxic metal accumulation as a consequence of impaired detoxification in autism and provides insight into the etiological mechanism of autism. C1 [Alabdali, Altaf; El-Ansary, Afaf] King Saud Univ, Coll Sci, Dept Biochem, Riyadh 11495, Saudi Arabia. [Al-Ayadhi, Laila; El-Ansary, Afaf] Autism Res & Treatment Ctr, Riyadh, Saudi Arabia. [Al-Ayadhi, Laila; El-Ansary, Afaf] King Saud Univ, Shaik AL Amodi Autism Res Chair, Riyadh 11495, Saudi Arabia. [Al-Ayadhi, Laila] King Saud Univ, Fac Med, Dept Physiol, Riyadh 11495, Saudi Arabia. [El-Ansary, Afaf] Natl Res Ctr, Dept Med Chem, Cairo, Egypt. RP El-Ansary, A (reprint author), King Saud Univ, Coll Sci, Dept Biochem, POB 22452, Riyadh 11495, Saudi Arabia. EM elansary@ksu.edu.sa FU research center of the center for female scientific and medical colleges in King Saud University FX This research project was supported by a grant from the research center of the center for female scientific and medical colleges in King Saud University. 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Brain Funct. PD APR 28 PY 2014 VL 10 AR 14 DI 10.1186/1744-9081-10-14 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AH1DF UT WOS:000335859200001 PM 24776096 ER PT J AU Doherty, JL Owen, MJ AF Doherty, Joanne L. Owen, Michael J. TI Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice SO GENOME MEDICINE LA English DT Review ID DEFICIT HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; COPY-NUMBER VARIATION; DE-NOVO MUTATIONS; 22Q11.2 DELETION SYNDROME; RARE CHROMOSOMAL DELETIONS; BIPOLAR-DISORDER; INTELLECTUAL DISABILITY; MENTAL-RETARDATION AB Psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder and autism spectrum disorder are common and result in significantmorbidity andmortality. Although currently classified into distinct disorder categories, they show clinical overlap and familial co-aggregation, and share genetic risk factors. Recent advances in psychiatric genomics have provided insight into the potential mechanisms underlying the overlap between these disorders, implicating genes involved in neurodevelopment, synaptic plasticity, learning andmemory. Furthermore, evidence from copy number variant, exome sequencing and genome-wide association studies supports a gradient of neurodevelopmental psychopathology indexed by mutational load ormutational severity, and cognitive impairment. These findings have important implications for psychiatric research, highlighting the need for new approaches to stratifying patients for research. They also point the way for work aiming to advance our understanding of the pathways from genotype to clinical phenotype, which will be required in order to inform new classification systems and to develop novel therapeutic strategies. C1 [Owen, Michael J.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF24 4HQ, S Glam, Wales. Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff CF24 4HQ, S Glam, Wales. RP Owen, MJ (reprint author), Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Hadyn Ellis Buildin,Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales. EM owenmj@cardiff.ac.uk FU Medical Research Council Centre [G0800509, G0801418]; European Community's Seventh Framework Programme [HEALTH-F2-2010-241909]; National Institute of Mental Health [2 P50MH066392-05A1]; Wellcome Trust Strategic Award [100202/Z/12/Z)]; Wellcome Trust Clinical Research [102003/Z/13/Z] FX MJO is supported by the Medical Research Council Centre (G0800509) and Program Grants (G0801418), the European Community's Seventh Framework Programme (HEALTH-F2-2010-241909 (Project EU-GEI)), the National Institute of Mental Health (2 P50MH066392-05A1) and a Wellcome Trust Strategic Award (100202/Z/12/Z). JLD is supported by a Wellcome Trust Clinical Research Training Fellowship (102003/Z/13/Z). 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PD APR 28 PY 2014 VL 6 AR 29 DI 10.1186/gm546 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AG4RX UT WOS:000335409000001 PM 24944580 ER PT J AU Wang, XM Xu, Q Bey, AL Lee, Y Jiang, YH AF Wang, Xiaoming Xu, Qiong Bey, Alexandra L. Lee, Yoonji Jiang, Yong-hui TI Transcriptional and functional complexity of Shank3 provides a molecular framework to understand the phenotypic heterogeneity of SHANK3 causing autism and Shank3 mutant mice SO MOLECULAR AUTISM LA English DT Article DE Activity dependent gene regulation; Alternative splicing; Autism spectrum disorder; Phenotypic heterogeneity; Shank3 isoform ID DE-NOVO MUTATIONS; POSTSYNAPTIC DENSITY PROTEINS; SPECTRUM DISORDERS; DNA METHYLATION; FAMILY; EXPRESSION; BRAIN; BEHAVIORS; RECEPTOR; MOUSE AB Background: Considerable clinical heterogeneity has been well documented amongst individuals with autism spectrum disorders (ASD). However, little is known about the biological mechanisms underlying phenotypic diversity. Genetic studies have established a strong causal relationship between ASD and molecular defects in the SHANK3 gene. Individuals with various defects of SHANK3 display considerable clinical heterogeneity. Different lines of Shank3 mutant mice with deletions of different portions of coding exons have been reported recently. Variable synaptic and behavioral phenotypes have been reported in these mice, which makes the interpretations for these data complicated without the full knowledge of the complexity of the Shank3 transcript structure. Methods: We systematically examined alternative splicing and isoform-specific expression of Shank3 across different brain regions and developmental stages by regular RT-PCR, quantitative real time RT-PCR (q-PCR), and western blot. With these techniques, we also investigated the effects of neuronal activity and epigenetic modulation on alternative splicing and isoform-specific expression of Shank3. We explored the localization and influence on dendritic spine development of different Shank3 isoforms in cultured hippocampal neurons by cellular imaging. Results: The Shank3 gene displayed an extensive array of mRNA and protein isoforms resulting from the combination of multiple intragenic promoters and extensive alternative splicing of coding exons in the mouse brain. The isoform-specific expression and alternative splicing of Shank3 were brain-region/cell-type specific, developmentally regulated, activity-dependent, and involved epigenetic regulation. Different subcellular distribution and differential effects on dendritic spine morphology were observed for different Shank3 isoforms. Conclusions: Our results indicate a complex transcriptional regulation of Shank3 in mouse brains. Our analysis of select Shank3 isoforms in cultured neurons suggests that different Shank3 isoforms have distinct functions. Therefore, the different types of SHANK3 mutations found in patients with ASD and different exonic deletions of Shank3 in mutant mice are predicted to disrupt selective isoforms and result in distinct dysfunctions at the synapse with possible differential effects on behavior. Our comprehensive data on Shank3 transcriptional regulation thus provides an essential molecular framework to understand the phenotypic diversity in SHANK3 causing ASD and Shank3 mutant mice. C1 [Wang, Xiaoming; Xu, Qiong; Lee, Yoonji; Jiang, Yong-hui] Duke Univ, Sch Med, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. [Bey, Alexandra L.; Jiang, Yong-hui] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA. [Xu, Qiong] Fudan Univ, Childrens Hosp, Dept Child Hlth Care, Shanghai 201102, Peoples R China. RP Jiang, YH (reprint author), Duke Univ, Sch Med, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. EM yong-hui.jiang@duke.edu RI wang, xiaoming/I-2158-2013 OI wang, xiaoming/0000-0002-7763-690X FU Phelan-McDermid Syndrome Foundation; Natural Science Foundation of China, NSFC [81371270]; Ruth K. Broad Foundation; National Institutes of Health [R01MH098114-01]; Autism Speaks grant FX We thank Shengli Zhao and Tingting Wang for generous gifts of EGFP plasmids. We thank Xinyu Cao for technical assistance. XW is supported by a postdoctoral fellowship from Phelan-McDermid Syndrome Foundation. QX is supported by a grant from Natural Science Foundation of China, NSFC (No. 81371270). ALB is a pre-doctoral fellow supported by Ruth K. Broad Foundation. YHJ is supported by an Autism Speaks grant, Ruth K. Broad Foundation, and National Institutes of Health grant R01MH098114-01. 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Autism PD APR 25 PY 2014 VL 5 AR 30 DI 10.1186/2040-2392-5-30 PG 14 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AG7OG UT WOS:000335606800001 PM 25071925 ER PT J AU Tavassoli, T Hoekstra, RA Baron-Cohen, S AF Tavassoli, Teresa Hoekstra, Rosa A. Baron-Cohen, Simon TI The Sensory Perception Quotient (SPQ): development and validation of a new sensory questionnaire for adults with and without autism SO MOLECULAR AUTISM LA English DT Article DE autism spectrum conditions; sensory questionnaire; sensory perception quotient ID SPECTRUM QUOTIENT; YOUNG-CHILDREN; TYPICAL DEVELOPMENT; FUNCTIONING AUTISM; PROFILE; AQ; DISORDERS; ABNORMALITIES; DISABILITIES; PERFORMANCE AB Background: Questionnaire-based studies suggest atypical sensory perception in over 90% of individuals with autism spectrum conditions (ASC). Sensory questionnaire-based studies in ASC mainly record parental reports of their child's sensory experience; less is known about sensory reactivity in adults with ASC. Given the DSM-5 criteria for ASC now include sensory reactivity, there is a need for an adult questionnaire investigating basic sensory functioning. We aimed to develop and validate the Sensory Perception Quotient (SPQ), which assesses basic sensory hyper-and hyposensitivity across all five modalities. Methods: A total of 359 adults with (n = 196) and without (n = 163) ASC were asked to fill in the SPQ, the Sensory Over-Responsivity Inventory (SensOR) and the Autism-Spectrum Quotient (AQ) online. Results: Adults with ASC reported more sensory hypersensitivity on the SPQ compared to controls (P <.001). SPQ scores were correlated with AQ scores both across groups (r =.-38) and within the ASC (r = -.18) and control groups (r = -.15). Principal component analyses conducted separately in both groups indicated that one factor comprising 35 items consistently assesses sensory hypersensitivity. The SPQ showed high internal consistency for both the total SPQ (Cronbach's alpha =.92) and the reduced 35-item version (alpha =.93). The SPQ was significantly correlated with the SensOR across groups (r = -.46) and within the ASC (r = -.49) and control group (r = -.21). Conclusions: The SPQ shows good internal consistency and concurrent validity and differentiates between adults with and without ASC. Adults with ASC report more sensitivity to sensory stimuli on the SPQ. Finally, greater sensory sensitivity is associated with more autistic traits. The SPQ provides a new tool to measure individual differences on this dimension. C1 [Tavassoli, Teresa; Hoekstra, Rosa A.; Baron-Cohen, Simon] Univ Cambridge, Autism Res Ctr, Dept Psychiat, Cambridge CB2 8AH, England. 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TI Guidelines for investigating causality of sequence variants in human disease SO NATURE LA English DT Article ID DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; PROTEIN-CODING GENES; HUMAN GENOME; INTELLECTUAL DISABILITY; COMPLEX TRAITS; RARE VARIANTS; ASSOCIATION; POPULATION; PHENOTYPE AB The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. 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This neuronal hypertrophy is correlated with increased p-S6 and p-mTOR in individual neurons. We used this system to test whether an environmental factor that has been implicated in cellular hypertrophy could influence the severity of the Pten knockdown-induced hypertrophy. Implantation of mini-osmotic pumps delivering fatty acids results in increased neuronal hypertrophy and p-S6/p-mTOR staining. These hypertrophic effects were reversed in response to rapamycin treatment. However, we did not observe a similar increase in hypertrophy in response to dietary manipulations of fatty acids. Thus, we conclude that by driving growth signaling with fatty acids and knocking down a critical regulator of growth, Pten, we are able to observe an additive morphological phenotype of increased soma size mediated by the mTOR pathway. C1 [Fricano, Catherine J.; DeSpenza, Tyrone, Jr.; Frazel, Paul W.; Li, Meijie; Luikart, Bryan W.] Geisel Sch Med Dartmouth, Dept Physiol & Neurobiol, Lebanon, NH 03756 USA. [O'Malley, A. James] Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH 03756 USA. [Westbrook, Gary L.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA. RP Luikart, BW (reprint author), Geisel Sch Med Dartmouth, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM bryan.w.luikart@dartmouth.edu FU Autism Speaks Pilot Grant [7359]; [R01 MH097949-01] FX This work was supported by R01 MH097949-01 (Bryan W. Luikart) and Autism Speaks Pilot Grant #7359 (Bryan W. Luikart). The imaging was made possible by the Optical Cellular Imaging Shared Resource and the Norris Cotton Cancer Center at the Geisel School of Medicine at Dartmouth (5 P30 CA023108). 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PD APR 23 PY 2014 VL 7 AR 30 DI 10.3389/fnmol.2014.00030 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AZ0YZ UT WOS:000347969000001 PM 24795563 ER PT J AU Kerekes, N Lundstrom, S Chang, Z Tajnia, A Jern, P Lichtenstein, P Nilsson, T Anckarsater, H AF Kerekes, Nora Lundstrom, Sebastian Chang, Zheng Tajnia, Armin Jern, Patrick Lichtenstein, Paul Nilsson, Thomas Anckarsater, Henrik TI Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study SO PEERJ LA English DT Article DE Oppositional defiant disorder; Conduct disorder; Attention deficit hyperactivity disorder; Autism spectrum disorder; Social interaction; Boys; Girls ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; RELATIONAL AGGRESSION; SEX-DIFFERENCES; SYMPTOMS; CHILDREN; ADHD; PSYCHOPATHOLOGY; COVARIATION; ASSOCIATION AB Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD) and conduct disorder (CD). The aims of this study were to identify gender-specific associations between the behavioural problems-ODD/CD-like problems-and the neurodevelopmental disorders-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD)-and to investigate underlying genetic effects. Methods. 17,220 twins aged 9 or 12 were screened using the Autism-Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting. Results. Social interaction problems (one of the ASD subdomains) was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%-62% of the variance in behavioural problems, except in CD-like problems in girls (26%). Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls. Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD. C1 [Kerekes, Nora; Lundstrom, Sebastian; Tajnia, Armin; Nilsson, Thomas; Anckarsater, Henrik] Univ Gothenburg, Inst Neurosci & Physiol, Ctr Eth Law & Mental Health, CELAM, Gothenburg, Sweden. [Kerekes, Nora; Lundstrom, Sebastian] Swedish Prison & Probat Serv, Res & Dev Unit, Gothenburg, Sweden. [Lundstrom, Sebastian] Univ Gothenburg, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [Chang, Zheng; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Jern, Patrick] Abo Akad Univ, Dept Psychol & Logoped, Turku, Finland. [Jern, Patrick] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia. RP Kerekes, N (reprint author), Univ Gothenburg, Inst Neurosci & Physiol, Ctr Eth Law & Mental Health, CELAM, Gothenburg, Sweden. EM nora.kerekes@neuro.gu.se RI Kerekes, Nora/C-6474-2009 FU Swedish Council for Working Life and Social Research; Swedish Research Council (Medicine); Agreement on Medical Training and Research FX The CATSS-9/12-study is supported by the Swedish Council for Working Life and Social Research, the Swedish Research Council (Medicine) and by the Agreement on Medical Training and 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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TI Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism SO FRONTIERS IN PHYSIOLOGY LA English DT Review DE autism; brain; oxidative stress; mitochondrial dysfunction; inflammation ID NECROSIS-FACTOR-ALPHA; MAGNETIC-RESONANCE-SPECTROSCOPY; DISABILITIES MONITORING NETWORK; DORSOLATERAL PREFRONTAL CORTEX; GLUTATHIONE REDOX IMBALANCE; SPECTRUM DISORDERS; MICROGLIAL ACTIVATION; PSYCHIATRIC-DISORDERS; METABOLIC BIOMARKERS; CEREBROSPINAL-FLUID AB Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders that are defined solely on the basis of behavioral observations. Therefore, ASD has traditionally been framed as a behavioral disorder. However, evidence is accumulating that ASD is characterized by certain physiological abnormalities, including oxidative stress, mitochondrial dysfunction and immune dysregulation/inflammation. While these abnormalities have been reported in studies that have examined peripheral biomarkers such as blood and urine, more recent studies have also reported these abnormalities in brain tissue derived from individuals diagnosed with ASD as compared to brain tissue derived from control individuals. A majority of these brain tissue studies have been published since 2010. The brain regions found to contain these physiological abnormalities in individuals with ASD are involved in speech and auditory processing, social behavior, memory, and sensory and motor coordination. This manuscript examines the evidence linking oxidative stress, mitochondrial dysfunction and immune dysregulation/inflammation in the brain of ASD individuals, suggesting that ASD has a clear biological basis with features of known medical disorders. This understanding may lead to new testing and treatment strategies in individuals with ASD. C1 [Rossignol, Daniel A.] Rossignol Med Ctr, Irvine, CA 92618 USA. 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Physiol. PD APR 22 PY 2014 VL 5 AR 150 DI 10.3389/fphys.2014.00150 PG 15 WC Physiology SC Physiology GA AX6NN UT WOS:000347038900001 PM 24795645 ER PT J AU Chenier, S Yoon, G Argiropoulos, B Lauzon, J Laframboise, R Ahn, JW Ogilvie, CM Lionel, AC Marshall, CR Vaags, AK Hashemi, B Boisvert, K Mathonnet, G Tihy, F So, J Scherer, SW Lemyre, E Stavropoulos, DJ AF Chenier, Sebastien Yoon, Grace Argiropoulos, Bob Lauzon, Julie Laframboise, Rachel Ahn, Joo Wook Ogilvie, Caroline Mackie Lionel, Anath C. Marshall, Christian R. Vaags, Andrea K. Hashemi, Bita Boisvert, Karine Mathonnet, Geraldine Tihy, Frederique So, Joyce Scherer, Stephen W. Lemyre, Emmanuelle Stavropoulos, Dimitri J. TI CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; CHD2; Developmental delay; Epilepsy; Learning disability ID DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; GENOME-WIDE ASSOCIATION; COPY NUMBER VARIATION; SUSCEPTIBILITY LOCI; FAMILY; ENCEPHALOPATHIES; POPULATIONS; VARIANTS; PROTEINS AB Background: The chromodomain helicase DNA binding domain (CHD) proteins modulate gene expression via their ability to remodel chromatin structure and influence histone acetylation. Recent studies have shown that CHD2 protein plays a critical role in embryonic development, tumor suppression and survival. Like other genes encoding members of the CHD family, pathogenic mutations in the CHD2 gene are expected to be implicated in human disease. In fact, there is emerging evidence suggesting that CHD2 might contribute to a broad spectrum of neurodevelopmental disorders. Despite growing evidence, a description of the full phenotypic spectrum of this condition is lacking. Methods: We conducted a multicentre study to identify and characterise the clinical features associated with haploinsufficiency of CHD2. Patients with deletions of this gene were identified from among broadly ascertained clinical cohorts undergoing genomic microarray analysis for developmental delay, congenital anomalies and/or autism spectrum disorder. Results: Detailed clinical assessments by clinical geneticists showed recurrent clinical symptoms, including developmental delay, intellectual disability, epilepsy, behavioural problems and autism-like features without characteristic facial gestalt or brain malformations observed on magnetic resonance imaging scans. Parental analysis showed that the deletions affecting CHD2 were de novo in all four patients, and analysis of high-resolution microarray data derived from 26,826 unaffected controls showed no deletions of this gene. Conclusions: The results of this study, in addition to our review of the literature, support a causative role of CHD2 haploinsufficiency in developmental delay, intellectual disability, epilepsy and behavioural problems, with phenotypic variability between individuals. C1 [Chenier, Sebastien] CHU Sherbrooke, Dept Pediat, Div Med Genet, Sherbrooke, PQ J1H 5N4, Canada. [Yoon, Grace; Hashemi, Bita] Hosp Sick Children, Div Clin & Metab Genet, Dept Pediat, Toronto, ON M5G 1X8, Canada. [Yoon, Grace; Hashemi, Bita; Stavropoulos, Dimitri J.] Univ Toronto, Toronto, ON M5G 1X8, Canada. [Argiropoulos, Bob; Lauzon, Julie] Univ Calgary, Alberta Childrens Hosp Res Inst, Dept Med Genet, Calgary, AB T3B 6A8, Canada. [Laframboise, Rachel; Boisvert, Karine] Ctr Hosp Univ Quebec, Dept Pediat, Div Med Genet, Quebec City, PQ G1V 4G2, Canada. [Ahn, Joo Wook; Ogilvie, Caroline Mackie] Guys & St Thomas NHS Fdn Trust, Cytogenet Dept, London SE1 9RT, England. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Dept Mol Genet, Toronto, ON M5G 0A4, Canada. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, McLaughlin Ctr, Ctr Appl Genom, Toronto, ON M5G 0A4, Canada. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 0A4, Canada. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, Toronto, ON M5G 0A4, Canada. [Vaags, Andrea K.] Calgary Lab Serv, Cytogenet Lab, Div Anat Pathol & Cytopathol, Calgary, AB T3B 6A8, Canada. [Vaags, Andrea K.] Alberta Childrens Prov Gen Hosp, Calgary, AB T3B 6A8, Canada. [Mathonnet, Geraldine; Tihy, Frederique; Lemyre, Emmanuelle] Univ Montreal, Dept Pediat, Div Med Genet, Ctr Hosp Univ St Justine, Montreal, PQ H3T 1C5, Canada. [So, Joyce] Lakeridge Hlth Oshawa, Dept Clin Genet, Oshawa, ON L1G 2B9, Canada. [Stavropoulos, Dimitri J.] Hosp Sick Children, Dept Paediat Lab Med, Toronto, ON M5G 1X8, Canada. RP Stavropoulos, DJ (reprint author), Hosp Sick Children, Dept Paediat Lab Med, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM james.stavropoulos@sickkids.ca RI Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU University of Toronto McLaughlin Centre; Genome Canada through the Ontario Genomics Institute; Canadian Institutes of Health Research (CIHR); NeuroDevNet doctoral fellowship; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIDDK Central Repositories; National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI) [U01 HG004399]; National Institutes of Health [CA87969, CA55075, DK58845]; Gene Environment Association Studies GENEVA coordinating center [U01 HG004446]; National Center for Biotechnology Information; NIH GEI [U01 HG004424]; Division of Aging Biology, National Institute on Aging, NIH; Division of Geriatrics and Clinical Gerontology, National Institute on Aging, NIH; National Eye Institute, NIH; Gene Environment Association Studies (GENEVA) Coordinating Center [U01 HG004446]; University of Wisconsin Transdisciplinary Tobacco Use Research Center [P50 DA019706, P50 CA084724]; [1 X01 HG005274-01]; [P01 CA089392] FX The authors wish to thank the patients and their families for participating in this study. This work was supported by grants from the University of Toronto McLaughlin Centre, Genome Canada through the Ontario Genomics Institute, and the Canadian Institutes of Health Research (CIHR). ACL was supported by a NeuroDevNet doctoral fellowship. SWS holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children. The authors would like to thank Dr Marsha Speevak for permission to include statistics from the patient database at Credit Valley Hospital. Control data sets were obtained, along with permission for their use, from the database of Genotypes and Phenotypes (dbGaP) (http://www.ncbi.nlm.nih.gov/gap) through dbGaP accession numbers phs000143.v1.p1 (Starr County Health Studies' Genetics of Diabetes Study), phs000091.v2.p1 (GENEVA Genes and Environment Initiatives in Type 2 Diabetes (Nurses' Health Study/Health Professionals Follow-up Study), phs000169.v1.p1 (Whole Genome Association Study of Visceral Adiposity in the Health Aging and Body Composition (Health ABC) Study), phs000303.v1.p1 (Genetic Epidemiology of Refractive Error in the KORA (Kooperative Gesundheitsforschung in der Region Augsburg) Study) and phs000404.v1.p1 (Collaborative Genetic Study of Nicotine Dependence (COGEND); The Genetic Architecture of Smoking and Smoking Cessation). The Starr County Health Studies Genetics of Diabetes Study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the NIDDK Central Repositories. Support for the genome-wide association study (GWAS) of the GENEVA Genes and Environment Initiatives in Type 2 Diabetes (Nurses' Health Study/Health Professionals Follow-up Study) was provided by the National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI) (grant U01 HG004399). The participants in the GWAS derive from The Nurses' Health Study and Health Professionals' Follow-up Study, which are supported by National Institutes of Health grants CA87969, CA55075 and DK58845. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the Gene Environment Association Studies GENEVA coordinating center (grant U01 HG004446) and the National Center for Biotechnology Information. Support for genotyping, which was performed at the Broad Institute of the Massachusetts Institute of Technology and Harvard University, was provided by the NIH GEI (grant U01 HG004424). Support for the Johns Hopkins University Center for Inherited Disease Research (CIDR) Visceral Adiposity Study was provided through the Division of Aging Biology and the Division of Geriatrics and Clinical Gerontology, National Institute on Aging, NIH. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the Health Aging and Body Composition (Health ABC) Study Investigators. The KORA data set was obtained from the NEI Refractive Error Collaboration (NEIREC) Database, funding support for which was provided by the National Eye Institute, NIH. Funding support for genotyping of the COGEND samples, which was performed at the Center for Inherited Disease Research, was provided by grant 1 X01 HG005274-01. Assistance with genotype cleaning of the COGEND samples, as well as with general study coordination, was provided by the Gene Environment Association Studies (GENEVA) Coordinating Center (grant U01 HG004446).Funding support for collection of COGEND data sets and samples was provided by COGEND (grant P01 CA089392) and the University of Wisconsin Transdisciplinary Tobacco Use Research Center (grants P50 DA019706 and P50 CA084724). 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J., 2012, AM J PSYCHIAT, V169, P580 NR 60 TC 2 Z9 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD APR 22 PY 2014 VL 4 AR 4740 DI 10.1038/srep04740 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF4FO UT WOS:000334667300001 PM 24751935 ER PT J AU Zamzow, RM Christ, SE Saklayen, SS Moffitt, AJ Bodner, KE Higgins, KF Beversdorf, DQ AF Zamzow, Rachel M. Christ, Shawn E. Saklayen, Sanjida S. Moffitt, Amanda J. Bodner, Kimberly E. Higgins, Katherine F. Beversdorf, David Q. TI Effect of propranolol on facial scanning in autism spectrum disorder: A preliminary investigation SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Autism; Eye tracking; Noradrenergic; Facial scanning; Propranolol ID HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; BETA-ADRENERGIC MODULATION; COGNITIVE FLEXIBILITY; EYE-TRACKING; NORADRENERGIC MODULATION; FIXATION PATTERNS; ASPERGER-SYNDROME; WILLIAMS-SYNDROME; FACE RECOGNITION AB Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication impairments and restricted, repetitive behaviors. Whereas current pharmacological interventions for ASD focus primarily on psychiatric symptoms, including agitation and obsessive behaviors, few agents target core symptomatology. It has been previously hypothesized that abnormalities in facial scanning, such as reduced eye contact or increased mouth fixation, contribute to social communication deficits in ASD. In addition, previous reports have suggested elevated stress and anxiety in ASD, symptoms that are believed to impact facial scanning patterns. Objectives: The present pilot study sought to explore the effects of pharmacological intervention via propranolol, a nonselective beta-adrenergic antagonist and known anxiolytic, on facial scanning in ASD. Specifically, we wished to determine whether there is an increase in eye contact and a decrease in mouth fixation with administration of propranolol. Method: A sample of 14 participants with ASD and 14 matched controls participated in two study sessions in which propranolol and placebo were administered in a counterbalanced, double-blinded manner. At each session, ocular fixation data were collected during presentation of video stimuli of 16 human faces. Fixation time on the eye, nose, and mouth regions of the face stimuli was analyzed. Results: The baseline fixation patterns for the ASD and control groups did not significantly differ; however, administration of propranolol was associated with a significant reduction in mouth fixation for the ASD group. Additionally, mouth fixation was positively related to nonverbal communication impairment in the ASD group. Conclusions: Although eye fixation in ASD appears typical in the present study, the effect of propranolol in reducing mouth fixation suggests an important focus for further research. Future studies are needed to better characterize the relationship between stress and anxiety and facial scanning in ASD, as well as the effects of pharmacological intervention. C1 [Zamzow, Rachel M.] Univ Missouri, Interdisciplinary Neurosci Program, Columbia, MO USA. [Christ, Shawn E.; Moffitt, Amanda J.; Bodner, Kimberly E.; Beversdorf, David Q.] Univ Missouri, Dept Psychol Sci, Columbia, MO USA. [Christ, Shawn E.; Beversdorf, David Q.] Univ Missouri, Thompson Ctr Autism & Neurodev Disorders, Columbia, MO USA. [Saklayen, Sanjida S.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Saklayen, Sanjida S.] Ohio State Univ, Integrated Biomed Grad Program, Columbus, OH 43210 USA. [Higgins, Katherine F.] Univ Missouri, Coll Arts & Sci, Columbia, MO USA. [Beversdorf, David Q.] Univ Missouri, Dept Radiol, Columbia, MO USA. [Beversdorf, David Q.] Univ Missouri, Dept Neurol, Columbia, MO USA. RP Beversdorf, DQ (reprint author), Univ Missouri Hlth Care, Ctr Translat Neurosci, Dept Radiol, DC069-10,One Hosp Dr, Columbia, MO 65212 USA. EM beversdorfd@health.missouri.edu FU MU Thompson Center for Autism and Neurodevelopmental Disorders; Department of Radiology Research Investment Fund at the University of Missouri; University of Missouri Life Sciences Predoctoral Fellowship FX We acknowledge support from a Research Scholar grant from the MU Thompson Center for Autism and Neurodevelopmental Disorders, the Department of Radiology Research Investment Fund at the University of Missouri, and the University of Missouri Life Sciences Predoctoral Fellowship. 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Clin. Exp. Neuropsychol. PD APR 21 PY 2014 VL 36 IS 4 BP 431 EP 445 DI 10.1080/13803395.2014.904844 PG 15 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA AH0YS UT WOS:000335847300009 PM 24730708 ER PT J AU Breitenkamp, AFS Matthes, J Nass, RD Sinzig, J Lehmkuhl, G Nurnberg, P Herzig, S AF Breitenkamp, Alexandra F. S. Matthes, Jan Nass, Robert Daniel Sinzig, Judith Lehmkuhl, Gerd Nuernberg, Peter Herzig, Stefan TI Rare Mutations of CACNB2 Found in Autism Spectrum Disease-Affected Families Alter Calcium Channel Function SO PLOS ONE LA English DT Article ID GATED CA2+ CHANNELS; BETA-SUBUNITS; TIMOTHY-SYNDROME; HUMAN HEART; EXPRESSION; DISORDERS; GENETICS; LOCALIZATION; INACTIVATION; HETEROGENEITY AB Autism Spectrum Disorders (ASD) are complex neurodevelopmental diseases clinically defined by dysfunction of social interaction. Dysregulation of cellular calcium homeostasis might be involved in ASD pathogenesis, and genes coding for the L-type calcium channel subunits Ca(V)1.2 (CACNA1C) and Ca-V beta 2 (CACNB2) were recently identified as risk loci for psychiatric diseases. Here, we present three rare missense mutations of CACNB2 (G167S, S197F, and F240L) found in ASD-affected families, two of them described here for the first time (G167S and F240L). All these mutations affect highly conserved regions while being absent in a sample of ethnically matched controls. We suggest the mutations to be of physiological relevance since they modulate whole-cell Ba2+ currents through calcium channels when expressed in a recombinant system (HEK-293 cells). Two mutations displayed significantly decelerated time-dependent inactivation as well as increased sensitivity of voltage-dependent inactivation. In contrast, the third mutation (F240L) showed significantly accelerated time-dependent inactivation. By altering the kinetic parameters, the mutations are reminiscent of the CACNA1C mutation causing Timothy Syndrome, a Mendelian disease presenting with ASD. In conclusion, the results of our first-time biophysical characterization of these three rare CACNB2 missense mutations identified in ASD patients support the hypothesis that calcium channel dysfunction may contribute to autism. C1 [Breitenkamp, Alexandra F. S.; Matthes, Jan; Nass, Robert Daniel; Herzig, Stefan] Univ Cologne, Dept Pharmacol, D-50931 Cologne, Germany. [Sinzig, Judith] LVR Klin Bonn, Dept Child & Adolescent Psychiat & Psychotherapy, Bonn, Germany. [Sinzig, Judith; Lehmkuhl, Gerd] Univ Cologne, Dept Child & Adolescent Psychiat & Psychotherapy, D-50931 Cologne, Germany. [Nuernberg, Peter] Univ Cologne, Cologne Ctr Genom, D-50931 Cologne, Germany. [Herzig, Stefan] Univ Cologne, Ctr Mol Med, D-50931 Cologne, Germany. RP Herzig, S (reprint author), Univ Cologne, Dept Pharmacol, D-50931 Cologne, Germany. EM stefan.herzig@uni-koeln.de FU "Koeln Fortune'' program and DFG [KF 20/2006, KF 93/2007]; German Research Foundation [He 1578 15-1] FX This study was supported by the "Koeln Fortune'' program (KF 20/2006 and KF 93/2007) and DFG, the German Research Foundation, (He 1578 15-1). 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 adopting a social constructionist approach, the case study used a person-centred model to explore a parent's experiences and emerging narratives of ASD through the lens of VIG. Findings of the current study suggest that VIG offers an effective tool for in-depth exploration of complex, multi-storied understandings of ASD and the perceived parental role. The intervention was perceived to promote greater awareness of the child's communication skills, beyond the 'common' understandings of ASD, by providing a novel outsider perspective on interactions. The intervention also promoted parental efficacy through recognition of parenting skills in supporting the development of strength-based narratives. VIG was seen to provide a platform for an exploration of existing narratives and the construction of new, preferred realities. C1 Educ Psychol Serv, Stockton On Tees, England. RP Gibson, KA (reprint author), Educ Psychol Serv, Stockton On Tees, England. 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PD APR 21 PY 2014 VL 29 IS 4 BP 568 EP 582 DI 10.1080/09687599.2013.844096 PG 15 WC Rehabilitation; Social Sciences, Interdisciplinary SC Rehabilitation; Social Sciences - Other Topics GA AF7PM UT WOS:000334907000007 ER PT J AU Bernardini, S Porayska-Pomsta, K Smith, TJ AF Bernardini, Sara Porayska-Pomsta, Kaska Smith, Tim J. TI ECHOES: An intelligent serious game for fostering social communication in children with autism SO INFORMATION SCIENCES LA English DT Article DE Virtual social partner; Pedagogical agent; Autonomous intelligent agent; Artificial intelligence planning; Autism; Social communication ID SPECTRUM DISORDERS; VIRTUAL ENVIRONMENTS; ADOLESCENTS; INSTRUCTION; VOCABULARY; REALITY; AGENTS; MODEL AB This paper presents ECHOES, a serious game built to help young children with autism spectrum conditions practice social communication skills. We focus on the design and implementation of the interactive learning activities, which take place in a two-dimensional sensory garden, and the autonomous virtual agent, which acts as a credible social partner to children with autism. Both the activities and the agent are based on principles of best autism practice and input from users. Specification guidelines are given for building an autonomous socially competent agent that supports learning in this context. We present experimental results pertaining to the effectiveness of the agent based on an extensive evaluation of the ECHOES platform, which show encouraging tendencies for a number of children. (C) 2013 Elsevier Inc. All rights reserved. C1 [Bernardini, Sara] Kings Coll London, Dept Informat, London WC2R 2LS, England. [Porayska-Pomsta, Kaska] Inst Educ, London Knowledge Lab, London WC1N 3QS, England. [Smith, Tim J.] Birkbeck Coll, Dept Psychol Sci, London WC1E 7HX, England. RP Bernardini, S (reprint author), Kings Coll London, Dept Informat, London WC2R 2LS, England. EM sara.bernardini@kcl.ac.uk FU Engineering and Physical Sciences Research Council (EPSRC); Economic and Social Sciences Researcher Council (ESRC) under the TLRP-TEL programme [RES-139-25-0395-A] FX The ECHOES project has been funded jointly by the Engineering and Physical Sciences Research Council (EPSRC) and Economic and Social Sciences Researcher Council (ESRC) under the TLRP-TEL programme, Grant No.: RES-139-25-0395-A. We thank all the other members of the ECHOES project (A. Alcorn, K. Avramides, J. Chen, M.E. Foster, C. Frauenberger, J. Good, K. Guldberg, W. Keay-Bright, C. Kossyvaki, O. Lemon, L Mademtzi, R. Menzies, H. Pain, T. Rajendran, A. Waller, and S. Wass) for their contribution to the construction of the system and its evaluation. We are also very grateful to all the teachers, children and parents who have participated in the project for their insightful suggestions and their involvement in the game's evaluation. 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TI Blocking Metabotropic Glutamate Receptor Subtype 7 ( mGlu7) via the Venus Flytrap Domain ( VFTD) Inhibits Amygdala Plasticity, Stress, and Anxiety-related Behavior SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Glutamate Receptors Metabotropic; Neurotransmitter Release; Pharmacology; Stress; Synaptic Plasticity; Elevated Plus-Maze; Fear Conditioning; XAP044 ID PROTEIN-COUPLED RECEPTORS; CENTRAL-NERVOUS-SYSTEM; NEGATIVE ALLOSTERIC MODULATOR; CELL-DEPENDENT PLASTICITY; IN-VITRO; PHARMACOLOGICAL CHARACTERIZATION; LATERAL AMYGDALA; RELEASE SITES; MICE LACKING; ACTIVATION AB Background: Behavioral genetics identified mGlu7 as a key regulator of brain emotion circuits. Results: An mGlu7-selective, Venus flytrap domain (VFTD)-directed antagonist inhibits fear, synaptic plasticity, stress, and anxiety in rodents. Conclusion: Pharmacological blockers of mGlu7 may represent promising future anxiolytics and antidepressants in man. Significance: The VFTD region of class C GPCRs provides a promising target for computer-assisted drug design. The metabotropic glutamate receptor subtype 7 (mGlu7) is an important presynaptic regulator of neurotransmission in the mammalian CNS. mGlu7 function has been linked to autism, drug abuse, anxiety, and depression. Despite this, it has been difficult to develop specific blockers of native mGlu7 signaling in relevant brain areas such as amygdala and limbic cortex. Here, we present the mGlu7-selective antagonist 7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one (XAP044), which inhibits lateral amygdala long term potentiation (LTP) in brain slices from wild type mice with a half-maximal blockade at 88 nm. There was no effect of XAP044 on LTP of mGlu7-deficient mice, indicating that this pharmacological effect is mGlu7-dependent. Unexpectedly and in contrast to all previous mGlu7-selective drugs, XAP044 does not act via the seven-transmembrane region but rather via a binding pocket localized in mGlu7's extracellular Venus flytrap domain, a region generally known for orthosteric agonist binding. This was shown by chimeric receptor studies in recombinant cell line assays. XAP044 demonstrates good brain exposure and wide spectrum anti-stress and antidepressant- and anxiolytic-like efficacy in rodent behavioral paradigms. XAP044 reduces freezing during acquisition of Pavlovian fear and reduces innate anxiety, which is consistent with the phenotypes of mGlu7-deficient mice, the results of mGlu7 siRNA knockdown studies, and the inhibition of amygdala LTP by XAP044. Thus, we present an mGlu7 antagonist with a novel molecular mode of pharmacological action, providing significant application potential in psychiatry. Modeling the selective interaction between XAP044 and mGlu7's Venus flytrap domain, whose three-dimensional structure is already known, will facilitate future drug development supported by computer-assisted drug design. C1 [Gee, Christine E.; Bouhelal, Rochdi; Kaupmann, Klemens; Laue, Grit; Feuerbach, Dominik; Zimmermann, Kaspar; Ofner, Silvio; Cryan, John F.; van der Putten, Herman; Fendt, Markus; Vranesic, Ivo; Glatthar, Ralf; Flor, Peter J.] Novartis AG, Novartis Inst BioMed Res, CH-4057 Basel, Switzerland. [Gee, Christine E.] Univ Med Ctr Hamburg Eppendorf, Ctr Mol Neurobiol Hamburg, D-20249 Hamburg, Germany. [Peterlik, Daniel; Neuhaeuser, Christoph; Uschold-Schmidt, Nicole; Flor, Peter J.] Univ Regensburg, Fac Biol & Preclin Med, Lab Mol & Cellular Neurobiol, D-93053 Regensburg, Germany. [Cryan, John F.] Natl Univ Ireland Univ Coll Cork, Dept Anat & Neurosci, Cork, Ireland. [Fendt, Markus] Univ Magdeburg, Inst Pharmacol & Toxicol, D-39120 Magdeburg, Germany. [Fendt, Markus] Univ Magdeburg, Ctr Behav Brain Sci, D-39120 Magdeburg, Germany. RP Glatthar, R (reprint author), Novartis Pharma AG, CH-4057 Basel, Switzerland. EM ralf.glatthar@novartis.com; peter.flor@biologie.uni-regensburg.de FU German Research Foundation [FL 729/2-1] FX Supported by Grant FL 729/2-1 from the German Research Foundation. To whom correspondence may be addressed: Faculty of Biology and Preclinical Medicine, University of Regensburg, D-93053 Regensburg, Germany. Tel.: 49-941-3079; Fax: 49-941-3052; E-mail: peter.flor@biologie.uni-regensburg.de. 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Biol. Chem. PD APR 18 PY 2014 VL 289 IS 16 BP 10975 EP 10987 DI 10.1074/jbc.M113.542654 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AF3UT UT WOS:000334638500004 PM 24596089 ER PT J AU Zalla, T Amsellem, F Chaste, P Ervas, F Leboyer, M Champagne-Lavau, M AF Zalla, Tiziana Amsellem, Frederique Chaste, Pauline Ervas, Francesca Leboyer, Marion Champagne-Lavau, Maud TI Individuals with Autism Spectrum Disorders Do Not Use Social Stereotypes in Irony Comprehension SO PLOS ONE LA English DT Article ID HIGH-FUNCTIONING AUTISM; COMPUTER-MEDIATED COMMUNICATION; ASPERGER-SYNDROME; DIAGNOSTIC INTERVIEW; VERBAL IRONY; FAUX PAS; CHILDREN; MIND; LANGUAGE; SYNDROME. AB Social and communication impairments are part of the essential diagnostic criteria used to define Autism Spectrum Disorders (ASDs). Difficulties in appreciating non-literal speech, such as irony in ASDs have been explained as due to impairments in social understanding and in recognizing the speaker's communicative intention. It has been shown that social-interactional factors, such as a listener's beliefs about the speaker's attitudinal propensities (e.g., a tendency to use sarcasm, to be mocking, less sincere and more prone to criticism), as conveyed by an occupational stereotype, do influence a listener's interpretation of potentially ironic remarks. We investigate the effect of occupational stereotype on irony detection in adults with High Functioning Autism or Asperger Syndrome (HFA/AS) and a comparison group of typically developed adults. We used a series of verbally presented stories containing ironic or literal utterances produced by a speaker having either a "sarcastic'' or a "non-sarcastic'' occupation. Although individuals with HFA/AS were able to recognize ironic intent and occupational stereotypes when the latter are made salient, stereotype information enhanced irony detection and modulated its social meaning (i.e., mockery and politeness) only in comparison participants. We concluded that when stereotype knowledge is not made salient, it does not automatically affect pragmatic communicative processes in individuals with HFA/AS. C1 [Zalla, Tiziana; Ervas, Francesca] Ecole Normale Super, CNRS, Inst Jean Nicod, Inst Etud Cognit,UMR 8129, Paris, France. [Amsellem, Frederique; Chaste, Pauline; Leboyer, Marion] Hop Henri Mondor, INSERM, IMRB, U955, F-94010 Creteil, France. [Amsellem, Frederique; Chaste, Pauline; Leboyer, Marion] Univ Paris Est Creteil, Henri Mondor Albert Chenevier Hosp, AP HP, Dept Psychiat,Fdn FondaMental,French Natl Sci Fdn, Creteil, France. [Champagne-Lavau, Maud] Aix Marseille Univ, CNRS, LPL UMR 7309, F-13100 Aix En Provence, France. RP Zalla, T (reprint author), Ecole Normale Super, CNRS, Inst Jean Nicod, Inst Etud Cognit,UMR 8129, Paris, France. EM tiziana.zalla@ens.fr FU Fondation FondaMental and Fondation Orange; "Ville de Paris'' research grant; Fonds de la Recherche en Sante du Quebec grant; Agence Nationale de la Recherche grant [ANR-11-BSH2-006-01] FX This research was supported by Fondation FondaMental and Fondation Orange to TZ and ML, and by a "Ville de Paris'' research grant to FE, and by a Fonds de la Recherche en Sante du Quebec grant and the Agence Nationale de la Recherche grant ( ANR-11-BSH2-006-01) to MC-L. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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The endocannabinoid system is a key regulator of the immune system via the cannabinoid receptor type 2 (CB2R) which is highly expressed on macrophages and microglial cells. We have previously published significant differences in peripheral blood mononuclear cell CB2R gene expression in the autism population. The use of the Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation has demonstrated positive effects in the treatment of autistic children. In this current study, we investigated the in vitro effects of GcMAF treatment on the endocannabinoid system gene expression, as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from autistic patients compared to age-matched healthy developing controls. Methods: To achieve these goals, we used biomolecular, biochemical and immunocytochemical methods. Results: GcMAF treatment was able to normalize the observed differences in dysregulated gene expression of the endocannabinoid system of the autism group. GcMAF also down-regulated the over-activation of BMDMs from autistic children. Conclusions: This study presents the first observations of GcMAF effects on the transcriptionomics of the endocannabinoid system and expression of CB2R protein. These data point to a potential nexus between endocannabinoids, vitamin D and its transporter proteins, and the immune dysregulations observed with autism. C1 [Siniscalco, Dario] Univ Naples 2, Dept Expt Med, I-80138 Naples, Italy. [Siniscalco, Dario] Ctr Autism La Forza Silenzio, I-81036 Caserta, Italy. [Siniscalco, Dario] Cancellautismo No Profit Assoc Autism Care, I-50132 Florence, Italy. [Bradstreet, James Jeffrey] Brain Treatment Ctr Atlanta, Atlanta, GA 30518 USA. [Bradstreet, James Jeffrey] Western Univ Hlth Sci, Pomona, CA 91766 USA. [Cirillo, Alessandra] Natl Res Council Italy, Inst Biosci & Bioresources, I-80128 Naples, Italy. [Antonucci, Nicola] Biomed Ctr Autism Res & Treatment, I-70126 Bari, Italy. RP Siniscalco, D (reprint author), Univ Naples 2, Dept Expt Med, Via S Maria di Costantinopoli 16, I-80138 Naples, Italy. 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Okonkwo, Obi TI Deletion of PTEN produces autism-like behavioral deficits and alterations in synaptic proteins SO FRONTIERS IN MOLECULAR NEUROSCIENCE LA English DT Article DE Pten; PI3K/AKT/mTOR; FMRP; Kv4.2; autism spectrum disorders; autism; repetitive behavior; mGluR ID FRAGILE-X-SYNDROME; MENTAL-RETARDATION PROTEIN; TUBEROUS SCLEROSIS COMPLEX; LHERMITTE-DUCLOS-DISEASE; KNOCKOUT MOUSE MODEL; SPECTRUM DISORDERS; POTASSIUM CHANNELS; SOCIAL-INTERACTION; PYRAMIDAL NEURONS; MAMMALIAN TARGET AB Many genes have been implicated in the underlying cause of autism but each gene accounts for only a small fraction of those diagnosed with autism. There is increasing evidence that activity-dependent changes in neuronal signaling could act as a convergent mechanism for many of the changes in synaptic proteins. One candidate signaling pathway that may have a critical role in autism is the PI3K/AKT/mTOR pathway. A major regulator of this pathway is the negative repressor phosphatase and tensin homolog (PTEN). In the current study we examined the behavioral and molecular consequences in mice with neuron subset-specific deletion of PTEN. The knockout (KO) mice showed deficits in social chamber and social partition test. KO mice demonstrated alterations in repetitive behavior, as measured in the marble burying test and hole-board test. They showed no changes in ultrasonic vocalizations emitted on postnatal day 10 or 12 compared to wildtype (WT) mice. They exhibited less anxiety in the elevated-plus maze test and were more active in the open field test compared to WT mice. In addition to the behavioral alterations, KO mice had elevation of phosphorylated AKT, phosphorylated S6, and an increase in S6K. KO mice had a decrease in mGluR but an increase in total and phosphorylated fragile X mental retardation protein. The disruptions in intracellular signaling may be why the KO mice had a decrease in the dendritic potassium channel Kv4.2 and a decrease in the synaptic scaffolding proteins PSD-95 and SAP102. These findings demonstrate that deletion of PTEN results in long-term alterations in social behavior, repetitive behavior, activity, and anxiety. In addition, deletion of PTEN significantly alters mGluR signaling and many synaptic proteins in the hippocampus. Our data demonstrates that deletion of PTEN can result in many of the behavioral features of autism and may provide insights into the regulation of intracellular signaling on synaptic proteins. C1 [Lugo, Joaquin N.; White, Jessika; Holley, Andrew J.; Floruta, Crina M.; Ahmed, Nowrin; Gomez, Maribel C.; Okonkwo, Obi] Baylor Univ, Dept Psychol & Neurosci, Waco, TX 76798 USA. [Lugo, Joaquin N.; Smith, Gregory D.; Arbuckle, Erin P.] Baylor Univ, Inst Biomed Studies, Waco, TX 76798 USA. RP Lugo, JN (reprint author), Baylor Univ, Dept Psychol & Neurosci, One Bear Pl 97334, Waco, TX 76798 USA. EM joaquin_lugo@baylor.edu FU Baylor University Research Council grant; Baylor University Young Investigator Developmental Program grant; Epilepsy Foundation FX This study was supported from a Baylor University Research Council grant, Baylor University Young Investigator Developmental Program grant, and a research grant from the Epilepsy Foundation. We would also like to acknowledge the Baylor University Molecular Biosciences Center for the use of equipment used for this study and to acknowledge Dr, Brad Keele for the use of the Noldus Ethovision equipment for the behavioral studies. 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Molec. Neurosci. PD APR 16 PY 2014 VL 7 AR 27 DI 10.3389/fnmol.2014.00027 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AZ0YT UT WOS:000347968500001 PM 24795561 ER PT J AU Fusaro, VA Daniels, J Duda, M DeLuca, TF D'Angelo, O Tamburello, J Maniscalco, J Wall, DP AF Fusaro, Vincent A. Daniels, Jena Duda, Marlena DeLuca, Todd F. D'Angelo, Olivia Tamburello, Jenna Maniscalco, James Wall, Dennis P. TI The Potential of Accelerating Early Detection of Autism through Content Analysis of YouTube Videos SO PLOS ONE LA English DT Article ID DIAGNOSTIC OBSERVATION SCHEDULE; SPECTRUM DISORDER; HOME VIDEOTAPES; HIGH-RISK; INFANTS; CHILDREN; AGE; TODDLERS; PATTERNS; 1ST AB Autism is on the rise, with 1 in 88 children receiving a diagnosis in the United States, yet the process for diagnosis remains cumbersome and time consuming. Research has shown that home videos of children can help increase the accuracy of diagnosis. However the use of videos in the diagnostic process is uncommon. In the present study, we assessed the feasibility of applying a gold-standard diagnostic instrument to brief and unstructured home videos and tested whether video analysis can enable more rapid detection of the core features of autism outside of clinical environments. We collected 100 public videos from YouTube of children ages 1-15 with either a self-reported diagnosis of an ASD (N = 45) or not (N = 55). Four non-clinical raters independently scored all videos using one of the most widely adopted tools for behavioral diagnosis of autism, the Autism Diagnostic Observation Schedule-Generic (ADOS). The classification accuracy was 96.8%, with 94.1% sensitivity and 100% specificity, the inter-rater correlation for the behavioral domains on the ADOS was 0.88, and the diagnoses matched a trained clinician in all but 3 of 22 randomly selected video cases. Despite the diversity of videos and non-clinical raters, our results indicate that it is possible to achieve high classification accuracy, sensitivity, and specificity as well as clinically acceptable inter-rater reliability with nonclinical personnel. Our results also demonstrate the potential for video-based detection of autism in short, unstructured home videos and further suggests that at least a percentage of the effort associated with detection and monitoring of autism may be mobilized and moved outside of traditional clinical environments. C1 [Fusaro, Vincent A.; Daniels, Jena; Duda, Marlena; DeLuca, Todd F.; D'Angelo, Olivia; Tamburello, Jenna; Maniscalco, James; Wall, Dennis P.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02138 USA. [Wall, Dennis P.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Daniels, Jena; Duda, Marlena; Wall, Dennis P.] Stanford Univ, Dept Pediat, Div Syst Med, Stanford, CA 94305 USA. RP Wall, DP (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02138 USA. EM dpwall@stanford.edu FU Simons Foundation; Nancy Lurie Marks Family Foundation; Harvard Catalyst Program; National Institutes of Health [1R01MH090611-01A1]; National Library of Medicine [1K99LM011020-01] FX Work was supported in part by funds to DPW from the Simons Foundation, Nancy Lurie Marks Family Foundation, the Harvard Catalyst Program, and grant 1R01MH090611-01A1 from the National Institutes of Health. VAF was supported by grant 1K99LM011020-01 from the National Library of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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We report on a 9-year-old boy who presented with developmental delay, autism spectrum disorder, short stature, mild macrocephaly, lower facial weakness, hypertelorism, downward slanting palpebral fissures, brachydactyly, and clinodactyly. SNP-microarray analysis revealed 516 kb microduplication at 13q31.3 involving the entire MIR17HG gene encoding the miR-17 similar to 92 polycistronic miRNA cluster, and the first five exons of the GPC5 gene. Family study confirmed that the microduplication was maternally inherited by the proband and one of his five half-brothers; digit and other skeletal anomalies were exclusive to the family members harboring the microduplication. This case represents the smallest reported microduplication to date at 13q31.3 and provides evidence supporting the important role of miR-17 similar to 92 gene dosage in normal growth and skeletal development. 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Cytogenet. PD APR 16 PY 2014 VL 7 AR 27 DI 10.1186/1755-8166-7-27 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AG3TX UT WOS:000335343800001 PM 24739087 ER PT J AU Galicia-Connolly, E Adams, D Bateman, J Dagenais, S Clifford, T Baydala, L King, WJ Vohra, S AF Galicia-Connolly, Elaine Adams, Denise Bateman, Justin Dagenais, Simon Clifford, Tammy Baydala, Lola King, W. James Vohra, Sunita TI CAM Use in Pediatric Neurology: An Exploration of Concurrent Use with Conventional Medicine SO PLOS ONE LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ALTERNATIVE MEDICINE; SPECTRUM DISORDER; THERAPY USE; COMPLEMENTARY; CHILDREN; EPILEPSY; CANCER; ILLNESS; AUTISM AB Background: Previous studies have found that up to 60% of children with neurologic conditions have tried complementary and alternative medicine (CAM). Objective: To assess the use of CAM among patients presenting to neurology clinics at two academic centers in Canada. Methods: A survey instrument was developed to inquire about use of CAM products and therapies, including reasons for use, perceived helpfulness, and concurrent use with conventional medicine, and administered to patients or their parents/guardians at the Stollery Children's Hospital in Edmonton and the Children's Hospital of Eastern Ontario (CHEO) in Ottawa. Results: Overall CAM use at the Stollery was 78%, compared to 48% at CHEO. The most common CAM products used were multi-vitamins (84%), vitamin C (37%), homeopathic remedies (24%), and fish oil/omega 3 s (22%). The most common CAM practices used were massage (47%), chiropractic (37%), faith healing (18%), aromatherapy (16%), homeopathy (16%), and relaxation (16%). Many patients used CAM products at the same time as conventional medicine but just over half (57%) discussed this concurrent use with their physician. Conclusion: CAM use is common in pediatric neurology patients and most respondents felt that it was helpful, with few or no harms associated. However, this use is often undisclosed, increasing possibility of interactions with conventional drugs. We urge clinicians to inquire about CAM use during routine history taking at every patient visit. Parents would clearly like more information about CAM from their specialty clinics; such information would be easier to share if more primary data were available about the safety and effectiveness of commonly used therapies. C1 [Galicia-Connolly, Elaine; Adams, Denise] Univ Alberta, Dept Pediat, CARE Program, Edmonton, AB, Canada. [Bateman, Justin] Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada. [Dagenais, Simon] Palladian Hlth, West Seneca, NY USA. [Clifford, Tammy] Univ Ottawa, Dept Pediat, Ottawa, ON K1N 6N5, Canada. [Clifford, Tammy] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Clifford, Tammy] Canadian Agcy Drugs & Technol Hlth, Ottawa, ON, Canada. [Clifford, Tammy; Baydala, Lola] Univ Alberta, Dept Pediat, Fac Med & Dent, Edmonton, AB, Canada. [King, W. James] Univ Ottawa, Dept Pediat, Div Pediat Med, Ottawa, ON K1N 6N5, Canada. [King, W. James] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. [Vohra, Sunita] Univ Alberta, Dept Pediat, PedCAM Network, Fac Med & Dent,CARE Program, Edmonton, AB, Canada. [Vohra, Sunita] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada. RP Vohra, S (reprint author), Univ Alberta, Dept Pediat, PedCAM Network, Fac Med & Dent,CARE Program, Edmonton, AB, Canada. EM svohra@ualberta.ca FU SickKids Foundation; Alberta Innovates-Health Solutions FX This project was supported by a grant from the SickKids Foundation. Sunita Vohra receives salary support from Alberta Innovates-Health Solutions (formerly Alberta Heritage Foundation for Medical Research), which is a government agency that supports research in Alberta. 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 Heat Shock Alters the Expression of Schizophrenia and Autism Candidate Genes in an Induced Pluripotent Stem Cell Model of the Human Telencephalon SO PLOS ONE LA English DT Article ID CARDIO-FACIAL SYNDROME; MATERNAL IMMUNE ACTIVATION; NERVE GROWTH-FACTOR; GENOME-WIDE ASSOCIATION; COPY NUMBER VARIATIONS; SPECTRUM DISORDERS; PREFRONTAL CORTEX; BIPOLAR DISORDER; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE AB Schizophrenia (SZ) and autism spectrum disorders (ASD) are highly heritable neuropsychiatric disorders, although environmental factors, such as maternal immune activation (MIA), play a role as well. Cytokines mediate the effects of MIA on neurogenesis and behavior in animal models. However, MIA stimulators can also induce a febrile reaction, which could have independent effects on neurogenesis through heat shock (HS)-regulated cellular stress pathways. However, this has not been well-studied. To help understand the role of fever in MIA, we used a recently described model of human brain development in which induced pluripotent stem cells (iPSCs) differentiate into 3-dimensional neuronal aggregates that resemble a first trimester telencephalon. RNA-seq was carried out on aggregates that were heat shocked at 39 degrees C for 24 hours, along with their control partners maintained at 37 degrees C. 186 genes showed significant differences in expression following HS (p<0.05), including known HS-inducible genes, as expected, as well as those coding for NGFR and a number of SZ and ASD candidates, including SMARCA2, DPP10, ARNT2, AHI1 and ZNF804A. The degree to which the expression of these genes decrease or increase during HS is similar to that found in copy loss and copy gain copy number variants (CNVs), although the effects of HS are likely to be transient. The dramatic effect on the expression of some SZ and ASD genes places HS, and perhaps other cellular stressors, into a common conceptual framework with disease-causing genetic variants. The findings also suggest that some candidate genes that are assumed to have a relatively limited impact on SZ and ASD pathogenesis based on a small number of positive genetic findings, such as SMARCA2 and ARNT2, may in fact have a much more substantial role in these disorders - as targets of common environmental stressors. C1 [Lin, Mingyan; Zheng, Deyou; Lachman, Herbert M.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA. [Zhao, Dejian; Zheng, Deyou] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. [Hrabovsky, Anastasia; Pedrosa, Erika; Lachman, Herbert M.] Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA. [Zheng, Deyou; Lachman, Herbert M.] Albert Einstein Coll Med, Dominick Purpura Dept Neurosci, Bronx, NY 10467 USA. [Lachman, Herbert M.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Zheng, DY (reprint author), Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA. EM deyou.zheng@einstein.yu.edu; herb.lachman@einstein.yu.edu FU National Institute of Mental Health [MH073164, MH097893, MH087840] FX This work was supported by the National Institute of Mental Health (MH073164, MH097893 and MH087840). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Zhao HP, 2012, ADV PHARMACOL, V64, P1, DOI 10.1016/B978-0-12-394816-8.00001-5 NR 145 TC 2 Z9 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 15 PY 2014 VL 9 IS 4 AR e94968 DI 10.1371/journal.pone.0094968 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI5PW UT WOS:000336922600115 PM 24736721 ER PT J AU Anagnostou, E Zwaigenbaum, L Szatmari, P Fombonne, E Fernandez, BA Woodbury-Smith, M Brian, J Bryson, S Smith, IM Drmic, I Buchanan, JA Roberts, W Scherer, SW AF Anagnostou, Evdokia Zwaigenbaum, Lonnie Szatmari, Peter Fombonne, Eric Fernandez, Bridget A. Woodbury-Smith, Marc Brian, Jessica Bryson, Susan Smith, Isabel M. Drmic, Irene Buchanan, Janet A. Roberts, Wendy Scherer, Stephen W. TI Autism spectrum disorder: advances in evidence-based practice SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Review ID PERVASIVE DEVELOPMENTAL DISORDERS; SOCIAL COMMUNICATION QUESTIONNAIRE; INTENSIVE BEHAVIORAL INTERVENTION; MODIFIED CHECKLIST; EARLY IDENTIFICATION; MEDICAL DISORDERS; RISK-FACTORS; LARGE-SCALE; CHILDREN; TODDLERS C1 [Roberts, Wendy] Univ Toronto, Holland Bloorview Kids Rehabil Ctr, Toronto, ON, Canada. [Anagnostou, Evdokia; Brian, Jessica] Univ Toronto, Bloorview Res Inst, Toronto, ON, Canada. [Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. [Zwaigenbaum, Lonnie] Univ Alberta, Dept Pediat, Edmonton, AB, Canada. [Szatmari, Peter] Hosp Sick Children, Dept Psychiat, Toronto, ON M5G 1X8, Canada. [Drmic, Irene; Roberts, Wendy] Hosp Sick Children, Austism Res Unit, Toronto, ON M5G 1X8, Canada. [Buchanan, Janet A.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. [Szatmari, Peter] Ctr Addict & Mental Hlth, Dept Child & Adolescent Psychiat, Toronto, ON, Canada. [Fombonne, Eric] Montreal Childrens Hosp, Dept Psychiat, Montreal, PQ H3H 1P3, Canada. [Fombonne, Eric] McGill Univ, Montreal, PQ, Canada. [Fernandez, Bridget A.] Mem Univ Newfoundland, Discipline Genet, St John, NF, Canada. [Fernandez, Bridget A.] Mem Univ Newfoundland, Discipline Med, St John, NF, Canada. [Woodbury-Smith, Marc] McMaster Univ, Hamilton, ON, Canada. [Drmic, Irene] McMaster Univ, Offord Ctr Child Studies, Hamilton, ON, Canada. [Bryson, Susan; Smith, Isabel M.] Dalhousie Univ, Halifax, NS, Canada. [Bryson, Susan; Smith, Isabel M.] IWK Hlth Ctr, Autism Res Ctr, Halifax, NS, Canada. RP Scherer, SW (reprint author), Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. EM eanagnostou@hollandbloorview.ca; stephen.scherer@sickkids.ca RI Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU University of Toronto McLaughlin Centre FX Janet Buchanan's work on this article was supported by funds from the University of Toronto McLaughlin Centre. Lonnie Zwaigenbaum holds the Stollery Children's Hospital Foundation Chair in Autism. Peter Szatmari holds the Jamie and Patsy Anderson Chair in Child and Youth Mental Health at the Hospital for Sick Children, Centre for Addiction and Mental Health and University of Toronto. Eric Fombonne holds the Monique H. Bourgeois Chair for Research on Pervasive Developmental Disorders and a Canada Research Chair in Child Psychiatry Tier I. Susan Bryson holds the Joan and Jack Craig Chair in Autism Research at Dalhousie University. Stephen Scherer holds the GlaxoSmithKline Canadian Institutes of Health Research Pathfinder Chair in Genome Sciences at the University of Toronto and the Hospital for Sick Children. 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Med. Assoc. J. PD APR 15 PY 2014 VL 186 IS 7 BP 509 EP 519 DI 10.1503/cmaj.121756 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AE9BJ UT WOS:000334298500017 PM 24418986 ER PT J AU Lamperski, T AF Lamperski, Terry TI The Other Half of Asperger Syndrome (Autism Spectrum Disorder): A Guide to Living in an Intimate Relationship with a Partner Who Is on the Autism Spectrum SO LIBRARY JOURNAL LA English DT Book Review C1 [Lamperski, Terry] Carnegie Lib Pittsburgh, Pittsburgh, PA 15213 USA. RP Lamperski, T (reprint author), Carnegie Lib Pittsburgh, Pittsburgh, PA 15213 USA. CR ASTON M, 2014, OTHER HALF ASPERGER NR 1 TC 0 Z9 0 PU REED BUSINESS INFORMATION PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD APR 15 PY 2014 VL 139 IS 7 BP 98 EP 98 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA AE8PJ UT WOS:000334263500210 ER PT J AU Lazar, SM Evans, DW Myers, SM Moreno-De Luca, A Moore, GJ AF Lazar, Steven M. Evans, David W. Myers, Scott M. Moreno-De Luca, Andres Moore, Gregory J. TI Social cognition and neural substrates of face perception: Implications for neurodevelopmental and neuropsychiatric disorders SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE FMRI; Face processing; Autism spectrum disorder; Social cognition; Quantitative traits ID HIGH-FUNCTIONING AUTISM; EVENT-RELATED POTENTIALS; NORMAL SEX-DIFFERENCES; GENERAL-POPULATION; ASPERGER-SYNDROME; SYSTEMATIZING QUOTIENT; INDIVIDUAL-DIFFERENCES; SPECTRUM DISORDERS; MULTIPLE-INCIDENCE; CHILDRENS RITUALS AB Background: Social cognition is an important aspect of social behavior in humans. Social cognitive deficits are associated with neurodevelopmental and neuropsychiatric disorders. In this study we examine the neural substrates of social cognition and face processing in a group of healthy young adults to examine the neural substrates of social cognition. Methods: Fifty-seven undergraduates completed a battery of social cognition tasks and were assessed with electroencephalography (EEG) during a face-perception task. A subset (N=22) were administered a face-perception task during functional magnetic resonance imaging. Results: Variance in the N170 EEG was predicted by social attribution performance and by a quantitative measure of empathy. Neurally, face processing was more bilateral in females than in males. Variance in fMRI voxel count in the face-sensitive fusiform gyrus was predicted by quantitative measures of social behavior, including the Social Responsiveness Scale (SRS) and the Empathizing Quotient. Conclusions: When measured as a quantitative trait, social behaviors in typical and pathological populations share common neural pathways. The results highlight the importance of viewing neurodevelopmental and neuropsychiatric disorders as spectrum phenomena that may be informed by studies of the normal distribution of relevant traits in the general population. (C) 2014 Elsevier B.V. All rights reserved. C1 [Lazar, Steven M.; Evans, David W.; Myers, Scott M.; Moreno-De Luca, Andres; Moore, Gregory J.] Geisinger Bucknell Autism & Dev Med Ctr, Lewisburg, PA 17837 USA. RP Evans, DW (reprint author), Geisinger Bucknell Autism & Dev Med Ctr, 120 Hamm Dr, Lewisburg, PA 17837 USA. EM dwevans@bucknell.edu FU Bucknell-Geisinger Research Initiative Grant (BGRI) FX None of the authors reports any biomedical financial interests or potential conflicts of interest. The authors acknowledge financial support from the Bucknell-Geisinger Research Initiative Grant (BGRI), awarded to DWE and GJM. 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Brain Res. PD APR 15 PY 2014 VL 263 BP 1 EP 8 DI 10.1016/j.bbr.2014.01.010 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AE3NR UT WOS:000333883700001 PM 24462962 ER PT J AU Merali, Z Presti-Torres, J MacKay, JC Johnstone, J Du, L St-Jean, A Levesque, D Kent, P Schwartsmann, G Roesler, R Schroder, N Anisman, H AF Merali, Z. Presti-Torres, J. MacKay, J. C. Johnstone, J. Du, L. St-Jean, A. Levesque, D. Kent, P. Schwartsmann, G. Roesler, R. Schroder, N. Anisman, H. TI Long-term behavioral effects of neonatal blockade of gastrin-releasing peptide receptors in rats: Similarities to autism spectrum disorders SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Gastrin-releasing peptide receptor; RC-3095; Social interaction; Restrictive behavior; Learned fear; Autism spectrum disorder ID BOMBESIN-RELATED PEPTIDES; MEMORY CONSOLIDATION; NEURODEVELOPMENTAL DISORDERS; ANTAGONIST RC-3095; EXTENDED AMYGDALA; CONDITIONED FEAR; BIPOLAR DISORDER; CINGULATE CORTEX; SOCIAL APPROACH; MOUSE MODELS AB Gastrin releasing peptide, the mammalian counterpart of the amphibian peptide, bombesin, has been increasingly implicated in regulating normal brain function as well as in the pathogenesis of psychiatric and/or neurodevelopmental disorders. We have previously shown that the neonatal blockade of the gastrin-releasing peptide receptor (GRPr) in rats produces long-lasting consequences during central nervous system development that are commonly observed in neurodevelopmental disorders such as autism spectrum disorders. The present investigation assessed in further detail, long-term behavioral effects of neonatal GRPr blockade. During postnatal days 1-10, male Wistar rat pups (n = 5-10/litter) were injected (subcutaneously) with the GRPr antagonist, RC-3095 (1 mg/kg), or a vehicle (control), twice daily. Following the drug treatment regimen, several behaviors were assessed (starting on postnatal day 14) including specific social behaviors (namely, group huddling characteristics, social interaction, and social approach), restrictive/repetitive and stereotyped behaviors (y-maze, repetitive novel object contact task, observation for stereotypies) and anxiety/fear-related responses (open field, elevated plus maze and contextual fear conditioning). Rats treated neonatally with RC-3095 showed reduced sociability, restrictive interests, motor stereotypies and enhanced learned fear response compared to the controls (vehicle-treated rats). These behavioral abnormalities are consistent with those observed in autism spectrum disorders and provide further evidence that neonatal blockade of GRPr could potentially serve as a useful model to gain a better understanding of the underlying neurodevelopmental disruptions contributing to the expression of autism-relevant phenotypes. (C) 2014 Elsevier B.V. All rights reserved. C1 [Merali, Z.; MacKay, J. C.; Johnstone, J.; St-Jean, A.; Levesque, D.; Kent, P.] Univ Ottawa, Sch Psychol, Ottawa, ON K1N 6N5, Canada. [Merali, Z.] Univ Ottawa, Dept Psychiat, Ottawa, ON K1N 6N5, Canada. [Merali, Z.] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1N 6N5, Canada. [Anisman, H.] Carleton Univ, Inst Neurosci, Ottawa, ON K1S 5B6, Canada. [Merali, Z.; Presti-Torres, J.; MacKay, J. C.; Johnstone, J.; Du, L.; Kent, P.; Anisman, H.] Univ Ottawa, Mental Hlth Res Inst, Ottawa, ON K1Z 7K4, Canada. [Presti-Torres, J.; Schroder, N.] Pontifical Catholic Univ, Neurobiol & Dev Biol Lab, BR-90619900 Porto Alegre, RS, Brazil. [Schwartsmann, G.] Univ Fed Rio Grande do Sul, Sch Med, Dept Internal Med, BR-90035003 Porto Alegre, RS, Brazil. [Schwartsmann, G.; Roesler, R.] Univ Fed Rio Grande do Sul, Univ Hosp Res Ctr CPE HCPA, Canc Res Lab, BR-90035003 Porto Alegre, RS, Brazil. [Schwartsmann, G.; Roesler, R.; Schroder, N.] Natl Inst Translat Med INCT TM, BR-90035003 Porto Alegre, RS, Brazil. [Roesler, R.] Univ Fed Rio Grande do Sul, Inst Basic Hlth Sci, Dept Pharmacol, Lab Neuropharmacol & Neural Tumor Biol, BR-90050170 Porto Alegre, RS, Brazil. RP Merali, Z (reprint author), Univ Ottawa, Mental Hlth Res Inst, 1145 Carling Ave Rm 5432,Res Tower, Ottawa, ON K1Z 7K4, Canada. EM merali@uottawa.ca FU Canadian Institute of Health Research (CIHR); CNPq FX Technical contributions of Sarah Paluck, Samantha Graitson, Kaitlin Baenziger, Kelsey Johnston, Christian Cayer and Jonathan James are gratefully acknowledged. This research was supported by the Canadian Institute of Health Research (CIHR). J.P.T. is supported by a CNPq fellowship. 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Brain Res. PD APR 15 PY 2014 VL 263 BP 60 EP 69 DI 10.1016/j.bbr.2014.01.008 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AE3NR UT WOS:000333883700008 PM 24462726 ER PT J AU Kim, DS Ross, PJ Zaslavsky, K Ellis, J AF Kim, Dae-Sung Ross, P. 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Recent advances in induced pluripotent stem cell (iPSC) technology and neural differentiation techniques allow for detailed functional analyses of neurons generated from living individuals with ASD. Refinement of cortical neuron differentiation methods from iPSCs will enable mechanistic studies of specific neuronal subpopulations that may be preferentially impaired in ASD. In this review, we summarize recent accomplishments in differentiation of cortical neurons from human pluripotent stems cells and efforts to establish in vitro model systems to study ASD using personalized neurons. C1 [Kim, Dae-Sung; Ross, P. Joel; Zaslavsky, Kirill; Ellis, James] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 0A4, Canada. [Zaslavsky, Kirill; Ellis, James] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. RP Ellis, J (reprint author), Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Program Dev & Stem Cell Biol, Room 16-9-715,686 Bay St, Toronto, ON M5G 0A4, Canada. EM jellis@sickkids.ca RI Ellis, James/F-4789-2011 FU Canadian Institutes of Health Research [EPS-129129]; Ontario Brain Institute; Canadian Institute for Military and Veteran Health Research [W7714-125624/001/SV]; National Institutes of Health [R33MH087908]; National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2012039296]; Ontario Stem Cell Initiative; Canada Vanier Graduate Scholarship FX The authors thank Wesley Lai and Ugljesa Djuric for comments on the manuscript. This work was supported by grants from the Canadian Institutes of Health Research (EPS-129129), the Ontario Brain Institute, Canadian Institute for Military and Veteran Health Research (W7714-125624/001/SV), and the National Institutes of Health (R33MH087908). Dae-Sung Kim was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (#2012039296). P. Joel Ross was supported by postdoctoral fellowships from the Ontario Stem Cell Initiative and Kirill Zaslavsky was funded by the Canada Vanier Graduate Scholarship. 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PD APR 11 PY 2014 VL 8 AR 109 DI 10.3389/fncel.2014.00109 PG 16 WC Neurosciences SC Neurosciences & Neurology GA AE9PR UT WOS:000334340600001 PM 24782713 ER PT J AU Gabryel, B Kapalka, A Sobczyk, W Labuzek, K Gaweda, A Janas-Kozik, M AF Gabryel, Bozena Kapalka, Agata Sobczyk, Wojciech Labuzek, Krzysztof Gaweda, Agnieszka Janas-Kozik, Malgorzata TI Dysregulation of the mTOR signaling pathway in the pathogenesis of autism spectrum disorders SO POSTEPY HIGIENY I MEDYCYNY DOSWIADCZALNEJ LA Polish DT Review DE autism spectrum disorders; mTOR signaling pathway; rapamycin ID TUBEROUS SCLEROSIS COMPLEX; FRAGILE-X-SYNDROME; ACTIVATED PROTEIN-KINASE; NEUROFIBROMATOSIS TYPE-1; COGNITIVE DEFICITS; LEARNING-DEFICITS; BINDING PARTNER; COWDEN-SYNDROME; NERVOUS-SYSTEM; RAPAMYCIN TOR AB Mammalian target of rapamycin (mTor) plays multiple role in central nervous system and is involved in regulation of cell viability, differentiation, transcription, translation, protein degradation, actin cytoskeletal organization and autophagy. Recent experimental and clinical studies reveal that disturbances of mTOR signaling are involved in the pathogenesis of autism spectrum disorders (ASD). This article reviews current data on the alteration in the mTOR transduction cascade, which may contribute to common neurobehavioral disorders typical for ASD. Moreover, the results of the latest experimental studies on the potential of mTOR inhibitors for the treatment of ASD are reviewed. C1 [Gabryel, Bozena; Kapalka, Agata; Sobczyk, Wojciech] Slaski Uniwersytet Med, Zaklad Farmakol Katedry Farmakol, Wydzial Lekarski Katowicach, PL-40752 Katowice, Poland. [Labuzek, Krzysztof] Slaski Uniwersytet Med, Klin Chorob Wewnetrznych & Farmakol, Wydzial Lekarski Katowicach, Klin Katedry Farmakol, PL-40752 Katowice, Poland. [Gaweda, Agnieszka; Janas-Kozik, Malgorzata] Slaski Uniwersytet Med, Oddzial Klin Psychiat & Psychoterapii Wieku Rozwo, PL-40752 Katowice, Poland. [Janas-Kozik, Malgorzata] Slaski Uniwersytet Med, Katedra Psychiat & Psychoterapii, PL-40752 Katowice, Poland. RP Gabryel, B (reprint author), Slaski Uniwersytet Med, Zaklad Farmakol Katedry Farmakol, Ul Medykow 18, PL-40752 Katowice, Poland. 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Hig. Med. Dosw. PD APR 10 PY 2014 VL 68 BP 375 EP 383 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AK7VQ UT WOS:000338636200001 PM 24864089 ER PT J AU Zampieri, BL Fernandez, F Pearson, JN Stasko, MR Costa, ACS AF Zampieri, Bruna L. Fernandez, Fabian Pearson, Jennifer N. Stasko, Melissa R. Costa, Alberto C. S. TI Ultrasonic vocalizations during male-female interaction in the mouse model of Down syndrome Ts65Dn SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Down syndrome; Ultrasonic vocalizations; Ts65Dn; Speech impairment; Mouse models; Intellectual disability; USV; Spectral analysis; Voice; Sonograms ID FRAGILE-X-SYNDROME; SYNDROME CHILDREN; COMMUNICATION CALLS; LANGUAGE IMPAIRMENT; MICE; INDIVIDUALS; DISORDER; RODENTS; SPEECH; AUTISM AB Down syndrome (DS) is the leading cause of genetically defined intellectual disability. Although speech and language impairments are salient features of this disorder, the nature of these phenotypes and the degree to which they are exacerbated by concomitant oromotor dysfunction and/or hearing deficit are poorly understood. Mouse models like Ts65Dn, the most extensively used DS animal model, have been critical to understanding the genetic and developmental mechanisms that contribute to intellectual disability. In the present study, we characterized the properties of the ultrasonic vocalizations (USVs) emitted by Ts65Dn males during courtship episodes with female partners. USVs emitted by mice in this setting have been proposed to have some basic correlation to human speech. Data were collected and analyzed from 22 Ts65Dn mice and 22 of their euploid littermates. We found that both the minimum and maximum peak frequencies of Ts65Dn calls were lower than those produced by euploid mice, whereas the mean individual duration of "down" and "complex" syllable types was significantly longer. Peak, minimal and maximal, and the fundamental frequencies of short syllables generated by Ts65Dn mice were lower compared to those by euploid mice. Finally, Ts65Dn males made fewer multiple jumps calls during courtship and the mean total duration of their "arc", "u", and "complex" syllables was longer. We discuss the human correlates to these findings, their translational potential, and the limitations of this approach. To our knowledge, this is the first characterization of differences between adult Ts65Dn and euploid control mice with respect to USVs. (C) 2014 Elsevier Inc. All rights reserved. C1 [Zampieri, Bruna L.] Fac Med Sao Jose Rio Preto, Unidade Pesquisa Biol Mol & Genet, Sao Paulo, Brazil. [Zampieri, Bruna L.; Stasko, Melissa R.; Costa, Alberto C. S.] Case Western Reserve Univ, Dept Pediat, Div Pediat Neurol, Cleveland, OH 44106 USA. [Fernandez, Fabian] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. [Pearson, Jennifer N.] Univ Colorado, Neurosci Program, Aurora, CO USA. RP Costa, ACS (reprint author), Case Western Reserve Univ, Dept Pediat, Div Pediat Neurol, 11100 Euclid Ave,Mail Stop RBC 6090, Cleveland, OH 44106 USA. EM alberto.costa@case.edu FU Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil [CAPES 0191-12-4] FX The present study was supported in part by the Fondation Jerome Lejeune (FF, ACSC), Instituto Alana (ACSC), and the Awakening Angles Foundation (ACSC). B. L Zampieri was the recipient of a fellowship from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES 0191-12-4), Brazil. We thank Dr. Daniel Tollin at the University of Colorado for generously providing the ultrasound sensitive microphone used in the experiments described here. The authors have no conflicts of interest to declare. 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Behav. PD APR 10 PY 2014 VL 128 BP 119 EP 125 DI 10.1016/j.physbeh.2014.02.020 PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA AG0LE UT WOS:000335106200018 PM 24534182 ER PT J AU Madden, AMK Zup, SL AF Madden, Amanda M. K. Zup, Susan L. TI Effects of developmental hyperserotonemia on juvenile play behavior, oxytocin and serotonin receptor expression in the hypothalamus are age and sex dependent SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Serotonin receptor; Oxytocin; Juvenile play behavior; Sex difference; Autism; Hypothalamus ID MESSENGER-RNA EXPRESSION; FINCH SONG SYSTEM; SOCIAL PLAY; PARAVENTRICULAR NUCLEUS; RAT-BRAIN; 17-BETA-ESTRADIOL TREATMENT; HORSERADISH-PEROXIDASE; SPECTRUM DISORDERS; GONADAL-STEROIDS; PIONEER NEURONS AB There is a striking sex difference in the diagnosis of Autism Spectrum Disorder (ASD), such that males are diagnosed more often than females, usually in early childhood. Given that recent research has implicated elevated blood serotonin (hyperserotonemia) in perinatal development as a potential factor in the pathogenesis of ASD, we sought to evaluate the effects of developmental hyperserotonemia on social behavior and relevant brain morphology in juvenile males and females. Administration of 5-methoxytryptamine (5-MT) both pre- and postnatally was found to disrupt normal social play behavior in juveniles. In addition, alterations in the number of oxytocinergic cells in the lateral and medial paraventricular nucleus (PVN) were evident on postnatal day 18 (PND18) in 5-MT treated females, but not treated males. 5-MT treatment also changed the relative expression of 5-HT1A and 5-HT2A receptors in the PVN, in males at PND10 and in females at PND18. These data suggest that serotonin plays an organizing role in the development of the PVN in a sexually dimorphic fashion, and that elevated serotonin levels during perinatal development may disrupt normal organization, leading to neurochemical and behavioral changes. Importantly, these data also suggest that the inclusion of both juvenile males and females in studies will be necessary to fully understand the role of serotonin in development, especially in relation to ASD. (C) 2014 Elsevier Inc. All rights reserved. C1 Univ Massachusetts, Grad Program Dev & Brain Sci, Boston, MA 02125 USA. [Zup, Susan L.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. RP Zup, SL (reprint author), Univ Massachusetts, Dept Psychol, 100 Morrissey Blvd, Boston, MA 02125 USA. 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Behav. PD APR 10 PY 2014 VL 128 BP 260 EP 269 DI 10.1016/j.physbeh.2014.01.036 PG 10 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA AG0LE UT WOS:000335106200037 PM 24530263 ER PT J AU Correia, CT Conceicao, IC Oliveira, B Coelho, J Sousa, I Sequeira, AF Almeida, J Cafe, C Duque, F Mouga, S Roberts, W Gao, K Lowe, JK Thiruvahindrapuram, B Walker, S Marshall, CR Pinto, D Nurnberger, JI Scherer, SW Geschwind, DH Oliveira, G Vicente, AM AF Correia, Catarina T. Conceicao, Ines C. Oliveira, Barbara Coelho, Joana Sousa, Ines Sequeira, Ana F. Almeida, Joana Cafe, Catia Duque, Frederico Mouga, Susana Roberts, Wendy Gao, Kun Lowe, Jennifer K. Thiruvahindrapuram, Bhooma Walker, Susan Marshall, Christian R. Pinto, Dalila Nurnberger, John I. Scherer, Stephen W. Geschwind, Daniel H. Oliveira, Guiomar Vicente, Astrid M. TI Recurrent duplications of the annexin A1 gene (ANXA1) in autism spectrum disorders SO MOLECULAR AUTISM LA English DT Article DE ANXA1; Autism; Brain homeostasis; Copy number variants; Duplication; Glucocorticoids ID COPY NUMBER VARIATION; DE-NOVO MUTATIONS; HIDDEN-MARKOV MODEL; SNP GENOTYPING DATA; HUMAN GENOME; VARIANTS; CHILDREN; CORTISOL; GLUCOCORTICOIDS; ASSOCIATION AB Background: Validating the potential pathogenicity of copy number variants (CNVs) identified in genome-wide studies of autism spectrum disorders (ASD) requires detailed assessment of case/control frequencies, inheritance patterns, clinical correlations, and functional impact. Here, we characterize a small recurrent duplication in the annexin A1 (ANXA1) gene, identified by the Autism Genome Project (AGP) study. Methods: From the AGP CNV genomic screen in 2,147 ASD individuals, we selected for characterization an ANXA1 gene duplication that was absent in 4,964 population-based controls. We further screened the duplication in a follow-up sample including 1,496 patients and 410 controls, and evaluated clinical correlations and family segregation. Sequencing of exonic/ downstream ANXA1 regions was performed in 490 ASD patients for identification of additional variants. Results: The ANXA1 duplication, overlapping the last four exons and 3' UTR region, had an overall prevalence of 11/ 3,643 (0.30%) in unrelated ASD patients but was not identified in 5,374 controls. Duplication carriers presented no distinctive clinical phenotype. Family analysis showed neuropsychiatric deficits and ASD traits in multiple relatives carrying the duplication, suggestive of a complex genetic inheritance. Sequencing of exonic regions and the 3 ' UTR identified 11 novel changes, but no obvious variants with clinical significance. Conclusions: We provide multilevel evidence for a role of ANXA1 in ASD etiology. Given its important role as mediator of glucocorticoid function in a wide variety of brain processes, including neuroprotection, apoptosis, and control of the neuroendocrine system, the results add ANXA1 to the growing list of rare candidate genetic etiological factors for ASD. C1 [Correia, Catarina T.; Conceicao, Ines C.; Oliveira, Barbara; Coelho, Joana; Sousa, Ines; Sequeira, Ana F.; Vicente, Astrid M.] Inst Nacl Saude Doutor Ricardo Jorge, P-1649016 Lisbon, Portugal. [Correia, Catarina T.; Conceicao, Ines C.; Oliveira, Barbara; Coelho, Joana; Sousa, Ines; Sequeira, Ana F.; Vicente, Astrid M.] Univ Lisbon, Fac Sci, Ctr Biodivers Funct & Integrat Genom, P-1749016 Lisbon, Portugal. [Correia, Catarina T.; Conceicao, Ines C.; Oliveira, Barbara; Coelho, Joana; Sousa, Ines; Sequeira, Ana F.; Vicente, Astrid M.] Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal. [Almeida, Joana; Cafe, Catia; Duque, Frederico; Mouga, Susana; Oliveira, Guiomar] Ctr Hosp Coimbra, Hosp Pediat, Ctr Desenvolvimento Crianca, Unidade Neurodesenvolvimento & Autismo, P-3000602 Coimbra, Portugal. [Almeida, Joana; Cafe, Catia; Duque, Frederico; Mouga, Susana; Oliveira, Guiomar] Ctr Hosp Coimbra, Hosp Pediat, Ctr Invest & Formacao Clin, P-3000602 Coimbra, Portugal. [Almeida, Joana; Cafe, Catia; Duque, Frederico; Mouga, Susana; Oliveira, Guiomar] Univ Coimbra, P-3000602 Coimbra, Portugal. [Mouga, Susana; Oliveira, Guiomar] Univ Coimbra, Fac Med, Inst Biomed Imaging & Life Sci, P-3000548 Coimbra, Portugal. [Roberts, Wendy] Univ Toronto, Hosp Sick Children, Autism Res Unit, Toronto, ON M5G 1X8, Canada. [Roberts, Wendy] Univ Toronto, Bloorview Kids Rehab, Toronto, ON M5G 1X8, Canada. [Gao, Kun; Lowe, Jennifer K.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Autism Res & Treatment, Program Neurogenet,Dept Neurol,Semel Inst, Los Angeles, CA 90095 USA. [Thiruvahindrapuram, Bhooma; Walker, Susan; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 0A4, Canada. [Thiruvahindrapuram, Bhooma; Walker, Susan; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 0A4, Canada. [Pinto, Dalila] Mt Sinai Sch Med, Seaver Autism Ctr, Dept Psychiat, New York, NY 10029 USA. [Pinto, Dalila] Mt Sinai Sch Med, Seaver Autism Ctr, Dept Genet, New York, NY 10029 USA. [Pinto, Dalila] Mt Sinai Sch Med, Seaver Autism Ctr, Dept Genom Sci, New York, NY 10029 USA. [Pinto, Dalila] Mt Sinai Sch Med, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. [Nurnberger, John I.] Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA. [Nurnberger, John I.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5S 1A1, Canada. RP Vicente, AM (reprint author), Inst Nacl Saude Doutor Ricardo Jorge, P-1649016 Lisbon, Portugal. EM astrid.vicente@insa.min-saude.pt RI Scherer, Stephen /B-3785-2013; Duque, Frederico/H-3692-2014 OI Scherer, Stephen /0000-0002-8326-1999; Duque, Frederico/0000-0001-5684-1472 FU Autism Speaks (USA); Health Research Board (HRB, Ireland [AUT/2006/1, AUT/2006/2, PD/2006/48]; Medical Research Council (MRC,UK); Genome Canada/Ontario Genomics Institute and the Hilibrand Foundation (USA); US National Institutes of Health (NIH) [HD055751, HD055782, HD055784, MH52708, MH55284, MH061009, MH06359, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261]; NS049261), the Canadian Institutes for Health Research (CIHR), Assistance Publique - Hopitaux de Paris (France) FX We gratefully acknowledge the children with ASD and their families for their collaboration. We thank the AGP investigators for sharing data, resources, and scientific discussions. The AGP study was funded by Autism Speaks (USA), the Health Research Board (HRB, Ireland; AUT/2006/1,AUT/2006/2, PD/2006/48), The Medical Research Council (MRC,UK), Genome Canada/ Ontario Genomics Institute and the Hilibrand Foundation ( USA). Additional support for individual groups was provided by the US National Institutes of Health (NIH Grants: HD055751, HD055782, HD055784, MH52708, MH55284, MH061009, MH06359, MH066673, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261), the Canadian Institutes for Health Research (CIHR), Assistance Publique - Hopitaux de Paris ( France), Autism Speaks UK, Canada Foundation for Innovation/Ontario Innovation Trust, Deutsche Forschungsgemeinschaft ( Grant: Po 255/17-4) ( Germany), EC Sixth FP AUTISM MOLGEN, Fundacao Calouste Gulbenkian ( Portugal), Fondation de France, Fondation FondaMental ( France), Fondation Orange ( France), Fondation pour la Recherche Medicale ( France), Fundacao para a Clencia e Tecnologia ( Portugal), the Hospital for Sick Children Foundation and University of Toronto ( Canada), INSERM ( France), Institut Pasteur ( France), the Italian Ministry of Health ( convention 181 of 19 October 2001), the John P Hussman Foundation ( USA), McLaughlin Centre ( Canada), Ontario Ministry of Research and Innovation ( Canada), the Seaver Foundation ( USA), the Swedish Science Council, the Centre for Applied Genomics ( Canada), the Utah Autism Foundation ( USA), and the Wellcome Trust core award 075491/Z/04 ( UK). 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). Catarina Correia and Ines C. Conceicao are supported by grants SFRH/BPD/64281/2009 and SFRH/BPD/74739/2010, respectively, from Fundacao para a Clencia e Tecnologia. Ethical approval was obtained from: i) the Ethics Committee at Hospital Pediatrico de Coimbra ( Portugal) for the Portuguese cases not included in AGP; ii) the Ethics Committee at the Instituto Nacional de Sa de Doutor Ricardo Jorge ( Portugal) for the Portuguese controls; and iii) the Institutional Review Board at UCLA for the AGRE sample. The control data from OHI, approved by the Research Ethics Board of the University of Ottawa Heart Institute; PopGen, approved by the Ethics Committee of the Medical Faculty of Kiel and by the data protection officer of the University Hospital Schleswig-Holstein; CHOP, approved by the Children's Hospital of Philadelphia Institutional Review Board; and SAGE, approved by the Institutional Review Board at each contributing institution (COGA, FSCD, and COGEND) are published and available. The AGP data involves several research centres and has already been published; the data is available. 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Autism PD APR 10 PY 2014 VL 5 AR 28 DI 10.1186/2040-2392-5-28 PG 14 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AF4YG UT WOS:000334720000001 PM 24720851 ER PT J AU Belengeanu, V Gamage, TH Farcas, S Stoian, M Andreescu, N Belengeanu, A Frengen, E Misceo, D AF Belengeanu, V. Gamage, T. H. Farcas, S. Stoian, M. Andreescu, N. Belengeanu, A. Frengen, E. Misceo, D. TI A de novo 2.3 Mb deletion in 2q24.2q24.3 in a 20-month-old developmentally delayed girl SO GENE LA English DT Article DE 2q24.2q243 deletion; Developmental delay; PSMD14; TBR1; SLC4A10; DPP4; KCNH7; FIGN ID EXPRESSION; TBR1; MICRODELETION; DISRUPTION; EPILEPSY; SLC4A10; BRAIN; FETUS AB We report a 20-month-old girl ascertained at the age of 11 months for developmental delay. She presented with hypotonia and delayed motor development. The patient had severe language impairment and showed behaviour consistent with autism spectrum disorder. She was microcephalic with mild dysmorphic features and had joint hyperlaxity. We detected a 2.3 Mb de novo deletion in 2q242q243 on her paternal chromosome. We compare the clinical features of our patient to six previously published patients with a deletion in 2q24.2q24.3, and one patient reported in the ECARUCA database. Although the clinical presentation of these patients is not highly consistent, likely due to the different deletion size and gene content, the following features seem to be recurrent: disturbance in the central nervous system, poor growth, hypotonia, and joint hyperlaxity. The region deleted in our patient contains 13 genes including PSMD14, TBR1, SLC4A10, DPP4, KCNH7, and FIGN. We briefly review the knowledge of these genes and their possible involvement in the aetiology of this developmental delay syndrome. (C) 2014 Elsevier B.V. All rights reserved. C1 [Belengeanu, V.; Farcas, S.; Stoian, M.; Andreescu, N.] Univ Med & Pharm, Discipline Med Genet, Timisoara, Romania. [Gamage, T. H.; Frengen, E.; Misceo, D.] Univ Oslo, Dept Med Genet, N-0316 Oslo, Norway. [Gamage, T. H.; Frengen, E.; Misceo, D.] Oslo Univ Hosp, Dept Med Genet, N-0407 Oslo, Norway. [Belengeanu, A.] Univ Med & Pharm, Discipline Cellular & Mol Biol, Timisoara, Romania. RP Misceo, D (reprint author), Oslo Univ Hosp, Dept Med Genet, Kirkeveien 166, N-0407 Oslo, Norway. EM belvtim@yahoo.com; t.y.gamage@studmed.uio.no; sfarcas2004@yahoo.com; monistoian_dr@yahoo.com; nicollandreescu@yahoo.com; alinabele@yahoo.com; eirik.frengen@medisin.uio.no; doriana.misceo@medisin.uio.no FU Ulleval University Hospital Research Fund (VIRUUS); Anders Jahres fond til vitenskapens fremme FX We are grateful to the family for participating in this study. This work was supported by a grant from the Ulleval University Hospital Research Fund (VIRUUS). DM was supported by "Anders Jahres fond til vitenskapens fremme". 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One study suggested elevated steroidopathic symptoms ('steroidopathy') in women with ASC. As the symptoms are not independent, we conducted a latent class analysis (LCA). The objectives of the current study are: (1) to test if these findings replicate in a larger sample; and (2) to use LCA to uncover affected clusters of women with ASC. Methods: We tested two groups of women, screened using the Autism Spectrum Quotient -Group 1: n = 415 women with ASC (mean age 36.39 +/- 11.98 years); and Group 2: n = 415 controls (mean age 39.96 +/- 11.92 years). All participants completed the Testosterone-related Medical Questionnaire online. A multiple-group LCA was used to identify differences in latent class structure between women with ASC and controls. Results: There were significant differences in frequency of steroid-related conditions and symptoms between women with ASC and controls. A two-class semi-constrained model best fit the data. Based on response patterns, we identified the classes as 'Typical' and 'Steroidopathic'. The prevalence of the 'Steroidopathic' class was significantly increased within the ASC group (Delta G(2) = 15, df = 1, P = 0.0001). In particular, we confirmed higher frequencies of epilepsy, amenorrhea, dysmenorrhea, severe acne, gender dysphoria, and transsexualism, and differences in sexual preference in women with ASC. Conclusions: Women with ASC are at increased risk for symptoms and conditions linked to steroids. LCA revealed this steroidopathy despite the apparent underdiagnosis of PCOS. C1 [Pohl, Alexa; Cassidy, Sarah; Auyeung, Bonnie; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. [Cassidy, Sarah] Coventry Univ, Dept Psychol & Behav Sci, Coventry CV1 5LW, W Midlands, England. [Auyeung, Bonnie] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9AD, Midlothian, Scotland. 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Autism PD APR 9 PY 2014 VL 5 AR 27 DI 10.1186/2040-2392-5-27 PG 12 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AG4UH UT WOS:000335415300001 PM 24717046 ER PT J AU Corradi-Dell'Acqua, C Schwartz, S Meaux, E Hubert, B Vuilleumier, P Deruelle, C AF Corradi-Dell'Acqua, Corrado Schwartz, Sophie Meaux, Emilie Hubert, Benedicte Vuilleumier, Patrik Deruelle, Christine TI Neural responses to emotional expression information in high- and low-spatial frequency in autism: evidence for a cortical dysfunction SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism; facial expression; emotion expression; spatial frequency; fMRI ID PERVASIVE DEVELOPMENTAL DISORDER; FUSIFORM FACE AREA; HUMAN EXTRASTRIATE CORTEX; WEAK CENTRAL COHERENCE; SPECTRUM DISORDERS; ASPERGER-SYNDROME; HUMAN AMYGDALA; VISUAL-PERCEPTION; FACIAL EXPRESSIONS; FEARFUL FACES AB Despite an overall consensus that Autism Spectrum Disorder (ASD) entails atypical processing of human faces and emotional expressions, the role of neural structures involved in early facial processing remains unresolved. An influential model for the neurotypical brain suggests that face processing in the fusiform gyrus and the amygdala is based on both high-spatial frequency (HSF) information carried by a parvocellular pathway, and low-spatial frequency (LSF) information separately conveyed by a magnocellular pathway. Here, we tested the fusiform gyrus and amygdala sensitivity to emotional face information conveyed by these distinct pathways in ASD individuals (and matched Controls). During functional Magnetical Resonance Imaging (fMRI), participants reported the apparent gender of hybrid face stimuli, made by merging two different faces (one in LSF and the other in HSF), out of which one displayed an emotional expression (fearful or happy) and the other was neutral. Controls exhibited increased fusiform activity to hybrid faces with an emotional expression (relative to hybrids composed only with neutral faces), regardless of whether this was conveyed by LSFs or HSFs in hybrid stimuli. ASD individuals showed intact fusiform response to LSF, but not HSF, expressions. Furthermore, the amygdala (and the ventral occipital cortex) was more sensitive to HSF than LSF expressions in Controls, but exhibited an opposite preference in ASD. Our data suggest spared LSF face processing in ASD, while cortical analysis of HSF expression cues appears affected. These findings converge with recent accounts suggesting that ASD might be characterized by a difficulty in integrating multiple local information and cause global processing troubles unexplained by losses in low spatial frequency inputs. C1 [Corradi-Dell'Acqua, Corrado; Vuilleumier, Patrik] Univ Geneva, Swiss Ctr Affect Sci, CH-1211 Geneva, Switzerland. [Corradi-Dell'Acqua, Corrado; Schwartz, Sophie; Meaux, Emilie; Vuilleumier, Patrik] Univ Med Ctr, Dept Neurosci, Lab Neurol & Imaging Cognit, Geneva, Switzerland. [Corradi-Dell'Acqua, Corrado; Schwartz, Sophie; Meaux, Emilie; Vuilleumier, Patrik] Univ Med Ctr, Neurol Clin, Geneva, Switzerland. [Hubert, Benedicte] Univ Montreal, Hop Riviere de Praires, Montreal, PQ, Canada. [Hubert, Benedicte; Deruelle, Christine] Aix Marseille Univ, CNRS, Inst Inst Neurosci Timone, Marseille, France. RP Corradi-Dell'Acqua, C (reprint author), Univ Geneva CISA, Swiss Ctr Affect Sci, NCCR Affect Sci, Campus Biotech,24 Rue Gen Dufour, CH-1211 Geneva, Switzerland. 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PD APR 9 PY 2014 VL 8 AR 189 DI 10.3389/fnhum.2014.00189 PG 18 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AE5TA UT WOS:000334051000001 PM 24782735 ER PT J AU Itahashi, T Yamada, T Watanabe, H Nakamura, M Jimbo, D Shioda, S Toriizuka, K Kato, N Hashimoto, R AF Itahashi, Takashi Yamada, Takashi Watanabe, Hiromi Nakamura, Motoaki Jimbo, Daiki Shioda, Seiji Toriizuka, Kazuo Kato, Nobumasa Hashimoto, Ryuichiro TI Altered Network Topologies and Hub Organization in Adults with Autism: A Resting-State fMRI Study SO PLOS ONE LA English DT Article ID BRAIN FUNCTIONAL NETWORKS; ANTERIOR CINGULATE CORTEX; MAJOR DEPRESSIVE DISORDER; SUPERIOR TEMPORAL SULCUS; VOXEL-BASED MORPHOMETRY; MIRROR NEURON SYSTEM; SPECTRUM QUOTIENT AQ; SMALL-WORLD NETWORKS; GRAY-MATTER VOLUME; INHIBITORY CONTROL AB Recent functional magnetic resonance imaging (fMRI) studies on autism spectrum condition (ASC) have identified dysfunctions in specific brain networks involved in social and non-social cognition that persist into adulthood. Although increasing numbers of fMRI studies have revealed atypical functional connectivity in the adult ASC brain, such functional alterations at the network level have not yet been fully characterized within the recently developed graph-theoretical framework. Here, we applied a graph-theoretical analysis to resting-state fMRI data acquired from 46 adults with ASC and 46 age- and gender-matched controls, to investigate the topological properties and organization of autistic brain network. Analyses of global metrics revealed that, relative to the controls, participants with ASC exhibited significant decreases in clustering coefficient and characteristic path length, indicating a shift towards randomized organization. Furthermore, analyses of local metrics revealed a significantly altered organization of the hub nodes in ASC, as shown by analyses of hub disruption indices using multiple local metrics and by a loss of '' hubness '' in several nodes (e. g., the bilateral superior temporal sulcus, right dorsolateral prefrontal cortex, and precuneus) that are critical for social and non-social cognitive functions. In particular, local metrics of the anterior cingulate cortex consistently showed significant negative correlations with the Autism-Spectrum Quotient score. Our results demonstrate altered patterns of global and local topological properties that may underlie impaired social and non-social cognition in ASC. C1 [Itahashi, Takashi; Toriizuka, Kazuo] Showa Univ, Sch Med, Dept Pharmacognosy & Phytochem, Tokyo 142, Japan. [Yamada, Takashi; Watanabe, Hiromi; Nakamura, Motoaki; Kato, Nobumasa; Hashimoto, Ryuichiro] Showa Univ, Sch Med, Dept Psychiat, Tokyo 142, Japan. [Nakamura, Motoaki] Kinko Hosp, Kanagawa Psychiat Ctr, Kanagawa, Japan. [Jimbo, Daiki; Shioda, Seiji] Showa Univ, Sch Med, Dept Anat, Tokyo 142, Japan. [Hashimoto, Ryuichiro] Tokyo Metropolitan Univ, Grad Sch Humanities, Dept Language Sci, Tokyo 158, Japan. RP Hashimoto, R (reprint author), Showa Univ, Sch Med, Dept Psychiat, Tokyo 142, Japan. EM dbridges50@gmail.com FU Japan Society for the Promotion of Science (JSPS) [25870738]; Ministry of Education, Culture, Sports, Science, and Technology of Japan [23118003] FX A part of this study is the result of "Development of BMI Technologies for Clinical Application" carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan. This work was also supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Young Scientists (B) (25870738 to T. I.) and by a Grant-in-Aid for Scientific Research on Innovative Areas (23118003; Adolescent Mind & Self-Regulation to R. H.) from the Ministry of Education, Culture, Sports, Science, and Technology 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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For participants with DS, RBRI remained stable or increased over time. Time 1 RBRI predicted Time 2 adaptive behavior (measured by the Vineland Scales) in typically developing children, whereas for participants with DS, Time 1 RBRI predicted poor adaptive outcome (Child Behavior Checklist) at Time 2. The results add to the body of literature examining the adaptive and maladaptive nature of repetitive behavior. C1 [Evans, David W.; Slane, Mylissa M.] Geisinger Bucknell Autism & Dev Med Inst, Dev Neuropsychol Lab, Lewisburg, PA 17837 USA. [Evans, David W.] Bucknell Univ, Dept Neurosci, Lewisburg, PA 17837 USA. [Kleinpeter, F. Lee] River Parishes Community Coll, Dept Psychol, Sorrento, LA USA. [Boomer, K. B.] Bucknell Univ, Dept Math, Lewisburg, PA 17837 USA. RP Evans, DW (reprint author), Geisinger Bucknell Autism & Dev Med Inst, Dev Neuropsychol Lab, Lewisburg, PA 17837 USA. 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However, the genetic factors correlating with T2DM onset have not as yet been fully clarified. We previously found that copy number losses in the subtelomeric region on chromosome 4p16.3 were detected in early-onset Japanese T2DM patients (onset age,35 years) at a high frequency. Herein, we additionally found two novel copy number losses within the subtelomeric regions on chromosomes 16q24.2-3 and 22q13.31-33, which have significant associations with early-onset Japanese T2DM. The associations were statistically significant by Fisher's exact tests with P values of 5.19x10(-3) and 1.8x10(-3) and odds ratios of 5.7 and 4.4 for 16q24.2-3 and 22q13.31-33, respectively. Furthermore, copy number variation (CNV) analysis of the whole genome using the CNV BeadChip system verified simultaneous copy number losses in all three subtelomeric regions in 11 of our 100 T2DM subjects, while none of 100 non-diabetic controls showed the copy number losses in all three regions. Our results suggest that the mechanism underlying induction of CNVs is involved in the pathogenesis of early-onset T2DM. Thus, copy number losses within multiple subtelomeric regions are strongly associated with early-onset T2DM and examination of simultaneous CNVs in these three regions may lead to the development of an accurate and selective procedure for detecting genetic susceptibility to T2DM. C1 [Kodama, Shinjiro; Yamada, Tetsuya; Imai, Junta; Sawada, Shojiro; Takahashi, Kei; Tsukita, Sohei; Kaneko, Keizo; Uno, Kenji; Ishigaki, Yasushi; Oka, Yoshitomo; Katagiri, Hideki] Tohoku Univ, Grad Sch Med, Div Metab & Diabet, Sendai, Miyagi 980, Japan. [Katagiri, Hideki] Japan Sci & Technol Agcy, CREST, Tokyo, Japan. RP Katagiri, H (reprint author), Tohoku Univ, Grad Sch Med, Div Metab & Diabet, Sendai, Miyagi 980, Japan. EM katagiri@med.tohoku.ac.jp FU Ministry of Health, Labor, and Welfare of Japan [H19-genome-005]; Global-COE Programs for "Network Medicine" FX This study was supported by a Grant-in-Aid for Scientific Research to Y. Oka (H19-genome-005) from the Ministry of Health, Labor, and Welfare of Japan, and was also supported by a grant from the Global-COE Programs for "Network Medicine" to Y. Oka and H. Katagiri from the Ministry of Education, Culture, Sports, Science, and Technology 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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In addition to changes at the cortical level, we hypothesize that the anatomical shift that led to globularity also entailed significant changes at the subcortical level. We claim that the functional consequences of such changes must also be taken into account to gain a fuller understanding of our linguistic capacity. Here we focus on the thalamus, which we argue is central to language and human cognition, as it modulates fronto-parietal activity. With this new neurobiological perspective in place, we examine its possible molecular basis. We construct a candidate gene set whose members are involved in the development and connectivity of the thalamus, in the evolution of the human head, and are known to give rise to language-associated cognitive disorders. We submit that the new gene candidate set opens up new windows into our understanding of the genetic basis of our linguistic capacity. Thus, our hypothesis aims at generating new testing grounds concerning core aspects of language ontogeny and phylogeny. C1 [Boeckx, Cedric] Catalan Inst Adv Studies & Res ICREA, Barcelona, Spain. [Boeckx, Cedric] Univ Barcelona, Dept Linguist, E-08007 Barcelona, Spain. [Benitez-Burraco, Antonio] Univ Huelva, Dept Spanish Philol & Its Didact, Huelva, Spain. RP Boeckx, C (reprint author), Univ Barcelona, Dept Linguist, Gran Via Corts Catalanes 585, E-08007 Barcelona, Spain. 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Psychol. PD APR 4 PY 2014 VL 5 DI 10.3389/fpsyg.2014.00282 PG 23 WC Psychology, Multidisciplinary SC Psychology GA AE1VC UT WOS:000333757900001 PM 24772099 ER PT J AU Crewther, DP Crewther, DP AF Crewther, Daniel P. Crewther, David P. TI Peripheral global neglect in high vs. low autistic tendency SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE global percept; local percept; diamond illusion; magnocellular; parvocellular; autism; autistic tendency; AQ ID SPECTRUM DISORDERS; VISUAL-CORTEX; FUNCTIONING AUTISM; MOTION PERCEPTION; BORDER OWNERSHIP; COHERENCE; SEARCH; TASK; INTERFERENCE; MECHANISM AB In addition to its core social deficits, autism is characterized by altered visual perception, with a preference for local percept in those high in autistic tendency. Here, the balance of global vs. local percepts for the perceptually rivalrous diamond illusion was assessed between groups scoring high and low on the Autism Spectrum Quotient (AQ). The global percept of a diamond shape oscillating horizontally behind three occluders can as easily be interpreted as the local percept of four line elements, each moving vertically. Increasing the luminance contrast of the occluders with respect to background resulted in an increase of initial global percept in both groups, with no difference in sensitivity between groups. Presenting the target further into the periphery resulted in a marked increase in the percentage of global perception with visual field eccentricity. However, while the performance for centrally presented diamond targets was not different between AQ groups, the peripheral global performance of the High AQ group was significantly reduced compared with the Low AQ group. On the basis of other imaging studies, this peripheral but not foveal global perceptual neglect may indicate an abnormal interaction between striate cortex and the Lateral Occipital Complex (LOC), or to differences in the deployment of attention between the two groups. C1 [Crewther, Daniel P.; Crewther, David P.] Swinburne Univ Technol, Ctr Human Psychopharmacol, Melbourne, Vic 3122, Australia. RP Crewther, DP (reprint author), Swinburne Univ Technol, Ctr Human Psychopharmacol, 1 Alfred St, Melbourne, Vic 3122, Australia. 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Psychol. PD APR 4 PY 2014 VL 5 DI 10.3389/fpsyg.2014.00284 PG 6 WC Psychology, Multidisciplinary SC Psychology GA AE1VF UT WOS:000333758300001 ER PT J AU Tushir, JS Akbarian, S AF Tushir, J. S. Akbarian, S. TI CHROMATIN-BOUND RNA AND THE NEUROBIOLOGY OF PSYCHIATRIC DISEASE SO NEUROSCIENCE LA English DT Review DE polycomb repressor complex; antisense; brain-derived neurotrophic factor; dipeptidyl-peptidase 10; non-coding RNA; histone methylation ID AUTISM SPECTRUM DISORDER; LONG NONCODING RNAS; LINKED MENTAL-RETARDATION; TRANSCRIPTIONAL UP-REGULATION; H3 LYSINE 27; HISTONE METHYLATION; DNA METHYLATION; PREFRONTAL CORTEX; DEVELOPMENTAL REGULATION; NEUROTROPHIC FACTOR AB A large, and still rapidly expanding literature on epigenetic regulation in the nervous system has provided fundamental insights into the dynamic regulation of DNA methylation and post-translational histone modifications in the context of neuronal plasticity in health and disease. Remarkably, however, very little is known about the potential role of chromatin-bound RNAs, including many long non-coding transcripts and various types of small RNAs. Here, we provide an overview on RNA-mediated regulation of chromatin structure and function, with focus on histone lysine methylation and psychiatric disease. Examples of recently discovered chromatin-bound long non-coding RNAs important for neuronal health and function include the brain-derived neurotrophic factor antisense transcript (Bdnf-AS) which regulates expression of the corresponding sense transcript, and LOC389023 which is associated with human-specific histone methylation signatures at the chromosome 2q14.1 neurodevelopmental risk locus by regulating expression of DPP10, an auxillary subunit for voltage-gated K(+) channels. We predict that the exploration of chromatin-bound RNA will significantly advance our current knowledge base in neuroepigenetics and biological psychiatry. This article is part of a Special Issue entitled: Epigenetics in Brain Function. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Tushir, J. S.; Akbarian, S.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Psychiat, New York, NY 10029 USA. RP Akbarian, S (reprint author), Hess Ctr Sci & Med, Friedman Brain Inst, Room 9-105,1470 Madison Ave, New York, NY 10029 USA. EM Schahram.akbarian@mssm.edu FU National Institutes of Health FX Work in the authors' laboratory is supported by the research awards from the National Institutes of Health. The authors report no conflict. 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intervention; disability policies; autism; autism spectrum disorder ID INTENSIVE BEHAVIORAL INTERVENTION; YOUNG-CHILDREN; COMPREHENSIVE TREATMENTS; ADULTS; METAANALYSIS; MANAGEMENT; EMPLOYMENT; DIAGNOSIS; HISTORY; STATE AB Prevalence rates of autism spectrum disorder have risen dramatically over the past few decades (now estimated at 1:50 children). The estimated total annual cost to the public purse in the United States is US$137 billion, with an individual lifetime cost in the United Kingdom estimated at between 0.8 pound million and 1.23 pound million depending on the level of functioning. The United Nations Convention for the Rights of Persons with Disabilities has enshrined full and equal human rights-for example, for inclusion, education and employment-and there is ample evidence that much can be achieved through adequate support and early intensive behavioural interventions. Not surprisingly, most governments worldwide have devised laws, policies, and strategies to improve services related to autism spectrum disorder, yet intriguingly the approaches differ considerably across the globe. Using Northern Ireland as a case in point, we look at relevant governmental documents and offer international comparisons that illustrate inconsistencies akin to a "postcode lottery" of services. 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J. Disabil. Dev. Educ. PD APR 3 PY 2014 VL 61 IS 2 SI SI BP 134 EP 151 DI 10.1080/1034912X.2014.905059 PG 18 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH0WL UT WOS:000335841400004 ER PT J AU Ling, R AF Ling, Rebecca TI Co-opting the Smarts: Why Zak Kukoff's Autism Ambassadors Matters SO INTERNATIONAL JOURNAL OF DISABILITY DEVELOPMENT AND EDUCATION LA English DT Article C1 Univ Queensland, Sch Educ, Brisbane, Qld, Australia. RP Ling, R (reprint author), Univ Queensland, Sch Educ, Brisbane, Qld, Australia. EM r.ling@uq.edu.au CR ACARA (Australian Curriculum Assessment and Reporting Authority), 2010, AUSTR CURR VERS 6 0 Bandura A., 1986, SOCIAL FDN THOUGHT A Bronfenbrenner U., 1979, ECOLOGY HUMAN DEV EX Flans R., 2012, VENTURA COUNTY S AUG Hurwitz Z., 2012, JEWISH J JUL Katz G. 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TI Evaluation of a parenting program for children with behavioural problems: Signposts in Singapore SO JOURNAL OF INTELLECTUAL & DEVELOPMENTAL DISABILITY LA English DT Article DE cross-cultural implementation; challenging behaviour; program evaluation; Signposts parenting program; difficult behaviour; parent support ID INTELLECTUAL DISABILITY; SUPPORT PROGRAM; STRESS; MOTHERS; AUTISM; IMPLEMENTATION; DEPRESSION; COGNITIONS; EFFICACY AB Background The Signposts for Building Better Behaviour program, developed by the Parenting Research Centre, Victoria, Australia, was conducted at a public hospital facility in Singapore. Method More than 1,000 parents completed the program, and filled in questionnaires about their child's behaviours. Results Parents rated themselves in the questionnaires as being significantly less hassled, stressed, depressed, and anxious after attending the program. They were more confident and satisfied with managing their child, and rated their children's behaviours as having improved. Effect sizes ranged from 0.12 to 0.59. The findings were maintained 3 months after completion of the program. Conclusions The study provides evidence of the cross-cultural applicability of the principles underlying the Signposts program. As there are long-term repercussions when children's behaviour problems are not dealt with appropriately, such behaviour management programs should be made more available to parents and caregivers. C1 [Yap, Dorcas; Lau, Lily; Nasir, Nasriah; Tang, Hui Nee] KK Womens & Childrens Hosp, Dept Child Dev, Singapore 229899, Singapore. [Cameron, Christine; Matthews, Jan] Parenting Res Ctr, Melbourne, Vic, Australia. [Moore, Dennis W.] Monash Univ, Fac Educ, Melbourne, Vic 3004, Australia. RP Yap, D (reprint author), KK Womens & Childrens Hosp, Dept Child Dev, 100 Bukit Timah Rd, Singapore 229899, Singapore. 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PD APR 3 PY 2014 VL 39 IS 2 SI SI BP 214 EP 221 DI 10.3109/13668250.2014.899567 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AF7WP UT WOS:000334926300012 ER PT J AU Al-Ayadhi, LY Mostafa, GA AF Al-Ayadhi, Laila Yousef Mostafa, Gehan Ahmed TI Serum antinucleosome-specific antibody as a marker of autoimmunity in children with autism SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Antinucleosome-specific antibodies; Autism; Autoimmunity; Family history of autoimmunity ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DISEASE-ACTIVITY; NUCLEOSOME ANTIBODIES; SPECTRUM DISORDERS; NULL ALLELE; AUTOANTIBODIES; ASSOCIATION; FREQUENCY; NEPHRITIS; RESPONSES AB Background: Increasing evidence of autoimmune phenomena in some individuals with autism could represent the presence of altered or inappropriate immune responses in this disorder. The role of the nucleosome in the induction of antibody response in some autoimmune-mediated tissue damage may provide novel targets for treatment. Due to the paucity of studies investigating the frequency of systemic auto-antibodies in autism, we are the first to investigate the frequency of antinucleosome-specific antibodies in a group of autistic children. Methods: Serum antinucleosome-specific antibodies were measured by ELISA in 60 autistic children, between the ages of 3 and 12 years, in comparison to 60 healthy children. Autistic severity was assessed using the Childhood Autism Rating Scale (CARS). Results: Autistic children had significantly higher serum antinucleosome-specific antibodies than healthy children (P < 0.001). The seropositivity of antinucleosome-specific antibodies was found in 46.7% of autistic children. Autistic children with a family history of autoimmunity (40%) had a significantly higher frequency of serum antinucleosome-specific antibodies (83.3%) than patients without such a history (22.2%, P < 0.001). Conclusions: Serum levels of antinucleosome-specific antibodies were increased in some autistic children. However, these data should be treated with caution until further investigations are performed with a larger subject population to determine whether these antibodies have a role in the induction of autoimmunity in a subgroup of autistic children. The role of immunotherapy in children with autism should be also studied. C1 [Al-Ayadhi, Laila Yousef; Mostafa, Gehan Ahmed] King Saud Univ, Fac Med, Autism Res & Treatment Ctr, AL Amodi Autism Res Chair,Dept Physiol, Riyadh, Saudi Arabia. [Mostafa, Gehan Ahmed] Ain Shams Univ, Fac Med, Dept Pediat, Cairo 11511, Egypt. RP Mostafa, GA (reprint author), King Saud Univ, Fac Med, Autism Res & Treatment Ctr, AL Amodi Autism Res Chair,Dept Physiol, Riyadh, Saudi Arabia. EM gehan.mostafa2000@yahoo.com FU King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia; NPST, Health Research and Studies program at Kind Saud University FX This work was financially supported by the King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia. It was also supported by NPST, Health Research and Studies program at Kind Saud University. 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PD APR 3 PY 2014 VL 28 IS 2 BP 155 EP 171 DI 10.1080/02650533.2013.844114 PG 17 WC Social Work SC Social Work GA AF4ZK UT WOS:000334723300003 ER PT J AU Uljarevic, M Prior, MR Leekam, SR AF Uljarevic, Mirko Prior, Margot R. Leekam, Susan R. TI First evidence of sensory atypicality in mothers of children with Autism Spectrum Disorder (ASD) SO MOLECULAR AUTISM LA English DT Article DE Sensory atypicality; Parents; Autism spectrum disorders ID TYPICALLY DEVELOPING-CHILDREN; CANDIDATE GENE; SENSITIVITY; OVERRESPONSIVITY; DEFENSIVENESS; POPULATION; ANXIETY; TACTILE; GABRB3; ADULTS AB Background: Atypical reactions to sensory stimuli show heritability in the general population and are a known risk factor for affective disorders. As sensory problems are highly prevalent in individuals with ASD and their siblings, and the occurrence of affective disorders is elevated in parents of children with ASD, investigating sensory symptoms in parents is important both from clinical and theoretical standpoints. Fifty mothers of children and adolescents with ASD completed the Adolescent and Adult Sensory Profile (AASP). The AASP is a norm-referenced questionnaire that provides scores for four types of responses to sensory stimuli (sensory quadrants): hypo-sensitivity, hyper-sensitivity, sensation seeking, and sensory avoiding. Findings: Mothers' scores were compared with AASP norms. Ninety eight percent of mothers had sensory scores at least one standard deviation (SD) above the normative mean and 44% were two or more SDs above the mean for at least one sensory quadrant. Conclusions: This study provides the first evidence for sensory atypicality in parents of children with ASD. Further research is needed to elucidate the contribution of genetic and environmental influences on the expression of sensory problems in ASD. C1 [Uljarevic, Mirko; Leekam, Susan R.] Cardiff Univ, Sch Psychol, Wales Autism Res Ctr, Cardiff CF10 3A, S Glam, Wales. [Prior, Margot R.] Univ Melbourne, Melbourne Sch Psychol Sci, Melbourne, Vic 3010, Australia. RP Uljarevic, M (reprint author), Cardiff Univ, Sch Psychol, Wales Autism Res Ctr, 70 Pk Pl, Cardiff CF10 3A, S Glam, Wales. EM uljarevicm@cardiff.ac.uk FU Wales Office of Research and Development for Health and Social Care, National Institute for Social Care and Health Research; School of Psychology, Cardiff University FX This research was supported by PhD funding to MU and SL from the Wales Office of Research and Development for Health and Social Care, National Institute for Social Care and Health Research and the School of Psychology, Cardiff University. We deeply appreciate the support and time given by the parents who were involved in the research. We thank Dr Sarah Carrington for helpful comments. We also thank Lynda Morgan and Bev Winn for their help with recruitment. 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Autism PD APR 3 PY 2014 VL 5 AR 26 DI 10.1186/2040-2392-5-26 PG 4 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AF4YD UT WOS:000334719600001 PM 24694290 ER PT J AU Orlic-Milacic, M Kaufman, L Mikhailov, A Cheung, AYL Mahmood, H Ellis, J Gianakopoulos, PJ Minassian, BA Vincent, JB AF Orlic-Milacic, Marija Kaufman, Liana Mikhailov, Anna Cheung, Aaron Y. L. Mahmood, Huda Ellis, James Gianakopoulos, Peter J. Minassian, Berge A. Vincent, John B. TI Over-Expression of Either MECP2_e1 or MECP2_e2 in Neuronally Differentiated Cells Results in Different Patterns of Gene Expression SO PLOS ONE LA English DT Article ID SEVERE MENTAL-RETARDATION; RETT-SYNDROME PHENOTYPES; CPG-BINDING PROTEIN-2; CONGENITAL VARIANT; LANGUAGE DISORDER; FOXG1 MUTATIONS; TARGET GENES; COPY NUMBER; ISOFORM; AUTISM AB Mutations in MECP2 are responsible for the majority of Rett syndrome cases. MECP2 is a regulator of transcription, and has two isoforms, MECP2_e1 and MECP2_e2. There is accumulating evidence that MECP2_e1 is the etiologically relevant variant for Rett. In this study we aim to detect genes that are differentially transcribed in neuronal cells over-expressing either of these two MECP2 isoforms. The human neuroblastoma cell line SK-N-SH was stably infected by lentiviral vectors over-expressing MECP2_e1, MECP2_e2, or eGFP, and were then differentiated into neurons. The same lentiviral constructs were also used to infect mouse Mecp2 knockout (Mecp2(tm1.1Bird)) fibroblasts. RNA from these cells was used for microarray gene expression analysis. For the human neuronal cells, similar to 800 genes showed >three-fold change in expression level with the MECP2_e1 construct, and similar to 230 with MECP2_e2 (unpaired t-test, uncorrected p value <0.05). We used quantitative RT-PCR to verify microarray results for 41 of these genes. We found significant up-regulation of several genes resulting from overexpression of MECP2_e1 including SRPX2, NAV3, NPY1R, SYN3, and SEMA3D. DOCK8 was shown via microarray and qRT-PCR to be upregulated in both SK-N-SH cells and mouse fibroblasts. Both isoforms up-regulated GABRA2, KCNA1, FOXG1 and FOXP2. Down-regulation of expression in the presence of MECP2_e1 was seen with UNC5C and RPH3A. Understanding the biology of these differentially transcribed genes and their role in neurodevelopment may help us to understand the relative functions of the two MECP2 isoforms, and ultimately develop a better understanding of RTT etiology and determine the clinical relevance of isoform-specific mutations. C1 [Orlic-Milacic, Marija; Kaufman, Liana; Mikhailov, Anna; Mahmood, Huda; Gianakopoulos, Peter J.; Vincent, John B.] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Mol Neuropsychiat & Dev Lab, Toronto, ON, Canada. [Cheung, Aaron Y. L.; Ellis, James] Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON M5G 1X8, Canada. [Minassian, Berge A.] Hosp Sick Children, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada. [Minassian, Berge A.] Hosp Sick Children, Dept Paediat, Div Neurol, Toronto, ON M5G 1X8, Canada. [Vincent, John B.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Vincent, John B.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. RP Vincent, JB (reprint author), Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Mol Neuropsychiat & Dev Lab, Toronto, ON, Canada. EM john.vincent@camh.ca RI Ellis, James/F-4789-2011 FU International Rett Syndrome Foundation; Ontario Mental Health Foundation; Cure Autism Now FX This work was supported by funding from International Rett Syndrome Foundation, Ontario Mental Health Foundation, and Cure Autism Now to JBV and BAM. JBV is a National Alliance for Research on Schizophrenia and Depression Independent Investigator. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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The objection is this: since people with autism have no difficulty in engaging with mathematics even if they cannot pretend, it is not the case that engagement with mathematics involves pretence. I show that a previous response to the objection is inadequate as a defence of the kind of pretence hermeneutic fictionalism put forward as a semantic thesis about the discourse in question. I claim that a more general response to the Autism Objection is to deny the premise that people with autism cannot pretend. To motivate this response, I appeal to psychological studies suggesting that people with autism can understand pretence and they can pretend under certain conditions. Finally, I provide explanations for why it is the case that people with autism do not have a problem with engaging in mathematics whereas they have so much difficulty with other kinds of figurative language and pretence. C1 Ewha Womans Univ, Seoul, South Korea. 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TI Teaching students with autism spectrum disorder in mainstream post-primary schools in the Republic of Ireland SO INTERNATIONAL JOURNAL OF INCLUSIVE EDUCATION LA English DT Article DE initial teacher education; educational system; inclusive education; special educational needs; continuing professional development ID SPECIAL EDUCATIONAL-NEEDS; GENERAL-EDUCATION; INCLUSIVE EDUCATION; INCLUDING CHILDREN; SECONDARY-SCHOOLS; ASPERGER-SYNDROME; ATTITUDES; EXPERIENCES; CLASSROOMS; TEACHERS AB This qualitative study explored teachers' perceptions of the inclusive education of students with autism spectrum disorder (ASD) at the post-primary level, specifically those with Asperger syndrome. Semi-structured interviews were conducted with eight mainstream teachers in the Republic of Ireland. One of the main findings of the study was that the teachers' implicit model of inclusion was more consistent with integration than with inclusive education. Although systemic barriers to inclusive education were identified, the teachers' focus tended to be on managing within the system rather than on bringing about systemic change. Mainstream post-primary education was endorsed by teachers for their students with ASD, despite perceiving that these students were unhappy and socially excluded. The teachers were confident in teaching students with ASD, primarily as a result of their experience. The implications of the study for teacher educators and future researchers are discussed. C1 [McGillicuddy, Sarah; O'Donnell, Grainne M.] Natl Univ Ireland Univ Coll Dublin, Sch Educ, Roebuck Off, Dublin 4, Ireland. RP McGillicuddy, S (reprint author), Natl Univ Ireland Univ Coll Dublin, Sch Educ, Roebuck Off, Dublin 4, Ireland. 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J. Incl. Educ. PD APR 3 PY 2014 VL 18 IS 4 BP 323 EP 344 DI 10.1080/13603116.2013.764934 PG 22 WC Education & Educational Research SC Education & Educational Research GA AE5MQ UT WOS:000334033700001 ER PT J AU Skovlund, H AF Skovlund, Henrik TI Inclusive and exclusive aspects of diagnosed children's self-concepts in special needs institutions SO INTERNATIONAL JOURNAL OF INCLUSIVE EDUCATION LA English DT Article DE pragmatism; attention deficit hyperactivity disorder; autism; special needs institutions; self-concept ID LEARNING-DISABILITIES; ACADEMIC-ACHIEVEMENT; EMPOWERMENT; ADHD AB Eight children between 7 and 11 years of age were interviewed about their understanding of their own diagnoses. The diagnoses in question were attention deficit hyperactivity disorder, autism and nonverbal learning disorder. They were from different special schools that are segregated from state schools. In addition to the interviews, a role play setting with dolls representing a school teacher, parents, peers, a school psychologist and a doctor was used as a basis for speaking about the children's understanding of the special school in relation to their diagnoses. The study revealed that the children use a simplified medical model for understanding their diagnoses and behaviour. Furthermore, they partly perceive the special school as a medical institution, as well as an educational institution. Finally, the study showed that the children consider themselves different from normal children and incapable of participating in shared learning communities such as state schools. This is of particular interest in relation to these children's future transition from special schools to public learning institutions, especially with regard to their inclusion in the latter. C1 Univ Aarhus, Dept Educ, DK-2400 Copenhagen NV, Denmark. 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J. Incl. Educ. PD APR 3 PY 2014 VL 18 IS 4 BP 392 EP 410 DI 10.1080/13603116.2013.778336 PG 19 WC Education & Educational Research SC Education & Educational Research GA AE5MQ UT WOS:000334033700005 ER PT J AU Knott, F Taylor, A AF Knott, Fiona Taylor, Angela TI Life at university with Asperger syndrome: a comparison of student and staff perspectives SO INTERNATIONAL JOURNAL OF INCLUSIVE EDUCATION LA English DT Article DE student experience; high functioning autism; student support; student voice; Asperger syndrome; university ID HIGHER-EDUCATION; AUTISM SPECTRUM; DISABILITIES; DIAGNOSIS; SUPPORT AB Although increasing numbers of students with disabilities are accessing higher education, there is relatively little information about the needs of students with Asperger syndrome (AS). Crucially, students themselves have rarely been included in research examining their needs or the supports they might find helpful. Three focus groups, one with students with AS and two with staff were conducted to explore the challenges, barriers and supports to students' successful progress through one university in the UK. Thematic analysis revealed some key differences between staff and student perspectives, particularly with regard to impact of sensory sensitivities and daily life difficulties on academic progress. Students and staff also held differing views about what is helpful, relating to disclosure of diagnosis and the value of formal social supports. The study highlights the importance of developing services beyond traditional academic supports that students with AS themselves feel are valuable. C1 [Knott, Fiona; Taylor, Angela] Univ Reading, Sch Psychol & Clin Language Sci, Reading RG6 6AL, Berks, England. RP Knott, F (reprint author), Univ Reading, Sch Psychol & Clin Language Sci, Reading RG6 6AL, Berks, England. 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PD APR 3 PY 2014 VL 18 IS 4 BP 411 EP 426 DI 10.1080/13603116.2013.781236 PG 16 WC Education & Educational Research SC Education & Educational Research GA AE5MQ UT WOS:000334033700006 ER PT J AU Grozeva, D Carss, K Spasic-Boskovic, O Parker, MJ Archer, H Firth, HV Park, SM Canham, N Holder, SE Wilson, M Hackett, A Field, M Floyd, JAB Hurles, M Raymond, FL AF Grozeva, Detelina Carss, Keren Spasic-Boskovic, Olivera Parker, Michael J. Archer, Hayley Firth, Helen V. Park, Soo-Mi Canham, Natalie Holder, Susan E. Wilson, Meredith Hackett, Anna Field, Michael Floyd, James A. B. Hurles, Matthew Raymond, F. Lucy CA UK10K Consortium TI De Novo Loss-of-Function Mutations in SETD5, Encoding a Methyltransferase in a 3p25 Microdeletion Syndrome Critical Region, Cause Intellectual Disability SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID KABUKI SYNDROME; DELETION SYNDROME; PATIENT; SPECTRUM; FEATURES; GENES; MLL2; HAPLOINSUFFICIENCY; 3P25.3-P26.1; DISEASE AB To identify further Mendelian causes of intellectual disability (ID), we screened a cohort of 996 individuals with ID for variants in 565 known or candidate genes by using a targeted next-generation sequencing approach. Seven loss-of-function (LoF) mutations-four nonsense (c.1195A>T [p. Lys399*], c.1333C>T [p.Arg445*], c.1866C>G [p.Tyr622*], and c.3001C>T [p.Arg1001*]) and three frameshift (c.2177_2178del [p.Thr726Asnfs*39], c.3771dup [p.Ser1258Glufs*65], and c.3856del [p.Ser1286Leufs*84])-were identified in SETD5, a gene predicted to encode a methyltransferase. All mutations were compatible with de novo dominant inheritance. The affected individuals had moderate to severe ID with additional variable features of brachycephaly; a prominent high forehead with synophrys or striking full and broad eyebrows; a long, thin, and tubular nose; long, narrow upslanting palpebral fissures; and large, fleshy low-set ears. Skeletal anomalies, including significant leg-length discrepancy, were a frequent finding in two individuals. Congenital heart defects, inguinal hernia, or hypospadias were also reported. Behavioral problems, including obsessive-compulsive disorder, hand flapping with ritualized behavior, and autism, were prominent features. SETD5 lies within the critical interval for 3p25 microdeletion syndrome. The individuals with SETD5 mutations showed phenotypic similarity to those previously reported with a deletion in 3p25, and thus loss of SETD5 might be sufficient to account for many of the clinical features observed in this condition. Our findings add to the growing evidence that mutations in genes encoding methyltransferases regulating histone modification are important causes of ID. This analysis provides sufficient evidence that rare de novo LoF mutations in SETD5 are a relatively frequent (0.7%) cause of ID. C1 [Grozeva, Detelina; Spasic-Boskovic, Olivera; Raymond, F. Lucy] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 0XY, England. [Carss, Keren; Floyd, James A. B.; Hurles, Matthew; UK10K Consortium] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Parker, Michael J.] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield S10 2TH, S Yorkshire, England. [Archer, Hayley] Univ Hosp Wales, Inst Med Genet, Cardiff CF14 4XW, S Glam, Wales. [Firth, Helen V.; Park, Soo-Mi] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Treatment Ctr, Cambridge CB2 0QQ, England. [Canham, Natalie; Holder, Susan E.] North West London Hosp NHS Trust, Kennedy Galton Ctr, North West Thames Reg Genet Serv, Harrow HA1 3UJ, Middx, England. [Wilson, Meredith] Childrens Hosp Westmead, Dept Clin Genet, Westmead, NSW 2145, Australia. [Hackett, Anna] Hunter Genet, Genet Learning Disabil Serv, Waratah, NSW 2298, Australia. [Field, Michael] Royal N Shore Hosp, Dept Med Genet, St Leonards, NSW 2298, Australia. [Floyd, James A. B.] Queen Mary Univ London, John Vane Sci Ctr, Genome Ctr, London EC1M 6BQ, England. RP Raymond, FL (reprint author), Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 0XY, England. EM flr24@cam.ac.uk FU Wellcome Trust [WT091310]; Action Medical Research; Birth Defect Foundation; Cambridge National Institute for Health Research Biomedical Research Centre FX We are indebted to all individuals who participated in the study. This study made use of data generated by the UK10K Project. Funding for the UK10K Project was provided by the Wellcome Trust under award WT091310. A full list of consortium members can be found at the UK10K Project website. This study was supported by grants from Action Medical Research, the Birth Defect Foundation, and the Cambridge National Institute for Health Research Biomedical Research Centre. 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J. Hum. Genet. PD APR 3 PY 2014 VL 94 IS 4 BP 618 EP 624 DI 10.1016/j.ajhg.2014.03.006 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AE1XC UT WOS:000333765300012 PM 24680889 ER PT J AU Beaudry, O Roy-Charland, A Perron, M Cormier, I Tapp, R AF Beaudry, Olivia Roy-Charland, Annie Perron, Melanie Cormier, Isabelle Tapp, Roxane TI Featural processing in recognition of emotional facial expressions SO COGNITION & EMOTION LA English DT Article DE Facial expressions; Recognition task; Eye-tracking; Featural processing ID FACE; IDENTIFICATION; ORIENTATION; PERCEPTION; PROTOTYPES; INVERSION; PATTERNS; CHILDREN; AUTISM; ADULTS AB The present study aimed to clarify the role played by the eye/brow and mouth areas in the recognition of the six basic emotions. In Experiment 1, accuracy was examined while participants viewed partial and full facial expressions; in Experiment 2, participants viewed full facial expressions while their eye movements were recorded. Recognition rates were consistent with previous research: happiness was highest and fear was lowest. The mouth and eye/brow areas were not equally important for the recognition of all emotions. More precisely, while the mouth was revealed to be important in the recognition of happiness and the eye/brow area of sadness, results are not as consistent for the other emotions. In Experiment 2, consistent with previous studies, the eyes/brows were fixated for longer periods than the mouth for all emotions. Again, variations occurred as a function of the emotions, the mouth having an important role in happiness and the eyes/brows in sadness. The general pattern of results for the other four emotions was inconsistent between the experiments as well as across different measures. The complexity of the results suggests that the recognition process of emotional facial expressions cannot be reduced to a simple feature processing or holistic processing for all emotions. 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PD APR 3 PY 2014 VL 28 IS 3 BP 416 EP 432 DI 10.1080/02699931.2013.833500 PG 17 WC Psychology, Experimental SC Psychology GA 301AL UT WOS:000330505000002 PM 24047413 ER PT J AU Verma, D Chakraborti, B Karmakar, A Bandyopadhyay, T Singh, AS Sinha, S Chatterjee, A Ghosh, S Mohanakumar, KP Mukhopadhyay, K Rajamma, U AF Verma, Deepak Chakraborti, Barnali Karmakar, Arijit Bandyopadhyay, Tirthankar Singh, Asem Surindro Sinha, Swagata Chatterjee, Anindita Ghosh, Saurabh Mohanakumar, Kochupurackal P. Mukhopadhyay, Kanchan Rajamma, Usha TI Sexual dimorphic effect in the genetic association of monoamine oxidase A (MAOA) markers with autism spectrum disorder SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Article DE Allele; Autism spectrum disorder; Genetic association; Haplotype; Monoamine oxidase A; Sexual dimorphism ID POPULATION-BASED ASSOCIATION; FUNCTIONAL POLYMORPHISM; VNTR POLYMORPHISM; INDIAN POPULATION; PROMOTER-REGION; POINT MUTATION; A GENE; VARIANTS; BEHAVIOR; MICE AB Autism spectrum disorders are heritable and behaviorally-defined neurodevelopmental disorders having skewed sex ratio. Serotonin as modulator of behavior and implication of serotonergic dysfunction in ASD etiology corroborates that serotonergic system genes are potential candidates for autism susceptibility. In the current study X-chromosomal gene, MAOA responsible for degradation of serotonin is investigated for possible association with ASD using population-based approach. Study covers analysis of 8 markers in 421 subjects including cases and ethnically-matched controls from West Bengal. MAOA marker, rs6323 and various haplotypes formed between the markers show significant association with the disorder. Stratification on the basis of sex reveals significant genetic effect of rs6323 with low activity T allele posing higher risk in males, but not in females. Haplotypic association results also show differential effect both in males and females. Contrasting linkage disequilibrium pattern between pair of markers involving rs6323 in male cases and controls further supports the sex-bias in genetic association. Bioinformatic analysis shows presence of Y-encoded SRY transcription factor binding sites in the neighborhood of rs1137070. C allele of rs1137070 causes deletion of GATA-2 binding site and GATA-2 is known to interact with SRY. This is the first study highlighting male-specific effect of rs6323 marker and its haplotypes in ASD etiology and it suggests sexual dimorphic effect of MAOA in this disorder. Overall results of this study identify MAOA as a possible ASD susceptibility locus and the differential genetic effect in males and females might contribute to the sex ratio differences and molecular pathology of the disorder. (C) 2013 Elsevier Inc. All rights reserved. C1 [Verma, Deepak; Chakraborti, Barnali; Karmakar, Arijit; Bandyopadhyay, Tirthankar; Singh, Asem Surindro; Mukhopadhyay, Kanchan; Rajamma, Usha] Manovikas Kendra, Manovikas Biomed Res & Diagnost Ctr, Kolkata 700107, W Bengal, India. [Sinha, Swagata; Chatterjee, Anindita] Manovikas Kendra, Out Patients Dept, Kolkata 700107, W Bengal, India. [Mohanakumar, Kochupurackal P.] CSIR Indian Inst Chem Biol, Cell Biol & Physiol Div, Lab Clin & Expt Neurosci, Kolkata, W Bengal, India. [Ghosh, Saurabh] Indian Stat Inst, Human Genet Unit, Kolkata, W Bengal, India. RP Rajamma, U (reprint author), Manovikas Kendra, Manovikas Biomed Res & Diagnost Ctr, 482 Madudah,Plot I-24,Sect J,EM Bypass, Kolkata 700107, W Bengal, India. EM ushamvk@yahoo.co.in FU Department of Biotechnology (DBT), Govt. of India [BT/PR14637MED/30/561/2010]; Council of Scientific and Industrial Research (CSIR), Govt. of India (Junior Research Fellowship) [Admn 9/840(0009) EMR-I/2011] FX The present study is supported by the Department of Biotechnology (DBT), Govt. of India grant to KPM, KM and UR vide BT/PR14637MED/30/561/2010 dated 28/11/2011 and the Council of Scientific and Industrial Research (CSIR), Govt. of India (Junior Research Fellowship to DV, award no. Admn 9/840(0009) EMR-I/2011 dated 25/03/2011). BC and AK have been working for this project as Junior Research Fellows. TB was a summer project student who worked in this project. 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Neuro-Psychopharmacol. Biol. Psychiatry PD APR 3 PY 2014 VL 50 BP 11 EP 20 DI 10.1016/j.pnpbp.2013.11.010 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 302AQ UT WOS:000330574000002 PM 24291416 ER PT J AU Stewart, AM Nguyen, M Wong, K Poudel, MK Kalueff, AV AF Stewart, Adam Michael Nguyen, Michael Wong, Keith Poudel, Manoj K. Kalueff, Allan V. TI Developing zebrafish models of autism spectrum disorder (ASD) SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE Autism spectrum disorder; Behavioral tests; Social deficits; Translational research; Zebrafish ID ANXIETY-RELATED BEHAVIOR; SOCIAL APPROACH BEHAVIOR; BTBR MOUSE MODEL; DANIO-RERIO; REPETITIVE BEHAVIOR; OXYTOCIN SECRETION; DEVELOPING UTILITY; ADULT ZEBRAFISH; ANIMAL-MODELS; KNOCKOUT MICE AB Autismspectrumdisorder (ASD) is a serious neurodevelopmental disorder with complex symptoms and unclear, multi-factorial pathogenesis. Animal (rodent) models of ASD-like behavior are extensively used to study genetics, circuitry and molecular mechanisms of ASD. The evolutionarily conserved nature of social behavior and its molecular pathways suggests that alternative experimental models can be developed to complement and enhance the existing rodent ASD paradigms. The zebrafish (Danio rerio) is rapidly becoming a popular model organism in neuroscience and biological psychiatry to study brain function, model human brain disorders and explore their genetic or pharmacological modulation. Representing highly social animals, zebrafish emerge as a strong potential model organism to study normal and pathological social phenotypes, as well as several other ASD-like symptoms. Here, we discuss the developing utility of zebrafish in modeling ASD as a new emerging field in translational neuroscience and drug discovery. (C) 2013 Elsevier Inc. All rights reserved. C1 [Stewart, Adam Michael; Poudel, Manoj K.; Kalueff, Allan V.] ZENEREI Inst, Slidell, LA 70458 USA. [Stewart, Adam Michael; Poudel, Manoj K.; Kalueff, Allan V.] ZNRC, Slidell, LA 70458 USA. [Stewart, Adam Michael] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA. [Nguyen, Michael] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA. 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TI Symptoms as Solutions: Hypnosis and Biofeedback for Autonomic Regulation in Autism Spectrum Disorders SO AMERICAN JOURNAL OF CLINICAL HYPNOSIS LA English DT Article DE autism; autism spectrum disorder; autonomic regulation; biofeedback; hypnosis; repetitive behaviors ID COMPUTER-ASSISTED-INSTRUCTION; TERM-FOLLOW-UP; REPETITIVE BEHAVIOR; YOUNG-CHILDREN; ANIMAL-MODELS; SELF-HYPNOSIS; HEART-RATE; OXYTOCIN; ANXIETY; DYSFUNCTION AB The Autonomic Dysregulation Theory of autism posits that a phylogenetically early autonomic defect leads to overarousal and impairments in language and social engagement. Cognitive rigidity and repetitive behaviors manifest as mitigating efforts. Focusing on the implications of this premise may provide more productive therapeutic approaches than existing methods. It suggests that self-regulation therapy using hypnosis and biofeedback should be highly effective, especially for young people. 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PD APR 3 PY 2014 VL 56 IS 2 BP 152 EP 173 DI 10.1080/00029157.2013.768197 PG 22 WC Psychology, Clinical SC Psychology GA 212QB UT WOS:000323996800005 ER PT J AU McCarthy, M AF McCarthy, Michael TI Autism diagnoses in the US rise by 30%, CDC reports SO BMJ-BRITISH MEDICAL JOURNAL LA English DT News Item CR Parks SE, 2014, MMWR SURVEILL SUMM, V63, P1 NR 1 TC 1 Z9 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD APR 2 PY 2014 VL 348 AR g2520 DI 10.1136/bmj.g2520 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AE4TP UT WOS:000333977000014 PM 24696178 ER PT J AU Eisinger, BE Driessen, TM Zhao, CJ Gammie, SC AF Eisinger, Brian E. Driessen, Terri M. Zhao, Changjiu Gammie, Stephen C. TI Medial prefrontal cortex: genes linked to bipolar disorder and schizophrenia have altered expression in the highly social maternal phenotype SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE microarray; bipolar disorder; schizophrenia; maternal behavior; social behavior ID RIBONUCLEIC-ACID LEVELS; PDGF BETA-RECEPTOR; LATERAL SEPTUM; CAENORHABDITIS-ELEGANS; PSYCHIATRIC-DISORDERS; POSTPARTUM PSYCHOSIS; EMOTIONAL RESPONSES; STRESS RESPONSES; NERVOUS-SYSTEM; GROWTH-FACTOR AB The transition to motherhood involves CNS changes that modify sociability and affective state. However, these changes also put females at risk for post-partum depression and psychosis, which impairs parenting abilities and adversely affects children. Thus, changes in expression and interactions in a core subset of genes may be critical for emergence of a healthy maternal phenotype, but inappropriate changes of the same genes could put women at risk for post-partum disorders. This study evaluated microarray gene expression changes in medial prefrontal cortex (mPFC), a region implicated in both maternal behavior and psychiatric disorders. Post-partum mice were compared to virgin controls housed with females and isolated for identical durations. Using the Modular Single-set Enrichment Test (MSET), we found that the genetic landscape of maternal mPFC bears statistical similarity to gene databases associated with schizophrenia (5 of 5 sets) and bipolar disorder (BPD, 3 of 3 sets). In contrast to previous studies of maternal lateral septum (LS) and medial preoptic area (MPOA), enrichment of autism and depression-linked genes was not significant (2 of 9 sets, 0 of 4 sets). Among genes linked to multiple disorders were fatty acid binding protein 7 (Fabp7), glutamate metabotropic receptor 3 (Grm3), platelet derived growth factor, beta polypeptide (Pdgfrb), and nuclear receptor subfamily 1, group D, member 1 (Nr1d1). RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (Flt1) and proenkephalin (Penk). Systems-level methods revealed involvement of developmental gene networks in establishing the maternal phenotype and indirectly suggested a role for numerous microRNAs and transcription factors in mediating expression changes. Together, this study suggests that a subset of genes involved in shaping the healthy maternal brain may also be dysregulated in mental health disorders and put females at risk for post-partum psychosis with aspects of schizophrenia and BPD. C1 [Eisinger, Brian E.; Driessen, Terri M.; Zhao, Changjiu; Gammie, Stephen C.] Univ Wisconsin, Dept Zool, Madison, WI 53706 USA. [Gammie, Stephen C.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. RP Eisinger, BE (reprint author), Univ Wisconsin, Dept Zool, 430 Lincoln Dr, Madison, WI 53706 USA. EM beeisinger@wisc.edu RI Zhao, Changjiu/M-8263-2014 FU United States National Institutes of Health [R01 MH 085642] FX The authors wish to thank Sharon Stevenson for managerial support, Wayne Davis and the University of Wisconsin-Madison Gene Expression Center for microarray technical assistance, and Kate Skogen and Jeff Alexander for animal care. This work was supported by the United States National Institutes of Health Grant R01 MH 085642 to Stephen Gammie. 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Behav. Neurosci. PD APR 2 PY 2014 VL 8 AR 110 DI 10.3389/fnbeh.2014.00110 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AD9KB UT WOS:000333582800001 PM 24765068 ER PT J AU Simms, BA Zamponi, GW AF Simms, Brett A. Zamponi, Gerald W. TI Neuronal Voltage-Gated Calcium Channels: Structure, Function, and Dysfunction SO NEURON LA English DT Review ID HYPOKALEMIC PERIODIC PARALYSIS; IDIOPATHIC GENERALIZED EPILEPSY; STATIONARY NIGHT BLINDNESS; T-TYPE CHANNELS; CORTICAL SPREADING DEPRESSION; HEMIPLEGIC MIGRAINE MUTATIONS; CHILDHOOD ABSENCE EPILEPSY; AUTISM SPECTRUM DISORDERS; CEREBELLAR PURKINJE-CELLS; PROTEIN-INTERACTION SITE AB Voltage-gated calcium channels are the primary mediators of depolarization-induced calcium entry into neurons. There is great diversity of calcium channel subtypes due to multiple genes that encode calcium channel alpha 1 subunits, coassembly with a variety of ancillary calcium channel subunits, and alternative splicing. This allows these channels to fulfill highly specialized roles in specific neuronal subtypes and at particular subcellular loci. While calcium channels are of critical importance to brain function, their inappropriate expression or dysfunction gives rise to a variety of neurological disorders, including, pain, epilepsy, migraine, and ataxia. This Review discusses salient aspects of voltage-gated calcium channel function, physiology, and pathophysiology. C1 [Simms, Brett A.; Zamponi, Gerald W.] Univ Calgary, Hotchkiss Brain Inst, Dept Physiol & Pharmacol, Calgary, AB T2N 4N1, Canada. RP Zamponi, GW (reprint author), Univ Calgary, Hotchkiss Brain Inst, Dept Physiol & Pharmacol, Calgary, AB T2N 4N1, Canada. 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Foulkes, Lucy Kita, Sotaro TI Individual Differences in Frequency and Saliency of Speech-Accompanying Gestures: The Role of Cognitive Abilities and Empathy SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL LA English DT Article DE gesture production; working memory; spatial transformation ability; conceptualization ability; empathy ID CONVERSATIONAL HAND GESTURES; EXECUTIVE FUNCTIONS; LEXICAL MOVEMENTS; COMMUNICATION; AUTISM; RECOGNITION; INFORMATION; PERSONALITY; REGRESSION; RETRIEVAL AB The present study concerns individual differences in gesture production. We used correlational and multiple regression analyses to examine the relationship between individuals' cognitive abilities and empathy levels and their gesture frequency and saliency. We chose predictor variables according to experimental evidence of the functions of gesture in speech production and communication. We examined 3 types of gestures: representational gestures, conduit gestures, and palm-revealing gestures. Higher frequency of representational gestures was related to poorer visual and spatial working memory, spatial transformation ability, and conceptualization ability; higher frequency of conduit gestures was related to poorer visual working memory, conceptualization ability, and higher levels of empathy; and higher frequency of palm-revealing gestures was related to higher levels of empathy. The saliency of all gestures was positively related to level of empathy. These results demonstrate that cognitive abilities and empathy levels are related to individual differences in gesture frequency and saliency. C1 [Chu, Mingyuan] Max Planck Inst Psycholinguist, Neurobiol Language Dept, NL-6500 AH Nijmegen, Netherlands. [Meyer, Antje] Max Planck Inst Psycholinguist, Psychol Language Dept, NL-6500 AH Nijmegen, Netherlands. [Meyer, Antje] Radboud Univ Nijmegen, Sch Psychol, NL-6525 ED Nijmegen, Netherlands. [Foulkes, Lucy] UCL, Dept Clin Educ & Hlth Psychol, London, England. [Kita, Sotaro] Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England. RP Chu, MY (reprint author), Max Planck Inst Psycholinguist, Neurobiol Language Dept, POB 310, NL-6500 AH Nijmegen, Netherlands. EM mingyuan.chu@mpi.nl RI Kita, Sotaro/B-2860-2008 OI Kita, Sotaro/0000-0002-0088-3654 FU Economic and Social Research Council [RES-062-23-2002] FX This research was supported by Economic and Social Research Council Grant RES-062-23-2002 to Sotaro Kita and Antje Meyer. For more information about the research materials underlying this article, please contact the corresponding author. We thank Farzana Bhaiyat, Christina Chelioti, Dayal Dhiman, Rachel Furness, Alicia Griffiths, Beatrice Hannah, Sagar Jilka, Johnny King Lau, Valentina Lee, Zeshu Shao, Callie Steadman, and Laura Torney for their help with data collection and coding. We thank Birmingham City University, Bishop Vesey's Grammar School, City College Birmingham, CTC Kingshurst Academy, and University College Birmingham for their participation in our research. 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Exp. Psychol.-Gen. PD APR PY 2014 VL 143 IS 2 BP 694 EP 709 DI 10.1037/a0033861 PG 18 WC Psychology, Experimental SC Psychology GA CB6WR UT WOS:000349768000019 PM 23915128 ER PT J AU Wilkinson, KM O'Neill, T Mcllvane, WJ AF Wilkinson, Krista M. O'Neill, Tara Mcllvane, William J. TI Eye-Tracking Measures Reveal How Changes in the Design of Aided AAC Displays Influence the Efficiency of Locating Symbols by School-Age Children Without Disabilities SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE augmentative and alternative communication; children; developmental disorders; intervention ID SHORT-TERM-MEMORY; VISUAL-SEARCH; DOWN-SYNDROME; ATTENTION DEFICITS; WORKING-MEMORY; YOUNG-CHILDREN; COLOR; AUTISM; INDIVIDUALS; TARGET AB Purpose: Many individuals with communication impairments use aided augmentative and alternative communication (AAC) systems involving letters, words, or line drawings that rely on the visual modality. It seems reasonable to suggest that display design should incorporate information about how users attend to and process visual information. The organization of AAC symbols can influence the speed and accuracy with which children select a target symbol on a display. This research examined why some displays facilitate responding. Method: Eye-tracking technology recorded point-of-gaze while children without disabilities engaged in a visual search task with 2 AAC displays. In 1 display, symbols sharing an internal color were clustered together. In the other display, like-colored symbols were distributed. Dependent measures were (a) latency to fixate on the target compared with distracters and (b) the number of fixations to target and distracters. Results: Participants were significantly slower to fixate on the target when like-colored symbols were distributed; there was a significant increase in the number of fixations to distracters that did not share color with the target. Conclusions: Efficient search was related to minimizing fixations to nonrelevant distracters. Vulnerability to distraction can be a significant problem in individuals with disabilities who use AAC. Minimizing the intrusion of such distraction may, therefore, be of importance in AAC display design. C1 [Wilkinson, Krista M.; O'Neill, Tara] Penn State Univ, University Pk, PA 16802 USA. [Wilkinson, Krista M.; Mcllvane, William J.] Univ Massachusetts, Sch Med, Shriver Ctr, Amherst, MA 01003 USA. RP Wilkinson, KM (reprint author), Penn State Univ, University Pk, PA 16802 USA. EM kmw22@psu.edu FU National Institute of Child Health and Human Development [HD P01 25995]; UMMS-Shriver Center [P30 HD 004147]; Hintz Family Endowed Chair in Children's Communicative Competence FX This research was supported by Project 2 of National Institute of Child Health and Human Development Grant HD P01 25995 (awarded to the first author), UMMS-Shriver Center Grant P30 HD 004147 (awarded to the third author), and an award from the Hintz Family Endowed Chair in Children's Communicative Competence (awarded to the first author). Thanks to all the individuals who contributed their time and effort, including Kelly McStravock, Chihui Yong, Kara Weasen, Maggie Kennedy, and Megan Warrenfeltz (ISCAN analysis) and Hilary Lee, Amanda Lippert, and Jenn Nauss (TOBii analysis). We thank the participants and their families and the Families Interested in Research Studies (FIRSt) Families database at The Pennsylvania State University. 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PD APR PY 2014 VL 57 IS 2 BP 455 EP 466 DI 10.1044/2013_JSLHR-L-12-0159 PG 12 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AZ4MM UT WOS:000348195600016 PM 24129007 ER PT J AU Ellawadi, AB Weismer, SE AF Ellawadi, Allison Bean Weismer, Susan Ellis TI Assessing Gestures in Young Children With Autism Spectrum Disorder SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE assessment; autism; language; gestures ID EARLY LANGUAGE-DEVELOPMENT; JOINT ATTENTION; COMMUNICATION; INTERVENTION; DIAGNOSIS; TODDLERS; AGE AB Purpose: The purpose of this study was to determine whether scoring of the gestures point, give, and show were correlated across measurement tools used to assess gesture production in children with an autism spectrum disorder (ASD). Method: Seventy-eight children with ASD between the ages of 23 and 37 months participated. Correlational analyses were conducted to determine whether performance of 3 key gestures related to joint attention and behavior regulation (point, give, show) were correlated across 3 different measurement tools: the Autism Diagnostic Observation Schedule, the Early Social Communication Scale, and the MacArthur-Bates Communicative Development Inventory: Words and Gestures. To establish whether different measures were related at different points in development, children were subdivided into 2 groups based on their expressive language levels. Results: The scoring of gesture performance was not entirely consistent across assessment methods. The score that a child received appeared to be influenced by theoretical perspective, gesture definition, and assessment methodology, as well as developmental level. Conclusion: When assessing the gestures of children with ASD, clinicians should determine what aspects of gesture they are interested in profiling, gather data from multiple sources, and consider performance in light of the measurement tool. C1 [Ellawadi, Allison Bean; Weismer, Susan Ellis] Ohio State Univ, Columbus, OH 43210 USA. RP Ellawadi, AB (reprint author), Ohio State Univ, Columbus, OH 43210 USA. EM ellawadi.1@osu.edu FU National Institutes of Health [NIDCD R01 DC007223, T32 DC05359, NICHD P30 HD03352] FX This research was supported by the National Institutes of Health Grant NIDCD R01 DC007223 and Training Grant T32 DC05359 (S. Ellis Weismer, PI), as well as by a core grant to the Waisman Center, NICHD P30 HD03352 (M. Mailick, PI). We also wish to express our sincere thanks to the children and parents who participated in this research. 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PD APR PY 2014 VL 57 IS 2 BP 524 EP 531 DI 10.1044/2013_JSLHR-L-12-0244 PG 8 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AZ4MM UT WOS:000348195600021 PM 24129012 ER PT J AU Bernier, R Aaronson, B Kresse, A AF Bernier, Raphael Aaronson, Benjamin Kresse, Anna TI EEG Mu Rhythm in Typical and Atypical Development SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 86; Electroencephalography (EEG); mu rhythm; imitation; autism spectrum disorder; social cognition; mirror neuron system ID AUTISM SPECTRUM DISORDERS; HIGH-RESOLUTION EEG; FUNCTIONAL-SIGNIFICANCE; CHILDREN; DESYNCHRONIZATION; PERCEPTION; MOVEMENT; INFANTS; SUPPRESSION; ACTIVATION AB Electroencephalography (EEG) is an effective, efficient, and noninvasive method of assessing and recording brain activity. Given the excellent temporal resolution, EEG can be used to examine the neural response related to specific behaviors, states, or external stimuli. An example of this utility is the assessment of the mirror neuron system (MNS) in humans through the examination of the EEG mu rhythm. The EEG mu rhythm, oscillatory activity in the 8-12 Hz frequency range recorded from centrally located electrodes, is suppressed when an individual executes, or simply observes, goal directed actions. As such, it has been proposed to reflect activity of the MNS. It has been theorized that dysfunction in the mirror neuron system (MNS) plays a contributing role in the social deficits of autism spectrum disorder (ASD). The MNS can then be noninvasively examined in clinical populations by using EEG mu rhythm attenuation as an index for its activity. The described protocol provides an avenue to examine social cognitive functions theoretically linked to the MNS in individuals with typical and atypical development, such as ASD. C1 [Bernier, Raphael; Aaronson, Benjamin; Kresse, Anna] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Bernier, Raphael; Aaronson, Benjamin] Univ Washington, Dept Educ Psychol, Seattle, WA 98195 USA. RP Bernier, R (reprint author), Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. EM rab2@u.washington.edu FU Simons Foundation (SFARI) [89638] FX This work was supported by a grant from the Simons Foundation (SFARI #89638 to RB). 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Vis. Exp. PD APR PY 2014 IS 86 AR e5141 DI 10.3791/51412 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA0LK UT WOS:000348609000059 ER PT J AU Kreis, P Leondaritis, G Lieberam, I Eickholt, BJ AF Kreis, Patricia Leondaritis, George Lieberam, Ivo Eickholt, Britta J. TI Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders SO FRONTIERS IN MOLECULAR NEUROSCIENCE LA English DT Review DE PTEN phosphohydrolase; neuronal morphology; synaptic transmission; membranes; PI3K/AKT/mTOR ID TUMOR-SUPPRESSOR PTEN; AUTISM SPECTRUM DISORDERS; LHERMITTE-DUCLOS-DISEASE; GROWTH CONE COLLAPSE; LONG-TERM DEPRESSION; TENSIN HOMOLOG; NUCLEAR PTEN; PHOSPHATASE-ACTIVITY; PLASMA-MEMBRANE; IN-VIVO AB PTEN is a lipid and protein phosphatase that regulates a diverse range of cellular mechanisms. PTEN is mainly present in the cytosol and transiently associates with the plasma membrane to dephosphorylate P1(3,4,5)P3, thereby antagonizing the P13-Kinase signaling pathway. Recently, PTEN has been shown to associate also with organelles such as the endoplasmic reticulum (ER), the mitochondria, or the nucleus, and to be secreted outside of the cell. In addition, PTEN dynamically localizes to specialized sub-cellular compartments such as the neuronal growth cone or dendritic spines. The diverse localizations of PTEN imply a tight temporal and spatial regulation, orchestrated by mechanisms such as posttranslational modifications, formation of distinct protein-protein interactions, or the activation/recruitment of PTEN downstream of external cues. The regulation of PTEN function is thus not only important at the enzymatic activity level, but is also associated to its spatial distribution. In this review we will summarize (i) recent findings that highlight mechanisms controlling PTEN movement and sub-cellular localization, and (ii) current understanding of how PTEN localization is achieved by mechanisms controlling posttranslational modification, by association with binding partners and by PTEN structural or activity requirements. Finally, we will discuss the possible roles of compartmentalized PTEN in developing and mature neurons in health and disease. C1 [Kreis, Patricia; Leondaritis, George; Lieberam, Ivo; Eickholt, Britta J.] Kings Coll London, MRC Ctr Dev Neurobiol, London WC2R 2LS, England. [Leondaritis, George; Eickholt, Britta J.] Charite, Inst Biochem, D-10117 Berlin, Germany. RP Eickholt, BJ (reprint author), Charite, Inst Biochem, Charitepl 1, D-10117 Berlin, Germany. 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Molec. Neurosci. PD APR 1 PY 2014 VL 7 AR 23 DI 10.3389/fnmol.2014.00023 PG 19 WC Neurosciences SC Neurosciences & Neurology GA AZ0YK UT WOS:000347967600001 PM 24744697 ER PT J AU Chalkia, D Derbeneva, O Lvova, M Lakatos, A Leipzig, J Hadley, D Hakonarson, H Wallace, D AF Chalkia, Dimitra Derbeneva, Olga Lvova, Maria Lakatos, Anita Leipzig, Jeremy Hadley, Dexter Hakonarson, Hakon Wallace, Douglas TI A mitochondrial bioenergetic hypothesis for autism spectrum disorder SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Hadley, Dexter; Hakonarson, Hakon] Childrens Hosp Philadelphia, Div Genet, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Leipzig, Jeremy] Childrens Hosp Philadelphia, Res Inst, Ctr Biomed Informat, Philadelphia, PA 19104 USA. [Chalkia, Dimitra; Derbeneva, Olga; Lvova, Maria; Wallace, Douglas] Childrens Hosp Philadelphia, Res Inst, Ctr Mitochondrial & Epigen Med, Philadelphia, PA 19104 USA. [Wallace, Douglas] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Lakatos, Anita] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 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 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 570.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701437 ER PT J AU Hamlin, J Crook, T James, J Gonzales, D Hakkak, R AF Hamlin, JoAnna Crook, Tina James, Jill Gonzales, Dana Hakkak, Reza TI Correlation between dietary intake and plasma levels of choline and betaine in children with autism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Hamlin, JoAnna; Crook, Tina; James, Jill; Gonzales, Dana; Hakkak, Reza] UAMS, Little Rock, AR 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 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 827.1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705010 ER PT J AU Martinez, L Tejada-Simon, M AF Martinez, Luis Tejada-Simon, Maria TI Targeting hyperactive Rho GTPase regulatory proteins in autism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Martinez, Luis; Tejada-Simon, Maria] Univ Houston, Houston, TX 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 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 845.7 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705149 ER PT J AU Penn, A Lai, T Carver, L Taylor, S Schmid-Schonbein, G Dobkins, K AF Penn, Alexander Lai, Tiffany Carver, Leslie Taylor, Sharon Schmid-Schoenbein, Geert Dobkins, Karen TI Intestinal permeability as measured by lactulose mannitol ratio continues to decrease during infancy after 3 months of age for both control infants and infants at high risk for autism spectrum disorders SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Penn, Alexander; Lai, Tiffany; Carver, Leslie; Taylor, Sharon; Schmid-Schoenbein, Geert; Dobkins, Karen] Univ Calif San Diego, La Jolla, CA 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 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA LB751 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651005128 ER PT J AU Sealey, L Bagasra, O AF Sealey, Leanna Bagasra, Omar TI The male gender bias in autism may be due to preferential depletions of oxytocin and arginine-vasopressin receptors positive neurons exposed to certain fragrances during fetal development SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Sealey, Leanna; Bagasra, Omar] Claflin Univ, Orangeburg, SC 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 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA LB502 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651004443 ER PT J AU Cavalari, RNS DuBard, M Luiselli, JK AF Cavalari, Rachel N. S. DuBard, Melanie Luiselli, James K. TI Simplified Habit Reversal and Treatment Fading for Chronic Skin Picking in an Adolescent With Autism SO CLINICAL CASE STUDIES LA English DT Article DE skin picking; simplified habit reversal; competing response training; differential reinforcement; autism ID SELF-INJURIOUS-BEHAVIOR; POPULATION; PREVALENCE AB We evaluated the effects of simplified habit reversal (HR) that combined competing response training and differential reinforcement on skin picking by an adolescent female with autism attending a classroom at a specialized school. The competing response training procedure allowed her to manipulate preferred sensory stimuli independently and when instructed by classroom staff. Differential reinforcement included praise and tokens that she received following intervals without skin picking and when she performed competing response training. Compared with a baseline phase, skin picking decreased with simplified HR and during a subsequent phase when treatment was faded by implementing differential reinforcement without competing response training. We discuss the clinical implications of these findings. C1 [Cavalari, Rachel N. S.; Luiselli, James K.] May Inst, Randolph, MA USA. [DuBard, Melanie] May Inst, Educ Serv, Randolph, MA USA. [DuBard, Melanie] May Inst, Clin Serv, Randolph, MA USA. [Luiselli, James K.] May Inst, Training Predoctoral Internship Program Clin Psyc, Randolph, MA USA. [Luiselli, James K.] May Inst, Training Postdoctoral Fellowship Program Clin Psy, Randolph, MA USA. [Cavalari, Rachel N. 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TI Speech-Language Intervention for Children With Autism Spectrum Disorder in Brazil SO TOPICS IN LANGUAGE DISORDERS LA English DT Article DE autistic disorder; child language; language and hearing sciences; public policies; speech; Unified Health System AB Brazil has more than 200 million inhabitants living in an area of more than 8.5 million km(2) (Ministerio da Saude, Brasil, 2013a,b). Granting access to health and educational services for populations in such different environments clearly demands different actions and resources. Official policies regarding rehabilitation services and education to children and adolescents with autism spectrum disorders (ASDs) are being gradually defined and implemented. This article aims to present an overview of the Brazilian health system that considers health as a universal right and a state's duty. Some of the strategies created to provide services to persons with different needs living in different environments are outlined. Specifically in what refers to persons with ASD, there are laws, bills of rights, and guidelines, but their implementation is gradual and uneven. More developed regions provide more comprehensive support to these persons and their families, but some initiatives of outreach are being implemented. Speech-language pathology services are integrated to the health system and present their own challenges. Undergraduate programs for speech-language pathology include ASD as part of the mandatory training, and there are postgraduate studies in the field. Some challenges are being met by several initiatives by different groups as parents, scientific associations, and universities. Issues such as tests and protocols that can be used to Portuguese-speaking children and the identification of efficient methods that can be applied in different situations and orientation to parents and families have been object of research for some decades. There are still many challenges that must be addressed to provide adequate health and educational services to children with ASD and their families in Brazil. C1 [Miranda Fernandes, Fernanda Dreux; Defense-Netrval, Danielle A.; Molini-Avejonas, Daniela R.] Univ Sao Paulo FMUSP, Sch Med, Sao Paulo, Brazil. [Amato, Cibelle A. H.] FMUSP, Autism Spectrum Disorders Res Lab LIF DEA, Sao Paulo, Brazil. RP Fernandes, FDM (reprint author), Univ Sao Paulo, Fac Med, Dept Fisioterapia Fonoaudiol & Terapia Ocupac, Rua Cipotanea 51, BR-05360 Sao Paulo, Brazil. EM fernandadreux@usp.br CR ABC da Saude, 2013, AUTISMO Amato C. A., 2011, REVISTA DA SOCIEDADE, V16, P104 Andrade C. R., 2000, ABFW TESTE DE LINGUA, P89 [Anonymous], 2012, REVISTA DA SOCIEDADE [Anonymous], 2012, JORNAL DA SOCIEDADE [Anonymous], 2013, ACR AUDIOLOGY COMMUN Associacao amigos do Autista, 2013, DEFINICAO AUTISMO Autismo e Realidade, 2013, SOBRE O AUTISMO Balestro J. 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PD APR-JUN PY 2014 VL 34 IS 2 BP 155 EP 167 DI 10.1097/TLD.0000000000000011 PG 13 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA AT6CU UT WOS:000345027500006 ER PT J AU Lee, YJ Oh, SH Park, C Hong, MH Lee, AR Yoo, HJ Shin, CY Cheon, KA Bahn, GH AF Lee, Yeon Jung Oh, Soo Hyun Park, Chanmin Hong, Minha Lee, Ah Rah Yoo, Hee Jeong Shin, Chan Young Cheon, Keun-Ah Bahn, Geon Ho TI Advanced Pharmacotherapy Evidenced by Pathogenesis of Autism Spectrum Disorder SO CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE LA English DT Review DE Child development disorders; pervasive; Drug therapy; Etiology ID PERVASIVE DEVELOPMENTAL DISORDERS; OXYTOCIN-RECEPTOR GENE; OPEN-LABEL TRIAL; VITAMIN-D; ALTERNATIVE MEDICINE; N-ACETYLCYSTEINE; NEURODEGENERATIVE DISEASES; NEURONAL DIFFERENTIATION; TUBEROUS-SCLEROSIS; SOCIAL-INTERACTION AB In clinical practice, pharmacological treatment is mostly focused on behavioral symptoms in everyday life. Nevertheless, persistent effort continues to develop medication for causal treatment. Recent changes in diagnostic criteria from Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) to DSM-5 would affect not only diagnosing approaches, but also therapeutic approaches. Because previous pervasive developmental disorders have been integrated into a single entity, the autism spectrum disorder (ASD), we have to prepare for what medications are valuable for the ASD. In this article, we reviewed the following etiological treatment: acetylcholine and glutamate related medicine; amino acid medicine such as secret in, endogenous opioid, and oxytocin; complementary and alternative medicine such as chelating agents, vitamins, and omega-3; promising drugs related to the scope of pharmacogenetics currently under study. C1 [Lee, Yeon Jung; Park, Chanmin; Bahn, Geon Ho] Kyung Hee Univ, Sch Med, Dept Psychiat, Seoul 130702, South Korea. [Oh, Soo Hyun] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea. [Lee, Ah Rah] Kyung Hee Univ, Sch Med, Seoul 130702, South Korea. [Yoo, Hee Jeong] Seoul Natl Univ, Bundang Hosp, Dept Neuropsychiat, Songnam, South Korea. [Shin, Chan Young] Konkuk Univ, Sch Med, Dept Pharmacol, Seoul, South Korea. [Cheon, Keun-Ah] Yonsei Univ, Coll Med, Dept Psychiat, Seoul, South Korea. [Hong, Minha] Dankook Univ, Coll Med, Dept Psychiat, Chungnam, South Korea. RP Bahn, GH (reprint author), Kyung Hee Univ, Sch Med, Dept Psychiat, 23 Kyungheedae Ro, Seoul 130702, South Korea. EM mompeian@khu.ac.kr FU Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea [A120029] FX This work was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (No. A120029). 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Psychopharmacol. Neurosci. PD APR PY 2014 VL 12 IS 1 BP 19 EP 30 DI 10.9758/cpn.2014.12.1.19 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AQ5NJ UT WOS:000342855600003 PM 24851117 ER PT J AU Bone, D Lee, CC Narayanan, S AF Bone, Daniel Lee, Chi-Chun Narayanan, Shrikanth TI Robust Unsupervised Arousal Rating: A Rule-Based Framework with Knowledge-Inspired Vocal Features SO IEEE TRANSACTIONS ON AFFECTIVE COMPUTING LA English DT Article DE Arousal; activation; rule-based rating; knowledge-inspired features; cross-corpora classification; continuous affect tracking ID ACOUSTIC EMOTION RECOGNITION; ACTIVATION; SPEECH; MODEL; PERCEPTION; EXPRESSION; RESPONSES; AUTISM; SCALES AB Studies in classifying affect from vocal cues have produced exceptional within-corpus results, especially for arousal (activation or stress); yet cross-corpora affect recognition has only recently garnered attention. An essential requirement of many behavioral studies is affect scoring that generalizes across different social contexts and data conditions. We present a robust, unsupervised (rule-based) method for providing a scale-continuous, bounded arousal rating operating on the vocal signal. The method incorporates just three knowledge-inspired features chosen based on empirical and theoretical evidence. It constructs a speaker's baseline model for each feature separately, and then computes single-feature arousal scores. Lastly, it advantageously fuses the single-feature arousal scores into a final rating without knowledge of the true affect. The baseline data is preferably labeled as neutral, but some initial evidence is provided to suggest that no labeled data is required in certain cases. The proposed method is compared to a state-of-the-art supervised technique which employs a high-dimensional feature set. 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The author tries to highlight the ambiguity of this symptom, because both its semiological acceptation and his importance in schizophrenic symptomatology are not properly qualified. The study of its clinical manifestations leads to call into question both its accepted meaning and its interpretation. While most authors seem to agree that negativistic behavior is an effect of the withdrawal of object love and seems therefore to reinforce the autistic position of schizophrenic patient, the author underlines what is left unexplained by such theories: the common alternation between states of negativism and states of complete submission to an all-powerful object. This frequent reversal of the sign of the object relation shows that negativism could be precisely understood as an attempt to re-establish an object cathexis, that is to say, an attempt to heal. (C) 2012 Elsevier Masson SAS. All rights reserved. C1 [Lepoutre, Thomas] Univ Paris Diderot, CRPMS, Sorbonne Paris Cite, EA 3522, F-75205 Paris 13, France. [Lepoutre, Thomas] Etab Publ Sante Erasme, F-92161 Antony, France. RP Lepoutre, T (reprint author), Univ Paris Diderot, CRPMS, Sorbonne Paris Cite, 5 Rue Thomas Mann, F-75205 Paris 13, France. 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Psychiatr. PD APR-JUN PY 2014 VL 79 IS 2 BP 321 EP 344 DI 10.1016/j.evopsy.2012.09.008 PG 24 WC Psychiatry SC Psychiatry GA AJ6BZ UT WOS:000337776000010 ER PT J AU Vannucchi, G Masi, G Toni, C Dell'Osso, L Marazziti, D Perugi, G AF Vannucchi, Giulia Masi, Gabriele Toni, Cristina Dell'Osso, Liliana Marazziti, Donatella Perugi, Giulio TI Clinical features, developmental course, and psychiatric comorbidity of adult autism spectrum disorders SO CNS SPECTRUMS LA English DT Review DE Adult autistic spectrum disorders; mood disorders; personality disorders; psychiatric comorbidity; schizophrenia ID HIGH-FUNCTIONING AUTISM; OBSESSIVE-COMPULSIVE DISORDER; ASPERGER-SYNDROME; REPETITIVE BEHAVIORS; BIPOLAR DISORDER; FAMILY-HISTORY; PERSONALITY-DISORDER; MULTIPLE-INCIDENCE; INFANTILE-AUTISM; YOUNG-ADULTS AB Autism spectrum disorders (ASDs) include a heterogeneous group of neurodevelopmental disorders with early onset in childhood. ASDs should be considered lifelong clinical entities, although there is a certain variability in developmental trajectories, and therefore should be considered of great interest also for adulthood psychiatrists. A few studies have been carried out to explore the clinical picture and course development of these disorders during adulthood, or their relationship with other mental disorders. Indeed, ASDs often share overlapping features with other disorders, such as schizophrenia and obsessive-compulsive, mood, and personality disorders, and as a result misdiagnoses often occur. The aim of this review is to summarize the available literature on ASDs in adulthood with a specific focus on the clinical picture, course, and psychiatric comorbidity. It is proposed that a careful diagnostic screening for ASDs in adults would contribute to clarifying the relationship with comorbid psychiatric disorders, while improving the possibility of treatment and outcome of such conditions. 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PD APR PY 2014 VL 19 IS 2 BP 157 EP 164 DI 10.1017/S1092852913000941 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AJ5SM UT WOS:000337748000008 PM 24352005 ER PT J AU Koike, S Bundo, M Iwamoto, K Suga, M Kuwabara, H Ohashi, Y Shinoda, K Takano, Y Iwashiro, N Satomura, Y Nagai, T Natsubori, T Tada, M Yamasue, H Kasai, K AF Koike, S. Bundo, M. Iwamoto, K. Suga, M. Kuwabara, H. Ohashi, Y. Shinoda, K. Takano, Y. Iwashiro, N. Satomura, Y. Nagai, T. Natsubori, T. Tada, M. Yamasue, H. Kasai, K. TI A snapshot of plasma metabolites in first-episode schizophrenia: a capillary electrophoresis time-of-flight mass spectrometry study SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID AUTISM SPECTRUM DISORDERS; CREATINE-KINASE LEVELS; METHYLENETETRAHYDROFOLATE REDUCTASE; EARLY INTERVENTION; PERIPHERAL-BLOOD; AMINO-ACIDS; PSYCHOSIS; DISEASE; SERUM; HOMOCYSTEINE AB Few biomarkers have been known that can easily measure clinical conditions in mental illnesses such as schizophrenia. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) is a new method that can measure ionized and low-molecular-weight metabolites. To explore global metabolomic alterations that characterize the onset of schizophrenia and identify biomarkers, we profiled the relative and absolute concentrations of the plasma metabolites from 30 patients with first-episode schizophrenia (FESZ, four drug-naive samples), 38 healthy controls and 15 individuals with autism spectrum disorders using CE-TOFMS. Five metabolites had robust changes (increased creatine and decreased betaine, nonanoic acid, benzoic acid and perillic acid) in two independent sample sets. Altered levels of these metabolites are consistent with well-known hypotheses regarding abnormalities of the homocysteine metabolism, creatine kinase-emia and oxidative stress. Although it should be considered that most patients with FESZ received medication, these metabolites are candidate biomarkers to improve the determination of diagnosis, severity and clinical stages, especially for FESZ. C1 [Koike, S.; Suga, M.; Kuwabara, H.; Takano, Y.; Iwashiro, N.; Satomura, Y.; Nagai, T.; Natsubori, T.; Tada, M.; Yamasue, H.; Kasai, K.] Univ Tokyo, Grad Sch Med, Dept Neuropsychiat, Tokyo 1138655, Japan. [Koike, S.] Univ Tokyo, Div Counseling & Support, Tokyo 1138655, Japan. [Bundo, M.; Iwamoto, K.] Univ Tokyo, Grad Sch Med, Dept Mol Psychiat, Tokyo 1138655, Japan. [Kuwabara, H.] Univ Tokyo, Grad Sch Med, Dept Child Neuropsychiat, Tokyo 1138655, Japan. [Ohashi, Y.; Shinoda, K.] Human Metabolome Technol, Tsuruoka, Yamagata, Japan. [Yamasue, H.] Japan Sci & Technol Agcy, CREST, Tokyo, Japan. [Kasai, K.] Japan Sci & Technol Agcy, NBDC, Tokyo, Japan. RP Kasai, K (reprint author), Univ Tokyo, Grad Sch Med, Dept Neuropsychiat, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM kasaik-tky@umin.net FU Ministry of Health, Labour and Welfare (Health and Labour Sciences Research Grants); Research on Psychiatric and Neurological Diseases and Mental Health [H22seishin-ippan-015]; Health and Labour Science Research Grant for Comprehensive Research on Disability Health and Welfare [H23-seishin-ippan-002]; JSPS/MEXT [22791108, 24791200, 21249064]; Scientific Research on Innovative Areas (Comprehensive Brain Science Network and Adolescent Mind & Self-Regulation [23118001, 23118004]; Japan Health Sciences Foundation FX We thank Fumiko Sunaga for substantial support in sample management, and Chie Shimojyo, Aki Takei, Eriko Ichikawa, and Aya Kikutugi for substantial support in clinical data assessment and management. This study was supported by grants from the Ministry of Health, Labour and Welfare (Health and Labour Sciences Research Grants, Research on Psychiatric and Neurological Diseases and Mental Health H22seishin-ippan-015 to KK and Health and Labour Science Research Grant for Comprehensive Research on Disability Health and Welfare H23-seishin-ippan-002 to HY) and from the JSPS/MEXT (No. 22791108 & 24791200 to MS, and No. 21249064 & Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network and Adolescent Mind & Self-Regulation (23118001 & 23118004)) to KK), and by grant from Japan Health Sciences Foundation (publicprivate sector joint research on publicly essential drugs to KI). A portion of this study was also the result of a project entitled 'Development of biomarker candidates for social behavior' carried out under the Strategic Research Program for Brain Sciences by the MEXT. 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Psychiatr. PD APR PY 2014 VL 4 AR e379 DI 10.1038/tp.2014.19 PG 8 WC Psychiatry SC Psychiatry GA AJ2RV UT WOS:000337509000004 PM 24713860 ER PT J AU Rose, S Frye, RE Slattery, J Wynne, R Tippett, M Melnyk, S James, SJ AF Rose, S. Frye, R. E. Slattery, J. Wynne, R. Tippett, M. Melnyk, S. James, S. J. TI Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; SPARE RESPIRATORY CAPACITY; N-ACETYLCYSTEINE; COMPLEX-I; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; METHYL MERCURY; CYTOCHROME-C; DOUBLE-BLIND; APOPTOSIS AB There is an increasing recognition that mitochondrial dysfunction is associated with autism spectrum disorders. However, little attention has been given to the etiology of mitochondrial dysfunction and how mitochondrial abnormalities might interact with other physiological disturbances such as oxidative stress. Reserve capacity is a measure of the ability of the mitochondria to respond to physiological stress. In this study, we demonstrate, for the first time, that lymphoblastoid cell lines (LCLs) derived from children with autistic disorder (AD) have an abnormal mitochondrial reserve capacity before and after exposure to reactive oxygen species (ROS). Ten (44%) of 22 AD LCLs exhibited abnormally high reserve capacity at baseline and a sharp depletion of reserve capacity when challenged with ROS. This depletion of reserve capacity was found to be directly related to an atypical simultaneous increase in both proton-leak respiration and adenosine triphosphate-linked respiration in response to increased ROS in this AD LCL subgroup. In this AD LCL subgroup, 48-hour pretreatment with N-acetylcysteine, a glutathione precursor, prevented these abnormalities and improved glutathione metabolism, suggesting a role for altered glutathione metabolism associated with this type of mitochondrial dysfunction. The results of this study suggest that a significant subgroup of AD children may have alterations in mitochondrial function, which could render them more vulnerable to a pro-oxidant microenvironment as well as intrinsic and extrinsic sources of ROS such as immune activation and pro-oxidant environmental toxins. These findings are consistent with the notion that AD is caused by a combination of genetic and environmental factors. C1 [Rose, S.; Frye, R. E.; Slattery, J.; Wynne, R.; Tippett, M.; Melnyk, S.; James, S. J.] Univ Arkansas Med Sci, Arkansas Childrens Hosp Res Inst, Dept Pediat, Little Rock, AR 72202 USA. RP Frye, RE (reprint author), Univ Arkansas Med Sci, Arkansas Childrens Hosp Res Inst, Dept Pediat, Slot 512-41B,Room R4041,13 Childrens Way, Little Rock, AR 72202 USA. EM REFrye@uams.edu FU National Institute for Child Health and Development; Arkansas Biosciences Institute; Jane Botsford Johnson Foundation FX This research was funded by the National Institute for Child Health and Development (SJJ), the Arkansas Biosciences Institute (REF, SJJ), and the Jane Botsford Johnson Foundation (REF). 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Psychiatr. PD APR PY 2014 VL 4 AR e377 DI 10.1038/tp.2014.15 PG 8 WC Psychiatry SC Psychiatry GA AJ2RV UT WOS:000337509000002 PM 24690598 ER PT J AU Sampino, S Juszczak, GR Zacchini, F Swiergiel, AH Modlinski, JA Loi, P Ptak, GE AF Sampino, S. Juszczak, G. R. Zacchini, F. Swiergiel, A. H. Modlinski, J. A. Loi, P. Ptak, G. E. TI Grand-paternal age and the development of autism-like symptoms in mice progeny SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID DE-NOVO MUTATIONS; MOUSE MODEL; SPECTRUM DISORDERS; SOCIAL-BEHAVIOR; MUTANT MICE; RISK; RATS; SCHIZOPHRENIA; RELEVANT; VOCALIZATIONS AB Advanced paternal age (APA) contributes to the risk of autism spectrum disorders (ASDs) in children. In this study, we used a mouse model to investigate the effects of APA on behavioral features related to autistic syndromes (that is, social deficits, communication impairments and stereotypic/repetitive behaviors). We also examined whether such effects are transmitted across generations. To do this, males aged 15 months (APA) and 4 months (control) were bred with 4-month-old females, and the resulting offspring (F1) and their progeny (F2; conceived by 4-month-old parents) were tested for the presence and severity of ASD-like behaviors. Our results indicate that APA resulted in offspring that displayed distinctive symptoms of ASD. We found that both F1 conceived from old fathers and F2 derived from old grandfathers displayed increased ultrasound vocalization (USV) activity, decreased sociability, increased grooming activity and increased anxiety-like responses. Moreover, such abnormalities were partially transmitted to the second generation of mice, having APA grandfathers. In conclusion, our study suggests that the risk of ASD could develop over generations, consistent with heritable mutations and/or epigenetic alterations associated with APA. C1 [Sampino, S.; Zacchini, F.; Loi, P.; Ptak, G. E.] Univ Teramo, Fac Vet Med, I-64100 Teramo, Italy. [Sampino, S.; Juszczak, G. R.; Modlinski, J. A.; Ptak, G. E.] Polish Acad Sci, Inst Genet & Anim Breeding, Jastrzebiec, Poland. [Swiergiel, A. H.] Univ Gdansk, Fac Biol, PL-80952 Gdansk, Poland. [Swiergiel, A. H.] LSUHSC, Dept Pharmacol Toxicol & Neurosci, Shreveport, LA USA. RP Ptak, GE (reprint author), Univ Teramo, Fac Vet Med, Pza Aldo Moro 45, I-64100 Teramo, Italy. EM gptak@unite.it FU European Research Council [210103]; FECUND [312097, FP7-KBBE-2012.1.3-04]; MIUR/CNR; IGAB PAS project [S.III.1.3]; Programme FIRB; GenHome [B81J12002520001] FX This work was supported by the European Research Council (FP7/2007-2013)/Programme IDEAS GA no. 210103 to GEP; Programme FP7-KBBE-2012.1.3-04, GA no. 312097 Acronym: FECUND, to GEP; MIUR/CNR, Programme FIRB. GA n. B81J12002520001 Acronym: GenHome, to PL. This study was also partially financed by the IGAB PAS project (S.III.1.3). The authors are participating in the COST action FA 1201 'Epiconcept' Epigenetic and Periconception Environment. 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Psychiatr. PD APR PY 2014 VL 4 AR e386 DI 10.1038/tp.2014.27 PG 7 WC Psychiatry SC Psychiatry GA AJ2RV UT WOS:000337509000011 PM 24780920 ER PT J AU Rehg, JM Rozga, A Abowd, GD Goodwin, MS AF Rehg, James M. Rozga, Agata Abowd, Gregory D. Goodwin, Matthew S. TI Behavioral Imaging and Autism SO IEEE PERVASIVE COMPUTING LA English DT Editorial Material C1 [Rehg, James M.; Rozga, Agata; Abowd, Gregory D.] Georgia Inst Technol, Coll Comp, Atlanta, GA 30332 USA. [Goodwin, Matthew S.] Northeastern Univ, Dept Hlth Sci, Boston, MA USA. [Goodwin, Matthew S.] Northeastern Univ, Coll Comp & Informat Sci, Boston, MA USA. RP Rehg, JM (reprint author), Georgia Inst Technol, Coll Comp, Atlanta, GA 30332 USA. EM rehg@gatech.edu; agata@gatech.edu; abowd@gatech.edu; m.goodwin@neu.edu CR Cordero J., 2006, CDC ICDL COLLABORATI Oller DK, 2010, P NATL ACAD SCI USA, V107, P13354, DOI 10.1073/pnas.1003882107 Rehg JM, 2013, PROC CVPR IEEE, P3414, DOI 10.1109/CVPR.2013.438 Ye Z., 2012, P 2012 ACM C UB COMP, P699 NR 4 TC 1 Z9 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1536-1268 EI 1558-2590 J9 IEEE PERVAS COMPUT JI IEEE Pervasive Comput. PD APR-JUN PY 2014 VL 13 IS 2 BP 84 EP 87 PG 4 WC Computer Science, Information Systems; Engineering, Electrical & Electronic; Telecommunications SC Computer Science; Engineering; Telecommunications GA AI8FX UT WOS:000337146300015 ER PT J AU Ikeda, Y Okuzumi, H Kokubun, M AF Ikeda, Yoshifumi Okuzumi, Hideyuki Kokubun, Mitsuru TI Inhibitory control in children with intellectual disabilities with and without autism spectrum disorders in animal size tests SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES LA English DT Article DE inhibition; executive function; executive dysfunction; cognitive control; intellectual and developmental disabilities; Autistic ID AGE-RELATED TRENDS; EXECUTIVE FUNCTIONS; WILLIAMS-SYNDROME; INDIVIDUAL-DIFFERENCES; YOUNG-CHILDREN; DOWNS-SYNDROME; STROOP; INTERFERENCE; INTELLIGENCE; ATTENTION AB Objectives: Inhibitory control plays an important role in various aspects of child development. The aim of this study was to compare inhibitory control of children with intellectual disabilities (ID) of unknown etiology, children with ID and autism spectrum disorders (ASD), and typically developing (TD) children. Methods: This study examined 41 children in three groups: 11 children with ID of unknown etiology, 9 children with ID and ASD, and 21 TD children who were matched for mental age. Two Stroop-like tasks were administered: the Real Animal Size Test and the Pictorial Animal Size Test. In these tests, participants are presented with pictures of animals (large animals such as an elephant, a giraffe, and a whale vs. small animals such as a frog, a bird, and a squirrel) printed as either big or small images that are mismatched with the animal's real size. Participants must decide the size of the animals (big vs. small) based either on the size in real life or the size of the picture, resisting interference of irrelevant sizes in real life or in a picture. Results: Interference was greater in the Pictorial Animal Size Test for all groups. Interference was greater in children with ID of unknown etiology compared to TD children, whereas interference was comparable between children with ID and ASD and TD children. Conclusion: Results of this study suggest that inhibitory control is unimpaired in children with ID and ASD but impaired in children with ID of unknown etiology, relative to mental-age matched TD children. C1 [Ikeda, Yoshifumi; Okuzumi, Hideyuki; Kokubun, Mitsuru] Tokyo Gakugei Univ, Fac Educ, Tokyo 1848501, Japan. RP Ikeda, Y (reprint author), Tokyo Gakugei Univ, Fac Educ, 4-1-1 Nukuikita, Tokyo 1848501, Japan. 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D., 2002, BLACKWELL HDB CHILDH, P445, DOI DOI 10.1002/9780470996652.CH20 Zelazo P. D., 2011, WILEY BLACKWELL HDB, P574, DOI DOI 10.1002/9781444325485.CH22 NR 55 TC 0 Z9 0 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 2047-3869 EI 2047-3877 J9 INT J DEV DISABIL JI Int. J. Dev. Disabil. PD APR PY 2014 VL 60 IS 2 BP 80 EP 88 DI 10.1179/2047387713Y.0000000024 PG 9 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AI7SW UT WOS:000337099700003 ER PT J AU Ahmed-Husain, S Dunsmuir, S AF Ahmed-Husain, Sajda Dunsmuir, Sandra TI An evaluation of the effectiveness of Comic Strip Conversations in promoting the inclusion of young people with autism spectrum disorder in secondary schools SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES LA English DT Article DE Comic Strip Conversations; Autism Spectrum Disorder; intervention; evaluation ID QUANTITATIVE SYNTHESIS; ASPERGER-SYNDROME; SOCIAL STORIES; CHILDREN; LONELINESS; STUDENTS; BEHAVIOR; SKILLS AB Objectives: Comic Strip Conversations (CSCs; Gray 1994) can be used to improve the social skills of individuals on the autism spectrum as well as pupils with other learning and/or speech difficulties. This study aimed to evaluate this intervention to improve specific problematic target behaviours of eleven to fourteen year old pupils with Autism Spectrum Disorder (ASD), to ascertain whether or not including a written (visual) action plan or a discussion about actions (auditory action plan) would have an impact and to find out whether more effective action plans matched participants' visual and verbal skill profiles. Methods: A total of eight participants ranging from eleven to fourteen years of age received the intervention in school. Cognitive assessments were conducted to assess verbal and non-verbal functioning. A multiple baseline design across behaviours was implemented. Structured observations were conducted in order to determine whether or not the CSC intervention had an impact on target behaviours. Results: The percentage of data points exceeding the median (PEM) of the baseline phase and Tau-U analyses were calculated from the observational data. Combined with visual inspection of graphs, the intervention was found to be moderately to highly effective at reducing/improving target behaviours in seven out of eight participants. Conclusion: Although there was no general association between the type of action plan (visual or verbal) and outcome, the more successful action plans included highly specified, unambiguous target behaviours, realistic and implementable strategies/solutions, regular reviews of the CSC and a mode of presentation that matched the participants' skill preferences. C1 [Ahmed-Husain, Sajda] Civ Ctr, Hounslow Early Intervent Adults & Childrens Serv, Hounslow TW3 4DN, England. [Dunsmuir, Sandra] UCL, Res Dept Clin Educ & Hlth Psychol, London WC1E 0AP, England. RP Ahmed-Husain, S (reprint author), DECPsy, London, England. 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PD APR PY 2014 VL 60 IS 2 BP 89 EP 108 DI 10.1179/2047387713Y.0000000025 PG 20 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AI7SW UT WOS:000337099700004 ER PT J AU Bodur, S Ceylan, MF Iseri, E Sener, S Yucel, AA AF Bodur, Sahin Ceylan, Mehmet Fatih Iseri, Elvan Sener, Sahnur Yucel, Aysegul Atak TI Serum neopterin levels in patients with autism SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; autism spectrum disorder; neopterin; cellular immunity ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SPECTRUM DISORDER; CONGENITAL-RUBELLA; CHILDHOOD AUTISM; OXIDATIVE STRESS; INFANTILE-AUTISM; RATING-SCALES; RISK-FACTORS; CHILDREN; DISEASE AB Objective: Autism is a chronic neurodevelopmental disorder with an aetiology that is not fully understood. Published findings have identified widespread changes in the immune systems of children with autism. The latest findings show that the pathophysiology of autism may be associated with cellular immunity. Neopterin is a good indicator of cellular immunity, and changes in neopterin may have diagnostic importance. Methods: The study group consisted of 23 patients with autism. An age- and gender-matched control group was composed of 21 healthy subjects. Venous blood samples were collected, and the levels of neopterin were measured. Results: The levels of neopterin were significantly higher in the autistic children than in the comparison subjects. Conclusions: Cellular immunity may have a role in the aetiopathogenesis of autism. Increased serum neopterin levels may have diagnostic importance in autism. C1 [Bodur, Sahin; Ceylan, Mehmet Fatih] Dr Sami Ulus Childrens Hosp, Dept Child & Adolescent Psychiat, TR-06080 Ankara, Turkey. [Iseri, Elvan; Sener, Sahnur] Gazi Univ, Fac Med, Dept Child & Adolescent Psychiat, Ankara, Turkey. 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J. Dev. Disabil. PD APR PY 2014 VL 60 IS 2 BP 109 EP 115 DI 10.1179/2047387713Y.0000000029 PG 7 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AI7SW UT WOS:000337099700005 ER PT J AU Sarginson, C AF Sarginson, Catherine TI Practical mathematics for children with an autism spectrum disorder and other developmental delays SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES LA English DT Book Review CR ADKINS J, 2013, PRACTICAL MATH CHILD NR 1 TC 0 Z9 0 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 2047-3869 EI 2047-3877 J9 INT J DEV DISABIL JI Int. J. Dev. Disabil. PD APR PY 2014 VL 60 IS 2 BP 117 EP 118 PG 2 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AI7SW UT WOS:000337099700008 ER PT J AU Culling, E AF Culling, Ewan TI Development and brain systems in autism SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES LA English DT Book Review CR JUST MA, 2013, DEV BRAIN SYSTEMS AU NR 1 TC 0 Z9 0 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 2047-3869 EI 2047-3877 J9 INT J DEV DISABIL JI Int. J. Dev. Disabil. PD APR PY 2014 VL 60 IS 2 BP 118 EP 119 PG 2 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AI7SW UT WOS:000337099700009 ER PT J AU Streck, EL Goncalves, CL Furlanetto, CB Scaini, G Dal-Pizzol, F Quevedo, J AF Streck, Emilio L. Goncalves, Cinara L. Furlanetto, Camila B. Scaini, Giselli Dal-Pizzol, Felipe Quevedo, Joao TI Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders SO REVISTA BRASILEIRA DE PSIQUIATRIA LA English DT Article DE Mitochondria; central nervous system; neuroplasticity; cell death ID OBSESSIVE-COMPULSIVE DISORDER; LONG-TERM POTENTIATION; MAGNETIC-RESONANCE-SPECTROSCOPY; ENDOPLASMIC-RETICULUM CA2+; INCREASED OXIDATIVE STRESS; AUTISM SPECTRUM DISORDERS; MAJOR DEPRESSIVE DISORDER; GLUTATHIONE-S-TRANSFERASE; APOPTOSIS-INDUCING FACTOR; OXYGEN SPECIES PRODUCTION AB Introduction: Mitochondrial dysfunction has been postulated to participate in the development of many neuropsychiatric disorders, but there is no consensus as to its role. The aim of this paper is to review recent studies and to outline the current understanding of the association between mitochondrial dysfunction and psychiatric disorders. Methodology: We reviewed articles that evaluated mitochondrial dysfunction and psychiatric disorders, with a particular focus on depression, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, and autism spectrum disorder, and the association between mitochondrial dysfunction and development of these disorders. Results: Evidence suggests that alterations in mitochondrial morphology, brain energy metabolism, and mitochondrial enzyme activity may be involved in the pathophysiology of different neuropsychiatric disorders, given their key role in energy metabolism in the cell. Conclusions: Understanding the interactions between mitochondrial dysfunction and development of psychiatric disorders may help establish more effective therapeutic strategies for these disorders and thus lead to better outcomes for affected subjects. C1 [Streck, Emilio L.; Goncalves, Cinara L.; Furlanetto, Camila B.; Scaini, Giselli; Dal-Pizzol, Felipe] Univ Extremo Sul Catarinense UNESC, Bioenerget Lab, Grad Program Hlth Sci, Criciuma, SC, Brazil. [Streck, Emilio L.; Goncalves, Cinara L.; Furlanetto, Camila B.; Scaini, Giselli; Dal-Pizzol, Felipe; Quevedo, Joao] Natl Sci & Technol Inst Translat Med INCT TM, Porto Alegre, RS, Brazil. [Streck, Emilio L.; Goncalves, Cinara L.; Furlanetto, Camila B.; Scaini, Giselli; Dal-Pizzol, Felipe; Quevedo, Joao] Ctr Excellence Appl Neurosci Santa Catarina NENAS, Florianopolis, SC, Brazil. [Quevedo, Joao] Univ Extremo Sul Catarinense, Grad Program Hlth Sci, Neurosci Lab, Criciuma, SC, Brazil. RP Streck, EL (reprint author), Univ Extremo Sul Catarinense, Lab Bioenerget, Av Univ 1105, BR-88806000 Criciuma, SC, Brazil. EM emiliostreck@gmail.com RI Scaini, Giselli/G-1378-2014; Dal-Pizzol, Felipe/F-2756-2015 OI Scaini, Giselli/0000-0002-9880-0887; FU Graduate Program in Health Sciences at Universidade do Extremo Sul Catarinense (UNESC); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) FX This study was supported by grants from the Graduate Program in Health Sciences at Universidade do Extremo Sul Catarinense (UNESC), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). 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Bras. Psiquiatr. PD APR-JUN PY 2014 VL 36 IS 2 BP 156 EP 167 DI 10.1590/1516-4446-2013-1224 PG 12 WC Psychiatry SC Psychiatry GA AI8ZJ UT WOS:000337215200010 PM 24845118 ER PT J AU Iosa, M Morelli, D Nisi, E Sorbara, C Negrini, S Gentili, P Paolucci, S Fusco, A AF Iosa, Marco Morelli, Daniela Nisi, Enrica Sorbara, Carlo Negrini, Stefano Gentili, Paola Paolucci, Stefano Fusco, Augusto TI Assessment of upper body accelerations in young adults with intellectual disabilities while walking, running, and dual-task running SO HUMAN MOVEMENT SCIENCE LA English DT Article DE Kinematic analysis; Accelerometry; Down syndrome; Autism disorders; Pervasive developmental disorders; Biomechanics ID INERTIAL MEASUREMENT UNIT; GAIT ANALYSIS; TRIAXIAL ACCELEROMETER; AUTISTIC-CHILDREN; EXERCISE; RELIABILITY; BALANCE; PATTERNS; MOTION; LEVEL AB There is an increasing interest about upper body accelerations during locomotion and how they are altered by physical impairments. Recent studies have demonstrated that cognitive impairments affect gait stability in the elderly (i.e., their capacity for smoothing upper body accelerations during walking) but little attention has been paid to young adults with intellectual disabilities. The purpose of this study was to examine upright stability in young adults with intellectual disabilities during walking, running, and dual-task running (playing soccer). To this aim a wearable trunk-mounted device that permits on-field assessment was used to quantify trunk acceleration of 18 male teenagers with intellectual disabilities (IDG) and 7 mental-age-matched healthy children (HCG) who participated in the same soccer program. We did not find any significant difference during walking in terms of speed, whereas speed differences were found during running (p = .001). Upper body accelerations were altered in a pathology-specific manner during the dual task: the performance of subjects with autistic disorders was compromised while running and controlling the ball with the feet. Differences in upright locomotor patterns between IDG and HCG emerged during more demanding motor tasks in terms of a loss in the capacity of smoothing accelerations at the trunk level. Crown Copyright (C) 2014 Published by Elsevier B.V. All rights reserved. C1 [Iosa, Marco; Paolucci, Stefano; Fusco, Augusto] Fdn Santa Lucia, IRCCS, Clin Lab Expt Neurorehabil, I-00179 Rome, Italy. [Morelli, Daniela; Gentili, Paola; Paolucci, Stefano] Fdn Santa Lucia, IRCCS, I-00179 Rome, Italy. [Nisi, Enrica; Sorbara, Carlo] Totti Soccer Sch, Rome, Italy. [Negrini, Stefano] Univ Brescia, I-25121 Brescia, Italy. [Negrini, Stefano] Fdn Don C Gnocchi, IRCCS, Milan, Italy. RP Iosa, M (reprint author), Fdn Santa Lucia, IRCCS, Clin Lab Expt Neurorehabil, Via Ardeatina 306, I-00179 Rome, Italy. EM m.iosa@hsantalucia.it RI Negrini, Stefano/B-6667-2013; Fusco, Augusto/K-5794-2012 OI Negrini, Stefano/0000-0002-1878-2747; Fusco, Augusto/0000-0002-8528-7834 FU provincial government "Provincia di Roma" through the SPORT-AB (Sport-Ability); CARESS (from Childhood to Adulthood: Rehabilitation and Enabling Sport for Sociability) projects FX This study was supported by our Foundation and by the provincial government "Provincia di Roma" through the SPORT-AB (Sport-Ability) and CARESS (from Childhood to Adulthood: Rehabilitation and Enabling Sport for Sociability) projects, based on the initiatives of Antonio Rosati and Patrizia Prestipino. 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TI Addressing Sexuality in Youth with Autism Spectrum Disorders: Current Pediatric Practices and Barriers SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE autism spectrum disorder; adolescence; sexuality; puberty; prevention ID ADOLESCENTS; ADULTS; DISABILITIES; PERSPECTIVES; CHILDREN; ISSUES; SAMPLE AB Objective: Research on adolescents and young adults with autism spectrum disorders (ASDs) has focused on promoting independence and optimizing quality of life, yet the areas of sexual development and sexuality has been largely neglected. The American Academy of Pediatrics encourages pediatricians to address sexuality issues in youth with disabilities to foster healthy development and minimize negative consequences. However, it is unclear to what extent pediatricians address sexuality issues in this population. Methods: Two hundred three pediatricians who regularly care for youth with ASD completed an online survey about their experiences in providing sexuality-related care to families and youth with ASD. Results: Respondents discussed an average of 10.9 of 26 sexuality topics with all families at least once during routine visits. Experience in caring for youth with ASD correlated positively with the number of sexuality-related topics discussed and with self-reported comfort discussing sexuality with parents of youth with ASD. The most common barriers to providing comprehensive sexuality-related care to youth with ASD included logistical barriers, pediatrician and parent discomfort, lack of training, and absence of information and materials to help pediatricians address sexuality in this population. Conclusions: Although most pediatricians acknowledged the importance of addressing sexuality-related issues with youth with ASD and their families, several important sexuality-related topics were rarely discussed due to a variety of perceived barriers. Implications and recommendations are discussed. C1 [Holmes, Laura G.; Himle, Michael B.; Sewell, Kelsey K.; Strassberg, Donald S.] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. [Carbone, Paul S.; Murphy, Nancy A.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT 84112 USA. RP Himle, MB (reprint author), Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. 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Dev. Behav. Pediatr. PD APR PY 2014 VL 35 IS 3 BP 172 EP 178 PG 7 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA AI4QE UT WOS:000336849100002 PM 24651831 ER PT J AU Davignon, MN Friedlaender, E Cronholm, PF Paciotti, B Levy, SE AF Davignon, Meghan N. Friedlaender, Eron Cronholm, Peter F. Paciotti, Breah Levy, Susan E. TI Parent and Provider Perspectives on Procedural Care for Children with Autism Spectrum Disorders SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE autism spectrum disorders; medical procedures; communication; preparation; delivery of healthcare ID COMMUNICATION AB Objective: Children with autism spectrum disorders (CWASDs) have more difficulty tolerating hospital procedures than many other children. The aim of this study was to identify parent and provider perspectives on barriers and facilitators to procedural care for CWASDs. Methods: Semistructured interviews were conducted with medical staff and parents of CWASDs. Those parents whose child with autism required a procedure in a tertiary care sedation unit and those whose child was enrolled in autismMatch (a research registry for individuals with autism) were recruited. Staff providing direct patient care in the tertiary care sedation unit were recruited. Participants were asked open-ended questions about factors contributing to or interfering with successful completion of medical procedures for CWASDs. Interviews were audio-recorded, transcribed verbatim, coded, and analyzed using modified grounded theory techniques. Results: Twenty mothers and 20 medical staff members were interviewed. Participants described 2 domains essential to care of CWASDs but in which barriers existed: (1) productive interactions between providers and families, largely dependent on advanced preparation and (2) modifications to healthcare organization and delivery in the areas of patient flow and clinical environment. Individualized care is essential to quality care in both domains. Conclusions: Children with autism spectrum disorders require individualized interventions to maximize the quality of procedural care. However, many hospitals and providers are not sufficiently equipped to accommodate these children's needs. This study suggests that targeted improvements in preparation and communication between providers and families as well as modifications in patient flow and clinical environments have the potential to improve the quality and successful completion of procedures. C1 [Davignon, Meghan N.; Levy, Susan E.] Childrens Hosp Philadelphia, Dept Child Dev, Philadelphia, PA 19104 USA. [Davignon, Meghan N.] Permanente Med Grp Inc, Oakland, CA USA. [Davignon, Meghan N.] Kaiser Roseville Med Ctr, Roseville, CA USA. [Friedlaender, Eron] Childrens Hosp Philadelphia, Dept Emergency Med, Philadelphia, PA 19104 USA. [Friedlaender, Eron; Cronholm, Peter F.; Paciotti, Breah; Levy, Susan E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cronholm, Peter F.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Cronholm, Peter F.] Univ Penn, Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. [Cronholm, Peter F.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Levy, Susan E.] Ctr Autism Res, Philadelphia, PA USA. RP Davignon, MN (reprint author), Kaiser Permanente, Roseville Med Ctr, 1600 Eureka Rd,MOB 2,2nd Floor, Roseville, CA 95661 USA. EM davignonmeghan@gmail.com FU Maternal Child Health Bureau [T77MC00012, T73MC00051]; Health Resources and Services Administration; Department of Health and Human Services; Chairman's Initiative Grant of the Department of Pediatrics at The Children's Hospital of Philadelphia FX M. N. Davignon was supported by projects T77MC00012 and T73MC00051 from the Maternal Child Health Bureau (Public Health Service Act, Section 399BB(e)(1)(A), as amended by the Combating Autism Act of 2006), Health Resources and Services Administration, Department of Health and Human Services. The project was also supported by the Chairman's Initiative Grant of the Department of Pediatrics at The Children's Hospital of Philadelphia (E.F.). The authors declare no conflict of interest. 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Dev. Behav. Pediatr. PD APR PY 2014 VL 35 IS 3 BP 207 EP 215 PG 9 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA AI4QE UT WOS:000336849100007 PM 24662617 ER PT J AU Harstad, E Mauras, C Weissman, L Augustyn, M AF Harstad, Elizabeth Mauras, Carrie Weissman, Laura Augustyn, Marilyn TI Autism After DSM 5: The Potential Impact in One Child's Case SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material ID SPECTRUM DISORDER; DIAGNOSIS; CRITERIA; TODDLERS AB CASE: Max is a 21-month old boy with speech and language delay presenting for diagnostic clarification and treatment recommendations. Max was born at 37 weeks after a twin gestation. He is medically healthy and lives at home with supportive parents and a typically developing twin sister. Max began speech and language therapy when he was 14 months old. Max spoke his first word at 16 months. He uses fewer than 10 words or word approximations; however, he does not use these words spontaneously to communicate. Max has decreased use of eye contact and rarely uses nonverbal means of communication. Max whines but does not point or reference his parents to request their help when he wants something out of reach. Max responds to 1-step directions about 50% of the time. An audiology assessment was normal. Max does not bring objects of interest to show others, rarely initiates interactions and does not consistently respond to social overtures. Max is described as an easy-going child. He is content to play on his own and shows little interest in other children. He likes to spin wheels for the purpose of watching them. Max has no rigidities or rituals and is easy to redirect. He has no sensory seeking behaviors or aversions. He does not engage in any repetitive motor mannerisms. On formal evaluation, Max's cognitive skills were assessed within the average range; language and gross motor skills were below average. Performance on the Autism Diagnostic Observation Schedule, Toddler Module was concerning for an Autism Spectrum Disorder (ASD). Max's evaluation was concerning for deficits in social and communication functioning. A new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) was recently published, resulting in a change in the diagnostic criteria for ASDs. Max meets criteria for autistic disorder under DSM, 4th edition, text revision (DSM-4-TR), but does not meet criteria for an ASD under DSM-5. Specifically by DSM-4-TR, he met all criteria under social interaction, 2 criteria under communication, and 1 under restricted and repetitive behaviors. By DSM-5, he met all of criteria A and just 1 of criteria B. How would you proceed diagnostically and what treatment recommendations would you make? C1 [Harstad, Elizabeth; Mauras, Carrie; Weissman, Laura] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Dev Med, Boston, MA 02163 USA. [Augustyn, Marilyn] Boston Univ, Sch Med, Boston Med Ctr, Div Dev & Behav Pediat, Boston, MA 02118 USA. RP Harstad, E (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Dev Med, Boston, MA 02163 USA. 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PD APR PY 2014 VL 35 IS 3 BP 228 EP 229 PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA AI4QE UT WOS:000336849100010 PM 24695121 ER PT J AU Tragea, C Chrousos, GP Alexopoulos, EC Darviri, C AF Tragea, Christina Chrousos, George P. Alexopoulos, Evangelos C. Darviri, Christina TI A randomized controlled trial of the effects of a stress management programme during pregnancy SO COMPLEMENTARY THERAPIES IN MEDICINE LA English DT Article DE Anxiety; Stress; Pregnancy; Relaxation; Stress management ID MATERNAL PRENATAL STRESS; PSYCHOSOCIAL PREDICTORS; PERCEIVED STRESS; PRETERM BIRTH; RELAXATION; EXPOSURE; OUTCOMES; ANXIETY; AUTISM; WOMEN AB Background: Prenatal maternal stress is associated with adverse birth outcomes. Relaxation techniques might be effective in reducing stress during that period. The purpose of this study was to evaluate the effects of applied relaxation in reducing anxiety and stress in pregnant women in their second trimester, as well as raising their sense of control. Also we expected to see a difference in some lifestyle factors associated with stress. A randomized control trial with a prospective pretest-posttest experimental design was used. Methods: Sixty primigravida women in their second trimester were assigned randomly to receive a 6-week stress management programme (N = 31) (relaxation breathing and progressive muscle relaxation, RB-PMR, twice a day) or not (N = 29). Self-reported validated measures were used to evaluate perceived stress, health locus of control and anxiety at baseline and at the end of the 6-weeks follow-up. Results: The results of the study demonstrated significant benefits from the use of the techniques in the psychological state of the pregnant women. The systematic implementation of the proposed relaxation techniques contributed in the reduction of perceived stress (mean change -3.23, 95% Cl: -4.29 to -0.29) and increased the sense of control (mean change 1.99, 95% Cl: 0.02-3.7). Conclusion: The findings suggest beneficial effects of relaxation on reducing perceived stress as well as increment of sense of control in pregnant women. The results of this study support the claim that training in the proposed relaxation techniques may constitute an ideal, non-pharmaceutical, intervention that can promote well-being, at least during pregnancy. Longer studies will be necessary in the future, in order to examine the long-term effects of relaxation techniques. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Tragea, Christina; Chrousos, George P.; Alexopoulos, Evangelos C.; Darviri, Christina] Univ Athens, Postgrad Course Stress Management & Hlth Promot, Biomed Res Fdn, Sch Med,Acad Athens, GR-11527 Athens, Greece. [Chrousos, George P.] Univ Athens, Dept Pediat 1, Childrens Hosp Aghia Sofia, Sch Med, GR-11527 Athens, Greece. RP Darviri, C (reprint author), Soranou Ephessiou Str 4, GR-11527 Athens, Greece. EM cdarviri@yahoo.com FU Attikon maternity hospital in Attica from the Department of Foetal Medicine FX The research was specifically supported by the Attikon maternity hospital in Attica, more specifically from the Department of Foetal Medicine. We are grateful to Professor Kassanos who gave us access to the above department. We would also like to thank the obstetrician gynaecologists (Dr. Alexopoulos E., Dr. Salakos N., Dr. Mouzalas I., Dr. Tzeferakos A., and Dr. Athanasiou S.) who gave us access to their private clinics and for their support. 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Ther. Med. PD APR PY 2014 VL 22 IS 2 BP 203 EP 211 DI 10.1016/j.ctim.2014.01.006 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA AH9OR UT WOS:000336472200002 PM 24731890 ER PT J AU Cederlof, M Ostberg, P Pettersson, E Anckarsater, H Gumpert, C Lundstrom, S Lichtenstein, P AF Cederlof, M. Ostberg, P. Pettersson, E. Anckarsater, H. Gumpert, C. Lundstrom, S. Lichtenstein, P. TI Language and mathematical problems as precursors of psychotic-like experiences and juvenile mania symptoms SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Juvenile mania symptoms; language problems; mathematical problems; psychotic-like experiences ID BIPOLAR DISORDER; BIRTH-COHORT; SCHIZOPHRENIFORM DISORDER; TELEPHONE INTERVIEW; YOUNG-PEOPLE; AUTISM-TICS; A-TAC; CHILDHOOD; ANTECEDENTS; VALIDATION AB Background. Psychotic-like experiences (PLEs) and juvenile mania in adolescence index risk for severe psychopathology in adulthood. The importance of childhood problems with communication, reading, speech and mathematics for the development of PLEs and juvenile mania is not well understood. Method. Through the Child and Adolescent Twin Study in Sweden, we identified 5812 children. The parents were interviewed about their children's development at age 9 or 12 years. At age 15 or 18 years, children and parents completed questionnaires targeting current PLEs and juvenile mania symptoms. Logistic regressions were used to assess associations between problems with communication, reading, speech and mathematics and PLEs/juvenile mania symptoms. To evaluate the relative importance of genes and environment in these associations, we used bivariate twin analyses based on structural equation models. Results. Children with parent-endorsed childhood problems with communication, reading and mathematics had an increased risk of developing auditory hallucinations and parental-reported juvenile mania symptoms in adolescence. The most consistent finding was that children with childhood problems with communication, reading and mathematics had an increased risk of developing auditory hallucinations [for example, the risk for self-reported auditory hallucinations at age 15 was increased by 96% for children with communication problems: OR (odds ratio) 1.96, 95% confidence interval (CI) 1.33-2.88]. The twin analyses showed that genetic effects accounted for the increased risk of PLEs and juvenile mania symptoms among children with communication problems. Conclusions. Childhood problems with communication, reading and mathematics predict PLEs and juvenile mania symptoms in adolescence. Similar to the case for schizophrenia and bipolar disorder, PLEs and juvenile mania may share genetic aetiological factors. C1 [Cederlof, M.; Pettersson, E.; Lichtenstein, P.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Ostberg, P.] Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Speech & Language Pathol, SE-17177 Stockholm, Sweden. [Anckarsater, H.] Lund Univ, Dept Clin Sci, S-22100 Lund, Sweden. [Anckarsater, H.] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden. [Gumpert, C.] Karolinska Inst, Sect Forens Psychiat, Dept Clin Neurosci, SE-17177 Stockholm, Sweden. [Lundstrom, S.] Univ Gothenburg, Ctr Eth Law & Mental Hlth CELAM, Gothenburg, Sweden. [Lundstrom, S.] Univ Gothenburg, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. RP Cederlof, M (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, SE-17177 Stockholm, Sweden. EM Martin.Cederlof@ki.se FU Swedish Research Council [2011-2492] FX We thank the children and parents who participated in this study. M. C. received funding from the Swedish Research Council (grant no. 2011-2492). 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Caputi, Peter TI Family-focused autism spectrum disorder research: A review of the utility of family systems approaches SO AUTISM LA English DT Review DE support services; resilience; family functioning; subsystem; ambiguous loss; stress; holistic approaches; dyad; family systems; autism spectrum disorders; traumatic growth ID QUALITY-OF-LIFE; PARTNER INTERDEPENDENCE MODEL; HIGH-FUNCTIONING CHILDREN; ASPERGER-SYNDROME; DEVELOPMENTAL-DISABILITIES; LEARNING-DISABILITIES; SOCIAL-INTERACTION; BEHAVIOR PROBLEMS; YOUNG-CHILDREN; AMBIGUOUS LOSS AB A family member with an autism spectrum disorder presents pervasive and bidirectional influences on the entire family system, suggesting a need for family-focused autism spectrum disorder research. While there has been increasing interest in this research area, family-focused autism spectrum disorder research can still be considered relatively recent, and there are limitations to the existing literature. The purpose of this article is to provide theoretical and methodological directions for future family-focused autism spectrum disorder research. In particular, this article proposes Family Systems approaches as a common theoretical framework for future family-focused autism spectrum disorder research by considering theoretical concepts such as Boundaries, Ambiguous Loss, Resilience and Traumatic Growth. We discuss reasons why these concepts are important to researching families living with autism spectrum disorder and provide recommendations for future research. The potential for research grounded in Family Systems approaches to influence clinical support services is also discussed. C1 [Cridland, Elizabeth K.; Jones, Sandra C.; Magee, Christopher A.; Caputi, Peter] Univ Wollongong, Wollongong, NSW 2522, Australia. RP Cridland, EK (reprint author), Univ Wollongong, Ctr Hlth Initiat, Bldg 233 ITAMS,Innovat Campus,Northfields Ave, Wollongong, NSW 2522, Australia. 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TI Loneliness, friendship, and well-being in adults with autism spectrum disorders SO AUTISM LA English DT Article DE adults; anxiety; loneliness; friendship; depression; autism spectrum disorders ID HIGH-FUNCTIONING CHILDREN; GLOBAL SELF-ESTEEM; QUOTIENT AQ; SOCIAL RELATIONSHIPS; DEPRESSIVE SYMPTOMS; PEER RELATIONSHIPS; VALIDITY EVIDENCE; ASPERGER-SYNDROME; COLLEGE-STUDENTS; ADOLESCENT BOYS AB This study examined the relations among loneliness, friendship, and emotional functioning in adults (N = 108) with autism spectrum disorders. Participants completed self-report measures of symptoms of autism spectrum disorders, loneliness, number and nature of friendships, depression, anxiety, life satisfaction, and self-esteem. The results indicated that loneliness was associated with increased depression and anxiety and decreased life satisfaction and self-esteem, even after controlling for symptoms of autism spectrum disorders. 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These individuals have achieved social and language skills within the average range for their ages, receive little or no school support, and are referred to as having achieved "optimal outcomes." Performance of 32 individuals who achieved optimal outcomes, 41 high-functioning individuals with a current autism spectrum disorder diagnosis (high-functioning autism), and 34 typically developing peers was compared on measures of decoding, reading comprehension, mathematical problem solving, and written expression. Groups were matched on age, sex, and nonverbal IQ; however, the high-functioning autism group scored significantly lower than the optimal outcome and typically developing groups on verbal IQ. All three groups performed in the average range on all subtests measured, and no significant differences were found in performance of the optimal outcome and typically developing groups. The high-functioning autism group scored significantly lower on subtests of reading comprehension and mathematical problem solving than the optimal outcome group. These findings suggest that the academic abilities of individuals who achieved optimal outcomes are similar to those of their typically developing peers, even in areas where individuals who have retained their autism spectrum disorder diagnoses exhibit some ongoing difficulty. C1 [Troyb, Eva; Orinstein, Alyssa; Tyson, Katherine; Helt, Molly; Eigsti, Inge-Marie; Fein, Deborah] Univ Connecticut, Storrs, CT 06269 USA. [Stevens, Michael] Yale Univ, Sch Med, New Haven, CT 06520 USA. RP Troyb, E (reprint author), Univ Connecticut, Dept Psychol, 406 Babbidge Rd,Unit 1020, Storrs, CT 06269 USA. 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Hunter, Simon C. TI Maladaptive cognitive appraisals in children with high-functioning autism: Associations with fear, anxiety and theory of mind SO AUTISM LA English DT Article DE appraisal; fear; cognition ID PERVASIVE DEVELOPMENTAL DISORDERS; THREAT PERCEPTION ABNORMALITIES; OBSESSIVE-COMPULSIVE DISORDER; SPECTRUM DISORDERS; SOCIAL ANXIETY; ASPERGER-SYNDROME; CONTROLLED-TRIAL; CHILDHOOD ANXIETY; COVARIATION BIAS; SYMPTOMS AB Despite the well-documented success of cognitive restructuring techniques in the treatment of anxiety disorders, there is still little clarity on which cognitions underpin fear and anxiety in children with high-functioning autism spectrum disorder. This study examined whether certain cognitive appraisals, known to be associated with fear and anxiety in typically developing groups, may help explain these emotions in children with high-functioning autism spectrum disorder. It also investigated relations between these cognitive appraisals and theory of mind. Appraisals, fear and anxiety were assessed using a vignette approach in 22 children with high-functioning autism spectrum disorders and 22 typically developing children. The two groups differed significantly on all four appraisal types. Anxiety was negatively correlated with future expectancy and positively with problem-focused coping potential in the high-functioning autism spectrum disorder group but was not correlated with appraisals in the typically developing group. The two appraisals associated with fear were emotion-focused coping potential (in the high-functioning autism spectrum disorder group only) and self-accountability (in the typically developing group only). Linear regression analysis found that appraisals of emotion-focused coping potential, problem-focused coping potential and future expectancy were significant predictors of theory-of-mind ability in the high-functioning autism spectrum disorders group. 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TI Long-term outcomes of parent-assisted social skills intervention for high-functioning children with autism spectrum disorders SO AUTISM LA English DT Article DE social skills; autism; follow-up; intervention; children ID BEHAVIOR CHECKLIST; ASPERGER-SYNDROME; LONELINESS; INDIVIDUALS; ADOLESCENTS AB This study aims to evaluate the long-term outcome of Children's Friendship Training, a parent-assisted social skills intervention for children. Prior research has shown Children's Friendship Training to be superior to wait-list control with maintenance of gains at 3-month follow-up. Participants were families of children diagnosed with autism spectrum disorder who completed Children's Friendship Training 1-5 years earlier. They were recruited through mail, phone, and email. Information collected included parent and child completed questionnaires and a phone interview. Data were collected on 24 of 52 potential participants (46%). With an average of 35-month follow-up, participants had a mean age of 12.6 years. Results indicated that participants at follow-up were invited on significantly more play dates, showed less play date conflict, improved significantly in parent-reported social skills and problem behaviors, and demonstrated marginally significant decreases in loneliness when compared to pre-Children's Friendship Training. C1 [Mandelberg, Josh; Frankel, Fred; Cunningham, Tina; Gorospe, Clarissa; Laugeson, Elizabeth A.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. RP Frankel, F (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 300 UCLA Med Plaza, Los Angeles, CA 90095 USA. 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Abellan, Raquel Campos, Arturo Navarro, Ignacio Sevilla, Javier Pardo, Carlos Amati, Fabian TI Using Tic-Tac software to reduce anxiety-related behaviour in adults with autism and learning difficulties during waiting periods: A pilot study SO AUTISM LA English DT Article DE technology; autism; time perception; anxiety-related behaviours ID SPECTRUM DISORDERS; TIME PERCEPTION; CHILDREN; PERFORMANCE; THINKING AB Deficits in the perception of time and processing of changes across time are commonly observed in individuals with autism. This pilot study evaluated the efficacy of the use of the software tool Tic-Tac, designed to make time visual, in three adults with autism and learning difficulties. This research focused on applying the tool in waiting situations where the participants exhibited anxiety-related behaviour. The intervention followed a baseline and intervention (AB) design, and a partial interval recording procedure was used to code the presence of stereotypes, nervous utterances, wandering or other examples of nervousness during the selected waiting situations. The results showed that the use of Tic-Tac resulted in lower levels of anxiety-related behaviour in all three participants, compared to the baseline, suggesting that this software may be an effective technology for helping people with autism with organisation and predictability during waiting periods. The results are discussed in terms of limitations and implications for further study. C1 [Campillo, Cristina; Herrera, Gerardo; Abellan, Raquel; Campos, Arturo; Navarro, Ignacio; Sevilla, Javier; Pardo, Carlos; Amati, Fabian] Univ Valencia, Paterna Valencia 46980, Spain. [Remirez de Ganuza, Conchi; Cuesta, Jose L.] Autismo Burgos, Burgos, Spain. RP Herrera, G (reprint author), Univ Valencia, Autism & Learning Difficulties Grp, C Catedrat Jose Beltran 2, Paterna Valencia 46980, Spain. 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Landa, Rebecca J. TI Association between severity of behavioral phenotype and comorbid attention deficit hyperactivity disorder symptoms in children with autism spectrum disorders SO AUTISM LA English DT Article DE comorbidity; symptom severity; autism; attention deficit hyperactivity disorder ID PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT/HYPERACTIVITY DISORDER; ADHD; ADOLESCENTS; ANXIETY; PSYCHOPATHOLOGY; SAMPLE AB Autism spectrum disorder and attention deficit hyperactivity disorder are neurodevelopmental disorders that cannot be codiagnosed under existing diagnostic guidelines (Diagnostic and Statistical Manual of the American Psychiatric Association, 4th ed., text rev.). However, reports are emerging that attention deficit hyperactivity disorder is sometimes comorbid with autism spectrum disorder. In the current study, we examined rates of parent-reported clinically significant symptoms of attention deficit hyperactivity disorder in school-aged children (4-8 years) with autism spectrum disorder, most of whom were first enrolled in our research protocols as toddlers. Results revealed that children with autism spectrum disorder and attention deficit hyperactivity disorder had lower cognitive functioning, more severe social impairment, and greater delays in adaptive functioning than children with autism spectrum disorder only. Implications for clinical practice include the need to assess for attention deficit hyperactivity disorder symptoms at an early age in children diagnosed with autism spectrum disorder. Research is needed to determine efficacious interventions for young children with autism spectrum disorder with comorbid attention deficit hyperactivity disorder to optimize outcomes. C1 [Rao, Patricia A.; Landa, Rebecca J.] Kennedy Krieger Inst, Baltimore, MD 21211 USA. 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Bedford, Rachael Charman, Tony Elsabbagh, Mayada Johnson, Mark H. Hill, Elisabeth L. CA BASIS Team TI Motor development in children at risk of autism: A follow-up study of infant siblings SO AUTISM LA English DT Article DE autism spectrum disorder; motor development; infant siblings; broader autism phenotype; face processing ID BRUININKS-OSERETSKY TEST; HIGH-FUNCTIONING AUTISM; COORDINATION DISORDER; SPECTRUM DISORDERS; MOVEMENT-ABC; SHORT-FORM; IMPAIRMENT; SKILLS; FACE; IDENTIFICATION AB Recently, evidence of poor or atypical motor skills in autism spectrum disorder has led some to argue that motor impairment is a core feature of the condition. The current study uses a longitudinal prospective design to assess the development of motor skills of 20 children at increased risk of developing autism spectrum disorder, who were recruited and tested at 9 and 40 months of age, on the basis of having an older sibling diagnosed with the condition. All children completed a range of motor, face processing, IQ and diagnostic assessments at a follow-up visit (aged 5-7 years), providing a detailed profile of development in this group from a number of standardised, parental report and experimental measures. A higher proportion of children than expected demonstrated motor difficulties at the follow-up visit and those highlighted by parental report as having poor motor skills as infants and toddlers were also more likely to have lower face processing scores and elevated autism-related social symptoms at 5-7 years, despite having similar IQ levels. These data lend support to the argument that early motor difficulties may be a risk factor for later motor impairment as well as differences in social communication and cognition, traits that are related to autism spectrum disorder. C1 [Leonard, Hayley C.; Hill, Elisabeth L.] Univ London, London SE14 6NW, England. 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Manangan, Christen N. Sparrow, Joanne K. Wilson, Beverly J. TI The relation of parent-child interaction qualities to social skills in children with and without autism spectrum disorders SO AUTISM LA English DT Article DE social skills; parent-child interactions; autism spectrum disorders ID HIGH-FUNCTIONING AUTISM; YOUNG-CHILDREN; COMPETENCE; RECOMMENDATIONS; INTERVENTIONS; EXPRESSION; BEHAVIORS; MEDIATION; EMOTION; FAMILY AB This study examined associations between parent-child interactions and the development of social skills in 42 children (21 typically developing and 21 with autism spectrum disorders) between the ages of 3 years, 0 months and 6 years, 11 months. We expected that positive parent-child interaction qualities would be related to children's social skills and would mediate the negative relation between children's developmental status (typical development vs autism spectrum disorders) and social skills. Videotapes of parents and children during a 5-min wordless book task were coded for parent positive affect and emotional support as well as parent-child cohesiveness. Emotional support and cohesiveness were significantly related to children's social skills, such that higher emotional support and cohesiveness were associated with higher social skills, R-2 = .29, p = .02, and R-2 = .38, p = .002, respectively. Additionally, cohesiveness mediated the relation between children's developmental status and social skills. These findings suggest that parent emotional support and cohesiveness between parents and children positively influence children's social skills. Parent positive affect was unrelated to social skills. Implications of these findings for social skills interventions are discussed, particularly for young children with autism spectrum disorders. C1 [Haven, Erin L.; Manangan, Christen N.; Sparrow, Joanne K.; Wilson, Beverly J.] Seattle Pacific Univ, Seattle, WA 98119 USA. RP Haven, EL (reprint author), Seattle Pacific Univ, Dept Clin Psychol, 3307 3rd Ave West Suite 107, Seattle, WA 98119 USA. EM ehaven@spu.edu CR Baker JK, 2007, AM J MENT RETARD, V112, P375, DOI 10.1352/0895-8017(2007)112[0375:POSSIY]2.0.CO;2 Bellini S, 2007, REM SPEC EDUC, V28, P153, DOI 10.1177/07419325070280030401 Bennett KS, 2007, INT J DISABIL DEV ED, V54, P381, DOI 10.1080/10349120701654555 Bijstra JO, 1998, EUR J PSYCHOL EDUC, V13, P569 Carson JL, 1996, CHILD DEV, V67, P2217, DOI 10.1111/j.1467-8624.1996.tb01853.x Charlop M. 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R., 2004, BEHAV ASSESSMENT SYS, V2nd Shrout PE, 2002, PSYCHOL METHODS, V7, P422, DOI 10.1037//1082-989X.7.4.422 Siller M, 2008, DEV PSYCHOL, V44, P1691, DOI 10.1037/a0013771 Skibbe LE, 2010, READ WRIT, V23, P53, DOI 10.1007/s11145-008-9149-3 Vickerstaff S, 2007, J AUTISM DEV DISORD, V37, P1647, DOI 10.1007/s10803-006-0292-x White SW, 2009, J AUTISM DEV DISORD, V39, P1006, DOI 10.1007/s10803-009-0713-8 Wilson BJ, 2012, RELATIONS SELF UNPUB Zhou Q, 2002, CHILD DEV, V73, P893, DOI 10.1111/1467-8624.00446 NR 40 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 APR PY 2014 VL 18 IS 3 BP 292 EP 300 DI 10.1177/1362361312470036 PG 9 WC Psychology, Developmental SC Psychology GA AD7OY UT WOS:000333454700010 PM 24072662 ER PT J AU Begeer, S De Rosnay, M Lunenburg, P Stegge, H Terwogt, MM AF Begeer, Sander De Rosnay, Marc Lunenburg, Patty Stegge, Hedy Terwogt, Mark Meerum TI Understanding of emotions based on counterfactual reasoning in children with autism spectrum disorders SO AUTISM LA English DT Article DE upward; relief; counterfactual; downward; emotion; regret; autism ID HIGH-FUNCTIONING CHILDREN; FALSE BELIEF; AGE-DIFFERENCES; THINKING; REGRET; DISAPPOINTMENT; DISSOCIATION; PRESCHOOLERS; EXPERIENCE; LOOKING AB The understanding of emotions based on counterfactual reasoning was studied in children with high-functioning autism spectrum disorders (n = 71) and in typically developing children (n = 71), aged 6-12 years. Children were presented with eight stories about two protagonists who experienced the same positive or negative outcome, either due to their own action or by default. Relative to the comparison group, children with high-functioning autism spectrum disorder were poor at explaining emotions based on downward counterfactual reasoning (i.e. contentment and relief). There were no group differences in upward counterfactual reasoning (i.e. disappointment and regret). In the comparison group, second-order false-belief reasoning was related to children's understanding of second-order counterfactual emotions (i.e. regret and relief), while children in the high-functioning autism spectrum disorder group relied more on their general intellectual skills. Results are discussed in terms of the different functions of counterfactual reasoning about emotion and the cognitive style of children with high-functioning autism spectrum disorder. 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Kase, Colleen Mandell, David S. TI Comparing cognitive outcomes among children with autism spectrum disorders receiving community-based early intervention in one of three placements SO AUTISM LA English DT Article DE inclusion; autism spectrum disorders; preschool; early intervention; community practices ID INTENSIVE BEHAVIORAL INTERVENTION; YOUNG-CHILDREN; COMMUNICATION INTERVENTIONS; JOINT ATTENTION; FOLLOW-UP; PRESCHOOLERS; DISABILITIES; CLASSROOMS; SEVERITY; LANGUAGE AB Little comparative research examines which community-based preschool intervention placements produce the best outcomes for which children with autism spectrum disorders. Autism-specific placements can provide intensive evidence-based care; however, inclusion settings provide interaction with typically developing peers, the importance of which is increasingly recognized. This study examined the association between early intervention placement in three settings (autism-only, mixed disability, or inclusive) and cognitive outcomes upon entry into elementary school in an urban school district for 98 preschool-aged children with autism spectrum disorders. Initial child and demographic characteristics were similar among the three placements. Controlling for initial cognitive scores and other covariates, cognitive outcomes for children in inclusive placements were better than those of children in mixed disability settings. A consistent pattern emerged that suggested the particular importance of inclusive placements for children with initially greater social impairments, greater adaptive behavior impairments, and at least a baseline level of language skills. Opportunities to interact with typically developing peers may be particularly beneficial for certain subgroups of young children with autism spectrum disorders. 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Jain, Anjali Yang, Wenya Kelly, Jonathan P. Kaiser, Marygrace Becker, Laura Lawer, Lindsay Newschaffer, Craig J. TI Does a claims diagnosis of autism mean a true case? SO AUTISM LA English DT Article DE validation study; autism; Administrative data; chart review ID SPECTRUM DISORDERS; PSYCHIATRIC-DISORDERS; INSURED POPULATION; HEALTH PLAN; CHILDREN; MEDICAID; EXPENDITURES; VALIDATION; VALIDITY; SURVEILLANCE AB The purpose of this study was to validate autism spectrum disorder cases identified through claims-based case identification algorithms against a clinical review of medical charts. Charts were reviewed for 432 children who fell into one of the three following groups: (a) more than or equal to two claims with an autism spectrum disorder diagnosis code (n = 182), (b) one claim with an autism spectrum disorder diagnosis code (n = 190), and (c) those who had no claims for autism spectrum disorder but had claims for other developmental or neurological conditions (n = 60). The algorithm-based diagnoses were compared with documented autism spectrum disorders in the medical charts. The algorithm requiring more than or equal to two claims for autism spectrum disorder generated a positive predictive value of 87.4%, which suggests that such an algorithm is a valid means to identify true autism spectrum disorder cases in claims data. C1 [Burke, James P.; Becker, Laura] OptumInsight, Eden Prairie, MN USA. [Jain, Anjali; Yang, Wenya; Kelly, Jonathan P.] Lewin Grp, Falls Church, VA 22042 USA. [Kaiser, Marygrace] Eureka Coll, Eureka, CA USA. [Lawer, Lindsay; Newschaffer, Craig J.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA USA. RP Jain, A (reprint author), Lewin Grp, 3130 Fairview Pk Dr 500, Falls Church, VA 22042 USA. 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The Modified Checklist for Autism in Toddlers was filled out independently by 191 parents while they were waiting for the well-child examination of their child. A high screen-positive rate was found. Because of this high false-positive rate, a second study was done in which the Modified Checklist for Autism in Toddlers was administered by health-care staff in a short interview with two groups of parents. The first group (the high-risk group) comprised 80 children aged 18-36 months, who were initially diagnosed with pervasive developmental disorders. The second group (the low-risk group) comprised 538 children of the same age, who were followed regularly by the well-child clinic. Two screen positives were found in the low-risk group. These two children, a random sample of 120 children from the low-risk group, and all the high-risk group were invited to a clinical evaluation. The diagnostic power of the Modified Checklist for Autism in Toddlers was assessed against clinical diagnosis and the Childhood Autism Rating Scale. The positive predictive value of the Modified Checklist for Autism in Toddlers was found to be 75%. Our findings led us to conclude that the Modified Checklist for Autism in Toddlers is a useful tool in Turkey for screening of pervasive developmental disorders in primary care, but in our culture, it is completed more accurately when health-care personnel ask the parents the questions. This study shows that Modified Checklist for Autism in Toddlers screening should be adapted based on culture and setting. C1 [Kara, Bulent] Kocaeli Univ, Kocaeli, Turkey. [Mukaddes, Nahit Motavalli; Altinkaya, Isilay; Guentepe, Dilek; Gokcay, Gulbin; Ozmen, Meral] Istanbul Univ, TR-34390 Istanbul, Turkey. RP Mukaddes, NM (reprint author), Istanbul Univ, Dept Child & Adolescent Psychiat, Istanbul Sch Med, Valikonagi Cad 106 D 13 Nisantasi, TR-34390 Istanbul, Turkey. 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Sestan, Nenad TI The developmental transcriptome of the human brain: implications for neurodevelopmental disorders SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE autism spectrum disorder; gene co-expression analysis; genetics; psychiatric and neurologic disorders; schizophrenia; Williams syndrome ID AUTISM SPECTRUM DISORDERS; DE-NOVO MUTATIONS; HUMAN PREFRONTAL CORTEX; COPY NUMBER VARIATION; GENE-EXPRESSION; FUNCTIONAL IMPACT; SCHIZOPHRENIA; RISK; REVEALS; ASSOCIATION AB Purpose of reviewRecent characterizations of the transcriptome of the developing human brain by several groups have generated comprehensive datasets on coding and noncoding RNAs that will be instrumental for illuminating the underlying biology of complex neurodevelopmental disorders. This review summarizes recent studies successfully utilizing these data to increase our understanding of the molecular mechanisms of pathogenesis.Recent findingsSeveral approaches have successfully integrated developmental transcriptome data with gene discovery to generate testable hypotheses about when and where in the developing human brain disease-associated genes converge. Specifically, these include the projection neurons in the prefrontal and primary motor--somatosensory cortex during mid-fetal development in autism spectrum disorder and the frontal cortex during fetal development in schizophrenia.SummaryDevelopmental transcriptome data is a key to interpreting disease-associated mutations and transcriptional changes. Novel approaches integrating the spatial and temporal dimensions of these data have increased our understanding of when and where disease occurs. Refinement of spatial and temporal properties and expanding these findings to other neurodevelopmental disorders will provide critical insights for understanding disease biology. C1 [Tebbenkamp, Andrew T. N.; Sestan, Nenad] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA. [Tebbenkamp, Andrew T. N.; Sestan, Nenad] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA. [Willsey, A. Jeremy] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Willsey, A. Jeremy; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Sestan, N (reprint author), Yale Univ, Sch Med, Dept Neurobiol, 333 Cedar St C-323C, New Haven, CT 06510 USA. EM matthew.state@ucsf.edu; nenad.sestan@yale.edu FU National Institute of Mental Health [MH089956, MH081896]; Simons Foundation; Overlook International Foundation; Kavli Foundation; James S. McDonnell Foundation; Foster-Davis Foundation Inc.; Canadian Institutes of Health Research FX The authors acknowledge financial support from the National Institute of Mental Health (MH089956 to M. W. S., MH081896 to N.S.), the Simons Foundation (to M. W. S. and N.S.), the Overlook International Foundation (to M. W. S. and N.S.), the Kavli Foundation (to N.S.), the James S. McDonnell Foundation (to N.S.), the Foster-Davis Foundation Inc. (NARSAD DI to N.S.), and the Canadian Institutes of Health Research (Doctoral Foreign Study Award to A.J.W.). 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Today PD APR PY 2014 VL 19 IS 4 BP 510 EP 519 DI 10.1016/j.drudis.2014.01.013 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH5UL UT WOS:000336196500021 PM 24508819 ER PT J AU Washington, SD Gordon, EM Brar, J Warburton, S Sawyer, AT Wolfe, A Mease-Ference, ER Girton, L Hailu, A Mbwana, J Gaillard, WD Kalbfleisch, ML VanMeter, JW AF Washington, Stuart D. Gordon, Evan M. Brar, Jasmit Warburton, Samantha Sawyer, Alice T. Wolfe, Amanda Mease-Ference, Erin R. Girton, Laura Hailu, Ayichew Mbwana, Juma Gaillard, William D. Kalbfleisch, M. Layne VanMeter, John W. TI Dysmaturation of the Default Mode Network in Autism SO HUMAN BRAIN MAPPING LA English DT Article DE autism; default mode network; functional connectivity; development; Theory of Mind; synaptogenesis ID INDEPENDENT COMPONENT ANALYSIS; FUNCTIONAL CONNECTIVITY; BRAIN CONNECTIVITY; SPECTRUM DISORDER; MIND HYPOTHESIS; CHILDREN; FMRI; MEMORY; UNDERCONNECTIVITY; ACTIVATION AB Two hypotheses of autism spectrum disorder (ASD) propose that this condition is characterized by deficits in Theory of Mind and by hypoconnectivity between remote cortical regions with hyperconnectivity locally. The default mode network (DMN) is a set of remote, functionally connected cortical nodes less active during executive tasks than at rest and is implicated in Theory of Mind, episodic memory, and other self-reflective processes. We show that children with ASD have reduced connectivity between DMN nodes and increased local connectivity within DMN nodes and the visual and motor resting-state networks. We show that, like the trajectory of synaptogenesis, internodal DMN functional connectivity increased as a quadratic function of age in typically developing children, peaking between, 11 and 13 years. In children with ASD, these long-distance connections fail to develop during adolescence. These findings support the developmental disconnection model of ASD, provide a possible mechanistic explanation for the Theory-of-Mind hypothesis of ASD, and show that the window for effectively treating ASD could be wider than previously thought. Hum Brain Mapp 35:1284-1296, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Washington, Stuart D.; Brar, Jasmit; Warburton, Samantha; Sawyer, Alice T.; Wolfe, Amanda; Mease-Ference, Erin R.; Girton, Laura; Hailu, Ayichew; Mbwana, Juma; Kalbfleisch, M. Layne; VanMeter, John W.] Georgetown Univ, Med Ctr, Ctr Funct & Mol Imaging, Washington, DC 20057 USA. [Washington, Stuart D.; Brar, Jasmit; Warburton, Samantha; Sawyer, Alice T.; Wolfe, Amanda; Mease-Ference, Erin R.; Girton, Laura; Hailu, Ayichew; Mbwana, Juma; VanMeter, John W.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. [Washington, Stuart D.; Gaillard, William D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Gordon, Evan M.] Georgetown Univ, Med Ctr, Interdisciplinary Program Neurosci, Washington, DC 20057 USA. [Kalbfleisch, M. Layne] Krasnow Invest Dev Learning & Behav, Fairfax, VA USA. RP Washington, SD (reprint author), Georgetown Univ, Med Ctr, Room LM14,Preclin Sci Bldg,3900 Reservoir Rd NW, Washington, DC 20057 USA. EM sdw4@georgetown.edu; jwv5@georgetown.edu FU NICHD [T32HD046388]; STAART (Johns Hopkins University's Kennedy-Krieger Institute) [NIH/NIMH IU54MH066417-01]; Intellectual and Developmental Disorders Research Center [NIH/NICHD 2P30HD040677-06]; Georgetown General Clinical Research Center [NIH/NCRR 5M01RR023942-03] FX Contract grant sponsor: NICHD; Contract grant number: T32HD046388 (Dr. Washington by way of a post-doctoral training award, V. G.); Contract grant sponsor: STAART (Johns Hopkins University's Kennedy-Krieger Institute); Contract grant number: NIH/NIMH IU54MH066417-01, R. 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Brain Mapp. PD APR PY 2014 VL 35 IS 4 BP 1284 EP 1296 DI 10.1002/hbm.22252 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AE9MP UT WOS:000334332200016 PM 23334984 ER PT J AU Kuo, HC Wu, CM Chang, WP Kuo, CN Yeter, D Lin, CY Pai, JT Chi, YC Lin, CH Wang, LJ Chang, WC AF Kuo, Ho-Chang Wu, Chung-Min Chang, Wei-Pin Kuo, Chun-Nan Yeter, Deniz Lin, Chun-Yi Pai, Jei-Tsung Chi, Ying-Chen Lin, Chia-Hsien Wang, Liang-Jen Chang, Wei-Chiao TI Association between Kawasaki Disease and Autism: A Population-Based Study in Taiwan SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE Kawasaki disease; autism; population-based study; Taiwan population ID IMMUNOGLOBULIN TREATMENT FAILURE; SPECTRUM DISORDER; DIAGNOSIS; CHILDREN AB Objective: The association between Kawasaki disease and autism has rarely been studied in Asian populations. By using a nationwide Taiwanese population-based claims database, we tested the hypothesis that Kawasaki disease may increase the risk of autism in Taiwan. Materials and Methods: Our study cohort consisted of patients who had received the diagnosis of Kawasaki disease (ICD-9-CM: 446.1) between 1997 and 2005 (N = 563). For a comparison cohort, five age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 2,815). All subjects were tracked for 5 years from the date of cohort entry to identify whether they had developed autism (ICD-9-CM code 299.0) or not. Cox proportional hazard regressions were then performed to evaluate 5-year autism-free survival rates. Results: The main finding of this study was that patients with Kawasaki disease seem to not be at increased risk of developing autism. Of the total patients, four patients developed autism during the 5-year follow-up period, among whom two were Kawasaki disease patients and two were in the comparison cohort. Further, the adjusted hazard ratios (AHR) (AHR: 4.81; 95% confidence interval: 0.68-34.35; P = 0.117) did not show any statistical significance between the Kawasaki disease group and the control group during the 5-year follow-up. Conclusion: Our study indicated that patients with Kawasaki disease are not at increased risk of autism. C1 [Kuo, Ho-Chang] Kaohsiung Chang Gung Mem Hosp, Dept Pediat, Kaohsiung 833, Taiwan. [Kuo, Ho-Chang; Wang, Liang-Jen] Chang Gung Univ, Coll Med, Kaohsiung 833, Taiwan. [Wu, Chung-Min] Natl Taipei Univ Technol, Dept Business Management, Taipei 106, Taiwan. [Chang, Wei-Pin; Lin, Chun-Yi; Pai, Jei-Tsung] Yuanpei Univ, Dept Healthcare Management, Hsinchu 300, Taiwan. [Kuo, Chun-Nan; Chang, Wei-Chiao] Taipei Med Univ, Sch Pharm, Dept Clin Pharm, Taipei 110, Taiwan. [Chi, Ying-Chen] Taipei City Hosp, Dept Educ & Res, Taipei 106, Taiwan. [Lin, Chia-Hsien] Kainan Univ, Sch Hlth Care Management, Dept Hlth Ind Management, Taoyuan 338, Taiwan. [Wang, Liang-Jen] Kaohsiung Chang Gung Mem Hosp, Dept Child & Adolescent Psychiat, Kaohsiung 833, Taiwan. [Kuo, Chun-Nan; Chang, Wei-Chiao] Taipei Med Univ, Wan Fang Hosp, Dept Pharm, Taipei 116, Taiwan. [Chang, Wei-Chiao] Taipei Med Univ, Sch Pharm, Master Program Clin Pharmacogen & Pharmacoprote, Taipei 110, Taiwan. [Chang, Wei-Chiao] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Ctr Canc, Kaohsiung 807, Taiwan. RP Wang, LJ (reprint author), Kaohsiung Chang Gung Mem Hosp, Dept Child & Adolescent Psychiat, Kaohsiung 833, Taiwan. EM erickuo48@yahoo.com.tw; cmwu@ntut.edu.tw; wpchang@mail.ypu.edu.tw; rencouter@gmail.com; deniz.yeter@gmx.de; elaine_lin76@ymail.com; reitrong@mail.ypu.edu.tw; a0130@tpech.gov.tw; g870615@gmail.com; wangliangjen@gmail.com; wcc@tmu.edu.tw FU National Taipei University of Technology [NTUT-TMU-102-16, NTUT-TMU-103-14]; Taipei Medical University [NTUT-TMU-102-16, NTUT-TMU-103-14]; National Science Council, Taiwan [NSC 102-2314-B-182-053-MY3]; Chang Gung Memorial Hospital [CMRPG8C1081, CMRPG8B0211] FX This study was supported by the National Taipei University of Technology and Taipei Medical University Join Research Grants (NTUT-TMU-102-16 and NTUT-TMU-103-14). And grant from the National Science Council, Taiwan (NSC 102-2314-B-182-053-MY3) and grant from Chang Gung Memorial Hospital (CMRPG8C1081 and CMRPG8B0211). 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J. Environ. Res. Public Health PD APR PY 2014 VL 11 IS 4 BP 3705 EP 3716 DI 10.3390/ijerph110403705 PG 12 WC Environmental Sciences SC Environmental Sciences & Ecology GA AG9TM UT WOS:000335762700015 PM 24705358 ER PT J AU Koegel, LK Singh, AK Koegel, RL Hollingsworth, JR Bradshaw, J AF Koegel, Lynn Kern Singh, Anjileen K. Koegel, Robert L. Hollingsworth, Jessica R. Bradshaw, Jessica TI Assessing and Improving Early Social Engagement in Infants SO JOURNAL OF POSITIVE BEHAVIOR INTERVENTIONS LA English DT Article DE infants; social intervention; autism spectrum disorder; early intervention ID AUTISM SPECTRUM DISORDER; LOW-BIRTH-WEIGHT; JOINT ATTENTION; PRESCHOOL-CHILDREN; COMMUNICATION; INTERVENTION; TEMPERAMENT; RISK; TODDLERS; BEHAVIOR AB Empirical studies have documented a variety of social abnormalities in infancy that indicate risk for later social and behavioral difficulties. There is very little research illustrating the presence of such behavioral vulnerabilities with frequent repeated measures, and the feasibility of designing interventions for improving social engagement in infants less than 1 year of age. In the context of a multiple baseline research design, three young infants, ages 4, 7, and 9 months, referred for concerns about social engagement were assessed for affect, social interest, eye contact avoidance, and response to name. In addition, the feasibility of implementing an intervention to target social behaviors was examined. Results demonstrated that (a) consistently low or erratic levels of social behavior were evident throughout the baseline assessment period, (b) these patterns could be improved with a brief intervention (a modified Pivotal Response Treatment) showing an immediate increase and stability of social engagement, and (c) social engagement remained at a stable and high level at follow-up. The results are discussed in terms of implications of early assessment and intervention for clinical populations, including infants with autism spectrum disorder. C1 [Koegel, Lynn Kern; Singh, Anjileen K.; Koegel, Robert L.; Hollingsworth, Jessica R.; Bradshaw, Jessica] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. RP Koegel, LK (reprint author), Univ Calif Santa Barbara, Grad Sch Educ, Koegel Autism Ctr, Counseling Clin & Sch Psychol Dept, Santa Barbara, CA 93106 USA. 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Posit. Behav. Interv. PD APR PY 2014 VL 16 IS 2 BP 69 EP 80 DI 10.1177/1098300713482977 PG 12 WC Psychology, Clinical; Education, Special SC Psychology; Education & Educational Research GA AD8RK UT WOS:000333533100002 ER PT J AU Davis, JM AF Davis, J. M. TI DUF1220 Dosage Is Linearly Associated with Increasing Severity of the Three Primary Symptoms of Autism (vol 10, e1004241, 2014) SO PLOS GENETICS LA English DT Correction CR Davis JM, 2014, PLOS GENET, V10, DOI 10.1371/journal.pgen.1004241 NR 1 TC 0 Z9 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2014 VL 10 IS 4 AR e1004373 DI 10.1371/journal.pgen.1004373 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA AG6AB UT WOS:000335499600005 ER PT J AU Racine, SE Culbert, KM Burt, SA Klump, KL AF Racine, S. E. Culbert, K. M. Burt, S. A. Klump, K. L. TI Advanced paternal age at birth: phenotypic and etiologic associations with eating pathology in offspring SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Advanced paternal age; disordered eating; eating disorders; environmental; genetic; twin study ID AUTISM SPECTRUM DISORDERS; MODERATES GENETIC INFLUENCES; TWIN REGISTRY MSUTR; DE-NOVO MUTATIONS; ANOREXIA-NERVOSA; MENTAL-DISORDERS; BULIMIA-NERVOSA; PARENTAL AGE; YOUNG-WOMEN; RISK-FACTOR AB Background Advanced paternal age at birth has been linked to several psychiatric disorders in offspring (e.g. schizophrenia) and genetic mechanisms are thought to underlie these associations. This study is the first to investigate whether advanced paternal age at birth is associated with eating disorder risk using a twin study design capable of examining both phenotypic and genetic associations. Method In a large, population-based sample of female twins aged 8-17 years in mid-puberty or beyond (n=1722), we investigated whether advanced paternal age was positively associated with disordered eating symptoms and an eating disorder history [i.e. anorexia nervosa (AN), bulimia nervosa (BN) or binge eating disorder (BED)] in offspring. Biometric twin models examined whether genetic and/or environmental factors underlie paternal age effects for disordered eating symptoms. Results Advanced paternal age was positively associated with disordered eating symptoms and an eating disorder history, where the highest level of pathology was observed in offspring born to fathers 40 years old. The results were not accounted for by maternal age at birth, body mass index (BMI), socio-economic status (SES), fertility treatment or parental psychiatric history. Twin models indicated decreased genetic, and increased environmental, effects on disordered eating with advanced paternal age. Conclusions Advanced paternal age increased risk for the full spectrum of eating pathology, independent of several important covariates. However, contrary to leading hypotheses, environmental rather than genetic factors accounted for paternal age-disordered eating associations. These data highlight the need to explore novel (potentially environmental) mechanisms underlying the effects of advanced paternal age on offspring eating disorder risk. C1 [Racine, S. E.; Burt, S. A.; Klump, K. L.] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. [Culbert, K. M.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. RP Klump, KL (reprint author), Michigan State Univ, Dept Psychol, 316 Phys Rd 107B, E Lansing, MI 48824 USA. EM klump@msu.edu FU Michigan State University; Canadian Institutes of Health Research [MDR-96630]; National Institute of Mental Health [5 T32 MH082761, 1 F31 MH0844701, 1 R01 MH0820-54, 1 R01 MH092377-01] FX Data collection was supported by grants from Michigan State University (K. L. Klump and S. A. Burt). Data analysis was supported by grants from the Canadian Institutes of Health Research (MDR-96630; S. E. Racine) and the National Institute of Mental Health (5 T32 MH082761 and 1 F31 MH0844701; K. M. Culbert; 1 R01 MH0820-54 and 1 R01 MH092377-01; K. L. Klump and S. A. Burt). The content is solely the responsibility of the authors and does not necessarily represent the official views of Michigan State University, the Canadian Institutes of Health Research or the National Institute of Mental Health. 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TI Attention and inhibition in children with ASD, ADHD and co-morbid ASD plus ADHD: an event-related potential study SO PSYCHOLOGICAL MEDICINE LA English DT Article DE ADHD; ASD; children; co-morbidity; continuous performance test (CPT); event-related potentials (ERPs) ID DEFICIT-HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; CONTINGENT NEGATIVE-VARIATION; DEFICIT/HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION; ENVIRONMENTAL CONTRIBUTIONS; RESPONSE-INHIBITION; DIAGNOSTIC VALIDITY; CONDUCT DISORDER AB Background Substantial overlap has been reported between attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Deficits in executive function (EF) are characteristic of both disorders but these impairments have not been compared directly across pure and co-morbid cases using event-related potentials (ERPs). Method Behavioural parameters and ERPs were recorded during a flankered cued-continuous performance test (CPT-OX) administered to 8-13-year-old boys with ASD (n=19), ADHD (n=18), co-morbid ASD+ADHD (n=29) and typically developing controls (TD; n=26). Preparatory processing (contingent negative variation, CNV) and attentional orienting (Cue-P3) at cues, response execution at targets (Go-P3), inhibitory processing at non-targets (NoGo-P3) and conflict monitoring between target and non-target trials (Go-N2 v. NoGo-N2) were examined. Results Categorical diagnoses and quantitative trait measures indicated that participants with ADHD (ADHD/ASD+ADHD) made more omission errors and exhibited increased reaction-time (RT) variability and reduced amplitude of the Cue-P3 and NoGo-P3 compared to TD/ASD participants. Participants with ASD (ASD/ ASD+ADHD) demonstrated reduced N2 enhancement from Go to NoGo trials compared to TD/ADHD participants. Participants with ASD-only displayed enhanced CNV amplitude compared to ASD+ADHD and TD participants. Conclusions Children with ADHD show deficits in attentional orienting and inhibitory control whereas children with ASD show abnormalities in conflict monitoring and response preparation. Children with co-morbid ASD+ADHD present as an additive co-occurrence with deficits of both disorders, although non-additive effects are suggested for response preparation. Measuring ERPs that index attention and inhibition is useful in disentangling cognitive markers of ASD and ADHD and elucidating the basis of co-occurring ASD+ADHD to guide clinical assessment. C1 [Tye, C.; Asherson, P.; Bolton, P.; McLoughlin, G.] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Tye, C.; Ashwood, K. L.; Azadi, B.; Bolton, P.] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [McLoughlin, G.] Univ Calif San Diego, Inst Neural Computat, Swartz Ctr Computat Neurosci, San Diego, CA 92103 USA. RP Tye, C (reprint author), Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, De Crespigny Pk, London SE5 8AF, England. EM charlotte.tye@kcl.ac.uk RI Bolton, Patrick/E-8501-2010 OI Bolton, Patrick/0000-0002-5270-6262 FU National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health (BRC); Waterloo Foundation [G686984]; Steel Charitable Trust [G38575208]; NIHR; BRC at the South London and Maudsley National Health Service (NHS) Trust Hospital, London FX We thank the participating families and all staff involved in this study, in particular S. Cartwright, S. Lewis and S. Newman. This work was supported by a grant from the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health (BRC), the Waterloo Foundation (G686984) and the Steel Charitable Trust (G38575208). Professor Bolton is supported by an NIHR Senior Investigator award and the BRC at the South London and Maudsley National Health Service (NHS) Trust Hospital, London. 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D., 2006, BODY EMBODIMENT SYMB, P1 Zechmeister I, 2001, HEALTH CARE ANAL, V9, P387, DOI 10.1023/A:1013837511115 NR 68 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0038-0385 EI 1469-8684 J9 SOCIOLOGY JI Sociol.-J. Brit. Sociol. Assoc. PD APR PY 2014 VL 48 IS 2 BP 216 EP 232 DI 10.1177/0038038512472774 PG 17 WC Sociology SC Sociology GA AE1XY UT WOS:000333768300002 ER PT J AU Castellani, CA Awamleh, Z Melka, MG O'Reilly, RL Singh, SM AF Castellani, Christina A. Awamleh, Zain Melka, Melkaye G. O'Reilly, Richard L. Singh, Shiva M. TI Copy Number Variation Distribution in Six Monozygotic Twin Pairs Discordant for Schizophrenia SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Article DE monozygotic twins; discordance; schizophrenia; genomes; de novo; copy number variations ID GENOME-WIDE ASSOCIATION; AUTISM-SPECTRUM DISORDERS; BIPOLAR DISORDER; GENE-EXPRESSION; DE-NOVO; STRUCTURAL VARIATION; CANDIDATE GENES; NERVOUS-SYSTEM; RISK LOCI; VARIANTS AB We have evaluated copy number variants (CNVs) in six monozygotic twin pairs discordant for schizophrenia. The data from Affymetrix (R) Human SNP 6.0 arrays were analyzed using Affymetrix (R) Genotyping Console, Partek (R) Genomics Suite, PennCNV, and Golden Helix SVS. This yielded both program-specific and overlapping results. Only CNVs called by Affymetrix Genotyping Console, Partek Genomics Suite, and PennCNV were used in further analysis. This analysis included an assessment of calls in each of the six twin pairs towards identification of unique CNVs in affected and unaffected co-twins. Real time polymerase chain reaction (PCR) experiments confirmed one CNV loss at 7q11.21 that was found in the affected patient but not in the unaffected twin. The results identified CNVs and genes that were previously implicated in mental abnormalities in four of the six twin pairs. It included PYY (twin pairs 1 and 5), EPHA3 (twin pair 3), KIAA1211L (twin pair 4), and GPR139 (twin pair 5). They represent likely candidate genes and CNVs for the discordance of four of the six monozygotic twin pairs for this heterogeneous neurodevelopmental disorder. An explanation for these differences is ontogenetic de novo events that differentiate in the monozygotic twins during development. C1 [Castellani, Christina A.; Awamleh, Zain; Melka, Melkaye G.; Singh, Shiva M.] Univ Western Ontario, Dept Biol, London, ON N6A 5B7, Canada. 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Hum. Genet. PD APR PY 2014 VL 17 IS 2 BP 108 EP 120 DI 10.1017/thg.2014.6 PG 13 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA AD4EC UT WOS:000333198800006 PM 24556202 ER PT J AU MacDonald, M Lord, C Ulrich, DA AF MacDonald, Megan Lord, Catherine Ulrich, Dale A. TI Motor Skills and Calibrated Autism Severity in Young Children With Autism Spectrum Disorder SO ADAPTED PHYSICAL ACTIVITY QUARTERLY LA English DT Article DE autism; motor skills; young children; calibrated severity ID DIAGNOSTIC OBSERVATION SCHEDULE; COMMUNICATION; INTERVENTION; TODDLERS; BEHAVIOR; SIGNS AB In addition to the core characteristics of autism spectrum disorder (ASD), motor skill deficits are present, persistent, and pervasive across age. Although motor skill deficits have been indicated in young children with autism, they have not been included in the primary discussion of early intervention content. One hundred fifty-nine young children with a confirmed diagnosis of ASD (n = 110), PDD-NOS (n = 26), and non-ASD (n = 23) between the ages of 14-33 months participated in this study.(1) The univariate general linear model tested the relationship of fine and gross motor skills and social communicative skills (using calibrated autism severity scores). Fine motor and gross motor skills significantly predicted calibrated autism severity (p < .05). Children with weaker motor skills have greater social communicative skill deficits. Future directions and the role of motor skills in early intervention are discussed. C1 [MacDonald, Megan] Oregon State Univ, Exercise & Sport Sci Program, Corvallis, OR 97331 USA. [Lord, Catherine] Weill Cornell Med Coll, White Plains, NY USA. [Lord, Catherine] New York Presbyterian Hosp, White Plains, NY USA. [Ulrich, Dale A.] Univ Michigan, Sch Kinesiol, Ann Arbor, MI 48109 USA. RP MacDonald, M (reprint author), Oregon State Univ, Exercise & Sport Sci Program, Corvallis, OR 97331 USA. EM megan.macdonald@oregonstate.edu FU Simons Foundation; NICHD [U19 HD35482-01]; Neurobiology and Genetic of Autism [06/01/97-05/31/07]; NIMH [RO1 MH081873-01A1]; Longitudinal Studies of Autism Spectrum Disorders [09/01/08-05/31/13]; Blue Cross Blue Shield Foundation of Michigan Grant Motor skills FX Support for this project was provided in part from funding awarded to Dr. Lord from the Simons Foundation, First Words, and the following grants: NICHD U19 HD35482-01. The Neurobiology and Genetic of Autism. 06/01/97-05/31/07 (Lord). NIMH RO1 MH081873-01A1. Longitudinal Studies of Autism Spectrum Disorders: 2 to 23. 09/01/08-05/31/13 (Lord). Blue Cross Blue Shield Foundation of Michigan Grant Motor skills, calibrated severity & autism number 1687.SAP (MacDonald). 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Mouren, M. -C. Doyen, C. TI Anorexia nervosa in the light of neurocognitive functioning: New theoretical and therapeutic perspectives SO ENCEPHALE-REVUE DE PSYCHIATRIE CLINIQUE BIOLOGIQUE ET THERAPEUTIQUE LA French DT Article DE Anorexia nervosa; Cognitive science; Developmental disabilities; Cognitive therapy; Imaging ID AUTISM SPECTRUM DISORDERS; LOW BODY-WEIGHT; EATING-DISORDERS; EXECUTIVE FUNCTIONS; CENTRAL COHERENCE; ONSET; ALEXITHYMIA; CHILDREN; WOMEN; ENDOPHENOTYPE AB Introduction. Anorexia nervosa is a serious psychiatric disorder, for which very few validated therapeutic strategies exist. The specific sociocognitive style of anorexic patients has already been described in the 1960s: it involves a concrete style with abstraction difficulties. Current neuropsychological tests have contributed to a more precise definition of these difficulties. Neuropsychological data: is there a specific cognitive profile?. Contrary to common beliefs, these patients' intellectual performances are not superior to those of the general population. However, detailed comparisons of profiles on the Weschler Scales suggest difficulties in synthesizing information and better abilities in concrete problem solving. Excessive attention to details.- The dominant hypothesis concerning the attentional dimension is the existence of a weakness in central coherence, resulting in superior detail processing and a weakness in global integration. This trend appears to be stable even after the normalization of nutritional status. Impaired cognitive flexibility.- The impairment of set-shifting abilities leads to rigidity, expressed by inflexibility and perseveration, both in reasoning and behaviour. This reduced cognitive flexibility appears to persist after recovery, and may constitute a familial trait. In addition, this likely endophenotype seems to be independent from obsessional traits. Controversial social skill.- Alexithymia is frequently described in anorexic individuals. It is the verbal description of feelings which seems to be particularly impaired. It may explain underlying difficulties in empathy. Indeed, these subjects have lower scores on emotional tests drawn from the theory of mind. These cognitive abnormalities are well documented in pervasive developmental disorders. Neuroanatomical data: neuroimaging in support of limbic and fronto-striatal abnormalities. Evidence from neuroimaging suggests abnormalities in cortical and subcortical structures, involving the temporal and orbito-frontal lobes. Various functional hypotheses are formulated, involving fronto-striatothalamic circuits, amygdala or insula. Is anorexia nervosa a developmental disorder?.- Pervasive developmental disorders are over-represented among anorexic subjects in comparison to the general population. Conversely, restrictive and selective eating disorders are more frequent among individuals presenting an autistic spectrum disorder. Therapeutic implications and future directions.- In view of the common cognitive and neuroanatomical data that are found in anorexia nervosa and neurodevelopmental disorders, we adhere to the hypothesis that anorexia nervosa may be similar to a neurodevelopmental disorder. Clinical observations suggest that this hypothesis may be especially relevant in the early forms of anorexia nervosa. These cognitive data confirm the potential relevance of new therapeutic modalities such as cognitive remediation. Initial results from its application to anorexia nervosa seem promising. Conclusion.- A review of the recent literature highlights the possible existence of a developmental impairment of cortical and subcortical structures, associated with specific abnormalities in cognitive development such as a weakness in central coherence, reduced set-shifting ability and poor social skills. On this basis, cognitive remediation may be a promising therapeutic innovation. (C) L'Encephale, Paris, 2013. C1 [Martinez, G.; Cook-Darzens, S.; Chaste, P.; Mouren, M. -C.; Doyen, C.] Hop Robert Debre, Serv Psychopathol Enfant & Adolescent, F-75019 Paris, France. [Martinez, G.; Cook-Darzens, S.; Chaste, P.; Mouren, M. -C.; Doyen, C.] Ctr Hosp St Anne, F-75014 Paris, France. RP Doyen, C (reprint author), Hop Robert Debre, Serv Psychopathol Enfant & Adolescent, 48 Blvd Serurier, F-75019 Paris, France. 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Psychiatr. Clin. Biol. Ther. PD APR PY 2014 VL 40 IS 2 BP 160 EP 167 DI 10.1016/j.encep.2012.06.004 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AH0KI UT WOS:000335807500010 PM 23541918 ER PT J AU Beherec, L Quilici, G Rosier, A Gerardin, P Campion, D Guillin, O AF Beherec, L. Quilici, G. Rosier, A. Gerardin, P. Campion, D. Guillin, O. TI Pharmacological treatments in patients with pervasive developmental disorders: A review SO ENCEPHALE-REVUE DE PSYCHIATRIE CLINIQUE BIOLOGIQUE ET THERAPEUTIQUE LA French DT Review DE Pervasive development disorders; Autism spectrum disorders; Autistic disorder; Therapy; Treatment; Review ID AUTISM SPECTRUM DISORDERS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; INFANTILE-AUTISM; RETROSPECTIVE ANALYSIS; BEHAVIORAL SYMPTOMS; ADOLESCENT AUTISM; CROSSOVER TRIAL; SLEEP PROBLEMS; CHILDREN AB Background. - Pervasive developmental disorders (PDD) are neurodevelepmental disorders that are characterized by severe deficits in socialisation and communication, and the existence of repetitive and stereotyped interests and behaviours. It is estimated more than 60/100,000 children are suffering from PDD. Comorbid disorders are common in people with PDD, including intellectual deficiency, symptoms of attention deficit-hyperactivity, aggression and disruption, and pervasive repetitive behaviours or thoughts. These symptoms have a negative impact on the outcome and quality of life of the patients and their caregivers. The first-line management of comorbid disorders in PDD is behavioural intervention, but sometimes this is not sufficient, and the use of pharmacological treatment is needed. Method. - We conducted a review of studies of medical treatments used in patients with PDD to establish which treatments show good evidence of efficacy in PDD. We used the Medline database and the following keywords "pervasive development disorders" or "autism spectrum disorders" or "autistic disorder" and "therapy" or "treatment". Results. - The treatments that showed the best efficacy on irritability in well-designed studies are second generation antipsychotics, risperidone and aripiprazole. Some studies indicate that haloperidol is efficient as well, but the very high frequency of extra-pyramidal effects limits its use. Methylphenidate has shown some efficacy on impulsivity and hyperactivity in randomised placebo-controlled studies. First data concerning atomoxetine are promising but better-designed studies are needed. Selective serotonin re-uptake inhibitors: fluvoxamine and fluoxetine have shown some efficacy in the treatment of serious and pervasive repetitive behaviours. Alpha-adrenergic treatments, clonidine and guanfacine, can help in the management of disruptive behaviours in patients with PDD. Data concerning naltrexone are contradictory, indeed many case reports of its efficacy on aggressive (mostly auto-aggressive) behaviours are reported in the literature, but well-designed studies do not find any improvement in patients treated with naltrexone compared with patients treated with placebo. First data concerning ocytocin are promising, indeed, if they were to be confirmed, that would be the first treatment efficient on the core symptoms of PDD. (C) L'Encephale, Paris, 2013. C1 [Beherec, L.] Ctr Hosp St Anne, Serv Hosp Univ, F-75014 Paris, France. [Beherec, L.; Campion, D.; Guillin, O.] Ctr Hosp Rouvray, Pole Psychiat Gen Rouen Rive Droite, F-76300 Sottevilte Les Rouen, France. [Quilici, G.; Rosier, A.; Guillin, O.] Ctr Hosp Rouvray, Ctr Ressource Autisme Haute Normandie, F-76300 Sottevilte Les Rouen, France. [Campion, D.; Guillin, O.] Univ Rouen, Fac Med & Pharm, INSERM, Unite 614, F-76183 Rouen, France. [Gerardin, P.] CHU Charles Nicolle, Pole Femme Mere Enfant, F-76031 Rouen, France. RP Beherec, L (reprint author), Ctr Hosp St Anne, Serv Hosp Univ, 7 Rue Cabanis, F-75014 Paris, France. 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Psychiatr. Clin. Biol. Ther. PD APR PY 2014 VL 40 IS 2 BP 188 EP 196 DI 10.1016/j.encep.2012.01.014 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AH0KI UT WOS:000335807500014 PM 24369879 ER PT J AU Lyall, K Schmidt, RJ Hertz-Picciotto, I AF Lyall, Kristen Schmidt, Rebecca J. Hertz-Picciotto, Irva TI Maternal lifestyle and environmental risk factors for autism spectrum disorders SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Autism; environmental risk factors; air pollution; environmental chemicals; maternal nutrition; maternal smoking; maternal alcohol use ID FOLIC-ACID SUPPLEMENTS; POLYBROMINATED DIPHENYL ETHERS; SHORT INTERPREGNANCY INTERVALS; PRENATAL ALCOHOL EXPOSURE; HAZARDOUS AIR-POLLUTANTS; NEURAL-TUBE DEFECTS; URINARY BISPHENOL-A; CHILDHOOD AUTISM; PYRETHROID INSECTICIDES; PSYCHIATRIC-DISORDERS AB Background: Over the past 10 years, research into environmental risk factors for autism has grown dramatically, bringing evidence that an array of non-genetic factors acting during the prenatal period may influence neurodevelopment. Methods: This paper reviews the evidence on modifiable preconception and/or prenatal factors that have been associated, in some studies, with autism spectrum disorder (ASD), including nutrition, substance use and exposure to environmental agents. This review is restricted to human studies with at least 50 cases of ASD, having a valid comparison group, conducted within the past decade and focusing on maternal lifestyle or environmental chemicals. Results: Higher maternal intake of certain nutrients and supplements has been associated with reduction in ASD risk, with the strongest evidence for periconceptional folic acid supplements. Although many investigations have suggested no impact of maternal smoking and alcohol use on ASD, more rigorous exposure assessment is needed. A number of studies have demonstrated significant increases in ASD risk with estimated exposure to air pollution during the prenatal period, particularly for heavy metals and particulate matter. Little research has assessed other persistent and non-persistent organic pollutants in association with ASD specifically. Conclusions: More work is needed to examine fats, vitamins and other maternal nutrients, as well as endocrine-disrupting chemicals and pesticides, in association with ASD, given sound biological plausibility and evidence regarding other neurodevelopmental deficits. The field can be advanced by large-scale epidemiological studies, attention to critical aetiological windows and how these vary by exposure, and use of biomarkers and other means to understand underlying mechanisms. C1 [Lyall, Kristen; Schmidt, Rebecca J.; Hertz-Picciotto, Irva] Univ Calif Davis, Dept Publ Hlth Sci, MIND Med Invest Neurodev Disorders Inst, Davis, CA 95616 USA. RP Lyall, K (reprint author), Univ Calif Davis, Dept Publ Hlth Sci, 1 Shields Ave,Med Sci 1C, Davis, CA 95616 USA. EM kdodge@ucdavis.edu FU National Institutes of Health (NIH) [R01-ES015359, NIH R01-ES020392, NIH P01 ES11269, NIH K12HD051958]; U.S. Environmental Protection Agency (EPA) STAR [R829388, R833292] FX This work was supported by the following grants: National Institutes of Health (NIH) R01-ES015359, NIH R01-ES020392, NIH P01 ES11269, NIH K12HD051958 and U.S. Environmental Protection Agency (EPA) STAR #R829388 & R833292. The authors have no financial relationships relevant to this article. 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J. Epidemiol. PD APR PY 2014 VL 43 IS 2 BP 443 EP 464 DI 10.1093/ije/dyt282 PG 22 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AH1ZD UT WOS:000335919500014 PM 24518932 ER PT J AU Kim, YS State, MW AF Kim, Young Shin State, Matthew W. TI Recent challenges to the psychiatric diagnostic nosology: a focus on the genetics and genomics of neurodevelopmental disorders SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE nosology; genetics; genomics and etiology; neurodevelopmental disorders ID DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; CHROMOSOME 16P11.2; DISEASE RISK; POPULATION; SCHIZOPHRENIA; DELETIONS; PATTERNS; LOCI; CNVS AB Recent advances in the genetics of neurodevelopmental disorder (NDD) have demonstrated that rare mutations play a role not only in Mendelian syndromes, but in complex, common forms of NDDs as well. Strikingly, both common polymorphisms and rare variations in a single gene or genetic locus have been found to carry risk for conditions previously considered to be clinically and aetiologically distinct. Recent developments in the methods and tools available for studying complex NDDs have led to systematic and reliable genome-wide variant discovery. Both common as well as rare, and structural as well as sequence, genetic variations have been identified as contributing to NDDs. There are multiple examples in which the identical variant had been found to contribute to a wide range of formerly distinct diagnoses, including autism, schizophrenia, epilepsy, intellectual disability and language disorders. These include variations in chromosomal structure at 16p11.2, rare de novo point mutations at the gene SCN2A, and common single nucleotide polymorphisms (SNPs) mapping near loci encoding the genes ITIH3, AS3MT, CACNA1C and CACNB2. These selected examples point to the challenges to current diagnostic approaches. Widely used categorical schema have been adequate to provide an entre into molecular mechanisms of NDDs, but there is a need to develop an alternative, more biologically-relevant nosology. Thus recent advances in gene discovery in the area of NDDs are leading to a re-conceptualization of diagnostic boundaries. Findings suggest that epidemiological samples may provide important new insights into the genetics and diagnosis of NDDs and that other areas of medicine may provide useful models for developing a new diagnostic nosology, one that simultaneously integrates categorical diagnoses, biomarkers and dimensional variables. C1 [Kim, Young Shin] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. [Kim, Young Shin] Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA. [Kim, Young Shin] Yonsei Univ, Coll Med, Dept Psychiat, Seoul, South Korea. [State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP State, MW (reprint author), Univ Calif San Francisco, Dept Psychiat, Langley Porter Psychiat Inst & Hosp, 401 Parnassus Ave, San Francisco, CA 94143 USA. EM Matthew.State@ucsf.edu FU [ES021462]; [MH089956]; [MH081754]; [MH100027] FX This work was supported by grants ES021462 (Y.S.K.) and MH089956, MH081754 and MH100027(M.W.S.). 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J. Epidemiol. PD APR PY 2014 VL 43 IS 2 BP 465 EP 475 DI 10.1093/ije/dyu037 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AH1ZD UT WOS:000335919500015 PM 24618187 ER PT J AU D'Onofrio, BM Rickert, ME Frans, E Kuja-Halkola, R Almqvist, C Sjolander, A Larsson, H Lichtenstein, P AF D'Onofrio, Brian M. Rickert, Martin E. Frans, Emma Kuja-Halkola, Ralf Almqvist, Catarina Sjolander, Arvid Larsson, Henrik Lichtenstein, Paul TI Paternal Age at Childbearing and Offspring Psychiatric and Academic Morbidity SO JAMA PSYCHIATRY LA English DT Article ID DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; BIPOLAR DISORDER; MATERNAL SMOKING; PARENTAL AGE; ENVIRONMENTAL-INFLUENCES; PERSONALITY-TRAITS; RISK; SCHIZOPHRENIA; PREGNANCY AB IMPORTANCE Advancing paternal age is associated with increased genetic mutations during spermatogenesis, which research suggests may cause psychiatric morbidity in the offspring. The effects of advancing paternal age at childbearing on offspring morbidity remain unclear, however, because of inconsistent epidemiologic findings and the inability of previous studies to rigorously rule out confounding factors. OBJECTIVE To examine the associations between advancing paternal age at childbearing and numerous indexes of offspring morbidity. DESIGN, SETTING, AND PARTICIPANTS We performed a population-based cohort study of all individuals born in Sweden in 1973-2001 (N = 2 615 081), with subsets of the data used to predict childhood or adolescent morbidity. We estimated the risk of psychiatric and academic morbidity associated with advancing paternal age using several quasi-experimental designs, including the comparison of differentially exposed siblings, cousins, and first-born cousins. EXPOSURE Paternal age at childbearing. MAIN OUTCOMES AND MEASURES Psychiatric (autism, attention-deficit/hyperactivity disorder, psychosis, bipolar disorder, suicide attempt, and substance use problem) and academic (failing grades and low educational attainment) morbidity. RESULTS In the study population, advancing paternal age was associated with increased risk of some psychiatric disorders (eg, autism, psychosis, and bipolar disorders) but decreased risk of the other indexes of morbidity. In contrast, the sibling-comparison analyses indicated that advancing paternal age had a dose-response relationship with every index of morbidity, with the magnitude of the associations being as large or larger than the estimates in the entire population. Compared with offspring born to fathers 20 to 24 years old, offspring of fathers 45 years and older were at heightened risk of autism (hazard ratio [HR] = 3.45; 95% CI, 1.62-7.33), attention-deficit/hyperactivity disorder (HR = 13.13; 95% CI, 6.85-25.16), psychosis (HR = 2.07; 95% CI, 1.35-3.20), bipolar disorder (HR = 24.70; 95% CI, 12.12-50.31), suicide attempts (HR = 2.72; 95% CI, 2.08-3.56), substance use problems (HR = 2.44; 95% CI, 1.98-2.99), failing a grade (odds ratio [OR] = 1.59; 95% CI, 1.37-1.85), and low educational attainment (OR = 1.70; 95% CI, 1.50-1.93) in within-sibling comparisons. Additional analyses using several quasi-experimental designs obtained commensurate results, further strengthening the internal and external validity of the findings. CONCLUSIONS AND RELEVANCE Advancing paternal age is associated with increased risk of psychiatric and academic morbidity, with the magnitude of the risks being as large or larger than previous estimates. These findings are consistent with the hypothesis that new genetic mutations that occur during spermatogenesis are causally related to offspring morbidity. C1 [D'Onofrio, Brian M.; Rickert, Martin E.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Frans, Emma; Kuja-Halkola, Ralf; Almqvist, Catarina; Sjolander, Arvid; Larsson, Henrik; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Almqvist, Catarina] Astrid Lindgren Childrens Hosp, Lung & Allergy Unit, Stockholm, Sweden. RP D'Onofrio, BM (reprint author), Indiana Univ, Dept Psychol & Brain Sci, 1101 E 10th St, Bloomington, IN 47405 USA. EM bmdonofr@indiana.edu RI Maattanen, Laura/N-5424-2014 FU National Institute of Child Health and Human Development [HD061817]; Swedish Research Council (Medicine); Swedish Council for Working Life and Social Research FX The manuscript was supported by grant HD061817 from the National Institute of Child Health and Human Development (Drs D'Onofrio and Lichtenstein), the Swedish Research Council (Medicine) (Dr Lichtenstein), and the Swedish Council for Working Life and Social Research (Dr Lichtenstein). CR Academy of Medical Sciences Working Group, 2007, ID ENV CAUS DIS SHOU Allison P. 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TI Mania in an Adolescent with Autism and Premenstrual Mood Variation: A Diagnostic and Treatment Dilemma SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID COMORBID BIPOLAR DISORDER; PREVALENCE C1 [Vijapura, Sagar; Schofield, Molly; Maneta, Eleni] Harvard Univ, Sch Med, Dept Psychiat, Boston Childrens Hosp, Boston, MA 02115 USA. [Coffey, Barbara J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. RP Coffey, BJ (reprint author), Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM Barbara.coffey@mssm.edu FU Eli Lily Pharmaceutical; NIMH; NINDS; Tourette Syndrome Association; Otsuka; Shire; Bristol-Myers; Pfizer; Boehringer Ingelheim FX Drs. Vijapura and Maneta and Mrs. Schofield have no conflicts of interest or financial ties to disclose. Dr. Coffey has received research support from Eli Lily Pharmaceutical, NIMH, NINDS, Tourette Syndrome Association, Otsuka, Shire, Bristol-Myers, Pfizer, and Boehringer Ingelheim. 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PD APR PY 2014 VL 24 IS 3 BP 161 EP 164 DI 10.1089/cap.2014.2432 PG 4 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AH6HC UT WOS:000336230300008 PM 24725200 ER PT J AU Khan, A Harney, JW Zavackp, AM Sajdel-Sulkowskal, EM AF Khan, A. Harney, J. W. Zavackp, A. M. Sajdel-Sulkowskal, E. M. TI DISRUPTED BRAIN THYROID HORMONE HOMEOSTASIS AND ALTERED THYROID HORMONE-DEPENDENT BRAIN GENE EXPRESSION IN AUTISM SPECTRUM DISORDERS SO JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE autism spectrum disorders; brain region-dependent; sex-dependent; oxidative stress marker 3-nitrotrosine; type 2 deiodinase; 3',3,5-triiodothyronine ID CENTRAL-NERVOUS-SYSTEM; IODOTHYRONINE DEIODINASE; CEREBRAL-CORTEX; NEUROTROPHIC FACTOR; TYPE-2 DEIODINASE; MOLECULAR-BIOLOGY; OXIDATIVE STRESS; UP-REGULATION; RAT; EXPOSURE AB The present study examined human postmortem brains for changes consistent with the hypothesis of local brain TH deficiency in autism spectrum disorders (ASD). Brain levels of oxidative stress marker - 3-nitrotyrosine (3-NT), iodothyronine deiodinase type 2(D2) and type 3 (D3), 3',3,5-triiodothyronine (T3) content, mercury content and gene expression levels were analyzed and compared in the several regions of postmortem brains derived from both male and female control and ASD cases, age 4-16 years. We report that some parameters measured, such as D2 are subject to rapid postmortem inactivation, while others that were analyzed showed both brain region- and sex-dependent changes. Levels of 3-NT were overall increased, T3 was decreased in the cortical regions of ASD brains, while mercury levels measured only in the extracortical regions were not different. The expression of several thyroid hormone (TH)-dependent genes was altered in ASD. Data reported here suggest the possibility of brain region-specific disruption of TH homeostasis and gene expression in autism. C1 [Khan, A.; Sajdel-Sulkowskal, E. M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02163 USA. [Khan, A.; Harney, J. W.; Zavackp, A. M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Harney, J. W.; Zavackp, A. M.] Harvard Univ, Sch Med, Dept Med, Div Endocrinol Diabet & Hypertens,Thyroid Div, Boston, MA USA. [Sajdel-Sulkowskal, E. M.] Warsaw Univ Life Sci, Fac Vet Med, Vet Res Ctr, Warsaw, Poland. RP Sajdel-Sulkowskal, EM (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02163 USA. EM esulkowska@rics.bwh.harvard.edu FU SafeMinds; [NIDDK-DK76117] FX This research was supported by a grant from SafeMinds to Dr. Sajdel-Sulkowska and NIDDK-DK76117 grant to Dr. Zavacki. Human tissue was obtained from NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD. Authors thank Dr. Alessandro Marsili for help with brain T3 analysis. 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Physiol. Pharmacol. PD APR PY 2014 VL 65 IS 2 BP 257 EP 272 PG 16 WC Physiology SC Physiology GA AH3GA UT WOS:000336010500010 PM 24781735 ER PT J AU Memarzia, J Tracy, D Giaroli, G AF Memarzia, Jessica Tracy, Derek Giaroli, Giovanni TI The use of antipsychotics in preschoolers: A veto or a sensible last option? SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Review DE Antipsychotics; children (preschool); practice guideline; license; long-term effects; safety; treatment efficacy; review ID CHILDHOOD-ONSET SCHIZOPHRENIA; PERVASIVE DEVELOPMENTAL DISORDERS; DISRUPTIVE BEHAVIOR DISORDERS; AUTISM SPECTRUM DISORDERS; OPEN-LABEL TRIAL; DEFICIT HYPERACTIVITY DISORDER; PRIVATELY INSURED CHILDREN; PEDIATRIC BIPOLAR DISORDER; ADVERSE DRUG EVENTS; SCHOOL-AGE-CHILDREN AB Recent reports have illustrated a dramatic rise in the use of antipsychotics in preschool children, medications originally designed and licensed for the treatment of adult psychotic disorders. Within this context, the current usage and the associated diagnoses are reviewed and compared with official guidelines and licensing for such use, highlighting a controversial challenge for clinicians. A review of the evidence base of the relative efficacy of such medications for a range of disorders is given. Associated safety and side effects are discussed, with compelling evidence for increased adverse events associated with use of antipsychotics in preschoolers, and neurodevelopmental hypotheses are used to guide predictions of long-term risk. An apparent gap in the literature and evidence base supporting such use and elucidating the risks and benefits leaves a challenge for clinicians and researchers and hinders the development of appropriate guidelines. Pragmatism in clinical practice, mindful of the limited evidence base that does exist and the propensity for harm, is necessary; far more research is required in this important area. C1 [Memarzia, Jessica; Tracy, Derek; Giaroli, Giovanni] Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London WC2R 2LS, England. [Tracy, Derek] Oxleas NHS Fdn Trust, London, England. [Giaroli, Giovanni] North East London NHS Fdn Trust, London, England. RP Memarzia, J (reprint author), Univ Cambridge, Dept Psychiat, 18b Trumpington Rd, Cambridge CB2 8AH, England. EM jessica@memarzia.com FU Shire; Eli Lily; FlynnPharma FX Dr Giaroli has received honoraria for serving on a speakers' bureau for Eli Lily, FlynnPharma and Jannsen. He has also received reimbursement for travel expenses and conference attendance by Shire, Eli Lily and FlynnPharma. 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Psychopharmacol. PD APR PY 2014 VL 28 IS 4 BP 303 EP 319 DI 10.1177/0269881113519506 PG 17 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AC3UR UT WOS:000332447200002 PM 24451556 ER PT J AU Jungheim, M Miller, S Kuhn, D Ptok, M AF Jungheim, M. Miller, S. Kuehn, D. Ptok, M. TI Prosody, speech input and language acquisition SO HNO LA German DT Article DE Prosody; Language development; Child directed speech; Child language; Speech acoustics ID INFANT-DIRECTED SPEECH; NEUROPHYSIOLOGICAL INDEXES; PREVERBAL INFANTS; WORD SEGMENTATION; QUICHE MAYAN; CHILDREN; DISCRIMINATION; MOTHERS; AUTISM; RHYTHM AB Background. In order to acquire language, children require speech input. The prosody of the speech input plays an important role. In most cultures adults modify their code when communicating with children. Compared to normal speech this code differs especially with regard to prosody. Method. For this review a selective literature search in PubMed and Scopus was performed. Results. Prosodic characteristics are a key feature of spoken language. By analysing prosodic features, children gain knowledge about underlying grammatical structures. Child-directed speech (CDS) is modified in a way that meaningful sequences are highlighted acoustically so that important information can be extracted from the continuous speech flow more easily. CDS is said to enhance the representation of linguistic signs. Discussion. Taking into consideration what has previously been described in the literature regarding the perception of suprasegmentals, CDS seems to be able to support language acquisition due to the correspondence of prosodic and syntactic units. However, no findings have been reported, stating that the linguistically reduced CDS could hinder first language acquisition. 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The purpose of this review is to document the support for the involvement of this molecule in the maintenance of normal cognitive, emotional functioning, and to outline recent developments in the content of Autism spectrum disorder (ASD). Current and future treatment development can be guided by developing understanding of this molecule's actions in the brain and the ways the expression of BDNF can be planned. Over the years, research findings suggested a critical role played by BDNF in the development of autism including increased serum concentrations of BDNF in children with autism and identification of different forms of BDNF in families of autistic individuals. C1 [Halepoto, Dost Muhammad; Bashir, Shahid; AL-Ayadhi, Laila] King Saud Univ, Fac Med, Autism Res & Treatment Ctr, Dept Physiol, Riyadh 11461, Saudi Arabia. RP Halepoto, DM (reprint author), King Saud Univ, Al Amodi Autism Res Chair, KSU Autism Res & Treatment Ctr, Dept Physiol, POBB 2925, Riyadh 11461, Saudi Arabia. EM dr_m_halepota@yahoo.com FU Autism Research and Treatment Centre; Sheikh Al-Amoudi Autism research chair; King Abdul Aziz city for science and technology (KACST); Health Research and Studies program at (NPST); Kind Saud University FX We thank Autism Research and Treatment Centre, Sheikh Al-Amoudi Autism research chair, King Abdul Aziz city for science and technology (KACST), and Health Research and Studies program at (NPST), Kind Saud University for sponsoring and financial support. 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Coll. Physicians Surg. PD APR PY 2014 VL 24 IS 4 BP 274 EP 278 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AG7TJ UT WOS:000335621300014 PM 24709243 ER PT J AU White, SJ Frith, U Rellecke, J Al-Noor, Z Gilbert, SJ AF White, Sarah J. Frith, Uta Rellecke, Julian Al-Noor, Zainab Gilbert, Sam J. TI Autistic adolescents show atypical activation of the brain's mentalizing system even without a prior history of mentalizing problems SO NEUROPSYCHOLOGIA LA English DT Article DE Autism; Theory of mind; Social impairment; Development; Longitudinal ID FUNCTIONAL CONNECTIVITY MRI; MEDIAL PREFRONTAL CORTEX; SPECTRUM DISORDERS; ASPERGER-SYNDROME; SOCIAL BRAIN; DIAGNOSTIC INTERVIEW; MIND; CHILDREN; MECHANISMS; TASKS AB Some autistic children pass classic Theory of Mind (ToM) tasks that others fail, but the significance of this finding is at present unclear. We identified two such groups of primary school age (labelled ToM+ and ToM-) and a matched comparison group of typically developing children (TD). Five years later we tested these participants again on a ToM test battery appropriate for adolescents and conducted an fMRI study with a story based ToM task. We also assessed autistic core symptoms at these two time points. At both times the ToM-group showed more severe social communication impairments than the ToM+ group, and while showing an improvement in mentalizing performance, they continued to show a significant impairment compared to the NT group. Two independent ROI analyses of the BOLD signal showed activation of the mentalizing network including medial prefrontal cortex, posterior cingulate and lateral temporal cortices. Strikingly, both ToM+ and ToM- groups showed very similar patterns of heightened activation in comparison with the NT group. No differences in other brain regions were apparent. Thus, autistic adolescents who do not have a history of mentalizing as children who did have such a history. This finding indicates that heterogeneity at the behavioural level may nevertheless map onto a similar phenotype at the neuro-cognitive level. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved. C1 [White, Sarah J.; Frith, Uta; Al-Noor, Zainab; Gilbert, Sam J.] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. [Rellecke, Julian] Humboldt Univ, Dept Psychol, D-10099 Berlin, Germany. RP Gilbert, SJ (reprint author), Inst Cognit Neurosci, 17 Queen Sq, London WC1N 3AR, England. EM sam.gilbert@ucl.ac.uk RI White, Sarah/C-4084-2008; Gilbert, Sam/C-1909-2008 OI White, Sarah/0000-0001-6946-9155; Gilbert, Sam/0000-0002-3839-7045 FU Royal Society University Research Fellowship; British Academy Postdoctoral Fellowship FX SJG is supported by a Royal Society University Research Fellowship. SJW is supported by a British Academy Postdoctoral Fellowship. 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TI Effective Messages in Vaccine Promotion: A Randomized Trial SO PEDIATRICS LA English DT Article DE vaccines; myths; MMR; autism; false; misperceptions; misinformation ID PUBLIC-HEALTH; UNITED-STATES; PARENTS; MISINFORMATION; IMMUNIZATION; RISK; MEASLES; INFORMATION; EXEMPTIONS; COMMUNITY AB OBJECTIVES:To test the effectiveness of messages designed to reduce vaccine misperceptions and increase vaccination rates for measles-mumps-rubella (MMR).METHODS:A Web-based nationally representative 2-wave survey experiment was conducted with 1759 parents age 18 years and older residing in the United States who have children in their household age 17 years or younger (conducted June-July 2011). Parents were randomly assigned to receive 1 of 4 interventions: (1) information explaining the lack of evidence that MMR causes autism from the Centers for Disease Control and Prevention; (2) textual information about the dangers of the diseases prevented by MMR from the Vaccine Information Statement; (3) images of children who have diseases prevented by the MMR vaccine; (4) a dramatic narrative about an infant who almost died of measles from a Centers for Disease Control and Prevention fact sheet; or to a control group.RESULTS:None of the interventions increased parental intent to vaccinate a future child. Refuting claims of an MMR/autism link successfully reduced misperceptions that vaccines cause autism but nonetheless decreased intent to vaccinate among parents who had the least favorable vaccine attitudes. In addition, images of sick children increased expressed belief in a vaccine/autism link and a dramatic narrative about an infant in danger increased self-reported belief in serious vaccine side effects.CONCLUSIONS:Current public health communications about vaccines may not be effective. For some parents, they may actually increase misperceptions or reduce vaccination intention. Attempts to increase concerns about communicable diseases or correct false claims about vaccines may be especially likely to be counterproductive. More study of pro-vaccine messaging is needed. C1 [Nyhan, Brendan] Dartmouth Coll, Dept Govt, Hanover, NH 03755 USA. [Reifler, Jason] Univ Exeter, Dept Polit, Exeter, Devon, England. [Richey, Sean] Georgia State Univ, Dept Polit Sci, Atlanta, GA 30303 USA. [Freed, Gary L.] Univ Michigan, Div Gen Pediat, Child Hlth Evaluat & Res CHEAR Unit, Ann Arbor, MI 48109 USA. [Freed, Gary L.] Univ Michigan, Sch Publ Hlth, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA. RP Nyhan, B (reprint author), Dartmouth Coll, HB 6108, Hanover, NH 03755 USA. EM nyhan@dartmouth.edu FU Robert Wood Johnson Foundation Health and Society Scholars Program at the University of Michigan FX Funded by a grant from the Robert Wood Johnson Foundation Health and Society Scholars Program at the University of Michigan. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funders. 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EM daniel.almirall@gmail.com NR 0 TC 0 Z9 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S164 EP S164 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300628 ER PT J AU Reyna, V Chick, C Weldon, R Corbin, J Wilhelms, E AF Reyna, Valerie Chick, Christina Weldon, Rebecca Corbin, Jonathan Wilhelms, Evan TI ADOLESCENCE, AGING, AUTISM, AND ALZHEIMER'S DISEASE: A UNIFYING FRAMEWORK FOR UNDERSTANDING THE BRAIN AND ITS BIASES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Reyna, Valerie; Chick, Christina; Weldon, Rebecca; Corbin, Jonathan; Wilhelms, Evan] Cornell Univ, Human Neurosci Inst, Ithaca, NY USA. NR 0 TC 0 Z9 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. 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PD APR PY 2014 VL 41 IS 2 BP 214 EP 222 DI 10.1016/j.aip.2014.02.007 PG 9 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA AG3CZ UT WOS:000335294700011 ER PT J AU Hamilton, SM Green, JR Veeraragavan, S Yuva, L Mccoy, A Wu, YM Warren, J Little, L Ji, DN Cui, XX Weinstein, E Paylor, R AF Hamilton, Shannon M. Green, Jennie R. Veeraragavan, Surabi Yuva, Lisa Mccoy, Aaron Wu, Yumei Warren, Joe Little, Lara Ji, Diana Cui, Xiaoxia Weinstein, Edward Paylor, Richard TI Fmr1 and Nlgn3 Knockout Rats: Novel Tools for Investigating Autism Spectrum Disorders SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE behavior; Fmr1; neuroligin 3; rat; autism ID ZINC-FINGER NUCLEASES; X MENTAL-RETARDATION; EMBRYONIC STEM-CELLS; MOUSE MODEL; SOCIAL APPROACH; MICE; PLAY; ABNORMALITIES; TRANSMISSION; BEHAVIORS AB Animal models are critical for gaining insights into autism spectrum disorder (ASD). Despite their apparent advantages to mice for neural studies, rats have not been widely used for disorders of the human CNS, such as ASD, for the lack of convenient genome manipulation tools. Here we describe two of the first transgenic rat models for ASD, developed using zinc-finger nuclease (ZFN) methodologies, and their initial behavioral assessment using a rapid juvenile test battery. A syndromic and nonsyndromic rat model for ASD were created as two separate knockout rat lines with heritable disruptions in the genes encoding Fragile X mental retardation protein (FMRP) and Neuroligin3 (NLGN3). FMRP, a protein with numerous proposed functions including regulation of mRNA and synaptic protein synthesis, and NLGN3, a member of the neuroligin synaptic cell-adhesion protein family, have been implicated in human ASD. Juvenile subjects from both knockout rat lines exhibited abnormalities in ASD-relevant phenotypes including juvenile play, perseverative behaviors, and sensorimotor gating. These data provide important first evidence regarding the utility of rats as genetic models for investigating ASD-relevant genes. C1 [Hamilton, Shannon M.; Green, Jennie R.; Veeraragavan, Surabi; Yuva, Lisa] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Mccoy, Aaron; Wu, Yumei; Warren, Joe; Little, Lara; Ji, Diana; Cui, Xiaoxia; Weinstein, Edward] SAGE Labs, St Louis, MO USA. [Paylor, Richard] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Paylor, Richard] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. RP Paylor, R (reprint author), One Baylor Plaza,Room 436E, Houston, TX 77584 USA. EM rpaylor@bcm.edu FU Autism Speaks; NICHD Fragile X Center FX We thank and acknowledge Deanna Graham for providing important technical assistance and Autism Speaks and the NICHD Fragile X Center for funding assistance. 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Neurosci. PD APR PY 2014 VL 128 IS 2 BP 103 EP 109 DI 10.1037/a0035988 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AG2CX UT WOS:000335224500001 PM 24773431 ER PT J AU Robinson, LJ Freeston, MH AF Robinson, Lucy J. Freeston, Mark H. TI Emotion and internal experience in Obsessive Compulsive Disorder: Reviewing the role of alexithymia, anxiety sensitivity and distress tolerance SO CLINICAL PSYCHOLOGY REVIEW LA English DT Article DE Obsessive Compulsive Disorder; Alexithymia; Anxiety sensitivity; Distress tolerance; Experiential avoidance; Emotion ID AUTISM SPECTRUM DISORDERS; PSYCHOACTIVE SUBSTANCE DEPENDENCE; THOUGHT-ACTION FUSION; SYMPTOM-DIMENSIONS; HIERARCHICAL STRUCTURE; INITIAL VALIDATION; HOARDING BEHAVIORS; ABSTINENCE ATTEMPT; PANIC DISORDER; AVOIDANCE AB Increasing attention has focused on the role of emotion and internal experience in Obsessive Compulsive Disorder (OCD). This review examines three key constructs that capture different aspects of understanding, appraisal and tolerance of internal states in OCD alexithymia, anxiety sensitivity (AS) and distress tolerance (DT). The review examines the evidence for the role each of these constructs plays in OCD and considers whether conclusions can be drawn about the implications for our understanding and treatment of OCD. There is evidence that all three are elevated in clinical cases compared to controls, but there is no evidence that any of the three shows specificity for OCD over other anxiety disorders. However, the review has highlighted significant methodological heterogeneity and consequent variation in findings that currently limits broader conclusions from being drawn. There is an indication that this is a valuable area to explore and future studies should focus on deriving greater conceptual clarity around these constructs, independently replicating findings, and establishing a common methodology to enhance the comparability of studies. Studies exploring the ways in which internal experience, cognitions and symptoms may relate to one another would be of significant value in developing models that then lead to improved treatment approaches. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Robinson, Lucy J.; Freeston, Mark H.] Newcastle Univ, Sch Psychol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Freeston, Mark H.] Northumberland Tyne & Wear NHS Fdn Trust, Gosforth, England. RP Robinson, LJ (reprint author), Newcastle Univ, Sch Psychol, Ridley Bldg 1,Queen Victoria Rd, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. 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Psychol. Rev. PD APR PY 2014 VL 34 IS 3 BP 256 EP 271 DI 10.1016/j.cpr.2014.03.003 PG 16 WC Psychology, Clinical SC Psychology GA AG0GH UT WOS:000335093400007 PM 24682109 ER PT J AU Vila, R Castaner, R Cole, P AF Vila, R. Castaner, R. Cole, P. TI EXPERIMENTAl MODELS IN MAMMALS REPRODUCING HUMAN DISEASES SO DRUGS OF THE FUTURE LA English DT Article DE Experimental models; Animal models; Multiple sclerosis; Cancer; Cardiac repair; Hypertension; Depression ID ANIMAL-MODELS AB The development of new therapies can be greatly facilitated by the use of experimental models of disease, and the development of these models represents an active and exciting field of investigation. In a series of articles, we will survey some recent innovations in the creation and use of experimental models. The current piece highlights a selection of newly created models of pulmonary hypertension, atherothrombotic occlusion, multiple sclerosis, myelofibrosis, Alzheimer's disease and status epilepticus. The application of novel models to test treatments for lymphoma and non-small cell lung cancer are also covered. Further insights discussed include a novel means of analyzing brain function in nonhuman primates, how models have been used to identify new therapeutic targets in multiple sclerosis and autism spectrum disorders, the predictive capability of mouse models in cancer, the in vivo testing of a cardiac repair scaffold for myocardial infarction, and the development of a small mobile robot capable of inducing depression in rats. C1 [Vila, R.; Castaner, R.; Cole, P.] Thomson Reuters, Barcelona, Spain. RP Vila, R (reprint author), Thomson Reuters, Barcelona, Spain. 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Schupp, Clayton W. TI The cortisol awakening response (CAR) in male children with autism spectrum disorder SO HORMONES AND BEHAVIOR LA English DT Article DE Autism; ASD; Cortisol; CAR; Development; Children; Adolescence; HPA ID CIRCADIAN-RHYTHMS; STRESS; PROFILES; SALIVA; HERITABILITY; ADOLESCENCE; SLEEP AB Our ability to adapt to change is fundamental. The cortisol awakening response (CAR) is a sharp rise in cortisol 30 min after waking to help prepare an individual for ensuing stress. Children with autism spectrum disorder (ASD) often have difficulty adapting to change. Exploration of the CAR is warranted; yet, the few studies investigating it are inconclusive. The CAR was investigated in 94 pre-pubertal male children 8-to-12 years of age with ASD (46) and typical development (TD, 48). Salivary samples were collected over three diurnal cycles involving two morning samples: M1: Immediately upon Waking and M2: 30-min Post Waking (M2 - M1 =CAR). The magnitude of the CAR was measured by independent two sample t-tests, variability was measured using Levene's Test, the sequence of the CAR was analyzed by a linear mixed-effects model and proportion of children exhibiting a CAR by chi-square test of independence. There were no significant differences on the CAR between the groups based on magnitude (t(92) = -0.14, p = 0.89, d = 0.04), variability (F(45,47) =1.11, p = 0.72, eta(2) = 0.11) or the sequence over three days (F(2,88) = 0.26, p = 0.77, eta(2) = 0.01). No significant differences were shown in the proportion of children exhibiting a CAR across the groups based on child (chi(2)(1) = 0.02, p = 0.89) or adult criterion (chi(2)(1) = 1.82, p = 0.18). Despite group differences in the regulation and responsivity of cortisol, the CAR is indistinguishable between children with and without ASD. Inconsistencies across studies may be due to age, criterion used, and diagnostic distinctions. (C) 2014 Elsevier Inc. All rights reserved. C1 [Corbett, Blythe A.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37203 USA. [Corbett, Blythe A.] Vanderbilt Kennedy Ctr, Nashville, TN USA. [Schupp, Clayton W.] Canc Prevent Inst Calif, Fremont, CA USA. RP Corbett, BA (reprint author), Vanderbilt Univ, PMB 40,230 Appleton Pl, Nashville, TN 37203 USA. EM blythe.corbett@vanderbilt.edu FU National Institute of Health [R01 MH085717] FX This work was supported in part by the National Institute of Health R01 MH085717 awarded to Blythe Corbett. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health (NIMH) or the National Institute of Health. The NIMH had no further role in study design, in the collection, analysis and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication. 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Behav. PD APR PY 2014 VL 65 IS 4 BP 345 EP 350 DI 10.1016/j.yhbeh.2014.01.012 PG 6 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA AG3DC UT WOS:000335295000003 PM 24508619 ER PT J AU Babb, JA Carini, LM Spears, SL Nephew, BC AF Babb, Jessica A. Carini, Lindsay M. Spears, Stella L. Nephew, Benjamin C. TI Transgenerational effects of social stress on social behavior, corticosterone, oxytocin, and prolactin in rats SO HORMONES AND BEHAVIOR LA English DT Article DE Social stress; Early life stress; Postpartum depression; Anxiety; Autism; Corticosterone; Oxytocin; Prolactin; Transgenerational; Social behavior ID PITUITARY-ADRENAL AXIS; EARLY-LIFE STRESS; NEONATAL MATERNAL SEPARATION; ADULT MALE RATS; ANTENATAL DEPRESSION; FEMALE RATS; INTERGENERATIONAL TRANSMISSION; MENTAL-HEALTH; HPA AXIS; PERIPHERAL OXYTOCIN AB Social stressors such as depressed maternal care and family conflict are robust challenges which can have longterm physiological and behavioral effects on offspring and future generations. The current study investigates the transgenerational effects of an ethologically relevant chronic social stress on the behavior and endocrinology of juvenile and adult rats. Exposure to chronic social stress during lactation impairs maternal care in F0 lactating dams and the maternal care of the F1 offspring of those stressed F0 dams. The overall hypothesis was that the male and female F2 offspring of stressed Fl dams would display decreased social behavior as both juveniles and adults and that these behavioral effects would be accompanied by changes in plasma corticosterone, prolactin, and oxytocin. Both the female and male F2 offspring of dams exposed to chronic social stress displayed decreased social behavior as juveniles and adults, and these behavioral effects were accompanied by decreases in basal concentrations of corticosterone in both sexes, as well as elevated juvenile oxytocin and decreased adult prolactin in the female offspring. The data support the conclusion that social stress has transgenerational effects on the social behavior of the female and male offspring which are mediated by changes in the hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-gonadal axis. Social stress models are valuable resources in the study of the transgenerational effects of stress on the behavioral endocrinology of disorders such as depression, anxiety, autism, and other disorders involving disrupted social behavior. (C) 2014 Elsevier Inc. All rights reserved. C1 [Babb, Jessica A.; Carini, Lindsay M.; Spears, Stella L.; Nephew, Benjamin C.] Tufts Univ, Cummings Sch Vet Med, Dept Biomed Sci, North Grafton, MA 01536 USA. RP Nephew, BC (reprint author), Tufts Univ, Cummings Sch Vet Med, Dept Biomed Sci, Peabody Pavil Room 115, North Grafton, MA 01536 USA. EM bcnephew@aol.com FU NICHD ROO HD [HD059943]; Tufts CTSI Catalyst [NIH CTSA UL1 TR001064] FX We would like to thank the Tufts University Cummings School Laboratory Animals Medicine Service for its outstanding animal care. Gavin Nephew assisted with data collection. This project was funded by NICHD ROO HD HD059943 and a Tufts CTSI Catalyst grant NIH CTSA UL1 TR001064 to BCN. 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Behav. PD APR PY 2014 VL 65 IS 4 BP 386 EP 393 DI 10.1016/j.yhbeh.2014.03.005 PG 8 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA AG3DC UT WOS:000335295000009 PM 24657520 ER PT J AU Theoharides, TC Conti, P Economu, M AF Theoharides, Theoharis C. Conti, Pio Economu, Marina TI Brain Inflammation, Neuropsychiatric Disorders, and Immunoendocrine Effects of Luteolin SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material ID AUTISM SPECTRUM DISORDERS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HUMAN MAST-CELLS; MICROGLIAL ACTIVATION; ALZHEIMERS-DISEASE; FLAVONOID LUTEOLIN; MEDIATOR RELEASE; BIPOLAR DISORDER; CANCER-CELLS; T-CELLS C1 [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Tufts Med Ctr,Dept Integrat Physiol & Pathobiol, Mol Immunopharmacol & Drug Discovery Lab, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Tufts Med Ctr, Dept Biochem, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Tufts Med Ctr, Dept Internal Med, Boston, MA 02111 USA. [Theoharides, Theoharis C.] Tufts Univ, Sch Med, Tufts Med Ctr, Dept Psychiat, Boston, MA 02111 USA. [Conti, Pio] Univ G dAnnunzio, Dept Clin & Expt Med, Div Immunol, Chieti, Italy. [Economu, Marina] Aiginitio Hosp, Athens Med Sch, Dept Psychiat, Athens, Greece. RP Theoharides, TC (reprint author), Tufts Univ, Sch Med, Dept Integrat Physiol & Pathobiol, 136 Harrison Ave, Boston, MA 02111 USA. 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Clin. Psychopharmacol. PD APR PY 2014 VL 34 IS 2 BP 187 EP 189 DI 10.1097/JCP.0000000000000084 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AG3OC UT WOS:000335328000003 PM 24525647 ER PT J AU Valenti, M La Malfa, G Tomassini, A Masedu, F Tiberti, S Sorge, G AF Valenti, M. La Malfa, G. Tomassini, A. Masedu, F. Tiberti, S. Sorge, G. TI Burnout among therapists working with persons with autism after the 2009 earthquake in L'Aquila, Italy: a longitudinal comparative study SO JOURNAL OF PSYCHIATRIC AND MENTAL HEALTH NURSING LA English DT Article DE mental health; rehabilitation; scales and assessment; psychological trauma; disaster work ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSIS; FACTORIAL VALIDITY; INVENTORY; CONSISTENCY; INVARIANCE; EFFICACY; WORKERS AB Accessible summary This study was the first attempt to evaluate burnout occurrence in mental health therapists working in a highly exposed setting, characterized by prolonged exposure to an autism-related work frame and a post-earthquake aftermath. Results strongly suggest that autism therapists exposed to a disruptive earthquake are at higher risk of burnout than caregivers working in typical conditions. In presence of high-risk exposures, burnout occurs rapidly (1 year) with respect to times to event described in the literature (4 years or later). Efforts are required to help mental health workers, including psychiatric nurses, to cope with the devastating situation determined by an earthquake. Assuming that return to good work conditions, supervision support, and natural adaptation are plausible determinants in reducing burnout risk, a periodical monitoring of mental health status is recommended in mental health works. The aim of this study was to follow up the occurrence of burnout in therapists of children and adolescents with autism experiencing the 2009 earthquake in L'Aquila, and to discuss implications for burnout prevention after disasters. A longitudinal study was carried out, measuring burnout outcomes according to the Maslach Burnout Inventory in 11 exposed and 53 unexposed therapists. Staff in the exposed group appeared to report significantly higher levels of emotional exhaustion after 1 and 2 years of follow-up than the unexposed staff. As to lack of personal accomplishment, the exposed groups shows increasingly lower scores with respect to the unexposed group, with personal accomplishment (PA) values falling from 41.0 [standard deviation (SD) 3.7] to 33.4 (SD 4.1) after 2 years, whereas PA values remain stable over time in the unexposed group. As to depersonalization, data show no significant difference between groups. Burnout occurrence is induced by the exceptional stressors related with natural disasters like earthquakes. Efforts are required to help mental health workers, including psychiatric nurses, to cope with the devastating situation determined by an earthquake. A periodical monitoring of mental health status is recommended in mental health works, especially with regard to help with post-traumatic stress disorder, coping with work and therapeutic relationships, family and social life and economic impact. C1 [Valenti, M.; La Malfa, G.] Careggi Hosp Agcy, Dept Psychiat, Florence, Italy. [Tomassini, A.; Masedu, F.; Tiberti, S.] Univ Aquila, Dept Appl Clin Sci, I-67100 Laquila, Italy. [Sorge, G.] Il Cireneo Fdn Autism, Laquila, Italy. [Sorge, G.] Il Cireneo Fdn Autism, Vasto, Italy. RP Valenti, M (reprint author), Univ Aquila, Dept Appl Clin Sci, Coppito Hosp Delta 6, I-67100 Laquila, Italy. 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PD APR PY 2014 VL 21 IS 3 BP 234 EP 240 DI 10.1111/jpm.12054 PG 7 WC Nursing; Psychiatry SC Nursing; Psychiatry GA AB8NC UT WOS:000332046300007 PM 23552108 ER PT J AU Corominas, R Yang, XP Lin, GN Kang, SL Shen, Y Ghamsari, L Broly, M Rodriguez, M Tam, S Trigg, SA Fan, CY Yi, S Tasan, M Lemmens, I Kuang, XY Zhao, N Malhotra, D Michaelson, JJ Vacic, V Calderwood, MA Roth, FP Tavernier, J Horvath, S Salehi-Ashtiani, K Korkin, D Sebat, J Hill, DE Hao, T Vidal, M Iakoucheva, LM AF Corominas, Roser Yang, Xinping Lin, Guan Ning Kang, Shuli Shen, Yun Ghamsari, Lila Broly, Martin Rodriguez, Maria Tam, Stanley Trigg, Shelly A. Fan, Changyu Yi, Song Tasan, Murat Lemmens, Irma Kuang, Xingyan Zhao, Nan Malhotra, Dheeraj Michaelson, Jacob J. Vacic, Vladimir Calderwood, Michael A. Roth, Frederick P. Tavernier, Jan Horvath, Steve Salehi-Ashtiani, Kourosh Korkin, Dmitry Sebat, Jonathan Hill, David E. Hao, Tong Vidal, Marc Iakoucheva, Lilia M. TI Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism SO NATURE COMMUNICATIONS LA English DT Article ID DE-NOVO MUTATIONS; COPY-NUMBER VARIATION; GENOME-WIDE ANALYSIS; SPECTRUM DISORDERS; STRUCTURAL VARIATION; MENTAL-RETARDATION; COMMON VARIANTS; CONFERRING RISK; SCHIZOPHRENIA; DUPLICATIONS AB Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases. C1 [Corominas, Roser; Lin, Guan Ning; Kang, Shuli; Iakoucheva, Lilia M.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Yang, Xinping; Shen, Yun; Ghamsari, Lila; Broly, Martin; Rodriguez, Maria; Tam, Stanley; Trigg, Shelly A.; Fan, Changyu; Yi, Song; Calderwood, Michael A.; Roth, Frederick P.; Salehi-Ashtiani, Kourosh; Hill, David E.; Hao, Tong; Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Yang, Xinping; Shen, Yun; Ghamsari, Lila; Broly, Martin; Rodriguez, Maria; Tam, Stanley; Trigg, Shelly A.; Fan, Changyu; Yi, Song; Calderwood, Michael A.; Roth, Frederick P.; Salehi-Ashtiani, Kourosh; Hill, David E.; Hao, Tong; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Yang, Xinping; Shen, Yun; Ghamsari, Lila; Broly, Martin; Rodriguez, Maria; Tam, Stanley; Trigg, Shelly A.; Fan, Changyu; Yi, Song; Calderwood, Michael A.; Roth, Frederick P.; Salehi-Ashtiani, Kourosh; Hill, David E.; Hao, Tong; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Tasan, Murat; Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada. [Tasan, Murat; Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada. [Tasan, Murat; Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3E1, Canada. [Tasan, Murat; Roth, Frederick P.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5S 3E1, Canada. [Lemmens, Irma; Tavernier, Jan] Univ Ghent VIB, Dept Med Prot Res, B-9000 Ghent, Belgium. [Lemmens, Irma; Tavernier, Jan] Univ Ghent, Fac Med & Hlth Sci, Dept Biochem, B-9000 Ghent, Belgium. [Kuang, Xingyan; Zhao, Nan; Korkin, Dmitry] Univ Missouri, Dept Comp Sci, Columbia, MO 65203 USA. [Kuang, Xingyan; Zhao, Nan; Korkin, Dmitry] Univ Missouri, Inst Informat, Columbia, MO 65203 USA. [Malhotra, Dheeraj; Michaelson, Jacob J.; Sebat, Jonathan] Univ Calif San Diego, Beyster Ctr Genom Psychiat Dis, La Jolla, CA 92093 USA. [Malhotra, Dheeraj; Michaelson, Jacob J.; Sebat, Jonathan] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Vacic, Vladimir] New York Genome Ctr, New York, NY 10013 USA. [Horvath, Steve] Univ Calif Los Angeles, Dept Human Genet & Biostat, Los Angeles, CA 90095 USA. RP Hao, T (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. EM tong_hao@dfci.harvard.edu; marc_vidal@dfci.harvard.edu; lilyak@ucsd.edu RI Roth, Frederick/H-6308-2011 FU NICHD [ARRA R01HD065288]; NIMH [R01MH091350]; NHGRI [R01HG001715]; Ellison Foundation, Boston; Dana-Farber Cancer Institute Strategic Initiative; NIH [MH076431]; Simons Foundation Autism Research Initiative [275724]; Canadian Institute for Advanced Research Fellowship; Canada Excellence Research Chairs Program; National Science Foundation [DBI-0845196, IOS-1126992]; Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO); Fonds de la Recherche Scientifique (FRS-FNRS, Wallonia-Brussels Federation, Belgium) FX We thank all members of the DFCI Center for Cancer Systems Biology (CCSB) for helpful discussions throughout the course of this project. We also thank Dr Joseph Gleeson for valuable comments on the manuscript, the members of Dr Sebat laboratory for helpful discussions and Abhishek Bhandari, Ashleigh Schaffer and Naiara Akizu for technical assistance. This work was supported by NIH grants ARRA R01HD065288 from NICHD to L. M. I and K. S.-A. and by R01MH091350 from NIMH to L. M. I. and T. H., R01HG001715 from NHGRI to M. V., D. E. H., F. P. R. and J.T.; by The Ellison Foundation, Boston, MA to M. V.; by Institute Sponsored Research funds from the Dana-Farber Cancer Institute Strategic Initiative to M. V.; by NIH (MH076431) and the Simons Foundation Autism Research Initiative (275724) to J.S.; by a Canadian Institute for Advanced Research Fellowship and the Canada Excellence Research Chairs Program to F. P. R. and by National Science Foundation grants DBI-0845196 and IOS-1126992 to D. K. I. L. is a postdoctoral fellow with the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO). M. V. is a "Chercheur Qualifie Honoraire'' from the Fonds de la Recherche Scientifique (FRS-FNRS, Wallonia-Brussels Federation, Belgium). 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Commun. PD APR PY 2014 VL 5 AR 3650 DI 10.1038/comms4650 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2BZ UT WOS:000335221700005 PM 24722188 ER PT J AU McCray, AT Trevvett, P Frost, HR AF McCray, Alexa T. Trevvett, Philip Frost, H. Robert TI Modeling the Autism Spectrum Disorder Phenotype SO NEUROINFORMATICS LA English DT Article DE Ontologies; Autism spectrum disorder; Behavioral phenotype; Standardized diagnostic and screening instruments ID PERVASIVE DEVELOPMENTAL DISORDERS; DIFFERENTIAL ABILITY SCALES; ADAPTIVE-BEHAVIOR SCALES; CHILDRENS COMMUNICATION CHECKLIST; DIAGNOSTIC OBSERVATION SCHEDULE; COMPLEX FIGURE TEST; EXECUTIVE FUNCTION; COMBINING INFORMATION; REPETITIVE BEHAVIOR; MULTIPLE SOURCES AB Autism Spectrum Disorder (ASD) is highly heritable, and although there has been active research in an attempt to discover the genetic factors underlying ASD, diagnosis still depends heavily on behavioral assessments. Recently, several large-scale initiatives, including those of the Autism Consortium, have contributed to the collection of extensive information from families affected by ASD. Our goal was to develop an ontology that can be used 1) to provide improved access to the data collected by those who study ASD and other neurodevelopmental disorders, and 2) to assess and compare the characteristics of the instruments that are used in the assessment of ASD. We analyzed two dozen instruments used to assess ASD, studying the nature of the questions asked and items assessed, the method of delivery, and the overall scope of the content. These data together with the extensive literature on ASD contributed to our iterative development of an ASD phenotype ontology. The final ontology comprises 283 concepts distributed across three high-level classes, 'Personal Traits', 'Social Competence', and 'Medical History'. The ontology is fully integrated with the Autism Consortium database, allowing researchers to pose ontology-based questions. The ontology also allows researchers to assess the degree of overlap among a set of candidate instruments according to several objective criteria. The ASD phenotype ontology has promise for use in research settings where extensive phenotypic data have been collected, allowing a concept-based approach to identifying behavioral features of importance and for correlating these with genotypic data. C1 [McCray, Alexa T.; Trevvett, Philip; Frost, H. Robert] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Frost, H. Robert] Dartmouth Coll, Inst Quantitat Biomed Sci, Hanover, NH 03755 USA. RP McCray, AT (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, 10 Shattuck St, Boston, MA 02115 USA. EM alexa_mccray@hms.harvard.edu FU Anonymous Foundation; Autism Consortium; Harvard Clinical and Translational Science Center [NIH/NCRR UL1 RR025758-01] FX The authors were supported in part by grants from an Anonymous Foundation, the Autism Consortium, and the Harvard Clinical and Translational Science Center (NIH/NCRR UL1 RR025758-01). The authors thank Juliane Schneider and Cecilia Vernes for their contributions to the ontology and the team at MGH who developed the Autism Consortium database, including David Pauls and Julia O'Rourke. 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NR 0 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD APR PY 2014 VL 69 IS 4 BP 187 EP 189 DI 10.1097/OGX.0000000000000050 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AG4NQ UT WOS:000335397400003 ER PT J AU Johnson, S Marlow, N AF Johnson, Samantha Marlow, Neil TI Growing up after extremely preterm birth: Lifespan mental health outcomes SO SEMINARS IN FETAL & NEONATAL MEDICINE LA English DT Review DE Attention deficit hyperactivity disorder; Autism spectrum disorders; Comorbidity; Mental health; Outcomes; Preterm birth ID BORN EXTREMELY PRETERM; SOCIAL-EMOTIONAL DEVELOPMENT; SCHOOL-AGE OUTCOMES; CHILDREN BORN; BEHAVIORAL OUTCOMES; WEIGHT CHILDREN; ADOLESCENTS BORN; YOUNG ADULTHOOD; DIFFICULTIES QUESTIONNAIRE; PSYCHIATRIC OUTCOMES AB There is growing interest in the long-term mental health sequelae of extremely preterm birth. In this paper we review literature relating to mental health outcomes across the lifespan. Studies conducted in the preschool years, school age and adolescence, and adulthood show continuity in outcomes and point to an increased risk for inattention, socio-communicative problems and emotional difficulties in individuals born extremely preterm. Both behavioural and neuroimaging studies also provide evidence of a neurodevelopmental origin for mental health disorders in this population. Here we summarise contemporary evidence and highlight key methodological considerations for carrying out and interpreting studies in this field. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Johnson, Samantha] Univ Leicester, Dept Hlth Sci, Leicester LE1 6TP, Leics, England. [Marlow, Neil] UCL, Dept Acad Neonatol, Inst Womens Hlth, London, England. RP Johnson, S (reprint author), Univ Leicester, Dept Hlth Sci, 22-28 Princess Rd West, Leicester LE1 6TP, Leics, England. 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PD APR PY 2014 VL 69 IS 3 BP 249 EP 268 DI 10.1037/a0036320 PG 20 WC Psychology, Multidisciplinary SC Psychology GA AF4LZ UT WOS:000334685500003 PM 24750075 ER PT J AU Duan, F Watanabe, K Yoshimura, Y Kikuchi, M Minabe, Y Aihara, K AF Duan, Fang Watanabe, Katsumi Yoshimura, Yuko Kikuchi, Mitsuru Minabe, Yoshio Aihara, Kazuyuki TI Relationship between brain network pattern and cognitive performance of children revealed by MEG signals during free viewing of video SO BRAIN AND COGNITION LA English DT Article DE Small-world; Functional network; MEG; Child; Visual processing (Gv) ability; Free viewing of video ID SMALL-WORLD NETWORKS; STATE FUNCTIONAL CONNECTIVITY; GRAPH-THEORETICAL ANALYSIS; SCHIZOPHRENIA; ORGANIZATION; EFFICIENCY; FREQUENCY; DYNAMICS; AUTISM; EEG AB Application of graph theory to analysis of functional networks in the brain is an important research trend. Extensive research on the resting state has shown a "small-world" organization of the brain network as a whole. However, the small-worldness of children's brain networks in a working state has not yet been well characterized. In this paper, we used a custom-made, child-sized magnetoencephalography (MEG) device to collect data from children while they were watching cartoon videos. Network structures were analyzed and compared with scores on the Kaufman Assessment Battery for Children (K-ABC). The results of network analysis showed that (1) the small-world scalar showed a negative correlation with the simultaneous processing raw score, a measure of visual processing (Gv) ability, and (2) the children with higher simultaneous processing raw scores possessed network structures that can be more efficient for local information processing than children with lower scores. These results were compatible with previous studies on the adult working state. Additional results obtained from further analysis of the frontal and occipital lobes indicated that high cognitive performance could represent better local efficiency in task-related sub-networks. Under free viewing of cartoon videos, brain networks were no longer confined to their strongest small-world states; connections became clustered in local areas such as the frontal and occipital lobes, which might be a more useful configuration for handling visual processing tasks. (C) 2014 Elsevier Inc. All rights reserved. C1 [Duan, Fang; Aihara, Kazuyuki] Univ Tokyo, Grad Sch Engn, Dept Elect Engn & Informat Syst, Tokyo 1538904, Japan. [Watanabe, Katsumi] Univ Tokyo, Res Ctr Adv Sci & Technol, Tokyo 1538904, Japan. [Yoshimura, Yuko; Kikuchi, Mitsuru; Minabe, Yoshio] Kanazawa Univ, Grad Sch Med Sci, Res Ctr Child Mental Dev, Kanazawa, Ishikawa 9208641, Japan. [Aihara, Kazuyuki] Univ Tokyo, Inst Ind Sci, Tokyo 1538904, Japan. RP Duan, F (reprint author), Univ Tokyo, Grad Sch Engn, Dept Elect Engn & Informat Syst, Tokyo 1538904, Japan. EM duan@sat.t.u-tokyo.ac.jp FU Aihara Innovative Mathematical Modelling Project; Japan Society for the Promotion of Science (JSPS); Council for Science and Technology Policy (CSTP) FX This research is supported by the Aihara Innovative Mathematical Modelling Project, the Japan Society for the Promotion of Science (JSPS) through the "Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)", initiated by the Council for Science and Technology Policy (CSTP). 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PD APR PY 2014 VL 86 BP 10 EP 16 DI 10.1016/j.bandc.2014.01.011 PG 7 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AF2VP UT WOS:000334570900002 PM 24525012 ER PT J AU Ludlow, A Mohr, B Whitmore, A Garagnani, M Pulvermuller, F Gutierrez, R AF Ludlow, Amanda Mohr, Bettina Whitmore, Antony Garagnani, Max Pulvermueller, Friedmann Gutierrez, Roberto TI Auditory processing and sensory behaviours in children with autism spectrum disorders as revealed by mismatch negativity SO BRAIN AND COGNITION LA English DT Article DE EEG; Sensory behaviours; Auditory processing; Language ID EVENT-RELATED POTENTIALS; HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; TYPICAL DEVELOPMENT; SPEECH; DISCRIMINATION; PERCEPTION; FEATURES; MOTOR; ABNORMALITIES AB Sensory dysfunctions may underlie key characteristics in children with Autism Spectrum Disorders (ASD). The current study aimed to investigate auditory change detection in children with ASD in order to determine event-related potentials to meaningless and meaningful speech stimuli. 11 high functioning boys with a diagnosis of autism spectrum disorders (mean age = 13.0; SD = 1.08) and 11 typically developing boys (mean age = 13.7; SD = 1.5) participated in a mismatch negativity (MMN) paradigm. Results revealed that compared to TD controls, the children with ASD showed significantly reduced MMN responses to both words and pseudowords in the frontal regions of the brain and also a significant reduction in their activation for words in the Central Parietal regions. In order to test the relationship between sensory processing and auditory processing, children completed the Adult and Adolescent Sensory Profile. As predicted, the children with ASD showed more extreme sensory behaviours and were significantly higher than their typically developing controls across three of the sensory quadrants (sensory sensitivity, low registration and sensory avoidance). Importantly, only auditory sensory sensitivity was able to account for the differences displayed for words in the frontal and central parietal regions when controlling for the effect of group, revealing an inverse relationship of the higher sensory sensitivity scores the less activation in response for words. We discuss how the expression of sensory behaviours in ASD may result in deficient neurophysiological mechanisms underlying automatic language processing. (C) 2014 Elsevier Inc. All rights reserved. C1 [Ludlow, Amanda; Gutierrez, Roberto] Univ Hertfordshire, Dept Psychol, Hatfield AL10 9AB, Herts, England. [Ludlow, Amanda] Univ Birmingham, Sch Psychol, Edgbaston, England. [Mohr, Bettina] Charite, Dept Psychiat, D-13353 Berlin, Germany. [Whitmore, Antony] Anglia Ruskin Univ, Dept Psychol, Cambridge, England. [Garagnani, Max; Pulvermueller, Friedmann] Free Univ Berlin, Brain Language Lab, Berlin, Germany. RP Ludlow, A (reprint author), Univ Hertfordshire, Dept Psychol, Hatfield AL10 9AB, Herts, England. EM a.ludlow@herts.ac.uk FU Anglia Ruskin University, Cambridge FX We would like to thank all the children for taking part in the study and also their parents for their co-operation in our research. This work was supported by a Research Enhancement Grant from Anglia Ruskin University, Cambridge. 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Ted Flory, Michael Frackowiak, Janusz TI Autoantibodies against neuronal progenitors in sera from children with autism SO BRAIN & DEVELOPMENT LA English DT Article DE Autism; Autoantibodies; Neurogenesis; Cell culture; Neuronal progenitor cells ID ADULT HIPPOCAMPAL NEUROGENESIS; NEURAL PRECURSOR CELLS; SPECTRUM DISORDERS; ANTIBRAIN ANTIBODIES; FETAL-BRAIN; PROTEINS; DIFFERENTIATION; PROLIFERATION; ACTIVATION; OLFACTION AB The pathological role of autoantibodies in development of CNS disorders is a new idea with growing interest among neuroscientist The involvement of autoimmune response in the pathogenesis of autism spectrum disorders (ASD) has been suggested by the presence of multiple brain-specific autoantibodies in children with ASD and in their mothers. The possibility of the effect of autoimmunity on neurogenesis and postnatal brain plasticity has not been determined. The presence of autoantibodies against human neuronal progenitor cells (NPCs) stimulated for neuronal differentiation in culture was tested in sera from children with autism (n = 20) and age-matched controls (n = 18) by immunoblotting and immunocytochemistry. Immunoreactivity against multiple NPCs proteins of molecular sizes of approximately 55 kDa, 105 kDa, 150 kDa, and 210 kDa in sera from individuals with autism had a higher incidence and was stronger than in control sera which immunoreacted mainly with a 150 kDa protein. The sera from children with autism immunoreacted the strongest with NPCs expressing neuronal markers Tuj1 and doublecortin, but not astrocyte market GFAP. The epitopes recognized by antibodies from sera were not human-specific because they detected also NPCs in situ in murine hippocampus. The autoimmune reactions against NPCs suggest an impaired tolerance to neural antigens in autism. 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PD APR PY 2014 VL 36 IS 4 BP 322 EP 329 DI 10.1016/j.braindev.2013.04.015 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AF6JP UT WOS:000334821600009 PM 23838310 ER PT J AU Graham, F Rodger, S Ziviani, J AF Graham, Fiona Rodger, Sylvia Ziviani, Jenny TI Mothers' experiences of engaging in Occupational Performance Coaching SO BRITISH JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE Professional-patient relations; motor skills disorders; child behaviour disorders; child; parenting; patient satisfaction ID CHILDREN; PARENTS; PARTICIPATION; THERAPY; INTERVENTION; COMPETENCE; DISORDER; AUTISM; IMPACT; MODEL AB Introduction: Occupational Performance Coaching is an intervention provided to parents, which targets their goals in occupational performance for themselves and their children. Preliminary evidence points to its effectiveness; however, little is known about parents' experiences of engaging in Occupational Performance Coaching. Method: Within a larger mixed methods study, a purpose-designed survey comprising open and closed questions was used to explore parents' (N = 29) experiences of engaging in Occupational Performance Coaching. The survey targeted their impressions, learning experiences, and perceptions of the impact of Occupational Performance Coaching. Numerical data were analysed descriptively; written comments were analysed using content analysis. In this case all participants were mothers. Findings: Mothers' descriptions of Occupational Performance Coaching were largely positive. Learning experiences included gaining insights about themselves and their children alongside learning specific strategies to support their children's occupational performance. They reported greater understanding of their children and a perception that Occupational Performance Coaching had engendered a calmer, happier emotional tone within the family. Conclusion: Mothers perceived Occupational Performance Coaching as a valuable means to support their children and themselves to attain occupational performance goals. Findings prompt greater attention to coaching approaches and, more widely, the use of transformative learning as a means to enabling occupation. C1 [Graham, Fiona] Univ Otago Med, Christchurch, New Zealand. [Rodger, Sylvia] Autism CRC, Brisbane, Qld, Australia. [Rodger, Sylvia; Ziviani, Jenny] Univ Queensland, Sch Hlth & Rehabil Sci, Brisbane, Qld, Australia. [Ziviani, Jenny] Childrens Hlth Queensland, Childrens Allied Hlth Res, Brisbane, Qld, Australia. RP Graham, F (reprint author), Univ Otago, 7 Blakehall Pl, Christchurch 8024, New Zealand. 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PD APR PY 2014 VL 77 IS 4 BP 189 EP 197 DI 10.4276/030802214X13968769798791 PG 9 WC Rehabilitation SC Rehabilitation GA AF3WZ UT WOS:000334644700006 ER PT J AU Jacobson, L AF Jacobson, Lauren TI Hypothalamic-Pituitary-Adrenocortical Axis: Neuropsychiatric Aspects SO COMPREHENSIVE PHYSIOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; CORTICOTROPIN-RELEASING HORMONE; POSTTRAUMATIC-STRESS-DISORDER; DEXAMETHASONE-SUPPRESSION TEST; MAJOR DEPRESSIVE DISORDER; URINARY FREE-CORTISOL; GENERALIZED ANXIETY DISORDER; TREATMENT-RESISTANT DEPRESSION; II CORTICOSTEROID RECEPTORS; PLACEBO-CONTROLLED TRIAL AB Evidence of aberrant hypothalamic-pituitary-adrenocortical (HPA) activity in many psychiatric disorders, although not universal, has sparked long-standing interest in HPA hormones as biomarkers of disease or treatment response. HPA activity may be chronically elevated in melancholic depression, panic disorder, obsessive-compulsive disorder, and schizophrenia. The HPA axis may be more reactive to stress in social anxiety disorder and autism spectrum disorders. In contrast, HPA activity is more likely to be low in PTSD and atypical depression. Antidepressants are widely considered to inhibit HPA activity, although inhibition is not unanimously reported in the literature. There is evidence, also uneven, that the mood stabilizers lithium and carbamazepine have the potential to augment HPA measures, while benzodiazepines, atypical antipsychotics, and to some extent, typical antipsychotics have the potential to inhibit HPA activity. Currently, the most reliable use of HPA measures in most disorders is to predict the likelihood of relapse, although changes in HPA activity have also been proposed to play a role in the clinical benefits of psychiatric treatments. Greater attention to patient heterogeneity and more consistent approaches to assessing treatment effects on HPA function may solidify the value of HPA measures in predicting treatment response or developing novel strategies to manage psychiatric disease. (C) 2014 American Physiological Society. C1 Albany Med Coll, Albany, NY 12208 USA. RP Jacobson, L (reprint author), Albany Med Coll, Albany, NY 12208 USA. 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Sigafoos, Jeff Sutherland, Dean TI Comparing acquisition of and preference for manual signs, picture exchange, and speech-generating devices in nine children with autism spectrum disorder SO DEVELOPMENTAL NEUROREHABILITATION LA English DT Article DE Augmentative and alternative communication; autism spectrum disorder; iPad (R); iPod (R); manual sign; picture-exchange; preference assessment; speech-generating device ID COMMUNICATION-SYSTEM PECS; DEVELOPMENTAL-DISABILITIES; ALTERNATIVE COMMUNICATION; COMPARATIVE EFFICACY; STUDENTS; SKILLS; MODES AB Objective: To compare how quickly children with autism spectrum disorder (ASD) acquired manual signs, picture exchange, and an iPad (R)/iPod (R)-based speech-generating device (SGD) and to compare if children showed a preference for one of these options. Method: Nine children with ASD and limited communication skills received intervention to teach requesting preferred stimuli using manual signs, picture exchange, and a SGD. Intervention was evaluated in a non-concurrent multiple-baseline across participants and alternating treatments design. Results: Five children learned all three systems to criterion. Four children required fewer sessions to learn the SGD compared to manual signs and picture exchange. Eight children demonstrated a preference for the SGD. Conclusion: The results support previous studies that demonstrate children with ASD can learn manual signs, picture exchange, and an iPad (R)/iPod (R)-based SGD to request preferred stimuli. Most children showed a preference for the SGD. For some children, acquisition may be quicker when learning a preferred option. C1 [Couper, Llyween; Schaefer, Martina C. M.; McKenzie, Emma; McLay, Laurie; Sutherland, Dean] Univ Canterbury, Coll Educ, Sch Hlth Sci, Christchurch 8140, New Zealand. [van der Meer, Larah; Sigafoos, Jeff] Victoria Univ Wellington, Sch Educ Psychol, Wellington, New Zealand. [O'Reilly, Mark F.] Univ Texas Austin, Meadows Ctr Preventing Educ Risk, Austin, TX 78712 USA. [Lancioni, Giulio E.] Univ Bari, Dept Neurosci & Sense Organs, Bari, Italy. [Marschik, Peter B.] Med Univ Graz, Inst Physiol, iDN Interdisciplinary Dev Neurosci, Graz, Austria. RP Sutherland, D (reprint author), Univ Canterbury, Coll Educ, Sch Hlth Sci, Private Bag 4800, Christchurch 8140, New Zealand. EM dean.sutherland@canterbury.ac.nz FU New Zealand Government through the Marsden Fund Council; Victoria University of Wellington; University of Canterbury; New Zealand Institute of Language, Brain Behaviour FX This study was supported by a grant from the New Zealand Government through the Marsden Fund Council, administered by the Royal Society of New Zealand; and by Victoria University of Wellington, The University of Canterbury, and The New Zealand Institute of Language, Brain & Behaviour. 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Neurorehabil. PD APR PY 2014 VL 17 IS 2 BP 99 EP 109 DI 10.3109/17518423.2013.870244 PG 11 WC Clinical Neurology; Pediatrics; Rehabilitation SC Neurosciences & Neurology; Pediatrics; Rehabilitation GA AE9DA UT WOS:000334303400005 PM 24392652 ER PT J AU Allen, AA Shane, HC AF Allen, Anna A. Shane, Howard C. TI Autism spectrum disorders in the era of mobile technologies: Impact on caregivers SO DEVELOPMENTAL NEUROREHABILITATION LA English DT Article DE AAC; autism; mobile technology; parents; stress ID COMPUTER-BASED INTERVENTIONS; PARENTING STRESS; DEVELOPMENTAL-DISABILITIES; ALTERNATIVE COMMUNICATION; BEHAVIOR PROBLEMS; YOUNG-CHILDREN; INDIVIDUALS; CHALLENGES; MOTHERS; IPAD AB Objective: This paper explores possible connections among existing literature on parental stress, augmentative and alternative communication (AAC), and use of mobile technology for persons with autism spectrum disorder (ASD). Methods: A narrative review of the literature. Results: Parental support contributes to positive outcomes for children who use AAC. Parents identify communication as a high priority, but describe the process as challenging. AAC is often used with children with ASD, a population in which parental stress is especially high. Though there is research evidence that mobile technology is a promising tool for individuals with ASD, potentially misleading media anecdotes exist, and the effects on parental expectations and stress remain unstudied questions. Conclusion: Increased understanding of the connections in these research areas should help clarify the potential impact of mobile technologies on parental stress level, help to define appropriate future research directions, and contribute to development of appropriate caregiver training. C1 [Allen, Anna A.] MGH Inst Hlth Profess, Dept Commun Sci & Disorders, Boston, MA 02129 USA. [Shane, Howard C.] Boston Childrens Hosp, Ctr Commun Enhancement, Waltham, MA USA. RP Allen, AA (reprint author), MGH Inst Hlth Profess, Dept Commun Sci & Disorders, 36 1st Ave, Boston, MA 02129 USA. 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Neurorehabil. PD APR PY 2014 VL 17 IS 2 BP 110 EP 114 DI 10.3109/17518423.2014.882425 PG 5 WC Clinical Neurology; Pediatrics; Rehabilitation SC Neurosciences & Neurology; Pediatrics; Rehabilitation GA AE9DA UT WOS:000334303400006 PM 24694311 ER PT J AU Donato, C Shane, HC Hemsley, B AF Donato, Cynthia Shane, Howard C. Hemsley, Bronwyn TI Exploring the feasibility of the Visual Language in Autism program for children in an early intervention group setting: Views of parents, educators, and health professionals SO DEVELOPMENTAL NEUROREHABILITATION LA English DT Article DE Autism; children; disability; early intervention; visual language; visual supports ID SPECTRUM DISORDERS; DOWN-SYNDROME; GRAPHIC SYMBOLS; YOUNG-CHILDREN; COMMUNICATION; INDIVIDUALS; VOICE AB Objective: To explore the views of key stakeholders on using visual supports for children with developmental disabilities in early intervention group settings. Specifically, this study aimed to determine stakeholders' views on the barriers to and facilitators for the use of visual supports in these settings to inform the feasibility of implementing an immersive Visual Language in Autism program. Methods: This study involved three focus groups of parents, educators, and health professionals at one Australian early intervention group setting. Results: Lack of time, limited services, negative attitudes in society, and inconsistent use were cited as common barriers to using visual supports. Facilitators included having access to information and evidence on visual supports, increased awareness of visual supports, and the use of mobile technologies. Conclusion: The Visual Language in Autism program is feasible in early intervention group settings, if barriers to and facilitators for its use are addressed to enable an immersive visual language experience. C1 [Donato, Cynthia; Hemsley, Bronwyn] Univ Newcastle, Fac Educ & Arts, Sch Humanities & Social Sci, Callaghan, NSW 2308, Australia. [Shane, Howard C.] Harvard Univ, Dept Otolaryngol & Commun Enhancement, Boston Childrens Hosp, Boston, MA 02115 USA. RP Donato, C (reprint author), Univ Newcastle, Fac Educ & Arts, Sch Humanities & Social Sci, Level 2,Gen Purpose Bldg,Univ Dr, Callaghan, NSW 2308, Australia. EM cynthia.donato@uon.edu.au CR AAC-RERC, 2011, REH ENG RES CTR COMM American Psychiatric Association, 2013, DIAGN STAT MAN MENT American Speech Language and Hearing Association, 2010, EV BAS PRACT SPEECH Arthur-Kelly M, 2009, DISABIL REHABIL, V31, P1474, DOI 10.1080/09638280802590629 CARR EG, 1979, J AUTISM DEV DISORD, V9, P345, DOI 10.1007/BF01531444 Dollaghan C. 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PD APR PY 2014 VL 17 IS 2 BP 115 EP 124 DI 10.3109/17518423.2014.880526 PG 10 WC Clinical Neurology; Pediatrics; Rehabilitation SC Neurosciences & Neurology; Pediatrics; Rehabilitation GA AE9DA UT WOS:000334303400007 PM 24564265 ER PT J AU Tan, XY Trembath, D Bloomberg, K Iacono, T Caithness, T AF Tan, Xuet Ying Trembath, David Bloomberg, Karen Iacono, Teresa Caithness, Teena TI Acquisition and generalization of key word signing by three children with autism SO DEVELOPMENTAL NEUROREHABILITATION LA English DT Article DE Autism; manual sign; treatment; augmentative communication ID ALTERNATIVE COMMUNICATION; LANGUAGE; INTERVENTION AB Objective: The aim of this study was to examine the effect of Key Word Sign (KWS) intervention on the acquisition and generalization of manual signing among three children with Autism Spectrum Disorder (ASD), and to measure any changes in their production of spoken words and gestures following intervention. Methods: A multiple baseline single-case experimental design was used to measure changes for each of the three children. Results: All three children began using signs following the introduction of the KWS intervention, and generalized their use of some signs across activities. The introduction of the intervention was associated with either neutral, or statistically significantly positive, changes in the children's production of spoken words and natural gestures. Conclusion: The results provide preliminary evidence for the effectiveness of KWS for preschool children with ASD, which parents, therapists, and educators can use to inform clinical practice. C1 [Tan, Xuet Ying; Bloomberg, Karen; Caithness, Teena] La Trobe Univ, Melbourne, Vic, Australia. [Trembath, David] Griffith Univ, Griffith Hlth Inst, Southport, Qld 4222, Australia. [Trembath, David] La Trobe Univ, Olga Tennison Autism Res Ctr, Melbourne, Vic, Australia. [Iacono, Teresa] La Trobe Univ, La Trobe Rural Hlth Sch, Bendigo, Australia. RP Trembath, D (reprint author), Griffith Univ, Griffith Hlth Inst, Gold Coast Campus, Southport, Qld 4222, Australia. EM d.trembath@griffith.edu.au FU La Trobe University, Faculty of Health Sciences FX The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. The study was conducted with the support of a La Trobe University, Faculty of Health Sciences research grant. CR Balandin S., 1998, AUGMENTATIVE ALTERNA, V14, P147, DOI [10.1080/07434619812331278326, DOI 10.1080/07434619812331278326] BARRERA RD, 1980, J AUTISM DEV DISORD, V10, P21, DOI 10.1007/BF02408430 Beukelman D., 2005, AUGMENTATIVE ALTERNA, V3rd BRADY DO, 1978, J AUTISM CHILD SCHIZ, V8, P271, DOI 10.1007/BF01539630 Brownlie E, 2006, LETS PLAY SIGN Caithness T, 2012, GETTING STARTED KEY CARR EG, 1978, J APPL BEHAV ANAL, V11, P489, DOI 10.1901/jaba.1978.11-489 Cress C. 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PD APR PY 2014 VL 17 IS 2 BP 125 EP 136 DI 10.3109/17518423.2013.863236 PG 12 WC Clinical Neurology; Pediatrics; Rehabilitation SC Neurosciences & Neurology; Pediatrics; Rehabilitation GA AE9DA UT WOS:000334303400008 PM 24393060 ER PT J AU Ruppe, V Dilsiz, P Reiss, CS Carlson, C Devinsky, O Zagzag, D Weiner, HL Talos, DM AF Ruppe, Veronique Dilsiz, Pelin Reiss, Carol Shoshkes Carlson, Chad Devinsky, Orrin Zagzag, David Weiner, Howard L. Talos, Delia M. TI Developmental brain abnormalities in tuberous sclerosis complex: A comparative tissue analysis of cortical tubers and perituberal cortex SO EPILEPSIA LA English DT Article DE Epileptogenesis; Peri-tuber; Mammalian target of rapamycin; Hypomyelination; Axons ID WHITE-MATTER; MOUSE MODEL; CEREBRAL-CORTEX; TUMOR SUPPRESSORS; MAMMALIAN TARGET; SEVERE EPILEPSY; MOSSY FIBERS; FETAL-BRAIN; GIANT-CELLS; TSC1 AB Objective Genetic loss of Tsc1/Tsc2 function in tuberous sclerosis complex (TSC) results in altered mammalian target of rapamycin (mTOR) signaling and abnormal brain development. Although earlier studies have focused on characterization of cortical tubers, in this study we sought to examine the unique cellular and molecular features of the perituberal cortex in order to better understand its contribution to epileptogenesis, cognitive dysfunction, and autism. Methods Standard histologic and immunohistochemical labeling was used to assess structural abnormalities and cell-specific pattern of mTORC1 activation in surgically resected cortical tubers and perituberal cortex. Western blotting was performed to quantify the expression of the mTORC1 and mTORC2 biomarkers phospho-S6 (Ser235/236), phospho-S6 (Ser240/244), and phospho-Akt (Ser473), in addition to evaluating the differential expression levels of several neuronal and glial-specific proteins in tubers and peritubers, as compared to non-TSC epilepsy specimens. Results Tubers demonstrated mild to severe disruption of cortical lamination, the presence of pS6-positive dysplastic neurons and giant cells, an overall increase in mTORC1 and a decrease in mTORC2 activity, increased axonal connectivity and growth, and hypomyelination. Perituberal cortex presented similar histologic, immunohistochemical, and molecular features; however, they were overall milder. Axonal growth was specific for TSC and was negatively correlated with deficient myelination. Significance Our results show an extension of cellular dysplasia and dysregulated mTOR signaling in the perituberal tissue, and demonstrate for the first time aberrant connectivity in human TSC brain. This study provides new insights into the pathophysiology of neurologic dysfunction associated with TSC and supports the intrinsic epileptogenicity of normal-appearing perituberal cortex. A PowerPoint slide summarizing this article is available for download in the Supporting Information section . C1 [Ruppe, Veronique; Dilsiz, Pelin; Carlson, Chad; Devinsky, Orrin; Talos, Delia M.] NYU, Sch Med, Dept Neurol, New York, NY USA. [Reiss, Carol Shoshkes] NYU, Dept Biol & Neural Sci, New York, NY USA. [Devinsky, Orrin; Zagzag, David; Weiner, Howard L.] NYU, Sch Med, Dept Neurosurg, New York, NY USA. [Devinsky, Orrin] NYU, Sch Med, Dept Psychiat, New York, NY USA. 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Gillessen-Kaesbach, Gabriele Hoischen, Alexander Lohmann, Katja TI Exome sequencing identifies a de novo SCN2A mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscular hypotonia, and brain abnormalities SO EPILEPSIA LA English DT Article DE Epilepsy; Rett-like syndrome; Intellectual disability; Epileptic encephalopathy; Sodium channel ID NEONATAL-INFANTILE SEIZURES; HUMAN GENETIC-DISEASE; EPILEPTIC ENCEPHALOPATHIES; SODIUM; EPILEPSIES; CHILDREN; CHANNELS AB Epilepsy is a phenotypically and genetically highly heterogeneous disorder with >200 genes linked to inherited forms of the disease. To identify the underlying genetic cause in a patient with intractable seizures, optic atrophy, severe intellectual disability (ID), brain abnormalities, and muscular hypotonia, we performed exome sequencing in a 5-year-old girl and her unaffected parents. In the patient, we detected a novel, de novo missense mutation in the SCN2A (c.5645G>T; p.R1882L) gene encoding the alpha(II)-subunit of the voltage-gated sodium channel Na(v)1.2. A literature review revealed 33 different SCN2A mutations in 14 families with benign forms of epilepsy and in 21 cases with severe phenotypes. Although almost all benign mutations were inherited, the majority of severe mutations occurred de novo. Of interest, de novo SCN2A mutations have also been reported in five patients without seizures but with ID (n=3) and/or autism (n=3). In the present study, we successfully used exome sequencing to detect a de novo mutation in a genetically heterogeneous disorder with epilepsy and ID. Using this approach, we expand the phenotypic spectrum of SCN2A mutations. Our own and literature data indicate that SCN2A-linked severe phenotypes are more likely to be caused by de novo mutations. A PowerPoint slide summarizing this article is available for download in the Supporting Information section . C1 [Baasch, Anna-Lena; Lohmann, Katja] Med Univ Lubeck, Inst Neurogenet, D-23538 Lubeck, Germany. [Huening, Irina; Gillessen-Kaesbach, Gabriele] Med Univ Lubeck, Inst Humangenet, D-23538 Lubeck, Germany. [Gilissen, Christian; Veltman, Joris A.; Hoischen, Alexander] Radboud Univ Nijmegen Med Ctr, Nijmegen Ctr Mol Life Sci, Inst Genet & Metab Dis, Dept Human Genet, Nijmegen, Netherlands. [Klepper, Joerg] Childrens Hosp Aschaffenburg, Aschaffenburg, Germany. RP Lohmann, K (reprint author), Med Univ Lubeck, Inst Neurogenet, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM katja.lohmann@neuro.uni-luebeck.de RI Gilissen, Christian/E-5246-2012; Veltman, Joris/F-5128-2010 OI Gilissen, Christian/0000-0003-1693-9699; FU Renate Maass foundation; University of Lubeck FX The authors would like to thank the patients for their participation and support of this study. This work was supported by a grant from the Renate Maass foundation (to KL) and intramural funding of the University of Lubeck "Schwerpunktprogramm: Medizinische Genetik - Von seltenen Varianten zur Krankheitsentstehung" (to GGK and KL). 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Taylor, Julie Lounds TI Family Perspectives on a Successful Transition to Adulthood for Individuals With Disabilities SO INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE intellectual and developmental disabilities; transition to adulthood; families ID QUALITATIVE CONTENT-ANALYSIS; AUTISM SPECTRUM DISORDERS; YOUNG-ADULTS; HIGH-SCHOOL; OF-LIFE; PARENTS; ADOLESCENCE; CHILDHOOD; SERVICES; CHILDREN AB When researchers evaluate adult outcomes for individuals with intellectual and/or developmental disabilities (IDD), the perspective of families is not always considered. Parents of individuals with IDD (N = 198) answered an online survey about their definition of a successful transition to adulthood. Content analysis was used to describe themes and ideas present in the responses. 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TI Family Caregivers of Adults With Intellectual and Developmental Disabilities: Outcomes Associated With US Services and Supports SO INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE caregiver assessment; quality of life; disability service systems; formal and informal supports ID QUALITY-OF-LIFE; MENTAL-RETARDATION; AGING MOTHERS; DOWN-SYNDROME; PUBLIC-HEALTH; PARENTS; HOME; CHILDREN; AUTISM; NEEDS AB Individuals with intellectual and developmental disabilities (IDD) in the U.S. predominantly live with their family caregivers. As care delivery and support systems vary widely globally, consideration of caregiver outcomes specifically in the U.S. context is needed. A systematic literature review was conducted to identify U.S. family caregiver outcomes and their association with existing services and supports for family caregivers of adults with IDD. Twenty-four articles were compiled using the PubMed, Web of Knowledge, PsychInfo, and CINAHL databases. 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Department of Health and Human Services, 2012, HLTH PEOPL 2020 DIS U.S. Department of Health and Human Services, 2012, HHS ANN AV FUND HELP US Senate Commission on Long-Term Care, 2013, REP C Yamaki K, 2009, INTELLECT DEV DISAB, V47, P425, DOI 10.1352/1934-9556-47.6.425 NR 64 TC 1 Z9 1 PU AMER ASSOC INTELLECTUAL DEVELOPMENTAL DISABILITIES PI WASHINGTON PA 444 N CAPITOL ST, NW STE 846, WASHINGTON, DC 20001-1512 USA SN 1934-9491 EI 1934-9556 J9 INTELLECT DEV DISAB JI Intellect. Dev. Disabil. PD APR PY 2014 VL 52 IS 2 BP 147 EP 159 DI 10.1352/1934-9556-52.2.147 PG 13 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AF1WI UT WOS:000334504200006 PM 24725113 ER PT J AU Shadish, WR AF Shadish, William R. TI Analysis and meta-analysis of single-case designs: An introduction SO JOURNAL OF SCHOOL PSYCHOLOGY LA English DT Article DE Single-case designs; Statistics; Meta-analysis ID AUTISM SPECTRUM DISORDERS; NATURAL-LANGUAGE PARADIGM; OF-SCHOOL-PSYCHOLOGY; WRITING DIFFICULTIES; SUBJECT RESEARCH; CHILDREN; BEHAVIOR; FUTURE; STUDENTS; DISABILITIES AB The last 10 years have seen great progress in the analysis and meta-analysis of single-case designs (SCDs). This special issue includes five articles that provide an overview of current work on that topic, including standardized mean difference statistics, multilevel models, Bayesian statistics, and generalized additive models. Each article analyzes a common example across articles and presents syntax or macros for how to do them. These articles are followed by commentaries from single-case design researchers and journal editors. This introduction briefly describes each article and then discusses several issues that must be addressed before we can know what analyses will eventually be best to use in SCD research. These issues include modeling trend, modeling error covariances, computing standardized effect size estimates, assessing statistical power, incorporating more accurate models of outcome distributions, exploring whether Bayesian statistics can improve estimation given the small samples common in SCDs, and the need for annotated syntax and graphical user interfaces that make complex statistics accessible to SCD researchers. 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Natasha Van den Noortgate, Wim TI From a single-level analysis to a multilevel analysis of single-case experimental designs SO JOURNAL OF SCHOOL PSYCHOLOGY LA English DT Article DE Single-case experimental design; Multilevel analysis ID HIERARCHICAL LINEAR-MODELS; NATURAL-LANGUAGE PARADIGM; EFFECT SIZES; INTERVENTION; CHILDREN; AUTISM; AUTOCORRELATION; SIMULATION; INCREASE AB Multilevel modeling provides one approach to synthesizing single-case experimental design data. In this study, we present the multilevel model (the two-level and the three-level models) for summarizing single-case results over cases, over studies, or both. In addition to the basic multilevel models, we elaborate on several plausible alternative models. We apply the proposed models to real datasets and investigate to what extent the estimated treatment effect is dependent on the modeling specifications and the underlying assumptions. 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PD APR PY 2014 VL 52 IS 2 BP 191 EP 211 DI 10.1016/j.jsp.2013.11.003 PG 21 WC Psychology, Educational SC Psychology GA AF1OO UT WOS:000334483400005 PM 24606975 ER PT J AU Helsmoortel, C Vulto-van Silfhout, AT Coe, BP Vandeweyer, G Rooms, L van den Ende, J Schuurs-Hoeijmakers, JHM Marcelis, CL Willemsen, MH Vissers, LELM Yntema, HG Bakshi, M Wilson, M Witherspoon, KT Malmgren, H Nordgren, A Anneren, G Fichera, M Bosco, P Romano, C de Vries, BBA Kleefstra, T Kooy, RF Eichler, EE Van der Aa, N AF Helsmoortel, Celine Vulto-van Silfhout, Anneke T. Coe, Bradley P. Vandeweyer, Geert Rooms, Liesbeth van den Ende, Jenneke Schuurs-Hoeijmakers, Janneke H. M. Marcelis, Carlo L. Willemsen, Marjolein H. Vissers, Lisenka E. L. M. Yntema, Helger G. Bakshi, Madhura Wilson, Meredith Witherspoon, Kali T. Malmgren, Helena Nordgren, Ann Anneren, Goran Fichera, Marco Bosco, Paolo Romano, Corrado de Vries, Bert B. A. Kleefstra, Tjitske Kooy, R. Frank Eichler, Evan E. Van der Aa, Nathalie TI A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP SO NATURE GENETICS LA English DT Article ID DEPENDENT NEUROPROTECTIVE PROTEIN; CHROMATIN-REMODELING COMPLEX; COFFIN-SIRIS SYNDROME; SPECTRUM DISORDERS; INTELLECTUAL DISABILITY; NEURAL DEVELOPMENT; PEPTIDE; GENES; HAPLOINSUFFICIENCY; DIFFERENTIATION AB Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities(1), a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile- X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in nextgeneration sequencing, for the large majority of cases no molecular diagnosis can be established(2-7). Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/ SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD- associated genes known to date. C1 [Helsmoortel, Celine; Vandeweyer, Geert; Rooms, Liesbeth; Kooy, R. Frank; Van der Aa, Nathalie] Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium. [Vulto-van Silfhout, Anneke T.; Schuurs-Hoeijmakers, Janneke H. M.; Marcelis, Carlo L.; Willemsen, Marjolein H.; Vissers, Lisenka E. L. M.; Yntema, Helger G.; de Vries, Bert B. A.; Kleefstra, Tjitske] Radboud Univ Nijmegen, Med Ctr, Inst Genet & Metab Dis, Nijmegen Ctr Mol Life Sci,Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Coe, Bradley P.; Witherspoon, Kali T.; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. [Coe, Bradley P.; Witherspoon, Kali T.; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Vandeweyer, Geert] Univ Antwerp, Dept Math & Comp Sci, Biomed Informat Res Ctr Antwerpen Biomina, Edegem, Belgium. [van den Ende, Jenneke; Van der Aa, Nathalie] Univ Antwerp Hosp, Antwerp, Belgium. [Bakshi, Madhura] Westmead Hosp, Dept Med Genet, Sydney, NSW, Australia. [Wilson, Meredith] Childrens Hosp, Dept Clin Genet, Westmead, NSW, Australia. [Malmgren, Helena; Nordgren, Ann] Karolinska Inst, Dept Mol Med & Surg, Clin Genet Unit, Stockholm, Sweden. [Anneren, Goran] Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden. [Fichera, Marco] IRCCS, Assoc Oasi Maria Santissima, Neurol Unit, Troina, Italy. [Fichera, Marco] Univ Catania, Catania, Italy. [Bosco, Paolo] IRCCS, Assoc Oasi Maria Santissima, Lab Cytogenet, Troina, Italy. [Romano, Corrado] IRCCS, Assoc Oasi Maria Santissima, Unit Pediat & Med Genet, Troina, Italy. [de Vries, Bert B. A.; Kleefstra, Tjitske] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. RP Van der Aa, N (reprint author), Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium. EM frank.kooy@uantwerpen.be; nathalie.vanderaa@uza.be RI Romano, Corrado/B-9695-2008; Kleefstra, Tjitske/G-2619-2012; Vissers, Lisenka/A-2598-2015 OI Romano, Corrado/0000-0003-1049-0683; FU Belgian National Fund for Scientific Research-Flanders (FWO); University of Antwerp; Dutch Organization for Health Research and Development [917-86-319, 40-00812-98-12109, 907-00-365]; EU-funded GENCODYS project [EU-7th-2010-241995]; Simons Foundation Autism Research Initiative award [SFARI191889EE]; NIH [MH101221] FX This work was funded by the Belgian National Fund for Scientific Research-Flanders (FWO) to G.V. and R.F.K., the Special Research Fund of the University of Antwerp (Bijzonder Onderzoeksfonds (BOF- IWT)) to C.H., by grants from the Dutch Organization for Health Research and Development (917-86-319 and 40-00812-98-12109 to B.B.A. d.V. and 907-00-365 to T.K.), the EU-funded GENCODYS project (EU-7th-2010-241995 to A.T.V.-v.S., B.B.A.d.V. and T.K.), Simons Foundation Autism Research Initiative award (SFARI191889EE to E.E.E.) and NIH (MH101221 to E.E.E.). 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PD APR PY 2014 VL 46 IS 4 BP 380 EP + DI 10.1038/ng.2899 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AF1YP UT WOS:000334510100015 PM 24531329 ER PT J AU Ashburner, J Rodger, S Ziviani, J Jones, J AF Ashburner, Jill Rodger, Sylvia Ziviani, Jenny Jones, Judy TI Occupational therapy services for people with autism spectrum disorders: Current state of play, use of evidence and future learning priorities SO AUSTRALIAN OCCUPATIONAL THERAPY JOURNAL LA English DT Article DE autism; interventions; professional development ID CHILDREN AB BackgroundA dramatic increase in the prevalence of autism spectrum disorders and increased funding to support children with autism spectrum disorders have added to the demand for occupational therapy services. This study explored current practices and future learning priorities of Queensland occupational therapists who work in this field. MethodA survey in relation to occupational therapy services for people with autism spectrum disorders was distributed to all registered Queensland occupational therapists (N=2547). The development of the survey was informed by a series of focus groups comprising occupational therapy clinicians, supervisors and academics. The survey covered demographics, caseload composition, collaboration, context/setting, service-delivery models, information gathering, goal setting, interventions, perceived challenges and confidence, use of evidence, and experience of professional development and support, and future learning priorities. ResultsOf 818 surveys returned, 235 respondents provided services to clients with autism spectrum disorders, with young children being more likely to receive a service than adolescents or adults. A pervasive focus on sensory processing was apparent in relation to assessment, intervention, and key areas of knowledge. Around half the respondents indicated that they lacked confidence at least some of the time. Autism spectrum disorders-specific experience was a significant predictor of confidence. Many therapists reported challenges in finding useful information in the literature and reliance on conferences or workshops as their main source of evidence. Commonly identified learning priorities included new developments in the field, early intervention, school support, sensory processing and clinical reasoning. ConclusionThis research highlights the need for comprehensive autism spectrum disorders-specific, face-to-face training focusing on evidence-based and occupation-centred practices. C1 [Ashburner, Jill; Jones, Judy] Autism Queensland, Res & Dev, Sunnybank, Qld, Australia. [Rodger, Sylvia; Ziviani, Jenny] Univ Queensland, Sch Hlth & Rehabil Sci, Div Occupat Therapy, Brisbane, Qld, Australia. [Ziviani, Jenny] Queensland Hlth, Childrens Allied Hlth Res, Brisbane, Qld, Australia. RP Ashburner, J (reprint author), Autism Queensland, POB 354, Sunnybank, Qld 4109, Australia. EM jill.ashburner@autismqld.com.au FU Occupational Therapists Board of Queensland FX We thank the Occupational Therapists Board of Queensland for their funding of this project and the occupational therapists for their contribution of time to participation in the focus groups and/or completion of the surveys. CR American Academy of Pediatrics, 2012, PEDIATRICS, V129, P1186, DOI [10.1542/peds.2012-0876, DOI 10.1542/PEDS.2012-0876] American Psychiatric Association, 2000, DIAGN STAT MAN MENT Australian Government, 2013, HELP CHILDR AUT Ayres A. J., 1972, SENSORY INTEGRATION Baird G, 2006, LANCET, V368, P210, DOI 10.1016/S0140-6736(06)69041-7 Beery K. E., 2010, DEV TEST VISUAL MOTO Ben-Sasson A, 2009, J AUTISM DEV DISORD, V39, P1, DOI 10.1007/s10803-008-0593-3 Bondy A. 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PD APR PY 2014 VL 61 IS 2 BP 110 EP 120 DI 10.1111/1440-1630.12083 PG 11 WC Rehabilitation SC Rehabilitation GA AD8ZC UT WOS:000333553200010 PM 24118044 ER PT J AU Lyons, M Simmons, ES Paul, R AF Lyons, Megan Simmons, Elizabeth Schoen Paul, Rhea TI Prosodic Development in Middle Childhood and Adolescence in High-Functioning Autism SO AUTISM RESEARCH LA English DT Article DE perception; autism; production; prosody; language ID SPECTRUM DISORDERS; FOLLOW-UP; INTONATION ABILITIES; WILLIAMS-SYNDROME; ASPERGER-SYNDROME; CHILDREN; LANGUAGE; SPEECH; SPEAKERS; COMMUNICATION AB The present study aims to investigate the perception and production of several domains of prosodic performance in a cross-sectional sample of preadolescents and adolescents with and without high-functioning autism (HFA). To look at the role of language abilities on prosodic performance, the HFA groups were subdivided based on "high" and "low" language performance on the Clinical Evaluation of Language Fundamentals-Fourth Edition (CELF-4) (Semel, Wiig, & Secord). Social and cognitive abilities were also examined to determine their relationship to prosodic performance. No significant differences were seen in prosody scores in the younger versus older subgroups in typically developing (TD) group with age-appropriate language. There was small but significant improvement in performance with age in the groups with HFA. Comparing performance at each age level across diagnostic groups showed that preteens with HFA and higher language levels perform similarly to their TD peers on all prosodic tasks, whereas those with lower language skills scored significantly worse than both their higher language and TD peers when looking at composite perception and production findings. Teens with HFA showed no deficits on perception tasks; however, those with low language levels had difficulty on several production tasks when compared to the TD group. Regression analyses suggested that, for the preteen group with HFA, language was the strongest predictor of prosodic perception, whereas nonverbal IQ was most highly predictive of prosodic production. For adolescents with HFA, social skills significantly contributed to the prediction of prosodic perception and, along with language abilities, predicted prosodic production. Implications of these findings will be discussed. Autism Res 2014, 7: 181-196.. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Lyons, Megan; Simmons, Elizabeth Schoen] Yale Child, Study Ctr, New Haven, CT 06510 USA. [Paul, Rhea] Sacred Heart Univ, Fairfield, CT USA. [Paul, Rhea] Haskins Labs Inc, New Haven, CT USA. RP Lyons, M (reprint author), Yale Child, Study Ctr, 40 Temple St,Suite 7-D, New Haven, CT 06510 USA. 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L., 2001, GRAY ORAL READING TE NR 53 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-3792 EI 1939-3806 J9 AUTISM RES JI Autism Res. PD APR PY 2014 VL 7 IS 2 BP 181 EP 196 DI 10.1002/aur.1355 PG 16 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AE9WD UT WOS:000334361200001 PM 24634421 ER PT J AU Ruysschaert, L Warreyn, P Wiersema, JR Oostra, A Roeyers, H AF Ruysschaert, Lieselot Warreyn, Petra Wiersema, Jan R. Oostra, Ann Roeyers, Herbert TI Exploring the Role of Neural Mirroring in Children with Autism Spectrum Disorder SO AUTISM RESEARCH LA English DT Article DE ASD; children; mirror neurons; mu suppression; EEG ID MOTOR FACILITATION; MU-SUPPRESSION; EEG EVIDENCE; IMITATION; SYSTEM; INFANTS; OTHERS; ACTIVATION; HYPOTHESIS; EXECUTION AB Investigating the underlying neural mechanisms of autism spectrum disorder (ASD) has recently been influenced by the discovery of mirror neurons. These neurons, active during both observation and execution of actions, are thought to play a crucial role in imitation and other social-communicative skills that are often impaired in ASD. In the current electroencephalographic study, we investigated mu suppression, indicating neural mirroring in children with ASD between the ages of 24 and 48 months and age-matched typically developing children, during observation of goal-directed actions and non-goal-directed mimicked hand movements, as well as during action execution. Results revealed no significant group differences with significant central mu suppression in the ASD children and control children during both execution and observation of goal-directed actions and during observation of hand movements. Furthermore, no significant correlations between mu suppression on one hand and quality of imitation, age, and social communication questionnaire scores on the other hand were found. These findings challenge the "broken mirror" hypothesis of ASD, suggesting that impaired neural mirroring is not a distinctive feature of ASD. Autism Res 2014, 7: 197- 206. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Ruysschaert, Lieselot; Warreyn, Petra; Wiersema, Jan R.; Roeyers, Herbert] Univ Ghent, Dept Expt Clin & Hlth Psychol, B-9000 Ghent, Belgium. [Oostra, Ann] Ghent Univ Hosp, Ghent, Belgium. RP Ruysschaert, L (reprint author), Univ Ghent, Dept Expt Clin & Hlth Psychol, Henri Dunantlaan 2, B-9000 Ghent, Belgium. EM Lieselot.Ruysschaert@UGent.be FU Ghent University Research Fund (BOF); Marguerite-Marie Delacroix Fund FX This research was supported by the Ghent University Research Fund (BOF) and the Marguerite-Marie Delacroix Fund. 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The growth trajectories of joint attention skills (pointing, coordinated joint looking, and showing) and expressive language outcomes in these children were estimated based on five time points during the measurement period. The children were grouped by diagnosis at the last follow-up (autism, autism spectrum disorder (ASD), no diagnosis) and by their original treatment group assignment (joint attention, symbolic play, control), and differences between these groups were evaluated. Results showed that joint attention skills of coordinated joint looking and showing increased over time, and pointing to share interest increased over the first year measured and decreased thereafter. These trajectories were influenced by both original treatment assignment and diagnostic status at follow-up. In addition, a cross-lagged panel analysis revealed a causal relationship between early pointing and later language development. This study highlights the longitudinal and developmental importance of measures of early core deficits in autism, and suggests that both treatment and ASD symptomatology may influence growth in these skills over time. Autism Res 2014, 7: 207-215. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Gulsrud, Amanda C.; Freeman, Stephanny F. N.; Kasari, Connie] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Hellemann, Gerhard S.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. [Kasari, Connie] Univ Calif Los Angeles, Grad Sch Educ & Informat Studies, Los Angeles, CA 90024 USA. RP Gulsrud, AC (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,RM 68-237C, Los Angeles, CA 90024 USA. 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Pickles, Andrew Baird, Gillian Happe, Francesca Charman, Tony Simonoff, Emily TI The Association Between Social Cognition and Executive Functioning and Symptoms of Anxiety and Depression in Adolescents With Autism Spectrum Disorders SO AUTISM RESEARCH LA English DT Article DE social cognition; anxiety; ASD; executive functions; neuropsychology; depression ID PERVASIVE DEVELOPMENTAL DISORDERS; ATTENTIONAL CONTROL-THEORY; PSYCHIATRIC-DISORDERS; GENERALIZED ANXIETY; ASPERGERS SYNDROME; MAJOR DEPRESSION; ANIMATED SHAPES; STATE ANXIETY; MENTAL STATES; SPECIAL NEEDS AB While high levels of anxiety and depression are now recognized as major co-occurring problems in children and young people with an autism spectrum disorder (ASD), research examining possible associations with individual differences in neurocognitive functioning has been limited. This study included 90 adolescents with an ASD aged 14-16 years with a full-scale IQ > 50. Using structural equation modeling, we examined the independent relationships between multiple measures of executive functioning and social cognition on severity of anxiety or depressive symptoms. Results indicated a significant association between poorer executive functioning and higher levels of anxiety, but not depression. In contrast, social cognition ability was not associated with either anxiety or depression. This study is the first to report significant associations between executive functions and anxiety in ASD. This may suggest that poor executive functioning is one factor associated with the high prevalence of anxiety disorder in children and adolescents with ASD. Autism Res 2014, 7: 216-228. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Hollocks, Matthew J.; Simonoff, Emily] Kings Coll London, Dept Child & Adolescent Psychiat, Inst Psychiat, London SE5 8AF, England. [Jones, Catherine R. G.] Cardiff Univ, Sch Psychol, Cardiff CF10 3AX, S Glam, Wales. [Pickles, Andrew] Kings Coll London, Dept Biostat, Inst Psychiat, London SE5 8AF, England. [Pickles, Andrew] Kings Coll London, Biomed Res Ctr Mental Hlth, Inst Psychiat, London SE5 8AF, England. [Baird, Gillian] Guys & St Thomas NHS Fdn Trust, London, England. [Happe, Francesca] Kings Coll London, MRC SGDP Res Ctr, Inst Psychiat, London SE5 8AF, England. [Charman, Tony] Kings Coll London, Dept Psychol, Inst Psychiat, London SE5 8AF, England. [Simonoff, Emily] Kings Coll London, NIHR Biomed Res Ctr Mental Hlth, Inst Psychiat, London SE5 8AF, England. RP Hollocks, MJ (reprint author), Kings Coll London, Dept Child & Adolescent Psychiat, Inst Psychiat, PO85,De Crespigny Pk,Denmark Hill, London SE5 8AF, England. EM matthew.hollocks@kcl.ac.uk RI Charman, Tony/A-2085-2014; Jones, Catherine/E-4956-2013; Pickles, Andrew/A-9625-2011 OI Charman, Tony/0000-0003-1993-6549; Pickles, Andrew/0000-0003-1283-0346 FU Medical Research Council [G0400065]; Novartis FX The study was funded by the Medical Research Council (G0400065). We are grateful to the adolescents and families who took part in the study. We would like to thank Paramala Santosh for permission to reprint the relevant items from the PONS. A.P. receives royalties from the Social Communication Questionnaire and F. H. received a one-off consultancy payment from Novartis in March 2011. There are no other conflicts of interest, financial or otherwise. 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PD APR PY 2014 VL 7 IS 2 BP 216 EP 228 DI 10.1002/aur.1361 PG 13 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AE9WD UT WOS:000334361200004 PM 24737743 ER PT J AU Iarocci, G Armstrong, K AF Iarocci, Grace Armstrong, Kimberly TI Age-Related Changes in Conjunctive Visual Search in Children with and without ASD SO AUTISM RESEARCH LA English DT Article DE attention; perception; development; visual search ID AUTISM; SUPERIOR; ATTENTION; ADULTS; TARGET; TASKS AB Visual-spatial strengths observed among people with autism spectrum disorder (ASD) may be associated with increased efficiency of selective attention mechanisms such as visual search. In a series of studies, researchers examined the visual search of targets that share features with distractors in a visual array and concluded that people with ASD showed enhanced performance on visual search tasks. However, methodological limitations, the small sample sizes, and the lack of developmental analysis have tempered the interpretations of these results. In this study, we specifically addressed age-related changes in visual search. We examined conjunctive visual search in groups of children with (n = 34) and without ASD (n = 35) at 7-9 years of age when visual search performance is beginning to improve, and later, at 10-12 years, when performance has improved. The results were consistent with previous developmental findings; 10- to 12-year-old children were significantly faster visual searchers than their 7- to 9-year-old counterparts. However, we found no evidence of enhanced search performance among the children with ASD at either the younger or older ages. More research is needed to understand the development of visual search in both children with and without ASD. Autism Res 2014, 7: 229-236. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Iarocci, Grace; Armstrong, Kimberly] Simon Fraser Univ, Dept Psychol, Burnaby, BC V5A 1S6, Canada. RP Iarocci, G (reprint author), Simon Fraser Univ, Dept Psychol, 8888 Univ Dr, Burnaby, BC V5A 1S6, Canada. EM giarocci@sfu.ca FU Social Sciences and Humanities Research Council of Canada (SSHRC) [767-2011-2317]; Michael Smith Foundation for Health Research (MSFHR); Autism Research Training (ART) program; Canadian Institutes of Health Research (CIHR) [STN 63728] FX This research was supported by: Grant Sponsor: Social Sciences and Humanities Research Council of Canada (SSHRC); Grant Number: 767-2011-2317 to G. I.; Grant Sponsor: Michael Smith Foundation for Health Research (MSFHR); Scholar Award to G. I. Grant Sponsor: Autism Research Training (ART) program funded by the Canadian Institutes of Health Research (CIHR); Grant Number: STN 63728 to K.A. 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TI Time Estimation Among Low-Functioning Individuals With Autism Spectrum Disorders: Evidence of Poor Sensitivity to Variability of Short Durations SO AUTISM RESEARCH LA English DT Article DE perception; autism spectrum disorder; time; low-functioning ID PERCEPTION; CHILDREN; ADULTS; MEMORY; AGE AB Time estimation of short durations (under 1 sec) was examined in low-functioning individuals with autism spectrum disorder (ASD) and typically developing (TD) children matched on mental age. Temporal bisection and generalization tasks were used to examine basic perceptual timing mechanisms. For both tasks, the participants with ASD demonstrated less sensitivity to variability in short durations than the TD children, adding to a growing body of literature suggesting deficits in timing exist for longer durations. The results highlight the need to examine multiple levels of processing of time-related information from basic perceptual mechanisms to higher level cognitive mechanisms. 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PD APR PY 2014 VL 7 IS 2 BP 237 EP 244 DI 10.1002/aur.1364 PG 8 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AE9WD UT WOS:000334361200006 PM 24574256 ER PT J AU Yuan, H Dougherty, JD AF Yuan, Han Dougherty, Joseph D. TI Investigation of Maternal Genotype Effects in Autism by Genome-Wide Association SO AUTISM RESEARCH LA English DT Article DE autism; GWAS; SSC; maternal genotype effect; AGRE ID FETAL VALPROATE SYNDROME; SPECTRUM DISORDERS; CONGENITAL CYTOMEGALOVIRUS; RISK-FACTORS; TWIN PAIRS; ALCOHOL; MOTHERS; IDENTIFICATION; METAANALYSIS; MUTATIONS AB Like most psychiatric disorders, autism spectrum disorders have both a genetic and an environmental component. While previous studies have clearly demonstrated the contribution of in utero (prenatal) environment on autism risk, most of them focused on transient environmental factors. Based on a recent sibling study, we hypothesized that environmental factors could also come from the maternal genome, which would result in persistent effects across siblings. In this study, the possibility of maternal genotype effects was examined by looking for common variants (single-nucleotide polymorphisms or SNPs) in the maternal genome associated with increased risk of autism in children. A case/control genome-wide association study was performed using mothers of probands as cases, and either fathers of probands or normal females as controls. Autism Genetic Resource Exchange and Illumina Genotype Control Database were used as our discovery cohort (n = 1616). The same analysis was then replicated on Simon Simplex Collection and Study of Addiction: Genetics and Environment datasets (n = 2732). We did not identify any SNP that reached genome-wide significance (P < 10(-8)), and thus a common variant of large effect is unlikely. However, there was evidence for the possibility of a large number of alleles of effective size marginally below our power to detect. Autism Res 2014, 7: 245-253. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Yuan, Han; Dougherty, Joseph D.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Dougherty, Joseph D.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Dougherty, JD (reprint author), Washington Univ, Sch Med, Dept Genet, 4566 Scott Ave,Campus Box 8232, St Louis, MO 63110 USA. EM jdougherty@genetics.wustl.edu FU Mallinkrodt Foundation; National Institutes of Health (NIH) [4R00NS067239 -03, 9R01MH100027-06]; National Institute of Mental Health [1U24MH081810]; NIH Genes, Environment and Health Initiative (GEI) [U01 HG004422]; Gene Environment Association Studies (GENEVA) under GEI; Collaborative Study on the Genetics of Alcoholism (COGA) [U10 AA008401]; Collaborative Genetic Study of Nicotine Dependence (COGEND) [P01 CA089392]; Family Study of Cocaine Dependence (FSCD) [R01 DA013423]; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; NIH [HHSN268200782096C] FX We gratefully thank John Constantino, Jennifer K. Lowe, Don Conrad, Laura Bierut, Nancy Saccone, and members of Dougherty lab for their suggestions and support. Funding was provided by the Mallinkrodt Foundation (J. D. D.) and the National Institutes of Health (NIH): 4R00NS067239 -03 (J. D. D.) and 9R01MH100027-06. The authors declare no conflicts of interest.We are also grateful for 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 are likewise grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, Z. Warren, and E. Wijsman). Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative (GEI) (U01 HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392), and the Family Study of Cocaine Dependence (FSCD; R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease" (HHSN268200782096C). 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Jacob, Suma TI A Deletion Involving CD38 and BST1 Results in a Fusion Transcript in a Patient With Autism and Asthma SO AUTISM RESEARCH LA English DT Article DE CNV; oxytocin; fusion transcript; autism; CD38 ID RECEPTOR GENE OXTR; PERVASIVE DEVELOPMENTAL DISORDERS; AIRWAY SMOOTH-MUSCLE; SPECTRUM DISORDER; OXYTOCIN SECRETION; GENOMIC DISORDERS; BRAIN OXYTOCIN; ASSOCIATION; CHILDREN; BEHAVIOR AB CD38 encodes a ligand in the oxytocin signaling pathway. Some single nucleotide polymorphisms in this gene have been associated with low serum oxytocin levels in autism spectrum disorder (ASD) patients. Oxytocin disruption has been hypothesized to account for features of ASD, including impaired communication and social behavior, based on animal studies. Recent human studies have shown administration of oxytocin improving emotion recognition, promoting social behavior, and improving auditory processing of social stimuli in ASD patients. In addition to its role in oxytocin signaling, CD38 is involved in the regulation of calcium concentration in airway smooth muscle with impairment of CD38 being implicated in airway diseases like asthma. While a number of studies have implicated rare chromosomal deletions and duplications in helping determine genetic risk for autism, there are to our knowledge no reports describing rearrangements involving CD38 or deletions in patients with ASD. Here, we present two sisters diagnosed with autism and with features of regression-previously acquired speech lost in the second year of life. The younger sister, who also had asthma, inherited a maternal deletion of 4p15.32 that results in a BST1-CD38 fusion transcript. Their mother's deletion was mosaic and she was not affected. Although further work is required to assess functional consequences of the fusion transcript, we hypothesize that the proband's deletion may have served as a risk factor for autism that, when combined with other susceptibility variants, resulted in a more severe presentation than her sister. Autism Res 2014, 7: 254-263. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Ceroni, Fabiola; Maestrini, Elena] Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy. [Simpson, Nuala H.; Gawthrope, Alex J. T.; Newbury, Dianne F.; Monaco, Anthony P.; Pagnamenta, Alistair T.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Sagar, Angela; Tessman, Dorothy C.; Cook, Edwin H.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Pinto, Dalila] Icahn Sch Med, Dept Psychiat, New York, NY USA. [Monaco, Anthony P.] Tufts Univ, Dept Neurosci, Medford, MA 02155 USA. [Francis, Sunday M.; Jacob, Suma] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. RP Jacob, S (reprint author), Univ Minnesota, Wallin Med Biosci Bldg,2101 6th St SE, Minneapolis, MN 55455 USA. EM sjacob@umn.edu RI Monaco, Anthony/A-4495-2010; Jacob, Suma/J-7941-2013 OI Monaco, Anthony/0000-0001-7480-3197; Jacob, Suma/0000-0001-7434-7398 FU NIH Autism Center of Excellence [P50 HD055751, K23MH082121]; MRC [G1000569/1]; Wellcome Trust [090532/Z/09/Z]; NIHR Biomedical Research Centre Oxford; Department of Health's NIHR Biomedical Research Centres funding scheme; [5T32MH067631-07] FX We thank the patients and their 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.), NIH Autism Center of Excellence P50 HD055751 (E. H. C.), K23MH082121 (S.J.), the MRC [G1000569/1] (D.N.), the Wellcome Trust (090532/Z/09/Z), and the NIHR Biomedical Research Centre Oxford, with funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. Dianne Newbury is an MRC Career Development Fellow and a Junior Research Fellow at St John's College. We would like to acknowledge Zoe Holloway for technical assistance with the preliminary Western analysis, and Steve Guter for assistance with the clinical data. The authors have no conflicts of interest to disclose. 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TI Autism-Related Neuroligin-3 Mutation Alters Social Behavior and Spatial Learning SO AUTISM RESEARCH LA English DT Article DE animal models; neuroligin; intellectual disability; autism; behavioral analysis of animal models ID SYNAPTIC-TRANSMISSION; MICE; DISORDER; GENES AB Multiple candidate genes have been identified for autism spectrum disorders. While some of these genes reach genome-wide significance, others, such as the R451C point mutation in the synaptic cell adhesion molecule neuroligin-3, appear to be rare. Interestingly, two brothers with the same R451C point mutation in neuroligin-3 present clinically on seemingly disparate sides of the autism spectrum. These clinical findings suggest genetic background may play a role in modifying the penetrance of a particular autism-associated mutation. Animal models may contribute additional support for such mutations as functionally relevant and can provide mechanistic insights. Previously, in collaboration with the Sudhof laboratory, we reported that mice with an R451C substitution in neuroligin-3 displayed social deficits and enhanced spatial learning. While some of these behavioral abnormalities have since been replicated independently in the Sudhof laboratory, observations from the Crawley laboratory failed to replicate these findings in a similar neuroligin-3 mutant mouse model and suggested that genetic background may contribute to variation in observations across laboratories. Therefore, we sought to replicate our findings in the neuroligin-3 R451C point mutant knock-in mouse model (NL3R451C) in a different genetic background. We backcrossed our NL3R451C mouse line onto a 129S2/SvPasCrl genetic background and repeated a subset of our previous behavioral testing. NL3R451C mice on a 129S2/SvPasCrl displayed social deficits, enhanced spatial learning, and increased locomotor activity. These data extend our previous findings that NL3R451C mice exhibit autism-relevant behavioral abnormalities and further suggest that different genetic backgrounds can modify this behavioral phenotype through epistatic genetic interactions. Autism Res 2014, 7: 264-272. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Jaramillo, Thomas C.; Liu, Shunan; Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Pettersen, Ami; Birnbaum, Shari G.; Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Grad Program Neurosci, Dallas, TX 75390 USA. RP Powell, CM (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM craig.powell@utsouthwestern.edu FU NIMH [MH081164]; Autism Speaks; The Hartwell Foundation FX This work was supported by the NIMH MH081164 (CMP), Autism Speaks (CMP), and The Hartwell Foundation (CMP). TCJ and CMP conceived and designed the experiments; TCJ, SL, and AP carried them out with input from CMP and SB; TCJ performed statistical analysis; and TCJ and CMP wrote the paper with input from all authors. We thank Dr. Thomas C. Sudhof for the gift of NL3 mutant mice. The authors declare no competing interests. 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Mice injected subcutaneously with 600 mg/kg valproic acid (VPA600) at gestational day 12.5 show reduced social interaction in adulthood (at 8 weeks of age), and they have been proposed as a mouse model of autism. Here, we show that these adult animals present signs of chronic glial activation in the hippocampus and the cerebellum. Moreover, when they are challenged with a peripheral inflammatory stimulus (intraperitoneal lipopolysaccharides, LPS), VPA600 animals show an exacerbated inflammatory response. Two hours after LPS injection, VPA600 animals secrete more corticosterone to the blood than control mice, and show an increase in the levels of expression of proinflammatory cytokines in the spleen. After LPS challenge, VPA600 mice also show signs of increased neuroinflammation compared with control mice: they have more microglial cells in the hippocampus, and they show higher levels of proinflammatory cytokines in the cerebellum. Our results provide evidence of basal neuroinflammation and an altered inflammatory response in the VPA model of autism. We propose that this model can be used to evaluate the contribution of inflammatory reactivity to autism-related behaviors. These studies will contribute to elucidate the role of the inflammatory alterations observed in ASD individuals. Autism Res 2013, 7: 273-289. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Mara Depino, Amaicha] CONICET UBA, Inst Physiol Mol Biol & Neurosci, Buenos Aires, DF, Argentina. Univ Buenos Aires, FCEyN, Dept Physiol Mol & Cellular Biol, Buenos Aires, DF, Argentina. RP Depino, AM (reprint author), CONICET UBA, Inst Physiol Mol Biol & Neurosci, Int Guiraldes S-N,Ciudad Univ,Pabellon 2,2Do Piso, Buenos Aires, DF, Argentina. EM adepino@conicet.gov.ar FU CONICET [PIP2010-2012]; University of Buenos Aires [UBACyT GEF2010-2012]; ANPCyT [PICT2010-1334] FX This work was supported by a CONICET Grant PIP2010-2012, a University of Buenos Aires Grant UBACyT GEF2010-2012, and an ANPCyT Grant PICT2010-1334. A. M. D. is a member of the Research Career of the National Council of Scientific and Technological Research (CONICET), Argentina. L. L. is fellow of the CONICET. We would like to thank Dr. Fernando Pitossi for his support at the beginning of this project and the access to the StereoInvestigation equipment, and Dr. Lucia Chemes for critical reading of the manuscript. 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Kondova, Ivanela Scholz, Claus Juergen Haaf, Thomas TI Widespread differences in cortex DNA methylation of the "language gene" CNTNAP2 between humans and chimpanzees SO EPIGENETICS LA English DT Article DE CNTNAP2; human-specific communication; human brain evolution; DNA methylation; language; human-chimpanzee comparison ID AUTISM SPECTRUM DISORDER; EXPRESSION ANALYSES; PRIMATE CORTICES; BRAIN; GENOME; EVOLUTION; SPEECH; FOXP2; REVEAL; CONTACTIN-ASSOCIATED-PROTEIN-LIKE-2 AB CNTNAP2, one of the largest genes in the human genome, has been linked to human-specific language abilities and neurodevelopmental disorders. Our hypothesis is that epigenetic rather than genetic changes have accelerated the evolution of the human brain. To compare the cortex DNA methylation patterns of human and chimpanzee CNTNAP2 at ultra-high resolution, we combined methylated DNA immunoprecipitation (MeDIP) with NimbleGen tiling arrays for the orthologous gene and flanking sequences. Approximately 1.59 Mb of the 2.51 Mb target region could be aligned and analyzed with a customized algorithm in both species. More than one fifth (0.34 Mb) of the analyzed sequence throughout the entire gene displayed significant methylation differences between six human and five chimpanzee cortices. One of the most striking interspecies differences with 28% methylation in human and 59% in chimpanzee cortex (by bisulfite pyrosequencing) lies in a region 300 bp upstream of human SNP rs7794745 which has been associated with autism and parent-of-origin effects. Quantitative real-time RT PCR revealed that the protein-coding splice variant CNTNAP2-201 is 1.6-fold upregulated in human cortex, compared with the chimpanzee. Transcripts CNTNAP2-001, -002, and -003 did not show skewed allelic expression, which argues against CNTNAP2 imprinting, at least in adult human brain. 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Fortin, C. Levy-Rueff, M. Golse, B. Falissard, B. TI Subthreshold traits of the broad autistic spectrum are distributed across different subgroups in parents, but not siblings, of probands with autism SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Autism spectrum disorders; Parents and siblings; Broader autism phenotype ID PERVASIVE DEVELOPMENTAL DISORDERS; FAQ SELF-REPORT; SOCIAL RESPONSIVENESS; FAMILIAL AGGREGATION; DIAGNOSTIC INTERVIEW; QUOTIENT AQ; CHILDREN; PHENOTYPE; VALIDATION; MULTIPLEX AB Autism is a categorical developmental disorder characterized by impairment in socialization, communication, and by restricted and circumscribed interests. Several authors have described the presence of subthreshold autistic traits in the general population, pervasive developmental disorders representing the extreme end of their distribution. 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PD APR PY 2014 VL 23 IS 4 BP 225 EP 233 DI 10.1007/s00787-013-0451-5 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AE7KE UT WOS:000334175700006 ER PT J AU Raz, M AF Raz, Mical TI Deprived of touch How maternal and sensory deprivation theory converged in shaping early debates over autism SO HISTORY OF THE HUMAN SCIENCES LA English DT Article DE autism; sensory deprivation; history of psychiatry; maternal deprivation; history of ideas ID EARLY INFANTILE-AUTISM; CHILDHOOD SCHIZOPHRENIA; ISOLATION THERAPY; CHILDREN; PREFERENCE; CONTACT; PARENTS; WORK AB In 1943, a distinguished child psychiatrist at Johns Hopkins University, Leo Kanner, published what would become a landmark article: a description of 11 children who suffered from a distinct disorder he called 'infantile autism'. While initially quite obscure, in the early 1950s Kanner's report garnered much attention, as clinicians and researchers interpreted these case studies as exemplifying the ill-effects of maternal deprivation, a new theory that rapidly gained currency in the United States. Sensory deprivation experiments, performed in the mid-1950s, further complicated the picture, as experts debated whether maternal deprivation was unique or simply a form of environmental stimulation. As experts strove to make sense of this new disorder, they relied on concepts of maternal and sensory deprivation, both to promote their own theories and to critique or refute those of their colleagues. This interplay between the two theories also informed new forms of intervention, including 'rage reduction therapy', which served as a precursor for controversial forms of therapy today termed as the 'attachment therapies'. 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Hum. Sci. PD APR PY 2014 VL 27 IS 2 BP 75 EP 96 DI 10.1177/0952695113512491 PG 22 WC History & Philosophy Of Science; History Of Social Sciences SC History & Philosophy of Science; Social Sciences - Other Topics GA AE3OR UT WOS:000333886300005 ER PT J AU Mukherjee, S Rupani, K Dave, M Subramanyam, A Shah, H Kamath, R AF Mukherjee, Sayantani Rupani, Karishma Dave, Malay Subramanyam, Alka Shah, Henal Kamath, Ravindra TI Evaluation of Effectiveness of Integrated Intervention in Autistic Children SO INDIAN JOURNAL OF PEDIATRICS LA English DT Article DE Autism; Integrated therapy; Applied behavior analysis; Occupational therapy; Speech therapy; Progress ID BEHAVIORAL TREATMENT AB To assess the effectiveness of integrated therapy over the past 3 y on the recipient autistic children and its correlation with the following variables - age at admission, duration of therapy given and initial severity of symptoms. The index study was a retrospective study with 18 autistic children as subjects; the maximum duration of intervention was 3 y. The integrated approach consisted of special education using principles of applied behavior analysis, occupational and speech therapy. The progress records, the occupational therapy and the speech therapy progress reports were tabulated as data. The Childhood Autism Rating Scale (Schopler, Reichler and Renner, 1986) was used for evaluation of severity of symptoms at admission and in present day. The data was then compared and analyzed. The present study showed significant positive results. Only few domains requiring very high integrated cognitive and sensorimotor functioning showed non-significant results. Age at intervention correlated negatively and, duration of therapy given and initial severity of symptoms correlated positively with effectiveness of therapy. Continuous feedback and modification of the therapy is required to maintain performance and develop target interventions for problematic areas identified. Longitudinal as well as comparative studies are required to better understand the benefits of integrated approach. C1 [Mukherjee, Sayantani; Subramanyam, Alka; Shah, Henal; Kamath, Ravindra] Topiwalla Natl Med Coll, Dept Psychiat, Bombay, Maharashtra, India. [Mukherjee, Sayantani; Dave, Malay; Subramanyam, Alka; Shah, Henal; Kamath, Ravindra] BYL Nair Charitable Hosp, Bombay, Maharashtra, India. [Rupani, Karishma] Seth GS Med Coll & KEM Hosp, Bombay, Maharashtra, India. [Dave, Malay] Topiwalla Natl Med Coll, Bombay, Maharashtra, India. RP Mukherjee, S (reprint author), B-701 Laxmi Tower,Plot 07,Sect 42,Opposite Seawoo, Navi Mumbai 400706, Maharashtra, India. 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PD APR PY 2014 VL 81 IS 4 BP 339 EP 345 DI 10.1007/s12098-013-1169-6 PG 7 WC Pediatrics SC Pediatrics GA AE7JL UT WOS:000334173700004 PM 24057967 ER PT J AU Clawson, A Clayson, PE Worsham, W Johnston, O South, M Larson, MJ AF Clawson, Ann Clayson, Peter E. Worsham, Whitney Johnston, Oliver South, Mikle Larson, Michael J. TI How about watching others? Observation of error-related feedback by others in autism spectrum disorders SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE Self-monitoring; Other-monitoring; Feedback-related negativity; Error-related negativity; ERP; Autism ID EVENT-RELATED POTENTIALS; MEDIAL-FRONTAL-CORTEX; ANTERIOR CINGULATE CORTEX; HIGH-FUNCTIONING AUTISM; COGNITIVE CONTROL; REWARD PREDICTION; DIFFERENTIAL ACTIVATION; SOCIAL IMPAIRMENTS; BRAIN POTENTIALS; NEURAL BASIS AB Research indicates that individuals with autism spectrum disorders (ASD) may have a reduced ability to utilize performance feedback to regulate their behavior; however, it is unclear to what degree alterations in the environmental context affect feedback processing and contribute to the symptoms of ASD. We utilized the observational FRN (oFRN), an event-related potential (ERP) component that putatively indexes feedback processing while observing feedback directed toward another person, to examine the influence of motivational and social demands on feedback processing in ASD. High-density electroencephalogram recordings were collected from 38 youth with ASD and 31 control participants similar on age and IQ while they observed a confederate performing a modified Eriksen Flanker task. Participants were instructed to count the confederate's errors and were told that they would be awarded based on performance; the confederate would either earn points for the participant or herself. Both groups showed robust oFRN activity on traditional scalp-electrode waveforms and waveforms identified using temporospatial principal components analysis. Amplitude of oFRN did not differentiate groups. Results remained non-significant when comparing medicated to non-medicated participants. 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J. Psychophysiol. PD APR PY 2014 VL 92 IS 1 BP 26 EP 34 DI 10.1016/j.ijpsycho.2014.01.009 PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AE6XP UT WOS:000334141600004 ER PT J AU Schnaar, RL Gerardy-Schahn, R Hildebrandt, H AF Schnaar, Ronald L. Gerardy-Schahn, Rita Hildebrandt, Herbert TI SIALIC ACIDS IN THE BRAIN: GANGLIOSIDES AND POLYSIALIC ACID IN NERVOUS SYSTEM DEVELOPMENT, STABILITY, DISEASE, AND REGENERATION SO PHYSIOLOGICAL REVIEWS LA English DT Review ID CELL-ADHESION-MOLECULE; MYELIN-ASSOCIATED GLYCOPROTEIN; GUILLAIN-BARRE-SYNDROME; PSA-NCAM EXPRESSION; LONG-TERM POTENTIATION; SPINAL-CORD-INJURY; LACKING COMPLEX GANGLIOSIDES; ROSTRAL MIGRATORY STREAM; TEMPORAL-LOBE EPILEPSY; MILLER-FISHER-SYNDROME AB Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the compositions of which vary among different tissues and cell types. Many of the linear and branched glycans on cell surface glycoproteins and glycolipids of vertebrates are terminated with sialic acids, nine-carbon sugars with a carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with their display at the outmost end of cell surface glycans, provide for varied molecular interactions. Among their functions, sialic acids regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules, and are receptors for pathogens and toxins. In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid. Gangliosides, sialylated glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse genetic studies and human disorders of ganglioside metabolism implicate gangliosides in axon-myelin interactions, axon stability, axon regeneration, and the modulation of nerve cell excitability. Polysialic acid is a unique homopolymer that reaches >90 sialic acid residues attached to select glycoproteins, especially the neural cell adhesion molecule in the brain. Molecular, cellular, and genetic studies implicate polysialic acid in the control of cell-cell and cell-matrix interactions, intermolecular interactions at cell surfaces, and interactions with other molecules in the cellular environment. Polysialic acid is essential for appropriate brain development, and polymorphisms in the human genes responsible for polysialic acid biosynthesis are associated with psychiatric disorders including schizophrenia, autism, and bipolar disorder. Polysialic acid also appears to play a role in adult brain plasticity, including regeneration. Together, vertebrate brain sialoglycans are key regulatory components that contribute to proper development, maintenance, and health of the nervous system. C1 Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Hannover Med Sch, Inst Cellular Chem, Hannover, Germany. RP Schnaar, RL (reprint author), Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, 725 N Wolfe St, Baltimore, MD 21205 USA. EM schnaar@jhu.edu RI Hildebrandt, Herbert/A-7873-2010 OI Hildebrandt, Herbert/0000-0002-1044-0881 FU National Institute of Neurological Disorders and Stroke [NS037096, NS057338]; Deutsche Forschungsgemeinschaft; Deutsche Krebshilfe; European Commission; German Ministry for Research and Education in the frame of ERA-NET NEURON (NeuConnect) FX We acknowledge the support of National Institute of Neurological Disorders and Stroke Grants NS037096 and NS057338 (to R. L. Schnaar). Work at Hannover Medical School was supported by funds from the Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, the Sixth Framework Program of the European Commission (FP6 PROME-MORIA), and the German Ministry for Research and Education in the frame of ERA-NET NEURON (NeuConnect). 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Rev. PD APR PY 2014 VL 94 IS 2 BP 461 EP 518 DI 10.1152/physrev.00033.2013 PG 58 WC Physiology SC Physiology GA AF2YD UT WOS:000334577500005 PM 24692354 ER PT J AU Rizzolatti, G Cattaneo, L Fabbri-Destro, M Rozzi, S AF Rizzolatti, Giacomo Cattaneo, Luigi Fabbri-Destro, Maddalena Rozzi, Stefano TI CORTICAL MECHANISMS UNDERLYING THE ORGANIZATION OF GOAL-DIRECTED ACTIONS AND MIRROR NEURON-BASED ACTION UNDERSTANDING SO PHYSIOLOGICAL REVIEWS LA English DT Review ID VENTRAL PREMOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; PRIMARY MOTOR CORTEX; POSTERIOR PARIETAL CORTEX; AUTISM SPECTRUM DISORDERS; SUPERIOR TEMPORAL SULCUS; ENVIRONMENTAL DEPENDENCY SYNDROME; GRASP MOVEMENT REPRESENTATION; ADJACENT CINGULATE CORTEX; EXECUTION MATCHING SYSTEM AB Our understanding of the functions of motor system evolved remarkably in the last 20 years. This is the consequence not only of an increase in the amount of data on this system but especially of a paradigm shift in our conceptualization of it. Motor system is not considered anymore just a "producer" of movements, as it was in the past, but a system crucially involved in cognitive functions. In the present study we review the data on the cortical organization underlying goal-directed actions and action understanding. Our review is subdivided into two major parts. In the first part, we review the anatomical and functional organization of the premotor and parietal areas of monkeys and humans. We show that the parietal and frontal areas form circuits devoted to specific motor functions. We discuss, in particular, the visuo-motor transformation necessary for reaching and for grasping. In the second part we show how a specific neural mechanism, the mirror mechanism, is involved in understanding the action and intention of others. This mechanism is located in the same parieto-frontal circuits that mediate goal-directed actions. We conclude by indicating future directions for studies on the mirror mechanism and suggest some major topics for forthcoming research. C1 [Rizzolatti, Giacomo] Univ Parma, Dept Neurosci, I-43100 Parma, Italy. Univ Trento, Ctr Mind Brain Sci, Trento, Italy. Italian Inst Technol, Brain Ctr Motor & Social Cognit, Parma, Italy. RP Rizzolatti, G (reprint author), Univ Parma, Dept Neurosci, Via Volturno,39-E, I-43100 Parma, Italy. EM giacomo.rizzolatti@unipr.it FU European Grant "Cog-systems"; Rete Multidisciplinare Tecnolgica (RTM-IIT) FX This study was supported by the European Grant "Cog-systems" and by Rete Multidisciplinare Tecnolgica (RTM-IIT). 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Rev. PD APR PY 2014 VL 94 IS 2 BP 655 EP 706 DI 10.1152/physrev.00009.2013 PG 52 WC Physiology SC Physiology GA AF2YD UT WOS:000334577500008 PM 24692357 ER PT J AU Brett, M McPherson, J Zang, ZJ Lai, A Tan, ES Ng, I Ong, LC Cham, B Tan, P Rozen, S Tan, EC AF Brett, Maggie McPherson, John Zang, Zhi Jiang Lai, Angeline Tan, Ee-Shien Ng, Ivy Ong, Lai-Choo Cham, Breana Tan, Patrick Rozen, Steve Tan, Ene-Choo TI Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel SO PLOS ONE LA English DT Article ID DE-NOVO MUTATIONS; PERIVENTRICULAR NODULAR HETEROTOPIA; MENTAL-RETARDATION; JOUBERT-SYNDROME; IDENTIFICATION; ENZYME; FOXP1; AHI1 AB Developmental delay and/or intellectual disability (DD/ID) affects 1-3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81-84% of the targeted regions achieved read depths of at least 20x, with average read depths overlapping targets ranging from 322x to 798x. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism. C1 [Brett, Maggie; Tan, Ene-Choo] KK Womens & Childrens Hosp, KK Res Ctr, Singapore, Singapore. [McPherson, John; Tan, Patrick; Rozen, Steve] Duke NUS Grad Med Sch, Singapore, Singapore. [Zang, Zhi Jiang; Tan, Patrick] Natl Canc Ctr, Singapore, Singapore. [Lai, Angeline; Tan, Ee-Shien; Ng, Ivy; Cham, Breana] KK Womens & Childrens Hosp, Genet Serv, Singapore, Singapore. [Ong, Lai-Choo] Univ Malaya Med Ctr, Petaling Jaya, Malaysia. RP Tan, EC (reprint author), KK Womens & Childrens Hosp, KK Res Ctr, Singapore, Singapore. EM tanec@bigfoot.com FU Agency for Science and Technology and Research [BMRC 06/1/50/19/485]; National Medical Research Council, Ministry of Health, Republic of Singapore [NMRC/PPG/KKH12010-Theme3] FX This study is funded by Grant number BMRC 06/1/50/19/485 from the Agency for Science and Technology and Research; and NMRC/PPG/KKH12010-Theme3 from the National Medical Research Council, Ministry of Health, Republic of Singapore. 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 this short review, we examine these issues through the lens of emerging research on autism spectrum disorder (ASD). We begin by describing the current state of iPSC technology in research on ASD. Then we discuss how the social history of and current controversies in autism research combined with the emergence of autism-specific iPSC biobanks indicate an urgent need for researchers to clearly communicate the limitations and possibilities of iPSC research to ensure research participants have the ability to provide fully informed, voluntary consent. We conclude by offering recommendations to bolster informed consent for research involving iPSC biobanks, both in the specific context of ASD and more broadly. C1 [Liu, Emily Yang; Scott, Christopher Thomas] Stanford Univ, Ctr Biomed Eth, Stanford, CA 94305 USA. [Scott, Christopher Thomas] Stanford Univ, Program Stem Cells Soc, Stanford, CA 94305 USA. RP Liu, EY (reprint author), Stanford Univ, Ctr Biomed Eth, Stanford, CA 94305 USA. EM eyliu@stanford.edu FU Stanford Center for Biomedical Ethics; NIH [P50 HG003389]; Stanford Institute for Stem Cell Biology and Regenerative Medicine FX EYL is supported by the Stanford Center for Biomedical Ethics and NIH grant P50 HG003389 (Center for Integrating Ethics and Genetics Research). CTS is supported by the Stanford Center for Biomedical Ethics and the Stanford Institute for Stem Cell Biology and Regenerative Medicine. The authors thank Lauren C. Milner for her contribution to the conceptual phase of this work and Vittorio Sebastiano for his valuable assistance with the manuscript. 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Rep. PD APR PY 2014 VL 10 IS 2 BP 145 EP 150 DI 10.1007/s12015-014-9497-0 PG 6 WC Cell & Tissue Engineering; Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AE6CZ UT WOS:000334077900001 PM 24488263 ER PT J AU Keysers, C Gazzola, V AF Keysers, Christian Gazzola, Valeria TI Dissociating the ability and propensity for empathy SO TRENDS IN COGNITIVE SCIENCES LA English DT Editorial Material ID PSYCHOPATHY; RECOGNITION; BRAIN AB Neuroimaging suggests psychopaths have reduced vicarious activations when simply witnessing pain but less so when asked to empathize. This inspired us to distinguish the ability from the propensity to empathize. We argue that (i) this ability-propensity distinction is crucial to characterizing empathy in psychiatric disorders such as psychopathy and autism, (ii) that costly helping might be best predicted by the propensity for empathy, and (iii) suggest how social neuroscientists can start exploring this distinction. C1 [Keysers, Christian; Gazzola, Valeria] Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Social Brain Lab, NL-1105 BA Amsterdam, Netherlands. [Keysers, Christian; Gazzola, Valeria] Univ Groningen, Univ Med Ctr Groningen, Dept Neurosci, Groningen, Netherlands. RP Keysers, C (reprint author), Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Social Brain Lab, Meibergdreef 47, NL-1105 BA Amsterdam, Netherlands. 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PD APR PY 2014 VL 18 IS 4 BP 163 EP 166 DI 10.1016/j.tics.2013.12.011 PG 4 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA AE6UA UT WOS:000334132200001 PM 24484764 ER PT J AU Calvo, PL Brunati, A Spada, M Romagnoli, R Corso, G Parenti, G Rossi, M Baldi, M Carbonaro, G David, E Pucci, A Amoroso, A Salizzoni, M AF Calvo, P. L. Brunati, A. Spada, M. Romagnoli, R. Corso, G. Parenti, G. Rossi, M. Baldi, M. Carbonaro, G. David, E. Pucci, A. Amoroso, A. Salizzoni, M. TI Liver Transplantation in Defects of Cholesterol Biosynthesis: The Case of Lathosterolosis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Autism spectrum disorder; cholestasis; defects of cholesterol biosyntesis; lathosterolosis; liver transplantation ID LEMLI-OPITZ-SYNDROME; DEFICIENCY; RETARDATION; PHENOTYPE AB We report the outcome of liver transplantation (LT) in the only surviving patient with lathosterolosis, a defect of cholesterol biosynthesis characterized by high lathosterol levels associated with progressive cholestasis, multiple congenital anomalies and mental retardation. From her diagnosis at age 2 she had shown autistic behavior, was unable to walk unaided and her sight was impaired by cataracts. By age 7 she developed end-stage liver disease. After a soul-searching discussion within the transplantation team, she was treated with LT as this represented her only lifesaving option. At 1-year follow-up, her lathosterol levels had returned to normal (0.61mg/dL from 13.042.65) and her nutrition improved. She began exploring her environment and walking by holding onto an adult's hand and then independently. Her brain magnetic resonance imaging (MRI) had shown a normal picture at age 1, whereas a volume reduction of white matter with ex vacuo ventricular dilatation and defective myelinization were observed before transplant. At 5-year follow-up, a complete biochemical recovery, an arrest of mental deterioration and a stable MRI picture were achieved, with a return to her every day life albeit with limitations. Timely liver transplant in defects of cholesterol biosynthesis might arrest the progression of neurological damage. Liver transplantation corrects the metabolic unbalance in a child with lathosterolosis (OMIM #607330) and favors amelioration of her neurodevelopmental delay. C1 [Calvo, P. L.; Spada, M.; Baldi, M.; Pucci, A.] Univ Turin, Dept Pediat, Azienda Osped Citta Salute & Sci, I-10124 Turin, Italy. [Brunati, A.; Romagnoli, R.; Carbonaro, G.; Salizzoni, M.] Univ Turin, Liver Transplantat Ctr, Azienda Osped Citta Salute & Sci, Turin, Italy. [Corso, G.] Univ Foggia, Dept Clin & Expt Med, Foggia, Italy. [Parenti, G.; Rossi, M.] Univ Naples Federico II, Dept Translat Med Sci, Naples, Italy. [David, E.] Azienda Osped Citta Salute & Sci, Dept Pathol, Turin, Italy. [Amoroso, A.] Univ Turin, Transplantat Immunol Serv, Azienda Osped Citta Salute & Sci, Turin, Italy. RP Calvo, PL (reprint author), Univ Turin, Dept Pediat, Azienda Osped Citta Salute & Sci, I-10124 Turin, Italy. 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PD APR PY 2014 VL 14 IS 4 BP 960 EP 965 DI 10.1111/ajt.12645 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA AD5UN UT WOS:000333318800027 PM 24621408 ER PT J AU Zhu, HL Fan, YB Guo, H Huang, D He, SL AF Zhu, Huilin Fan, Yuebo Guo, Huan Huang, Dan He, Sailing TI Reduced interhemispheric functional connectivity of children with autism spectrum disorder: evidence from functional near infrared spectroscopy studies SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID BRAIN ACTIVITY; GLOBAL SIGNAL; NETWORKS; FMRI; UNDERCONNECTIVITY; ORGANIZATION; ACTIVATION; HEAD; MRI AB Autism spectrum disorder (ASD) is a neuro-developmental disorder, which has been associated with atypical neural synchronization. In this study, functional near infrared spectroscopy (fNIRS) was used to study the differences in functional connectivity in bilateral inferior frontal cortices (IFC) and bilateral temporal cortices (TC) between ASD and typically developing (TD) children between 8 and 11 years of age. As the first report of fNIRS study on the resting state functional connectivity (RSFC) in children with ASD, ten children with ASD and ten TD children were recruited in this study for 8 minute resting state measurement. Compared to TD children, children with ASD showed reduced interhemispheric connectivity in TC. Children with ASD also showed significantly lower local connectivity in bilateral temporal cortices. In contrast to TD children, children with ASD did not show typical patterns of symmetry in functional connectivity in temporal cortex. These results support the feasibility of using the fNIRS method to assess atypical functional connectivity of cortical responses of ASD and its potential application in diagnosis. (C) 2014 Optical Society of America C1 [Zhu, Huilin; He, Sailing] S China Normal Univ, ZJU SCNU Joint Res Ctr Photon, Ctr Opt & Electromagnet Res, Guangzhou 510006, Guangdong, Peoples R China. [Zhu, Huilin; Guo, Huan] S China Normal Univ, Sch Psychol, Guangzhou 510631, Guangdong, Peoples R China. [Fan, Yuebo; Huang, Dan] Guangzhou Rehabil & Res Ctr Children ASD, Guangzhou 510540, Guangdong, Peoples R China. [He, Sailing] Royal Inst Technol, Sch Elect Engn, Dept Elect Engn, JORCEP, S-10044 Stockholm, Sweden. RP He, SL (reprint author), S China Normal Univ, ZJU SCNU Joint Res Ctr Photon, Ctr Opt & Electromagnet Res, Guangzhou 510006, Guangdong, Peoples R China. EM sailing@kth.se RI He, Sailing/C-2438-2009 OI He, Sailing/0000-0002-3401-1125 FU Guangdong Innovative Research Team Program [201001D0104799318]; National Basic Research Program (973) of China [2011CB503700]; Guangdong Science and Technology Program [2012B03180000]; Macau Foundation [CUM-16]; Swedish Research Council; SOARD FX This work was supported by Guangdong Innovative Research Team Program (No. 201001D0104799318), the National Basic Research Program (973) of China (2011CB503700), Guangdong Science and Technology Program (2012B03180000), Macau Foundation (CUM-16), the Swedish Research Council and SOARD. We thank Prof. Jun Li in Centre for Optical and Electromagnetic Research of SCNU for helping with data analysis and imaging processing. We also thank Profs. Heyong Shen and Lan Gao of SCNU for discussion, and Zhifang Zhu, Lina Qiu, Xinge Li and Wei Cao for experiments. 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Cogn. Neurosci. PD APR PY 2014 VL 8 BP 1 EP 6 DI 10.1016/j.dcn.2014.02.002 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AE5HW UT WOS:000334019400001 PM 24613509 ER PT J AU Vander Wyk, BC Hoffman, F Pelphrey, KA AF Vander Wyk, Brent C. Hoffman, Ferdinand Pelphrey, Kevin A. TI Equivalent neural responses in children and adolescents with and without autism during judgments of affect SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Article DE Emotion; Autism; fMRI; Self referential processing; Connectivity ID MEDIAL PREFRONTAL CORTEX; DIAGNOSTIC OBSERVATION SCHEDULE; ASPERGER-SYNDROME; SPECTRUM DISORDER; BIOLOGICAL MOTION; SOCIAL COGNITION; SELF; BRAIN; EMOTION; EMPATHY AB Previous research has noted disrupted patterns of neural activation during emotion, processing in individuals with autism spectrum disorders (ASD). However, prior research relied on, designs that may place greater cognitive load on individuals with ASD. In order to address this issue, we adapted the fMRI task of Ochsner et al. (2004a) for children by, presenting fewer stimuli, with fewer valence levels, and longer stimuli duration. A localizer sample of, typically developing children (n = 26) was used to construct regions of interest involved in emotional, processing. Activations in these regions during self- and other-referential emotion processing was, compared in age, IQ, gender matched groups (n = 17 ASD, n = 16 TD). Matched samples replicate, condition contrasts of the localizer, but no group differences were found in behavior measures or, neural activation. An exploratory functional connectivity analysis in a subset of the matched groups, also did not detect striking differences between the groups. These findings suggest that disruptions in activation in emotion processing neural networks in ASD is partially a function of task related cognitive load. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved. C1 [Vander Wyk, Brent C.; Pelphrey, Kevin A.] Yale Univ, New Haven, CT 06520 USA. [Hoffman, Ferdinand] Max Planck Inst Human Cognit & Brain Sci, D-04303 Leipzig, Germany. RP Vander Wyk, BC (reprint author), Yale Univ, 230 South Frontage Rd, New Haven, CT 06520 USA. EM brent.vanderwyk@yale.edu FU NIMH; Simons Foundation FX This work was supported by grants from the NIMH and the Simons Foundation. 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A., 2004, J AM ACAD CHILD ADOL, V43, P481 Webb SJ, 2010, CHILD NEUROPSYCHOL, V16, P255, DOI 10.1080/09297041003601454 Weigelt S, 2012, NEUROSCI BIOBEHAV R, V36, P1060, DOI 10.1016/j.neubiorev.2011.12.008 NR 58 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1878-9293 EI 1878-9307 J9 DEV COGN NEUROS-NETH JI Dev. Cogn. Neurosci. PD APR PY 2014 VL 8 BP 121 EP 130 DI 10.1016/j.dcn.2013.08.001 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AE5HW UT WOS:000334019400014 PM 24016745 ER PT J AU Luyster, RJ Powell, C Tager-Flusberg, H Nelson, CA AF Luyster, Rhiannon J. Powell, Christine Tager-Flusberg, Helen Nelson, Charles A. TI Neural measures of social attention across the first years of life: Characterizing typical development and markers of autism risk SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Article DE Autism; ASD; ERP; Event-related potentials; Infancy ID EVENT-RELATED POTENTIALS; SPECTRUM DISORDERS; FACE RECOGNITION; 6-MONTH-OLD INFANTS; FAMILIAR FACES; YOUNG-CHILDREN; ATYPICAL FACE; EYE GAZE; ERP; SENSITIVITY AB Few studies employing event-related potentials (ERPs) to examine infant perception/cognition have systematically characterized age-related changes over the first few years of life. Establishing a 'normative' template of development is important in its own right, and doing so may also better highlight points of divergence for high-risk populations of infants, such as those at elevated genetic risk for autism spectrum disorder (ASD). The present investigation explores the developmental progression of the P1, N290, P400 and Nc components for a large sample of young children between 6 and 36 months of age, addressing age-related changes in amplitude, sensitivity to familiar and unfamiliar stimuli and hemispheric lateralization. Two samples of infants are included: those at low- and high-risk for ASD. The four components of interest show differential patterns of change over time and hemispheric lateralization; however, infants at low- and high-risk for ASD do not show significant differences in patterns of neural response to faces. These results will provide a useful point of reference for future developmental cognitive neuroscience research targeting both typical development and vulnerable populations. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved. C1 [Luyster, Rhiannon J.] Emerson Coll, Dept Commun Sci & Disorders, Boston, MA 02116 USA. [Luyster, Rhiannon J.; Nelson, Charles A.] Harvard Univ, Sch Med, Boston Childrens Hosp, Cambridge, MA 02138 USA. [Powell, Christine] Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA. [Tager-Flusberg, Helen] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Luyster, RJ (reprint author), Emerson Coll, Dept Commun Sci & Disorders, 120 Boylston St, Boston, MA 02116 USA. EM rhiannon_luyster@emerson.edu FU NIH [R21DC08637]; NIDCD [1R01DC010290-01]; Simons Foundation [137186]; Autism Speaks Pilot Grants Program FX We would like to thank the Infant Sibling Project staff, past and present, for their hard work in collecting these data. We are very grateful for the assistance of Brandon Keehn, Alexandra Libby and Ella Kipervasser with data processing, and we thank Vanessa Vogel-Farley for her constant guidance. Finally, we want to acknowledge the very dedicated families who committed years of their lives to the Infant Sibling Project and who made this work possible. Funding was provided by NIH (R21DC08637) to H.T-F., NIDCD (1R01DC010290-01) to C.A.N. and H. T-F., the Simons Foundation (137186) to C.A.N. and the Autism Speaks Pilot Grants Program to H.T-F. 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Cogn. Neurosci. PD APR PY 2014 VL 8 BP 131 EP 143 DI 10.1016/j.dcn.2013.09.006 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AE5HW UT WOS:000334019400015 PM 24183618 ER PT J AU Rice, K Viscomi, B Riggins, T Redcay, E AF Rice, Katherine Viscomi, Brieana Riggins, Tracy Redcay, Elizabeth TI Amygdala volume linked to individual differences in mental state inference in early childhood and adulthood SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Article DE Social cognition; Theory of mind; Amygdala; Individual differences; Early childhood ID AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; FACIAL EXPRESSIONS; BRAIN-DEVELOPMENT; ASPERGER-SYNDROME; STRUCTURAL MRI; TEMPORAL-LOBE; FALSE BELIEF; MIND; CHILDREN AB We investigated the role of the amygdala in mental state inference in a sample of adults and in a sample of children aged 4 and 6 years. This period in early childhood represents a time when mentalizing abilities undergo dramatic changes. Both children and adults inferred mental states from pictures of others' eyes, and children also inferred the mental states of others from stories (e. g., a false belief task). We also collected structural MRI data from these participants, to determine whether larger amygdala volumes (controlling for age and total gray matter volume) were related to better face-based and story-based mentalizing. For children, larger amygdala volumes were related to better face-based, but not story-based, mentalizing. In contrast, in adults, amygdala volume was not related to face-based mentalizing. We next divided the face-based items into two subscales: cognitive (e. g., thinking, not believing) versus affective (e. g., friendly, kind) items. For children, performance on cognitive items was positively correlated with amygdala volume, but for adults, only performance on affective items was positively correlated with amygdala volume. These results indicate that the amygdala's role in mentalizing may be specific to face-based tasks and that the nature of its involvement may change over development. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved. C1 [Rice, Katherine; Viscomi, Brieana; Riggins, Tracy; Redcay, Elizabeth] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. RP Redcay, E (reprint author), Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. EM redcay@umd.edu FU NSF GRF; UMD Dean's Research Initiative; Maryland Neuroimaging Center Seed grant FX The authors wish to thank Jeremiah Baker, Viviana Bauman, Sarah Blankenship, Seleste Braddock, Robert Cai, Shannon Coveney, Nina Lichtenberg, Ruth Ludlum, Daniel O'Young, and Lauren Weiss for their assistance. The authors also thank Dan Kennedy for comments on a previous version of this manuscript. This study was supported by an NSF GRF to K. R. and by a UMD Dean's Research Initiative and a Maryland Neuroimaging Center Seed grant to E. R. and T.R. 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We review the known synaptic function and role in social behaviors of selected post-synaptic structural proteins (Shank, SAPAP and neuroligin) and regulators of protein synthesis (TSC1/2, FMRP and PTEN). While manipulations of proteins involved in group-I mGluR and iGluR scaffolding or crosstalk frequently lead to profound alterations in synaptic function and one or more components of social behavior, the neuronal circuits responsible for impairments in specific social behaviors are often poorly defined. We argue for an improved understanding of the neuronal circuits underlying specific social behaviors to aid the development of new ASD therapies. C1 [O'Connor, Eoin C.; Bariselli, Sebastiano; Bellone, Camilla] Univ Geneva, Fac Med, Dept Basic Neurosci, CH-1211 Geneva, Switzerland. RP Bellone, C (reprint author), Univ Geneva, Fac Med, Dept Basic Neurosci, 1 Rue Michel Servet, CH-1211 Geneva, Switzerland. EM camilla.bellone@unige.ch FU Swiss National Science Foundation; SFARI (Simons Foundation); Ambizione program of the Swiss National Science Foundation FX We thank Christian Luscher for helpful discussions and suggestions regarding the manuscripts. E.O.C. is supported by the Swiss National Science Foundation S.B. is supported by SFARI (Simons Foundation). C.B. is supported by the Ambizione program of the Swiss National Science Foundation. 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PD APR PY 2014 VL 39 IS 7 SI SI BP 1114 EP 1129 DI 10.1111/ejn.12510 PG 16 WC Neurosciences SC Neurosciences & Neurology GA AE3PE UT WOS:000333887600007 PM 24712991 ER PT J AU Palumbo, P Antona, V Palumbo, O Piccione, M Nardello, R Fontana, A Carella, M Corsello, G AF Palumbo, Pietro Antona, Vincenzo Palumbo, Orazio Piccione, Maria Nardello, Rosaria Fontana, Antonina Carella, Massimo Corsello, Giovanni TI Variable phenotype in 17q12 microdeletions: Clinical and molecular characterization of a new case SO GENE LA English DT Article DE HNF1B; 17q12; SNP array; Renal Cysts and Diabetes syndrome; Intellectual disability ID HEPATOCYTE NUCLEAR FACTOR-1-BETA; DEVELOPMENTAL LANGUAGE DISORDERS; GENOMIC REARRANGEMENTS; CHROMOSOME 17Q12; RENAL CYSTS; SPECTRUM; AUTISM; SCHIZOPHRENIA; DELETION; RISK AB Microdeletions of 17q12 including the hepatocyte nuclear factor 1 beta (HNF1B) gene, as well as point mutations of this gene, are associated with the Renal Cysts and Diabetes syndrome (RCAD, OMIM 137920) and genitourinary alterations. Also, microdeletions encompassing HNF1B were identified as a cause of Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH, OMIM 277000) in females and, recently, were associated with intellectual disability, autistic features, cerebral anomaly and facial dysmorphisms. In this report, we describe a boy with a deletion in 17q12 region detected by SNP array, encompassing the HNF1B gene, that showed dysmorphic features, intellectual disability (ID), serious speech delay and autistic features. In addition, obesity was observed. In order to study the parental origin of the rearrangement, we analyzed selected SNPs in the deleted area in the patient and his parents, showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of maternal origin. Our case confirms the incomplete penetrance and variable expressivity of this deletion, its complex clinical variability, and strengthens the evidence that ID and stereotyped behaviors may be part of the phenotypic spectrum characterizing the affected patients. Also, it is useful to further delineate the phenotypes associated to the deletion being the first case in which obesity has been documented. We present a genotype-phenotype correlation discussing the possible role of some genes, encompassed by the deletion, in the etiology of the observed phenotypes. (C) 2014 Elsevier B.V. All rights reserved. C1 [Palumbo, Pietro; Palumbo, Orazio; Carella, Massimo] IRCCS Casa Sollievo Sofferenza, Med Genet Unit, I-71013 San Giovanni Rotondo, FG, Italy. [Palumbo, Pietro] Univ Bari, Dept Biol, Bari, Italy. [Antona, Vincenzo; Piccione, Maria; Nardello, Rosaria; Fontana, Antonina; Corsello, Giovanni] Univ Palermo, Dipartimento Sci Promoz Salute & Materno Infantil, Palermo, Italy. RP Carella, M (reprint author), IRCCS Casa Sollievo Sofferenza, Med Genet Unit, I-71013 San Giovanni Rotondo, FG, Italy. EM m.carella@operapadrepio.it RI Palumbo, Pietro/H-9533-2014; PALUMBO, ORAZIO/C-1133-2014 OI Palumbo, Pietro/0000-0001-9498-9902; PALUMBO, ORAZIO/0000-0001-6583-3482 FU Italian Ministry of Health FX This study was supported by a grant from the Italian Ministry of Health (Ricerca Corrente 2013) and by the "5x1000" voluntary contributions to MC. We would like to thank the patient and his family for their cooperation. 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Simpson, N. H. Baird, G. O'Hare, A. Conti-Ramsden, G. Bolton, P. F. Hennessy, E. R. Ring, S. M. Smith, G. Davey Francks, C. Paracchini, S. Monaco, A. P. Fisher, S. E. Newbury, D. F. CA SLI Consortium TI Genome- wide association analyses of child genotype effects and parent- of- origin effects in specific language impairment SO GENES BRAIN AND BEHAVIOR LA English DT Article DE ALSPAC; GWAS; imprinting; neurodevelopmental disorder; specific language impairment ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; NUCLEOTIDE EXCHANGE FACTOR; RHO-GTPASES; COMMUNICATION CHECKLIST; HYPERACTIVITY DISORDER; DEVELOPMENTAL DYSLEXIA; SUSCEPTIBILITY LOCUS; SUGGESTIVE LINKAGE; MENTAL-RETARDATION; READING-DISABILITY AB Specific language impairment (SLI) is a neurodevelopmental disorder that affects linguistic abilities when development is otherwise normal. We report the results of a genome-wide association study of SLI which included parent-of-origin effects and child genotype effects and used 278 families of language-impaired children. The child genotype effects analysis did not identify significant associations. We found genome-wide significant paternal parent-of-origin effects on chromosome 14q12 (P=3.74x10(-8)) and suggestive maternal parent-of-origin effects on chromosome 5p13 (P=1.16x10(-7)). A subsequent targeted association of six single-nucleotide-polymorphisms (SNPs) on chromosome 5 in 313 language-impaired individuals and their mothers from the ALSPAC cohort replicated the maternal effects, albeit in the opposite direction (P=0.001); as fathers' genotypes were not available in the ALSPAC study, the replication analysis did not include paternal parent-of-origin effects. The paternally-associated SNP on chromosome 14 yields a non-synonymous coding change within the NOP9 gene. This gene encodes an RNA-binding protein that has been reported to be significantly dysregulated in individuals with schizophrenia. The region of maternal association on chromosome 5 falls between the PTGER4 and DAB2 genes, in a region previously implicated in autism and ADHD. The top SNP in this association locus is a potential expression QTL of ARHGEF19 (also called WGEF) on chromosome 1. Members of this protein family have been implicated in intellectual disability. In summary, this study implicates parent-of-origin effects in language impairment, and adds an interesting new dimension to the emerging picture of shared genetic etiology across various neurodevelopmental disorders. C1 [Nudel, R.; Simpson, N. H.; Monaco, A. P.; Newbury, D. F.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Baird, G.] Evelina Childrens Hosp, Newcomen Ctr, London, England. [O'Hare, A.] Univ Edinburgh, Dept Reprod & Dev Sci, Edinburgh, Midlothian, Scotland. [Conti-Ramsden, G.] Univ Manchester, Sch Psychol Sci, Manchester, Lancs, England. [Bolton, P. F.] Kings Coll London, Dept Child & Adolescent Psychiat, Inst Psychiat, London WC2R 2LS, England. [Bolton, P. F.] Kings Coll London, Dept Social Genet, Inst Psychiat, London WC2R 2LS, England. [Bolton, P. F.] Kings Coll London, Dev Psychiat Ctr, Inst Psychiat, London WC2R 2LS, England. [Hennessy, E. R.] Univ Aberdeen, Univ Child Hlth, Aberdeen, Scotland. [Hennessy, E. R.] Univ Aberdeen, DMDE, Aberdeen, Scotland. [Ring, S. M.; Smith, G. Davey] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Ring, S. M.; Smith, G. Davey] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England. [Francks, C.; Fisher, S. E.] Max Planck Inst Psycholinguist, Nijmegen, Netherlands. [Francks, C.; Fisher, S. E.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [Paracchini, S.] Univ St Andrews, Sch Med, St Andrews, Fife, Scotland. [Monaco, A. P.] Tufts Univ, Medford, MA 02155 USA. RP Newbury, DF (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. EM dianne@well.ox.ac.uk RI Fisher, Simon/E-9130-2012; Monaco, Anthony/A-4495-2010; Davey Smith, George/A-7407-2013; Bolton, Patrick/E-8501-2010 OI Fisher, Simon/0000-0002-3132-1996; Monaco, Anthony/0000-0001-7480-3197; Davey Smith, George/0000-0002-1407-8314; Bolton, Patrick/0000-0002-5270-6262 FU Medical Research Council [G1000569/1, MR/J003719/1, G0800523/86473]; University of Oxford Nuffield Department of Medicine Prize Studentship; Max Planck Society; Wellcome Trust [060774, 076566, 092731]; National Institute of Health Research (UK); Biomedical Research Centre in Mental Health at the South London & Maudsley NHS Trust Hospital, London FX We would like to thank all the families, professionals and individuals who participated in this research. In particular, we would like to thank Simon Fiddy for his assistance with data transformation. Dianne Newbury is an MRC Career Development Fellow and a Junior Research Fellow at St John's College, University of Oxford. The work of the Newbury lab is funded by the Medical Research Council [G1000569/1 and MR/J003719/1]. Ron Nudel is funded by a University of Oxford Nuffield Department of Medicine Prize Studentship. The genotyping of samples was funded by the Max Planck Society. Silvia Paracchini is a Royal Society University Research Fellow. The analyses of the ALSPAC cohort were supported by a grant from the Medical Research Council [G0800523/86473]. The collection of the SLIC samples was supported by the Wellcome Trust (060774 and 076566). Patrick Bolton is supported by a National Institute of Health Research (UK) Senior Investigator award and the Biomedical Research Centre in Mental Health at the South London & Maudsley NHS Trust Hospital, London. The work of the Wellcome Trust Centre in Oxford is supported by the Wellcome Trust [090532/Z/09/Z]. The authors declare no conflicts of interest.We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and the Wellcome Trust (Grant ref: 092731) and the University of Bristol provide core support for ALSPAC. 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PD APR PY 2014 VL 13 IS 4 BP 418 EP 429 DI 10.1111/gbb.12127 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AE3PD UT WOS:000333887500007 PM 24571439 ER PT J AU Sandhu, KV Lang, D Muller, B Nullmeier, S Yanagawa, Y Schwegler, H Stork, O AF Sandhu, K. V. Lang, D. Mueller, B. Nullmeier, S. Yanagawa, Y. Schwegler, H. Stork, O. TI Glutamic acid decarboxylase 67 haplodeficiency impairs social behavior in mice SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Aggressive behavior; amygdala; animal model; c-Fos immunohistochemistry; GABA; GAD67; olfactory bulb; social interaction; social odor ID ACCESSORY OLFACTORY-BULB; GAMMA-AMINOBUTYRIC-ACID; IN-SITU HYBRIDIZATION; GENE-EXPRESSION; AGGRESSIVE-BEHAVIOR; ESTROGEN-RECEPTOR; BIPOLAR DISORDER; MESSENGER-RNA; COMPARATIVE LOCALIZATION; PREFRONTAL CORTEX AB Reduced glutamic acid decarboxylase (GAD)67 expression may be causally involved in the development of social withdrawal in neuropsychiatric states such as autism, schizophrenia and bipolar disorder. In this study, we report disturbance of social behavior in male GAD67 haplodeficient mice. GAD67(+/-) mice, compared to GAD67(+/+) littermates, show reduced sociability and decreased intermale aggression, but normal nest building and urine marking behavior, as well as unchanged locomotor activity and anxiety-like behavior. Moreover, the mutants display a reduced sensitivity to both social and non-social odors, indicating a disturbance in the detection and/or processing of socially relevant olfactory stimuli. Indeed, we observed reduced activation of the lateral septum, medial preoptic area, bed nucleus of the stria terminalis, medial and cortical amygdala upon exposure of GAD67(+/-) mice to social interaction paradigm, as indicated by c-Fos immunohistochemistry. These data suggest a disturbance of stimulus processing in the brain circuitry controlling social behavior in GAD67(+/-) mice, which may provide a useful model for studying the impact of a reduced GAD67 expression on alterations of social behavior related to neuropsychiatric disorders. C1 [Sandhu, K. V.; Lang, D.; Mueller, B.; Stork, O.] Univ Magdeburg, Dept Genet & Mol Neurobiol, Inst Biol, D-39120 Magdeburg, Germany. [Nullmeier, S.; Schwegler, H.] Univ Magdeburg, Inst Anat, D-39120 Magdeburg, Germany. [Yanagawa, Y.] Gunma Univ, Dept Genet & Behav Neurosci, Grad Sch Med, Maebashi, Gumma 371, Japan. [Yanagawa, Y.] CREST, JST, Maebashi, Gumma, Japan. [Schwegler, H.; Stork, O.] Ctr Behav Brain Sci, Magdeburg, Germany. RP Stork, O (reprint author), Univ Magdeburg, Dept Genet & Mol Neurobiol, Inst Biol, Leipziger Str 44,Hs91, D-39120 Magdeburg, Germany. EM oliver.stork@ovgu.de FU German Research Foundation [SFB779, TPB5]; Federal State of Sachsonia Anhalt (Center of Behavioral Brain Sciences); MEXT, Japan; NIPS, Japan; Takeda Science Foundation FX We are grateful to F. Webers and S. Stork for expert technical assistance and to A. Deter and T. Nawrath for excellent animal care. The work was supported by grants of the German Research Foundation (SFB779, TPB5 to O.S. and H.S.) and the Federal State of Sachsonia Anhalt (Center of Behavioral Brain Sciences). This work was further supported by Grants-in-Aid for Scientific Research from the MEXT, Japan, a grant from the Cooperative Study Program of NIPS, Japan, and Takeda Science Foundation (to Y.Y.). All the authors declared no conflicts of interest. 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PD APR PY 2014 VL 13 IS 4 BP 439 EP 450 DI 10.1111/gbb.12131 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AE3PD UT WOS:000333887500009 PM 24612522 ER PT J AU Garcia-Cazorla, A Oyarzabal, A Fort, J Robles, C Castejon, E Ruiz-Sala, P Bodoy, S Merinero, B Lopez-Sala, A Dopazo, J Nunes, V Ugarte, M Artuch, R Palacin, M Rodriguez-Pombo, P AF Garcia-Cazorla, Angels Oyarzabal, Alfonso Fort, Joana Robles, Concepcion Castejon, Esperanza Ruiz-Sala, Pedro Bodoy, Susanna Merinero, Begona Lopez-Sala, Anna Dopazo, Joaquin Nunes, Virginia Ugarte, Magdalena Artuch, Rafael Palacin, Manuel Rodriguez-Pombo, Pilar CA Working Grp TI Two Novel Mutations in the BCKDK (Branched-Chain Keto-Acid Dehydrogenase Kinase) Gene Are Responsible for a Neurobehavioral Deficit in Two Pediatric Unrelated Patients SO HUMAN MUTATION LA English DT Article DE BCKDK; neurobehavioral deficit; dietary treatment; branched-chain keto-acid dehydrogenase complex ID PROTEIN PHOSPHATASE 2CM; DNA-SEQUENCING DATA; CATABOLISM; RAT; PHOSPHORYLATION; CELLS; METABOLISM; EXPRESSION; FRAMEWORK; VARIANTS AB Inactivating mutations in the BCKDK gene, which codes for the kinase responsible for the negative regulation of the branched-chain -keto acid dehydrogenase complex (BCKD), have recently been associated with a form of autism in three families. In this work, two novel exonic BCKDK mutations, c.520C>G/p.R174G and c.1166T>C/p.L389P, were identified at the homozygous state in two unrelated children with persistently reduced body fluid levels of branched-chain amino acids (BCAAs), developmental delay, microcephaly, and neurobehavioral abnormalities. Functional analysis of the mutations confirmed the missense character of the c.1166T>C change and showed a splicing defect r.[520c>g;521_543del]/p.R174Gfs1*, for c.520C>G due to the presence of a new donor splice site. Mutation p.L389P showed total loss of kinase activity. Moreover, patient-derived fibroblasts showed undetectable (p.R174Gfs1*) or barely detectable (p.L389P) levels of BCKDK protein and its phosphorylated substrate (phospho-E1), resulting in increased BCKD activity and the very rapid BCAA catabolism manifested by the patients' clinical phenotype. Based on these results, a protein-rich diet plus oral BCAA supplementation was implemented in the patient homozygous for p.R174Gfs1*. This treatment normalized plasma BCAA levels and improved growth, developmental and behavioral variables. Our results demonstrate that BCKDK mutations can result in neurobehavioral deficits in humans and support the rationale for dietary intervention. C1 [Garcia-Cazorla, Angels; Lopez-Sala, Anna] CIBER Enfermedades Raras CIBERER, Hosp Sant Joan Deu HSJD, Dept Neurol, Barcelona, Spain. [Oyarzabal, Alfonso; Ruiz-Sala, Pedro; Merinero, Begona; Ugarte, Magdalena; Rodriguez-Pombo, Pilar; Working Grp] Univ Autonoma Madrid, Dept Biol, Ctr Biol Mol Severo Ochoa CSIC UAM,IDIPAZ, Ctr Diagnost Enfermedades Mol CEDEM,CIBER Enferme, Madrid, Spain. [Fort, Joana; Bodoy, Susanna; Palacin, Manuel] Univ Barcelona, Inst Res Biomed IRB Barcelona, Dept Biochem & Mol Biol, Fac Biol,CIBER Enfermedades Raras CIBERER, Barcelona, Spain. [Robles, Concepcion] San Cecilio Hosp, Dept Paediat, Granada, Spain. [Castejon, Esperanza] Hosp San Juan Dios, Dept Gastroenterol, Barcelona, Spain. [Dopazo, Joaquin] Ctr Invest Principe Felipe, Computat Genom Dept, Valencia, Spain. [Dopazo, Joaquin] CIPF, Funct Genom Node, INB, Valencia, Spain. [Dopazo, Joaquin] CIBER Enfermedades Raras CIBERER, Valencia, Spain. [Nunes, Virginia] Univ Barcelona, Fac Med, Genet Mol Lab, IDIBELL,Dept Ciencies Fisiol 2,U 730 CIBER Enferm, Barcelona 7, Spain. [Artuch, Rafael] CIBER Enfermedades Raras CIBERER, Hosp Sant Joan Deu, Dept Biochem, Barcelona, Spain. Natl Ctr Genom Anal, Barcelona, Spain. RP Rodriguez-Pombo, P (reprint author), Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, C Nicolas Cabrera 1, E-28049 Madrid, Spain. EM mprodriguez@cbm.csic.es RI Dopazo, Joaquin/A-9270-2014 OI Dopazo, Joaquin/0000-0003-3318-120X FU Fundacion Ramon Areces [CIVP16A1853]; Spanish Ministerio de Economia y Competitividad [PI12/02078, SAF2012-40080-C02-01, SAF2009-12606-C02-02]; Generalitat de Catalunya [SGR2009-1355, SGR2009-1490]; Programa de intensificacion de la actividad investigadora (FIS); Fundacion Ramon Areces FX Contract grant sponsors: Fundacion Ramon Areces (CIVP16A1853); Spanish Ministerio de Economia y Competitividad (PI12/02078), (SAF2012-40080-C02-01), (SAF2009-12606-C02-02); Generalitat de Catalunya (SGR2009-1355), (SGR2009-1490); Programa de intensificacion de la actividad investigadora (FIS); Fundacion Ramon Areces. 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Mutat. PD APR PY 2014 VL 35 IS 4 BP 470 EP 477 DI 10.1002/humu.22513 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AC8UG UT WOS:000332810000009 PM 24449431 ER PT J AU Julich, K Sahin, M AF Juelich, Kristina Sahin, Mustafa TI Mechanism-Based Treatment in Tuberous Sclerosis Complex SO PEDIATRIC NEUROLOGY LA English DT Review DE tuberous sclerosis complex; rapamycin; neuronal connectivity; mTOR ID AUTISTIC-LIKE BEHAVIOR; WHITE-MATTER; MOUSE MODEL; SYNAPTIC PLASTICITY; AXON GUIDANCE; MAMMALIAN TARGET; CORTICAL TUBERS; RAPAMYCIN; MTOR; DIFFUSION AB BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic multisystem disorder that affects the brain in almost every patient. It is caused by a mutation in the TSC1 or TSC2 genes, which regulate mammalian target of rapamycin (mTOR), a key player in control of cellular growth and protein synthesis. The most frequent neurological symptoms are seizures, which occur in up to 90% of patients and often are intractable, followed by autism spectrum disorders, intellectual disability, attention deficit-hyperactivity disorder, and sleep problems. Conventional treatment has frequently proven insufficient for neurological and behavioral symptoms, particularly seizure control. This review focuses on the role of TSC/mTOR in neuronal development and network formation and recent mechanism-based treatment approaches. METHODS: We performed a literature review to identify ongoing therapeutic challenges and novel strategies. RESULTS: To achieve a better quality of life for many patients, current therapy approaches are directed at restoring dysregulated mTOR signaling. Studies in animals have provided insight into aberrant neuronal network formation caused by constitutive activation of the mTOR pathway, and initial studies in TSC patients using magnetic resonance diffusion tensor imaging and electroencephalogram support a model of impaired neuronal connectivity in TSC. Rapamycin, an mTOR inhibitor, has been used successfully in Tsc-deficient mice to prevent and treat seizures and behavioral abnormalities. There is recent evidence in humans of improved seizure control with mTOR inhibitors. CONCLUSIONS: Current research provides insight into aberrant neuronal connectivity in TSC and the role of mTOR inhibitors as a promising therapeutic approach. C1 [Juelich, Kristina; Sahin, Mustafa] Harvard Univ, Sch Med, Boston Childrens Hosp, FM Kirby Ctr Neurobiol,Dept Neurol, Boston, MA USA. RP Sahin, M (reprint author), Boston Childrens Hosp, Dept Neurol, 300 Longwood Ave,CLS13074, Boston, MA 02115 USA. EM mustafa.sahin@childrens.harvard.edu FU NIH [U01 NS082320, P20 NS080199, P30 HD018655]; Department of Defense; Tuberous Sclerosis Alliance; Autism Speaks; Nancy Lurie Marks Family Foundation; Boston Children's Hospital Translational Research Program; Novartis; Roche; Shire FX The authors first acknowledge the generous and essential contributions of the children and families who participated in the studies reviewed here. We also thank all members of the TSC community for many helpful discussions. Due to limited space we have not quoted all literature in the field, and we apologize to those whose articles are not referenced. Research in the Sahin's laboratory is funded by the NIH (U01 NS082320, P20 NS080199, P30 HD018655), Department of Defense, Tuberous Sclerosis Alliance, Autism Speaks, Nancy Lurie Marks Family Foundation, Boston Children's Hospital Translational Research Program, Novartis, Roche and Shire. 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Neurol. PD APR PY 2014 VL 50 IS 4 BP 290 EP 296 DI 10.1016/j.pediatrneurol.2013.12.002 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AE3GY UT WOS:000333866200004 PM 24486221 ER PT J AU Berry-Kravis, E AF Berry-Kravis, Elizabeth TI Mechanism-Based Treatments in Neurodevelopmental Disorders: Fragile X Syndrome SO PEDIATRIC NEUROLOGY LA English DT Review DE fragile X syndrome; autism; FMRP; metobotropic glutamate receptors; GABA agonists; signal transduction; dendritic translation; synaptic plasticity ID MENTAL-RETARDATION; OPEN-LABEL; SYNAPTIC PLASTICITY; TREATMENT TRIAL; KNOCKOUT MICE; MOUSE MODEL; FMR1 GENE; MINOCYCLINE; CHILDREN; PREVALENCE AB BACKGROUND: Fragile X syndrome (FXS) is the most common identifiable genetic cause of intellectual disability and autistic spectrum disorders. Recent major advances have been made in the understanding of the neurobiology and functions of fragile X mental retardation protein, the FMR1 gene product, which is absent or reduced in FXS, largely based on work in the fmr1 knockout mouse model. FXS has emerged as a disorder of synaptic plasticity associated with abnormalities of long-term depression and long-term potentiation and immature dendritic spine architecture, related to dysregulation of dendritic translation typically activated by group I mGluR and other receptors. This work has led to efforts to develop treatments for FXS with neuroactive molecules targeted to pathways dysregulated in the absence of fragile X mental retardation protein. CONCLUSION: These agents have been shown to rescue molecular, spine, and behavioral phenotypes in the FXS mouse model, and clinical trials are underway to translate findings in animal models of FXS to humans, raising complex issues about trial design and outcome measures to assess disease-modifying changes that might be associated with treatment. Genes known to be causes of autistic spectrum disorders interact with the translational pathway defective in FXS and it is likely that there will be substantial overlap in molecular pathways and mechanisms of synaptic dysfunction. Thus targeted treatment and clinical trial strategies in FXS may serve as a model for ASD and other cognitive disorders. C1 [Berry-Kravis, Elizabeth] Rush Univ, Med Ctr, Dept Pediat, Chicago, IL 60612 USA. [Berry-Kravis, Elizabeth] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Berry-Kravis, Elizabeth] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. 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Neurol. PD APR PY 2014 VL 50 IS 4 BP 297 EP 302 DI 10.1016/j.pediatrneurol.2013.12.001 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AE3GY UT WOS:000333866200005 PM 24518745 ER PT J AU Baines, C AF Baines, Chris TI CBT for Children and Adolescents with High-Functioning Autism Spectrum Disorders SO PSYCHOLOGIST LA English DT Book Review CR SCARPA A, CBT CHILDREN ADOLESC NR 1 TC 0 Z9 0 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 0952-8229 J9 PSYCHOLOGIST JI Psychologist PD APR PY 2014 VL 27 IS 4 BP 82 EP 82 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AE3GB UT WOS:000333863900037 ER PT J AU Peters, S Slattery, DA Uschold-Schmidt, N Reber, SO Neumann, ID AF Peters, Sebastian Slattery, David A. Uschold-Schmidt, Nicole Reber, Stefan O. Neumann, Inga D. TI Dose-dependent effects of chronic central infusion of oxytocin on anxiety, oxytocin receptor binding and stress-related parameters in mice SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Oxytocin; Receptor binding; Chronic subordinate colony housing; Anxiety ID CHRONIC PSYCHOSOCIAL STRESS; PITUITARY-ADRENAL AXIS; BEHAVIORAL CONSEQUENCES; PARAVENTRICULAR NUCLEUS; CENTRAL AMYGDALA; INDUCED COLITIS; BRAIN OXYTOCIN; DEFICIENT MICE; SOCIAL DEFEAT; MALE RATS AB Chronic psychosocial stress is a recognized risk factor for various affective and somatic disorders. In an established murine model of chronic psychosocial stress, exposure to chronic subordinate colony housing (CSC) results in an alteration of physiological, behavioral, neuroendocrine and immunological parameters, including a long-lasting increase in anxiety, adrenal hypertrophy and thymus atrophy. Based on the stress-protective and anxiolytic properties of oxytocin (OXT) after acute administration in rodents and humans, the major aims of our study were to assess whether chronic administration of OXT dose-dependently affects the behavior and physiology of male mice, as for therapeutic use in humans, mostly chronic treatment approaches will be used. Further, we studied, whether chronic administration during CSC prevents stress-induced consequences. Our results indicate that chronic intracerebroventricular (ICV) infusion of OXT (15 days) at high (10 ng/h), but not at low (1 ng/h) dose, induces an anxiogenic phenotype with a concomitant reduction of OXT receptor (OXTR) binding within the septum, the basolateral and medial amygdala, as well as the median raphe nucleus. Further, we demonstrate that chronic ICV infusion of OXT (1 ng/h) during a 19-day CSC exposure prevents the hyper-anxiety, thymus atrophy, adrenal hypertrophy, and decreased in vitro adrenal ACTH sensitivity. Thus, given both negative, but also beneficial effects seen after chronic OXT treatment, which appear to be dose-dependent, a deeper understanding of long-lasting treatment effects is required before OXT can be considered for long-term therapeutic use for the treatment of psychopathologies such as autism, schizophrenia or anxiety-disorders. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Peters, Sebastian; Slattery, David A.; Uschold-Schmidt, Nicole; Reber, Stefan O.; Neumann, Inga D.] Univ Regensburg, Dept Behav & Mol Neurobiol, D-93053 Regensburg, Germany. RP Neumann, ID (reprint author), Univ Regensburg, Dept Behav & Mol Neurobiol, D-93053 Regensburg, Germany. EM inga.neumann@biologie.uni-regensburg.de FU Deutsche Forschungsgemeinschaft; Elitenetwork of Bavaria FX This work was supported by research grants from the Deutsche Forschungsgemeinschaft to IDN, SOR and DAS, and by the Elitenetwork of Bavaria. 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Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AE5AM UT WOS:000334000200024 PM 24636519 ER PT J AU Martinez, F Rosello, M Mayo, S Monfort, S Oltra, S Orellana, C AF Martinez, Francisco Rosello, Monica Mayo, Sonia Monfort, Sandra Oltra, Silvestre Orellana, Carmen TI Duplication at Xq13.3-q21.1 With Syndromic Intellectual Disability, a Probable Role for the ATRX Gene SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE XLID; autism; hyperactivity; MECP2; array CGH ID SEVERE MENTAL-RETARDATION; COPY NUMBER VARIANTS; CRITICAL REGION; X SYNDROME; MUTATIONS; MECP2; REARRANGEMENTS; INACTIVATION; ANOMALIES; DELETION AB Here we report on two unrelated male patients with syndromic intellectual disability (ID) due to duplication at Xq13.3-q21.1, a region of about 6Mb and 25 genes. Among these, the most outstanding is ATRX, the causative gene of X-linked alpha-thalassemia/mental retardation. ATRX belongs to the growing list of genes implied in chromatin remodeling causing ID. Many these genes, such as MECP2, are dose-sensitive so that not only deletions and point mutations, but also duplications cause ID. Both patients have severe ID, absent expressive speech, early hypotonia, behavior problems (hyperactivity, repetitive self-stimulatory behavior), postnatal growth deficiency, microcephaly, micrognathia, cryptorchidism, low-set, posteriorly angulated ears, and downslanting palpebral fissures. These findings are also usually present among patients with loss-of-function mutations of the ATRX gene. Completely skewed X inactivation was observed in the only informative carrier mother, a constant finding among female carriers of inactivating point mutations of this gene. Participation of other duplicated genes cannot be excluded; nevertheless we propose that the increased dosage of ATRX is the major pathogenic mechanism of this X-linked disorder, a syndrome reminiscent of MECP2 duplication. (c) 2014 Wiley Periodicals, Inc. C1 [Martinez, Francisco; Rosello, Monica; Mayo, Sonia; Monfort, Sandra; Oltra, Silvestre; Orellana, Carmen] Hosp Univ & Politecn La Fe, Unidad Genet & Diagnost Prenatal, Valencia 46009, Spain. RP Martinez, F (reprint author), Hosp Univ & Politecn La Fe, Unidad Genet & Diagnost Prenatal, Valencia 46009, Spain. EM francisco@gva.es RI Oltra, Silvestre/A-2697-2009; Martinez, Francisco/A-2543-2009; Rosello, Monica/B-2319-2009; Monfort, Sandra/B-2860-2009; Orellana, Carmen/B-1925-2009 OI Oltra, Silvestre/0000-0001-6863-4382; Martinez, Francisco/0000-0002-0589-2584; Rosello, Monica/0000-0001-9234-2953; Orellana, Carmen/0000-0003-4271-5859 FU Plan Nacional I+D+I (ISCIII -Subdireccion General de Evaluacion y Fomento de la Investigacion) [PI11/00389]; FEDER (Fondo Europeo de Desarrollo Regional, EU); Fundacion Ramon Areces FX Grant sponsor: Plan Nacional I+D+I 2008-2011 (ISCIII -Subdireccion General de Evaluacion y Fomento de la Investigacion); Grant number: PI11/00389; Grant sponsor: FEDER (Fondo Europeo de Desarrollo Regional, EU); Grant sponsor: Fundacion Ramon Areces. 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A PD APR PY 2014 VL 164 IS 4 BP 918 EP 923 DI 10.1002/ajmg.a.36371 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AD4CL UT WOS:000333193800033 PM 24458433 ER PT J AU Alfieri, P Piccini, G Caciolo, C Perrino, F Gambardella, ML Mallardi, M Cesarini, L Leoni, C Leone, D Fossati, C Selicorni, A Digilio, MC Tartaglia, M Mercuri, E Zampino, G Vicari, S AF Alfieri, Paolo Piccini, Giorgia Caciolo, Cristina Perrino, Francesca Gambardella, Maria Luigia Mallardi, Maria Cesarini, Laura Leoni, Chiara Leone, Daniela Fossati, Chiara Selicorni, Angelo Digilio, Maria Cristina Tartaglia, Marco Mercuri, Eugenio Zampino, Giuseppe Vicari, Stefano TI Behavioral Profile in RASopathies SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE behavior; Noonan syndrome; Noonan-like syndrome with loose anagen hair; LEOPARD syndrome; Costello syndrome; cardiofaciocutaneous syndrome; RAS; MAPK cascade; genotype-phenotype correlation analyses ID SOCIAL COMMUNICATION QUESTIONNAIRE; AUTISM SPECTRUM DISORDERS; COSTELLO-SYNDROME; NOONAN-SYNDROME; INTELLECTUAL DISABILITY; SYNAPTIC PLASTICITY; CHILDREN; FEATURES; CASCADE; MAPK AB Here, we describe neurobehavioral features in patients with RASopathies (i.e., Noonan syndrome, LEOPARD syndrome, Costello syndrome, and cardiofaciocutaneous syndrome), developmental disorders caused by mutations in genes coding transducers participating in the RAS-MAPK signaling cascade. Parents of 70 individuals with a RASopathy were asked to fill out the following questionnaires: Child Behavior Checklist (CBCL), Social Communication Questionnaire version lifetime (SCQ-L), and Modified Checklist for Autism in toddlers (M-CHAT). Data analysis indicated high rates of internalizing (37%) and externalizing problems (31%) on CBCL. Scores over the cut-off were documented in 64% of patients with cardiofaciocutaneous syndrome, 44% with Costello syndrome, and 12% with Noonan syndrome on SCQ-L/M-CHAT. Our findings indicate that mutations promoting dysregulation of the RAS-MAPK cascade mark an increased psychopathological risk and highlight that autistic-like behavior could be underdiagnosed in patients with RASopathies. (c) 2014 Wiley Periodicals, Inc. C1 [Alfieri, Paolo; Piccini, Giorgia; Caciolo, Cristina; Vicari, Stefano] IRCCS, Dipartimento Neurosci, Bambino Gesu Childrens Hosp, Rome, Italy. [Piccini, Giorgia] LUMSA Libera Univ Maria SS Assunta, Rome, Italy. [Perrino, Francesca; Leoni, Chiara; Zampino, Giuseppe] Univ Cattolica Sacro Cuore, Dipartimento Tutela Salute Donna Vita Nascente Ba, I-00168 Rome, Italy. [Gambardella, Maria Luigia; Mallardi, Maria; Cesarini, Laura; Leone, Daniela; Mercuri, Eugenio] Univ Cattolica Sacro Cuore, Dipartimento Pediat Neurol & Psichiatria Infantil, I-00168 Rome, Italy. [Fossati, Chiara; Selicorni, Angelo] AO San Gerardo, Fdn MBBM, Monza, Italy. [Digilio, Maria Cristina] IRCCS, Dipartimento Genet Med, Bambino Gesu Childrens Hosp, Rome, Italy. [Tartaglia, Marco] Ist Super Sanita, Dipartimento Ematol Oncol & Med Mol, I-00161 Rome, Italy. RP Alfieri, P (reprint author), IRCCS, Dipartimento Neurosci, Bambino Gesu Childrens Hosp, Rome, Italy. EM paolo.alfieri@opbg.net FU Telethon-Italy [GGP13107]; Associazione Italiana Sindromi di Costello e Cardiofaciocutanea FX We are grateful to the patient and his family who contributed to this study. This work was, in part, supported by grants from Telethon-Italy [GGP13107] and "Associazione Italiana Sindromi di Costello e Cardiofaciocutanea". 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We identified an individual with BPES and additional phenotypic features who did not have a FOXL2 mutation. We used whole exome sequencing to identify a de novo mutation in KAT6B (lysine acetyltransferase 6B) in this individual. The mutation was a 2-bp insertion leading to a frameshift which resulted in a premature stop codon. The resulting truncated protein does not have the C-terminal serine/methionine transcription activation domain necessary for interaction with other transcriptional and epigenetic regulators. This mutation likely has a dominant-negative or gain-of-function effect, similar to those observed in other genetic disorders resulting from KAT6B mutations, including Say-Barber-Biesecker-Young-Simpson (SBBYSS) and genitopatellar syndrome (GTPTS). Thus, our subject's phenotype broadens the spectrum of clinical findings associated with mutations in KAT6B. Furthermore, our results suggest that individuals with BPES without a FOXL2 mutation should be tested for KAT6B mutations. The transcriptional and epigenetic regulation mediated by KAT6B appears crucial to early developmental processes, which when perturbed can lead to a wide spectrum of phenotypic outcomes. (c) 2014 Wiley Periodicals, Inc. C1 [Yu, Hung-Chun; Geiger, Elizabeth A.; Shaikh, Tamim H.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA. [Medne, Livija; Zackai, Elaine H.] Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA. [Shaikh, Tamim H.] Univ Colorado, Sch Med, Genet Sect, Aurora, CO 80045 USA. [Shaikh, Tamim H.] Univ Colorado, Sch Med, Colorado Intellectual & Dev Disabil Res Ctr IDDRC, Aurora, CO 80045 USA. RP Shaikh, TH (reprint author), Univ Colorado, Sch Med, Dept Pediat, 12800 E 19th Ave,Room P18-3104, Aurora, CO 80045 USA. EM tamim.shaikh@ucdenver.edu FU National Institutes of Health [GM081519] FX Grant sponsor: National Institutes of Health; Grant number: GM081519. 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J. Med. Genet. A PD APR PY 2014 VL 164 IS 4 BP 950 EP 957 DI 10.1002/ajmg.a.36379 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AD4CL UT WOS:000333193800037 PM 24458743 ER PT J AU Amarillo, IE Li, WL Li, XM Vilain, E Kantarci, S AF Amarillo, Ina E. Li, Wenhui Laura Li, Xinmin Vilain, Eric Kantarci, Sibel TI De Novo Single Exon Deletion of AUTS2 in a Patient with Speech and Language Disorder: A Review of Disrupted AUTS2 and Further Evidence for Its Role in Neurodevelopmental Disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE AUTS2; autism susceptibility candidate 2; 7q11; 22; neurodevelopmental disorders ID AUTISM-SUSCEPTIBILITY-CANDIDATE-2 AUTS2; TRANSLOCATION BREAKPOINT; DEVELOPMENTAL DELAY; SPECTRUM DISORDERS; HUMAN GENOME; GENE; AUTISM; CONTACTIN-ASSOCIATED-PROTEIN-LIKE-2; IDENTIFICATION AB The autism susceptibility candidate 2 (AUTS2) gene is suggested to play a critical role in early brain development, and its association with intellectual disability (ID), autism spectrum disorders, and other neurodevelopmental disorders (NDDs) has recently gained more attention. Genomic rearrangements and copy number variations (CNVs) involving AUTS2 have been implicated in a range of NDDs with or without congenital malformations and dysmorphic features. Here we report a 62kb de novo deletion encompassing exon 6 of AUTS2 detected by chromosomal microarray analysis (CMA) in a 4.5 year-old female patient with severe speech and language disorder, history of tonic-clonic movements, and pes planus with eversion of the feet. This is one of the smallest de novo intragenic deletions of AUTS2 described in patients with NDDs. We reviewed previously reported small pathogenic CNVs (<300kb) in 19 cases, and correlated their specific locations within AUTS2 as well as presence of enhancers, regulatory elements, and CpG islands with the clinical findings of these cases and our patient. Our report provides additional insight into the clinical spectrum of AUTS2 disruptions. (c) 2014 Wiley Periodicals, Inc. C1 [Amarillo, Ina E.; Li, Wenhui Laura; Li, Xinmin; Kantarci, Sibel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90024 USA. [Amarillo, Ina E.; Li, Wenhui Laura; Li, Xinmin; Kantarci, Sibel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Lab Med, Los Angeles, CA 90024 USA. [Vilain, Eric] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet & Pediat, Los Angeles, CA 90024 USA. RP Kantarci, S (reprint author), Univ Calif Los Angeles, Clin & Mol Cytogenet Lab, Los Angeles, CA 90024 USA. EM skantarci@mednet.ucla.edu CR Arlt MF, 2011, P NATL ACAD SCI USA, V108, P17360, DOI 10.1073/pnas.1109272108 Bakkaloglu B, 2008, AM J HUM GENET, V82, P165, DOI 10.1016/j.ajhg.2007.09.017 Bedogni F, 2010, GENE EXPR PATTERNS, V10, P9, DOI 10.1016/j.gep.2009.11.005 Ben-David E, 2011, HUM MOL GENET, V20, P3632, DOI 10.1093/hmg/ddr283 Beunders G, 2013, AM J HUM GENET, V92, P210, DOI 10.1016/j.ajhg.2012.12.011 de la Barra F, 1986, Rev Chil Pediatr, V57, P549 Elia J, 2010, MOL PSYCHIATR, V15, P637, DOI 10.1038/mp.2009.57 Firth HV, 2009, AM J HUM GENET, V84, P524, DOI 10.1016/j.ajhg.2009.03.010 GARDINERGARDEN M, 1987, J MOL BIOL, V196, P261, DOI 10.1016/0022-2836(87)90689-9 Girirajan S, 2011, PLOS GENET, V7, DOI 10.1371/journal.pgen.1002334 Green RE, 2010, SCIENCE, V328, P710, DOI 10.1126/science.1188021 Huang XL, 2010, AM J MED GENET A, V152A, P2112, DOI 10.1002/ajmg.a.33497 Iafrate AJ, 2004, NAT GENET, V36, P949, DOI 10.1038/ng1416 Jolley A, 2013, AM J MED GENET A, V161A, P1508, DOI 10.1002/ajmg.a.35922 Kalscheuer VM, 2007, HUM GENET, V121, P501, DOI 10.1007/s00439-006-0284-0 Kent WJ, 2002, GENOME RES, V12, P996, DOI 10.1101/gr.229102 Mefford HC, 2010, PLOS GENET, V6, DOI 10.1371/journal.pgen.1000962 Nagamani SCS, 2013, EUR J HUM GENET, V21, P343, DOI 10.1038/ejhg.2012.157 Oksenberg N, 2013, PLOS GENET, V9, DOI 10.1371/journal.pgen.1003221 Pennacchio LA, 2006, NATURE, V444, P499, DOI 10.1038/nature05295 Strauss KA, 2006, NEW ENGL J MED, V354, P1370, DOI 10.1056/NEJMoa052773 Sultana R, 2002, GENOMICS, V80, P129, DOI 10.1006/geno.2002.6810 Talkowski ME, 2012, CELL, V149, DOI 10.1016/j.cell.2012.03.028 Thierry-Mieg D., 2006, GENOME BIOL S1, V7, P11, DOI 10.1186/gb-2006-7-s1-s12 Verkerk AJMH, 2003, GENOMICS, V82, P1, DOI 10.1016/S0888-7543(03)00097-1 NR 25 TC 3 Z9 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR PY 2014 VL 164 IS 4 BP 958 EP 965 DI 10.1002/ajmg.a.36393 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AD4CL UT WOS:000333193800038 PM 24459036 ER PT J AU Tan, WH Bird, LM Thibert, RL Williams, CA AF Tan, Wen-Hann Bird, Lynne M. Thibert, Ronald L. Williams, Charles A. TI If Not Angelman, What Is It? A Review of Angelman- like Syndromes SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Angelman syndrome; differential diagnoses; Phelan-McDermid syndrome; MBD5 deficiency; KANSL1 deficiency; Pitt-Hopkins syndrome; Christianson syndrome; Mowat-Wilson syndrome; Kleefstra syndrome; HERC2 deficiency; Adenylosuccinase lyase deficiency; ADSL deficiency; Rett syndrome; CDKL5 syndrome; FOXG1 syndrome; MECP2 duplication; MEF2C syndrome; ATRX ID PITT-HOPKINS-SYNDROME; ADENYLOSUCCINATE LYASE DEFICIENCY; SEVERE MENTAL-RETARDATION; MOWAT-WILSON-SYNDROME; 17Q21.31 MICRODELETION SYNDROME; MECP2 DUPLICATION SYNDROME; AUTISM SPECTRUM DISORDER; 22Q13 DELETION SYNDROME; OF-THE-LITERATURE; BEHAVIORAL-PHENOTYPE AB Angelman syndrome (AS) is caused by a lack of expression of the maternally inherited UBE3A gene in the brain. However, about 10% of individuals with a clinical diagnosis of AS do not have an identifiable molecular defect. It is likely that most of those individuals have an AS-like syndrome that is clinically and molecularly distinct from AS. These AS-like syndromes can be broadly classified into chromosomal microdeletion and microduplication syndromes, and single-gene disorders. The microdeletion/microduplication syndromes are now easily identified by chromosomal microarray analysis and include Phelan-McDermid syndrome (chromosome 22q13.3 deletion), MBD5 haploinsufficiency syndrome (chromosome 2q23.1 deletion), and KANSL1 haploinsufficiency syndrome (chromosome 17q21.31 deletion). The single-gene disorders include Pitt-Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat-Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome. They also include disorders due to mutations in HERC2, adenylosuccinase lyase (ADSL), CDKL5, FOXG1, MECP2 (duplications), MEF2C, and ATRX. Although many of these single-gene disorders can be caused by chromosomal microdeletions resulting in haploinsufficiency of the critical gene, the individual disorders are often caused by intragenic mutations that cannot be detected by chromosomal microarray analysis. We provide an overview of the clinical features of these syndromes, comparing and contrasting them with AS, in the hope that it will help guide clinicians in the diagnostic work-up of individuals with AS-like syndromes. (c) 2014 Wiley Periodicals, Inc. C1 [Tan, Wen-Hann; Bird, Lynne M.] NIH, Rare Dis Clin Res Network, Angelman Rett & Prader Willi Syndromes Consortium, Birmingham, AL USA. [Tan, Wen-Hann] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Tan, Wen-Hann; Thibert, Ronald L.] Harvard Univ, Sch Med, Boston, MA USA. [Bird, Lynne M.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Bird, Lynne M.] Rady Childrens Hosp San Diego, Div Genet Dysmorphol, San Diego, CA USA. [Thibert, Ronald L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Williams, Charles A.] Univ Florida, Coll Med, Raymond C Philips Unit, Div Genet & Metab, Gainesville, FL 32610 USA. RP Williams, CA (reprint author), Univ Florida, Coll Med, Raymond C Philips Unit, Div Genet & Metab, 1600 SW Archer Rd,M-351,POB 100296, Gainesville, FL 32610 USA. EM willicx@peds.ufl.edu FU National Center for Research Resources (NCRR) [NIH U54 RR019478]; National Institute of Child Health and Human Development [NIH U54 HD061222]; NIH Office of Rare Diseases Research (ORDR); Angelman Syndrome Foundation - Western Area Chapter; Food and Drug Administration (FDA) Office of Orphan Products Development [R01 FD003523-01A2] FX Grant sponsor: National Center for Research Resources (NCRR); Grant number: NIH U54 RR019478; Grant sponsor: National Institute of Child Health and Human Development; Grant number: NIH U54 HD061222; Grant sponsor: NIH Office of Rare Diseases Research (ORDR); Grant sponsor: Angelman Syndrome Foundation - Western Area Chapter; Grant sponsor: Food and Drug Administration (FDA) Office of Orphan Products Development; Grant number: R01 FD003523-01A2. 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TI MECP2 Duplication: Possible Cause of Severe Phenotype in Females SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE MECP2; MECP2 duplication syndrome; neurodevelopmental disorder; chromosome X ID SEVERE MENTAL-RETARDATION; 4 UNRELATED PATIENTS; RETT-SYNDROME; FUNCTIONAL DISOMY; XQ28 DUPLICATIONS; COPY-NUMBER; GENE; REGION; INACTIVATION; SYMPTOMS AB MECP2 duplication syndrome, originally described in 2005, is an X-linked neurodevelopmental disorder comprising infantile hypotonia, severe to profound intellectual disability, autism or autistic-like features, spasticity, along with a variety of additional features that are not always clinically apparent. The syndrome is due to a duplication (or triplication) of the gene methyl CpG binding protein 2 (MECP2). To date, the disorder has been described almost exclusively in males. Female carriers of the duplication are thought to have no or mild phenotypic features. Recently, a phenotype for females began emerging. We describe a family with approximate to 290kb duplication of Xq28 region that includes the MECP2 gene where the proposita and affected family members are female. Twin sisters, presumed identical, presented early with developmental delay, and seizures. Evaluation of the proposita at 25 years of age included microarray comparative genomic hybridization (aCGH) which revealed the MECP2 gene duplication. The same duplication was found in the proposita's sister, who is more severely affected, and the proband's mother who has mild intellectual disability and depression. X-chromosome inactivation studies showed significant skewing in the mother, but was uninformative in the twin sisters. We propose that the MECP2 duplication caused for the phenotype of the proband and her sister. These findings support evidence for varied severity in some females with MECP2 duplications. (c) 2014 Wiley Periodicals, Inc. C1 [Schwoerer, Jessica Scott; Giampietro, Philip F.] Univ Wisconsin, Dept Pediat, Madison, WI USA. [Laffin, Jennifer; Raca, Gordana] Univ Wisconsin, Wisconsin State Lab Hyg, UW Cytogenet Serv, Madison, WI 53706 USA. [Haun, Joanne] Univ Wisconsin, Waisman Ctr, Dept Genet, Madison, WI 53705 USA. [Raca, Gordana] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Friez, Michael J.] Greenwood Genet Ctr, Greenwood, SC 29646 USA. RP Schwoerer, JS (reprint author), 1500 Highland Ave,Rm 341, Madison, WI 53705 USA. 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Devine, Owen TI Population attributable fractions for three perinatal risk factors for autism spectrum disorders, 2002 and 2008 autism and developmental disabilities monitoring network SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Autism; Birth weight; Cesarean section; Population; Premature birth; Risk factors ID PREVALENCE; CHILDREN; ADULTS AB Purpose: Numerous studies establish associations between adverse perinatal outcomes/complications and autism spectrum disorder (ASD). There has been little assessment of population attributable fractions (PAFs). Methods: We estimated average ASD PAFs for preterm birth (PTB), small for gestational age (SGA), and Cesarean delivery (CD) in a U.S. population. Average PAF methodology accounts for risk factor co-occurrence. ASD cases were singleton non-Hispanic white, non-Hispanic black, and Hispanic children born in 1994 (n = 703) or 2000 (n = 1339) who resided in 48 U.S. counties included within eight Autism and Developmental Disabilities Monitoring Network sites. Cases were matched on birth year, sex, and maternal county of residence, race-ethnicity, age, and education to 20 controls from U.S. natality files. Results: For the 1994 cohort, average PAFs were 4.2%, 0.9%, and 7.9% for PTB, SGA, and CD, respectively. The summary PAF was 13.0% (1.7%-19.5%). For the 2000 cohort, average PAFs were 2.0%, 3.1%, and 6.7% for PTB, SGA, and CD, respectively, with a summary PAF of 11.8% (7.5%-15.9%). Conclusions: Three perinatal risk factors notably contribute to ASD risk in a U.S. population. Because each factor represents multiple etiologic pathways, PAF estimates are best interpreted as the proportion of ASD attributable to having a suboptimal perinatal environment resulting in PTB, SGA, and/or CD. Published by Elsevier Inc. C1 [Schieve, Laura A.; Tian, Lin H.; Baio, Jon; Wiggins, Lisa; Yeargin-Allsopp, Marshalyn; Rice, Catherine; Devine, Owen] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. [Rankin, Kristin; Rosenberg, Deborah] Univ Illinois, Sch Publ Hlth, Chicago, IL USA. [Maenner, Matthew J.; Durkin, Maureen] Univ Wisconsin Madison, Waisman Ctr, Madison, WI USA. [King, Lydia] Med Univ S Carolina, Charleston, SC USA. [Kirby, Russell S.] Univ S Florida, Sch Publ Hlth, Tampa, FL USA. [Wingate, Martha S.] Univ Alabama Birmingham, Coll Publ Hlth, Birmingham, AL USA. RP Schieve, LA (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, MS E-86,1600 Clifton Rd, Atlanta, GA 30333 USA. 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TI Inability to empathize: brain lesions that disrupt sharing and understanding another's emotions SO BRAIN LA English DT Review DE empathy; stroke; emotion; focal lesion studies ID VENTROMEDIAL PREFRONTAL CORTEX; FRONTOTEMPORAL LOBAR DEGENERATION; SOCIAL COGNITION; FUNCTIONAL NEUROANATOMY; ORBITOFRONTAL CORTEX; HUNTINGTONS-DISEASE; BEHAVIORAL VARIANT; NEURAL MECHANISMS; ASPERGER-SYNDROME; RIGHT-HEMISPHERE AB Imaging studies reveal activation of numerous brain regions in healthy individuals performing emotional empathy tasks. To identify regions critical for empathy, Hillis reviews studies of patients with impaired empathy after focal injury. Lesions to several areas disrupt empathy, but selective deficits in specific underlying cognitive processes are rarely reported.Emotional empathy-the ability to recognize, share in, and make inferences about another person's emotional state-is critical for all social interactions. The neural mechanisms underlying emotional empathy have been widely studied with functional imaging of healthy participants. However, functional imaging studies reveal correlations between areas of activation and performance of a task, so that they can only reveal areas engaged in a task, rather than areas of the brain that are critical for the task. Lesion studies complement functional imaging, to identify areas necessary for a task. Impairments in emotional empathy have been mostly studied in neurological diseases with fairly diffuse injury, such as traumatic brain injury, autism and dementia. The classic 'focal lesion' is stroke. There have been scattered studies of patients with impaired empathy after stroke and other focal injury, but these studies have included small numbers of patients. This review will bring together data from these studies, to complement evidence from functional imaging. Here I review how focal lesions affect emotional empathy. I will show how lesion studies contribute to the understanding of the cognitive and neural mechanisms underlying emotional empathy, and how they contribute to the management of patients with impaired emotional empathy. C1 [Hillis, Argye E.] Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Hillis, Argye E.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Hillis, Argye E.] Johns Hopkins Univ Hosp, Dept Cognit Sci, Baltimore, MD 21287 USA. RP Hillis, AE (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, Meyer 6-113,600 North Wolfe St, Baltimore, MD 21287 USA. EM argye@JHMI.edu FU National Institute of Neurological Disorders and Stroke [RO1NS47691] FX This work was supported by: National Institute of Neurological Disorders and Stroke, grant # [RO1NS47691]. 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PD APR PY 2014 VL 137 BP 981 EP 997 DI 10.1093/brain/awt317 PN 4 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AD4ZM UT WOS:000333260900015 PM 24293265 ER PT J AU Hartley, C Allen, ML AF Hartley, Calum Allen, Melissa L. TI Intentions vs. resemblance: Understanding pictures in typical development and autism SO COGNITION LA English DT Article DE Understanding pictures; Intentions; Resemblance; Typical development; Autism ID ACCIDENTAL ACTIONS; 18-MONTH-OLD INFANTS; SPECTRUM DISORDERS; COGNITIVE-STYLE; CHILDREN; LANGUAGE; IMITATION; DRAWINGS; REPRESENTATIONS; REENACTMENT AB Research has debated whether children reflect on artists' intentions when comprehending pictures, or instead derive meaning entirely from resemblance. We explore these hypotheses by comparing how typically developing toddlers and low-functioning children with autism (a population impaired in intentional reasoning) interpret abstract pictures. In Experiment 1, both groups mapped familiar object names onto abstract pictures, however, they related the same representations to different 3-D referents. Toddlers linked abstract pictures with intended referents they did not resemble, while children with autism mapped picture-referent relations based on resemblance. Experiment 2 showed that toddlers do not rely upon linguistic cues to determine intended referential relations. Experiment 3 confirmed that the responding of children with autism was not due to perseveration or associative word learning, and also provided independent evidence of their intention-reading difficulties. We argue that typically developing children derive meaning from the social-communicative intentions underlying pictures when resemblance is an inadequate cue to meaning. By contrast, children with autism do not reflect on artists' intentions and simply relate pictures to whatever they happen to resemble. (C) 2013 Elsevier B.V. All rights reserved. C1 [Hartley, Calum; Allen, Melissa L.] Univ Lancaster, Dept Psychol, Lancaster LA1 4YF, England. 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Soulis, Spyros Hyphantis, Thomas TI The association of illness perceptions with depressive symptoms and general psychological distress in parents of an offspring with autism spectrum disorder SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Autism spectrum disorder; Depression; Illness perceptions; Parents; PHQ-9; GHQ-28 ID MENTAL-HEALTH; PRESCHOOL-CHILDREN; DEVELOPMENTAL DELAY; BEHAVIOR PROBLEMS; STRESS PROFILES; YOUNG-CHILDREN; GREEK VERSION; MOTHERS; QUESTIONNAIRE; FATHERS AB Background: Raising a child with an autism spectrum disorder (ASD) is a severe stressor and parents often present high levels of depression. Depression is associated with illness perceptions but this association has not been studied in parents of ASD offspring. Objective: We aimed to assess the prevalence of psychological distress symptoms and their associations with illness perceptions in parents with an ASD offspring. Methods: In 111 parents of ASD offspring we assessed depressive symptoms (PHQ-9), illness perceptions (B-IPQ) and general psychological distress (GHQ-28). Multiple linear and logistic regressions were used to assess their independent associations. Results: The prevalence of parental clinically significant depressive symptoms was 34.2%, while 55% presented clinically significant levels of general psychological distress. Younger parents and those with lower financial resources had greater psychological distress and more severe depressive symptoms. Parents felt that the condition impacted their lives and believed it would be chronic. Their beliefs about the consequences and the chronicity of the disorder were significant independent correlates of their psychological distress and depressive symptoms severity. Conclusions: These findings indicate that a remarkable proportion of parents with an ASD offspring present clinically significant depressive symptoms, which were associated with illness perceptions relevant to the consequences and the chronicity of the disorder. Our data encourage psychotherapeutic interventions aiming to support parents to deal with the consequences and chronicity of their offspring's disorder, in order to reduce parental psychological distress. (C) 2014 Elsevier Inc. All rights reserved. C1 [Gatzoyia, Dimitra; Soulis, Spyros] Univ Ioannina, Dept Primary Educ Special & Intercultural Educ, GR-45110 Ioannina, Greece. [Kotsis, Konstantinos; Koullourou, Iouliani; Goulia, Panagiota; Hyphantis, Thomas] Univ Ioannina, Sch Med, Dept Psychiat, GR-45110 Ioannina, Greece. [Carvalho, Andre F.] Univ Fed Ceara, Fac Med, Dept Clin Med, Fortaleza, Ceara, Brazil. RP Hyphantis, T (reprint author), Univ Ioannina, Sch Med, Dept Psychiat, GR-45110 Ioannina, Greece. 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PD APR PY 2014 VL 7 IS 2 BP 173 EP 180 DI 10.1016/j.dhjo.2013.10.008 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA AD7FM UT WOS:000333427800007 PM 24680046 ER PT J AU Lin, CW Chen, CY Cheng, SJ Hu, HT Hsueh, YP AF Lin, Chia-Wen Chen, Chiung-Ya Cheng, Sin-Jhong Hu, Hsiao-Tang Hsueh, Yi-Ping TI Sarm1 deficiency impairs synaptic function and leads to behavioral deficits,which can be ameliorated by an mGluR allosteric modulator SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE autism; CDPPB; innate immunity; long-term potentiation; long-term depression; metabotrophic glutamate receptor; N-methyl-D-aspartate receptor ID AUTISM SPECTRUM DISORDERS; LONG-TERM POTENTIATION; MENTAL-RETARDATION; HIPPOCAMPAL CA1; TNF-ALPHA; MICE; PROTEIN; PLASTICITY; EXPRESSION; MUTATIONS AB Innate immune responses have been shown to influence brain development and function. Dysregulation of innate immunity is significantly associated with psychiatric disorders such as autism spectrum disorders and schizophrenia, which are well-known neurodevelopmental disorders. Recent studies have revealed that critical players of the innate immune response are expressed in neuronal tissues and regulate neuronal function and activity. For example, Sarm1, a negative regulator that acts downstream of Toll-like receptor (TLR) 3 and 4, is predominantly expressed in neurons. We have previously shown that Sarm1 regulates neuronal morphogenesis and the expression of inflammatory cytokines in the brain, which then affects learning ability, cognitive flexibility, and social interaction. Because impaired neuronal morphogenesis and dysregulation of cytokine expression may disrupt neuronal activity, we investigated whether Sarm1 knockdown affects the synaptic responses of neurons. We here show that reduced Sarm1 expression impairs metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) formation but enhances N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation production in hippocampal CA1 neurons. The expression levels of post-synaptic proteins, including NR2a, NR1, Shank1 and Shank3, are also altered in Sarm1 knockdown mice, suggesting a role for Sarm1 in the maintenance of synaptic homeostasis. The addition of a positive allosteric modulator of mGluR5, CDPPB, ameliorates the LTD defects in slice recording and the behavioral deficits in social interaction and associative memory. These results suggest an important role for mGluR5 signaling in the function of Sarm1. In conclusion, our study demonstrates a role for Sarm1 in the regulation of synaptic plasticity. Through these mechanisms, Sarm1 knockdown results in the impairment of associative memory and social interactions in mice. C1 [Lin, Chia-Wen; Chen, Chiung-Ya; Hu, Hsiao-Tang; Hsueh, Yi-Ping] Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan. [Cheng, Sin-Jhong] Acad Sinica, Neurosci Program, Taipei 115, Taiwan. [Hu, Hsiao-Tang; Hsueh, Yi-Ping] Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan. RP Hsueh, YP (reprint author), Acad Sinica, Inst Mol Biol, 128 Acad Rd,Sect 2, Taipei 115, Taiwan. EM yph@gate.sinica.edu.tw FU Academia Sinica [AS-103-TP-B05]; National Science Council [NSC 102-2321-B-001-029, 102-2321-B-001-054, NSC 102-2811-B-001-037] FX This work was supported by grants from Academia Sinica (AS-103-TP-B05 to Yi-Ping Hsueh) and the National Science Council (NSC 102-2321-B-001-029 and 102-2321-B-001-054 to Yi-Ping Hsueh). Chiung-Ya Chen was supported by National Science Council (NSC 102-2811-B-001-037). 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Cell. Neurosci. PD APR 1 PY 2014 VL 8 AR 87 DI 10.3389/fncel.2014.00087 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AD9BE UT WOS:000333558700001 PM 24744698 ER PT J AU Sarasua, SM Dwivedi, A Boccuto, L Chen, CF Sharp, JL Rollins, JD Collins, JS Rogers, RC Phelan, K DuPont, BR AF Sarasua, Sara M. Dwivedi, Alka Boccuto, Luigi Chen, Chin-Fu Sharp, Julia L. Rollins, Jonathan D. Collins, Julianne S. Rogers, R. Curtis Phelan, Katy DuPont, Barbara R. TI 22q13.2q13.32 genomic regions associated with severity of speech delay, developmental delay, and physical features in Phelan-McDermid syndrome SO GENETICS IN MEDICINE LA English DT Article DE genotype-phenotype; language delay; Phelan-McDermid syndrome; SHANK3; 22q13 deletion syndrome ID AUTISM SPECTRUM DISORDERS; 22Q13.3 DELETION SYNDROME; MOLECULAR CHARACTERIZATION; INTELLECTUAL DISABILITY; RHO-GTPASES; GENE; SHANK3; LANGUAGE; MUTATIONS; TARGETS AB Purpose: Phelan-McDermid syndrome is a developmental disability syndrome with varying deletions of 22q13 and varying clinical severity. We tested the hypothesis that, in addition to loss of the telomeric gene SHANK3, specific genomic regions within 22q13 are associated with important clinical features. Methods: We used a customized oligo array comparative genomic hybridization of 22q12.3-terminus to obtain deletion breakpoints in a cohort of 70 patients with terminal 22q13 deletions. We used association and receiver operating characteristic statistical methods in a novel manner and also incorporated protein interaction networks to identify 22q13 genomic locations and genes associated with clinical features. Results: Specific genomic regions and candidate genes within 22q13.2q13.32 were associated with severity of speech/language delay, neonatal hypotonia, delayed age at walking, hair-pulling behaviors, male genital anomalies, dysplastic toenails, large/fleshy hands, macrocephaly, short and tall stature, facial asymmetry, and atypical reflexes: We also found regions suggestive of a negative association with autism spectrum disorders. Conclusion: This work advances the field of research beyond the observation of a correlation between deletion size and phenotype and identifies candidate 22q13 loci, and in some cases specific genes, associated with singular clinical features observed in Phelan-McDermid syndrome. Our statistical approach may be useful in genotype-phenotype analyses for other microdeletion or microduplication syndromes. C1 [Sarasua, Sara M.; Dwivedi, Alka; Boccuto, Luigi; Chen, Chin-Fu; Collins, Julianne S.; Rogers, R. Curtis; DuPont, Barbara R.] Greenwood Genet Ctr, Greenwood, SC 29646 USA. Clemson Univ, Dept Math Sci, Clemson, SC USA. [Sharp, Julia L.; Rollins, Jonathan D.] Med Univ S Carolina, Charleston, SC 29425 USA. [Phelan, Katy] Tulane Univ, Sch Med, Hayward Genet Ctr, New Orleans, LA 70112 USA. RP Sarasua, SM (reprint author), Greenwood Genet Ctr, Greenwood, SC 29646 USA. EM ssarasua@ggc.org FU Phelan-McDermid Syndrome Foundation; Genetics Endowment of South Carolina; South Carolina Department of Disabilities and Special Needs FX We thank the patients and family members who participated in this study and made this work possible. We thank the Phelan-McDermid Syndrome Foundation which organized the biannual family conferences where much of the study data collection took place. We thank Amy Lawton-Rauh and Charles E. Schwartz for helpful comments on the manuscript. We thank Gail Stapleton and Cindy Skinner who coordinated study operations. We dedicate this article to the late J.S.C. This work was supported by the Phelan-McDermid Syndrome Foundation (to S.M.S.); the Genetics Endowment of South Carolina; and the South Carolina Department of Disabilities and Special Needs. 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Med. PD APR PY 2014 VL 16 IS 4 BP 318 EP 328 DI 10.1038/gim.2013.144 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AE2BZ UT WOS:000333779600006 PM 24136618 ER PT J AU Bauminger-Zviely, N Karin, E Kimhi, Y Agam-Ben-Artzi, G AF Bauminger-Zviely, Nirit Karin, Eynat Kimhi, Yael Agam-Ben-Artzi, Galit TI Spontaneous peer conversation in preschoolers with high- functioning autism spectrum disorder versus typical development SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE High-functioning children with autism spectrum disorder (ASD); preschool; friendship; pragmatics; social conversation ID SOCIAL COMMUNICATION; LANGUAGE IMPAIRMENT; ASPERGER-SYNDROME; CHILDREN; FRIENDSHIP; PARENTS; SCALE; TALK AB BackgroundIn typical development, early peer talk is crucial for pragmatic development. The pragmatic deficit, reflected in remarkably deficient conversational capabilities, is considered the hallmark of the language deficit in autism spectrum disorder (ASD); yet, spontaneous peer talk in preschoolers with ASD was rarely explored. MethodWe conducted comparative assessment of spontaneous peer talk during 10-min free-play scenarios in preschoolers with high-functioning ASD (HFASD; n=27) versus those with typical development (n=30). Groups were matched on SES, verbal/nonverbal MA, IQ, and CA. Correlations with CA, IQ, VMA, and NVMA were examined. We compared the two groups' interactions with a friend-partner versus a nonfriend partner; in addition, in the HFASD group, we examined interactions with a typical partner (mixed dyads) versus a partner with HFASD (nonmixed dyads). Children's conversations were videotaped and coded to tap pragmatic capabilities and conversational quality. ResultsFindings revealed group differences in pragmatic abilities and conversational quality, with the typical group showing more intact capacities than the HFASD group. However, in the HFASD group, interactions with friends surpassed interactions with nonfriends on several key pragmatic capabilities and on all conversational quality measures (meshing, assertiveness, and responsiveness), thus suggesting that friendship may enable children to converse in a more socially complex and coregulated way. Also, children with higher cognitive capabilities, especially in the HFASD group, demonstrated more intact pragmatic capacities. ConclusionDespite the robust pragmatic deficit in HFASD, reflected in conversational capabilities, involvement in friendship relationships and high cognitive capabilities were linked to more intact pragmatic capacities. Theoretical and therapeutic implications are discussed. C1 [Bauminger-Zviely, Nirit; Karin, Eynat; Kimhi, Yael; Agam-Ben-Artzi, Galit] Bar Ilan Univ, Sch Educ, IL-52900 Ramat Gan, Israel. RP Bauminger-Zviely, N (reprint author), Bar Ilan Univ, Sch Educ, IL-52900 Ramat Gan, Israel. EM nirit.bauminger@biu.ac.il FU Israel Science Foundation FX This research was partially supported by the Israel Science Foundation through grant given to the first author. Special thanks are extended to the children who took part in this study. The authors would like to express their appreciation to Dee B. Ankonina for her editorial contribution and to Dov Har-Even for his statistical assistance. CR Adams C, 2002, J CHILD PSYCHOL PSYC, V43, P679, DOI 10.1111/1469-7610.00056 Adams C, 2002, J CHILD PSYCHOL PSYC, V43, P973, DOI 10.1111/1469-7610.00226 American Psychiatric Association, 2000, DIAGN STAT MAN MENT American Psychiatric Association, 2013, DIAGN STAT MAN MENT Bauminger N, 2008, J AUTISM DEV DISORD, V38, P1211, DOI 10.1007/s10803-007-0501-2 Bauminger-Zviely N., 2013, FRIENDSHIPS YO UNPUB Bauminger-Zviely N., 2013, SOCIAL ACAD ABILITIE Blum-Kulka S, 2004, DISCOURSE STUD, V6, P291, DOI 10.1177/1461445604044290 Blum-Kulka S, 2004, DISCOURSE STUD, V6, P307, DOI 10.1177/1461445604044291 Clark H. H., 2008, HDB PRAGMATICS, P365 de Villiers J, 2007, J AUTISM DEV DISORD, V37, P1375, DOI 10.1007/s10803-006-0264-1 Dunn J, 1999, SOC DEV, V8, P201, DOI 10.1111/1467-9507.00091 Garvey C., 1984, CHILDRENS TALK Hermelin B, 1985, COMMUNICATION PROBLE, P283 Howes C., 1996, CO THEY KEEP FRIENDS, P66 Hoyle S. 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Child Psychol. Psychiatry PD APR PY 2014 VL 55 IS 4 BP 363 EP 373 DI 10.1111/jcpp.12158 PG 11 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AD4JU UT WOS:000333218100009 PM 24304222 ER PT J AU Kenworthy, L Anthony, LG Naiman, DQ Cannon, L Wills, MC Caroline, LT Werner, MA Alexander, KC Strang, J Bal, E Sokoloff, JL Wallace, GL AF Kenworthy, Lauren Anthony, Laura Gutermuth Naiman, Daniel Q. Cannon, Lynn Wills, Meagan C. Caroline Luong-Tran Werner, Monica Adler Alexander, Katie C. Strang, John Bal, Elgiz Sokoloff, Jennifer L. Wallace, Gregory L. TI Randomized controlled effectiveness trial of executive function intervention for children on the autism spectrum SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Autism; executive function; RRBI; intervention; CBT ID YOUNG-CHILDREN; BEHAVIORAL SUPPORTS; SOCIAL-INTERACTION; ASPERGERS-SYNDROME; BRAIN-INJURY; REAL-WORLD; DISORDERS; ADOLESCENTS; ADULTS; MIND AB BackgroundUnstuck and On Target (UOT) is an executive function (EF) intervention for children with autism spectrum disorders (ASD) targeting insistence on sameness, flexibility, goal-setting, and planning through a cognitive-behavioral program of self-regulatory scripts, guided/faded practice, and visual/verbal cueing. UOT is contextually-based because it is implemented in school and at home, the contexts in which a child uses EF skills. MethodsTo evaluate the effectiveness of UOT compared with a social skills intervention (SS), 3rd-5th graders with ASD (mean IQ=108; UOT n=47; SS n=20) received interventions delivered by school staff in small group sessions. Students were matched for gender, age, race, IQ, ASD symptomotolgy, medication status, and parents' education. Interventions were matched for dose' of intervention and training. Measures of pre-post change included classroom observations, parent/teacher report, and direct child measures of problem-solving, EF, and social skills. Schools were randomized and evaluators, but not parents or teachers, were blinded to intervention type. ResultsInterventions were administered with high fidelity. Children in both groups improved with intervention, but mean change scores from pre- to postintervention indicated significantly greater improvements for UOT than SS groups in: problem-solving, flexibility, and planning/organizing. Also, classroom observations revealed that participants in UOT made greater improvements than SS participants in their ability to follow rules, make transitions, and be flexible. Children in both groups made equivalent improvements in social skills. ConclusionsThese data support the effectiveness of the first contextually-based EF intervention for children with ASD. UOT improved classroom behavior, flexibility, and problem-solving in children with ASD. Individuals with variable background/training in ASD successfully implemented UOT in mainstream educational settings. C1 [Kenworthy, Lauren; Anthony, Laura Gutermuth; Wills, Meagan C.; Caroline Luong-Tran; Strang, John; Bal, Elgiz; Sokoloff, Jennifer L.] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD USA. [Kenworthy, Lauren; Anthony, Laura Gutermuth; Strang, John] George Washington Univ, Sch Med, Washington, DC USA. [Naiman, Daniel Q.] Johns Hopkins Univ, Dept Appl Math & Stat, Baltimore, MD USA. [Cannon, Lynn; Werner, Monica Adler; Alexander, Katie C.] Ivymount Sch, Rockville, MD USA. [Wallace, Gregory L.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Anthony, LG (reprint author), 15245 Shady Grove Rd,Suite 350, Rockville, MD 20850 USA. EM lkenwort@cnmc.org; lanthony@cnmc.org RI Strang, John/H-5460-2011 OI Strang, John/0000-0002-5413-2725 FU National Institute of Mental Health (NIMH) [R34MH083053]; Organization for Autism Research; Isadore and Bertha Gudelsky Family Foundation; NIH, NIMH FX This project was supported by Grant Number R34MH083053 from the National Institute of Mental Health (NIMH), the Organization for Autism Research, and the Isadore and Bertha Gudelsky Family Foundation. G. L. W. was supported by the Intramural Research Program of the NIH, NIMH. L. K. receives financial compensation for use of the BRIEF. L. C., L. K., K. A., M. A. W. and L. G. A. receive financial compensation for the use of Unstuck and On Target manuals. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NIH or the other funders. The authors thank the children, families, and schools who participated (Archdiocese of Washington and Fairfax County). The authors also thank their many advisors, especially Connie Kasari, UCLA. The study's statistical expert is Daniel Naiman. CR Akshoomoff N, 2005, DEV NEUROPSYCHOL, V27, P307, DOI 10.1207/s15326942dn2703_1 American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th Baker J. 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PD APR PY 2014 VL 53 IS 4 BP 392 EP 394 DI 10.1016/j.jaac.2014.01.011 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AE1YK UT WOS:000333770200003 PM 24655647 ER PT J AU Ozonoff, S Young, GS Belding, A Hill, M Hill, A Hutman, T Johnson, S Miller, M Rogers, SJ Schwichtenberg, AJ Steinfeld, M Iosif, AM AF Ozonoff, Sally Young, Gregory S. Belding, Ashleigh Hill, Monique Hill, Alesha Hutman, Ted Johnson, Scott Miller, Meghan Rogers, Sally J. Schwichtenberg, A. J. Steinfeld, Marybeth Iosif, Ana-Maria TI The Broader Autism Phenotype in Infancy: When Does It Emerge? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autism spectrum disorder; broader autism phenotype; siblings; social-communication; infancy ID SPECTRUM DISORDERS; HIGH-RISK; CHILDREN; SIBLINGS; COMMUNICATION; TEMPERAMENT; ENGAGEMENT; PRECURSORS; RELATIVES; COGNITION AB Objective: This study had 3 goals, which were to examine the following: the frequency of atypical development, consistent with the broader autism phenotype, in high-risk infant siblings of children with autism spectrum disorder (ASD); the age at which atypical development is first evident; and which developmental domains are affected. Method: A prospective longitudinal design was used to compare 294 high-risk infants and 116 low-risk infants. Participants were tested at 6, 12, 18, 24, and 36 months of age. At the final visit, outcome was classified as ASD, Typical Development (I'll), or Non-TD (defined as elevated Autism Diagnostic Observation Schedule [ADOS] score, low Mullen Scale scores, or both). Results: Of the high-risk group, 28% were classified as Non-TD at 36 months of age. Growth curve models demonstrated that the Non-TD group could not be distinguished from the other groups at 6 months of age, but differed significantly from the Low-Risk TD group by 12 months on multiple measures. The Non-TD group demonstrated atypical development in cognitive, motor, language, and social domains, with differences particularly prominent in the social-communication domain. Conclusions: These results demonstrate that features of atypical development, consistent with the broader autism phenotype, are detectable by the first birthday and affect development in multiple domains. This highlights the necessity for dose developmental surveillance of infant siblings of children with ASD, along with implementation of appropriate interventions as needed. C1 [Ozonoff, Sally; Young, Gregory S.; Belding, Ashleigh; Hill, Monique; Hill, Alesha; Miller, Meghan; Rogers, Sally J.; Steinfeld, Marybeth; Iosif, Ana-Maria] Univ Calif Davis, Davis, CA USA. [Hutman, Ted; Johnson, Scott] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Schwichtenberg, A. J.] Purdue Univ, W Lafayette, IN 47907 USA. RP Ozonoff, S (reprint author), Univ Calif Davis Hlth Syst, MIND Inst, 2825 50th St, Sacramento, CA 95817 USA. EM sally.ozonoff@ucdmc.ucdavis.edu FU National Institute of Mental Health [RO1 MH0638398 (SO.), U54 MH068172] FX This study was supported by the National Institute of Mental Health grants, RO1 MH0638398 (SO.) and U54 MH068172 (Marian Sigman, PhD [deceased]). 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Psychiatr. PD APR PY 2014 VL 19 IS 4 BP 410 EP 416 DI 10.1038/mp.2013.196 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AD6ZB UT WOS:000333409100006 PM 24468823 ER PT J AU Iafrati, J Orejarena, MJ Lassalle, O Bouamrane, L Chavis, P AF Iafrati, J. Orejarena, M. J. Lassalle, O. Bouamrane, L. Chavis, P. TI Reelin, an extracellular matrix protein linked to early onset psychiatric diseases, drives postnatal development of the prefrontal cortex via GluN2B-NMDARs and the mTOR pathway SO MOLECULAR PSYCHIATRY LA English DT Article DE early onset psychiatric diseases; fear memory; ketamine; prefrontal cortex; reelin; synaptic plasticity ID LONG-TERM DEPRESSION; HIPPOCAMPAL SYNAPTIC PLASTICITY; NR2B-CONTAINING NMDA RECEPTORS; DENDRITIC SPINE DENSITY; BEHAVIORAL-PHENOTYPE; CORTICAL DEVELOPMENT; FEAR MEMORY; IN-VITRO; SCHIZOPHRENIA; MOUSE AB Defective brain extracellular matrix (ECM) is a factor of vulnerability in various psychiatric diseases such as schizophrenia, depression and autism. The glycoprotein reelin is an essential building block of the brain ECM that modulates neuronal development and participates to the functions of adult central synapses. The reelin gene ( RELN) is a strong candidate in psychiatric diseases of early onset, but its synaptic and behavioral functions in juvenile brain circuits remain unresolved. Here, we found that in juvenile reelin-haploinsufficient heterozygous reeler mice (HRM), abnormal fear memory erasure is concomitant to reduced dendritic spine density and anomalous long-term potentiation in the prefrontal cortex. In juvenile HRM, a single in vivo injection with ketamine or Ro25-6981 to inhibit GluN2B-N-methyl-D-aspartate receptors (NMDARs) restored normal spine density, synaptic plasticity and converted fear memory to an erasure-resilient state typical of adult rodents. The functional and behavioral rescue by ketamine was prevented by rapamycin, an inhibitor of the mammalian target of rapamycin pathway. Finally, we show that fear memory erasure persists until adolescence in HRM and that a single exposure to ketamine during the juvenile period reinstates normal fear memory in adolescent mice. Our results show that reelin is essential for successful structural, functional and behavioral development of juvenile prefrontal circuits and that this developmental period provides a critical window for therapeutic rehabilitation with GluN2B-NMDAR antagonists. C1 [Iafrati, J.; Orejarena, M. J.; Lassalle, O.; Bouamrane, L.; Chavis, P.] INSERM, UMR 901, Marseille, France. [Iafrati, J.; Orejarena, M. J.; Lassalle, O.; Bouamrane, L.; Chavis, P.] Aix Marseille Univ, Unite Mixte Rech 901, Marseille, France. [Iafrati, J.; Orejarena, M. J.; Lassalle, O.; Bouamrane, L.; Chavis, P.] INMED, Marseille, France. RP Chavis, P (reprint author), INSERM, INMED, U901, Parc Sci Luminy BP 13,163 Ave Luminy, F-13273 Marseille, France. EM pascale.chavis@inserm.fr FU INSERM; French Ministere de la Recherche (MENRT); JMO; Fondation pour la Recherche Medicale FX Work in Dr P Chavis laboratory was supported by INSERM. JI and LB were supported by the French Ministere de la Recherche (MENRT) and JMO by Fondation pour la Recherche Medicale. We thank the National Institute of Mental Health's Chemical Synthesis and Drug Supply Program for providing DNQX. We thank Dr O. Manzoni for helpful discussions and critical reading of the manuscript, Dr H Martin for critical reading of the manuscript, all members of the Chavis laboratory for stimulating discussions, Dr C Herry for helpful discussions on fear conditioning and R Martinez for his expert technical help during the installation of our laboratory. 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Although the aetiology of ASD has a strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating a role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant MZ twin pairs provide an ideal model for examining the contribution of environmentally driven epigenetic factors in disease. We performed a genome-wide analysis of DNA methylation in a sample of 50 MZ twin pairs (100 individuals) sampled from a representative population cohort that included twins discordant and concordant for ASD, ASD-associated traits and no autistic phenotype. Within-twin and between-group analyses identified numerous differentially methylated regions associated with ASD. In addition, we report significant correlations between DNA methylation and quantitatively measured autistic trait scores across our sample cohort. 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EM jonathan.mill@kcl.ac.uk RI Wong, Chloe/B-3679-2012; Ronald, Angelica/C-7812-2009; Jeffries, Aaron/D-1256-2014; Price, Thomas/B-7372-2008; Schalkwyk, Leonard/A-2150-2010; Mill, Jonathan/B-3276-2010 OI Wong, Chloe/0000-0003-4886-8506; Ronald, Angelica/0000-0002-9576-2176; Jeffries, Aaron/0000-0002-1235-8291; Price, Thomas/0000-0001-7356-2109; Schalkwyk, Leonard/0000-0001-7030-5756; Mill, Jonathan/0000-0003-1115-3224 FU Autism Speaks Grant [4743]; UK Medical Research Council (MRC) [G0901245, G0500079]; US National Institutes of Health [HD044454, HD046167]; National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award; St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust; MRC Research Professorship award [G19/2]; European Advanced Investigator Award [295366]; UK MRC; NARSAD Young Investigator Award FX This work was supported, in part, by the Autism Speaks Grant 4743 (RP, Principal Investigator). The twins were selected from the Twins Early Development Study which has been funded continuously since 1995 by a UK Medical Research Council (MRC) program grant to RP (G0901245, and previously G0500079), with additional support from the US National Institutes of Health (HD044454; HD046167). We acknowledge the use of BRC Core Facilities provided by the financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. RP is supported by an MRC Research Professorship award (G19/2) and a European Advanced Investigator Award (295366). CCYW was a PhD student who was funded by the UK MRC. JM was supported by an NARSAD Young Investigator Award. 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Psychiatr. PD APR PY 2014 VL 19 IS 4 BP 495 EP 503 DI 10.1038/mp.2013.41 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AD6ZB UT WOS:000333409100016 PM 23608919 ER PT J AU Skafidas, E Testa, R Zantomio, D Chana, G Everall, IP Pantelis, C AF Skafidas, E. Testa, R. Zantomio, D. Chana, G. Everall, I. P. Pantelis, C. TI Predicting the diagnosis of autism spectrum disorder using gene pathway analysis SO MOLECULAR PSYCHIATRY LA English DT Article DE autistic disorder/diagnosis; classification; childhood development disorders; predictive testing ID COPY NUMBER VARIATION; SUSCEPTIBILITY LOCI; ASSOCIATION; ACTIVATION; LINKAGE; ABNORMALITIES; EXPRESSION; GENOME; NEUROINFLAMMATION; INDIVIDUALS AB Autism spectrum disorder (ASD) depends on a clinical interview with no biomarkers to aid diagnosis. The current investigation interrogated single-nucleotide polymorphisms (SNPs) of individuals with ASD from the Autism Genetic Resource Exchange (AGRE) database. SNPs were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived pathways to identify affected cellular processes and develop a diagnostic test. This test was then applied to two independent samples from the Simons Foundation Autism Research Initiative (SFARI) and Wellcome Trust 1958 normal birth cohort (WTBC) for validation. Using AGRE SNP data from a Central European (CEU) cohort, we created a genetic diagnostic classifier consisting of 237 SNPs in 146 genes that correctly predicted ASD diagnosis in 85.6% of CEU cases. This classifier also predicted 84.3% of cases in an ethnically related Tuscan cohort; however, prediction was less accurate (56.4%) in a genetically dissimilar Han Chinese cohort (HAN). Eight SNPs in three genes (KCNMB4, GNAO1, GRM5) had the largest effect in the classifier with some acting as vulnerability SNPs, whereas others were protective. Prediction accuracy diminished as the number of SNPs analyzed in the model was decreased. Our diagnostic classifier correctly predicted ASD diagnosis with an accuracy of 71.7% in CEU individuals from the SFARI (ASD) and WTBC (controls) validation data sets. In conclusion, we have developed an accurate diagnostic test for a genetically homogeneous group to aid in early detection of ASD. While SNPs differ across ethnic groups, our pathway approach identified cellular processes common to ASD across ethnicities. Our results have wide implications for detection, intervention and prevention of ASD. C1 [Skafidas, E.] Univ Melbourne, Ctr Neural Engn, Parkville, Vic 3052, Australia. [Testa, R.; Pantelis, C.] Univ Melbourne, Dept Psychiat, Melbourne Neuropsychiat Ctr, Parkville, Vic 3052, Australia. [Testa, R.; Pantelis, C.] Melbourne Hlth, Melbourne, Vic, Australia. [Testa, R.] Monash Univ, Dept Psychol, Clayton, Vic 3168, Australia. [Zantomio, D.] Austin Hlth, Dept Haematol, Heidelberg, Vic, Australia. [Chana, G.; Everall, I. P.; Pantelis, C.] Univ Melbourne, Dept Psychiat, Parkville, Vic 3052, Australia. RP Pantelis, C (reprint author), NNF, Level 3,161 Barry St, Carlton, Vic 3053, Australia. EM cpant@unimelb.edu.au FU NHMRC Senior Principal Research Fellowship [628386]; National Institute of Mental Health [1U24MH081810]; Medical Research Council [G1234567]; Wellcome Trust [012345] FX Professor Christos Pantelis was supported by a NHMRC Senior Principal Research Fellowship (ID 628386). AGRE: 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). SFARI: We are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A Beaudet, R Bernier, J Constantino, E Cook, E Fombonne, D Geschwind, R Goin-Kochel, E Hanson, D Grice, A Klin, D Ledbetter, C Lord, C Martin, D Martin, R Maxim, J Miles, O Ousley, K Pelphrey, B Peterson, J Piggot, C Saulnier, M State, W Stone, J Sutcliffe, C Walsh, Z Warren, E Wijsman). WTBC: We acknowledge use of the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G1234567 and the Wellcome Trust grant 012345. 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Rev. Neurosci. PD APR PY 2014 VL 15 IS 4 BP 217 EP 232 DI 10.1038/nrn3707 PG 16 WC Neurosciences SC Neurosciences & Neurology GA AD4YB UT WOS:000333256600009 PM 24646670 ER PT J AU Huang, HP Michetti, C Busnelli, M Manago, F Sannino, S Scheggia, D Giancardo, L Sona, D Murino, V Chini, B Scattoni, ML Papaleo, F AF Huang, Huiping Michetti, Caterina Busnelli, Marta Manago, Francesca Sannino, Sara Scheggia, Diego Giancardo, Luca Sona, Diego Murino, Vittorio Chini, Bice Scattoni, Maria Luisa Papaleo, Francesco TI Chronic and Acute Intranasal Oxytocin Produce Divergent Social Effects in Mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE behavior; oxytocin receptors; social interaction; intranasal treatment; schizophrenia; autism ID AUTISM SPECTRUM DISORDERS; PREPULSE INHIBITION; RECOGNITION MEMORY; NEURAL CIRCUITRY; GENE-EXPRESSION; BRAIN OXYTOCIN; KNOCKOUT MOUSE; VASOPRESSIN; RECEPTOR; RATS AB Intranasal administration of oxytocin (OXT) might be a promising new adjunctive therapy for mental disorders characterized by social behavioral alterations such as autism and schizophrenia. Despite promising initial studies in humans, it is not yet clear the specificity of the behavioral effects induced by chronic intranasal OXT and if chronic intranasal OXT could have different effects compared with single administration. This is critical for the aforementioned chronic mental disorders that might potentially involve life-long treatments. As a first step to address these issues, here we report that chronic intranasal OXT treatment in wild-type C57BL/6J adult mice produced a selective reduction of social behaviors concomitant to a reduction of the OXT receptors throughout the brain. Conversely, acute intranasal OXT treatment produced partial increases in social behaviors towards opposite-sex novel-stimulus female mice, while on the other hand, it decreased social exploration of same-sex novel stimulus male mice, without affecting social behavior towards familiar stimulus male mice. Finally, prolonged exposure to intranasal OXT treatments did not alter, in wild-type animals, parameters of general health such as body weight, locomotor activity, olfactory and auditory functions, nor parameters of memory and sensorimotor gating abilities. These results indicate that a prolonged over-stimulation of a 'healthy' oxytocinergic brain system, with no inherent deficits in social interaction and normal endogenous levels of OXT, results in specific detrimental effects in social behaviors. C1 [Huang, Huiping; Manago, Francesca; Sannino, Sara; Scheggia, Diego; Papaleo, Francesco] Ist Italian Tecnol, Dept Neurosci & Brain Technol, Genoa, Italy. [Michetti, Caterina] Univ Roma La Sapienza, Dept Physiol & Pharmacol, I-00185 Rome, Italy. [Michetti, Caterina; Scattoni, Maria Luisa] Ist Super Sanita, Dept Cell Biol & Neurosci, Behav Neurosci Sect, I-00161 Rome, Italy. [Busnelli, Marta] Univ Milan, Dipartimento Biotecnol Med & Med Traslaz, Milan, Italy. [Busnelli, Marta; Chini, Bice] CNR, Inst Neurosci, I-20133 Milan, Italy. [Giancardo, Luca; Sona, Diego; Murino, Vittorio] Ist Italian Tecnol, Genoa, Italy. [Papaleo, Francesco] Univ Padua, Dipartimento Sci Farmaco, Padua, Italy. RP Papaleo, F (reprint author), Ist Italian Tecnol, Dept Neurosci & Brain Technol, Genoa, Italy. EM francesco.papaleo@iit.it FU Istituto Italiano di Tecnologia; Marie Curie FP7-Reintegration [268247]; Italian Ministry of Health [GR3, GR-2010-2315883]; Telethon Foundation Grant [GGP12207] FX This research was supported by the Istituto Italiano di Tecnologia, the Marie Curie FP7-Reintegration-Grant No 268247, the Italian Ministry of Health Grants (GR3)-Young Researcher 2008 and GR-2010-2315883, and the Telethon Foundation Grant (GGP12207). The authors declare no conflict of interest. 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Roman, Francois S. Beaulieu, Jean-Martin TI Stimulation of 5-HT2C Receptors Improves Cognitive Deficits Induced by Human Tryptophan Hydroxylase 2 Loss of Function Mutation SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cognitive flexibility; H-maze; perseveration; R439H-Tph2-KI mouse; reversal learning; 5-HT2C receptor ID DELAYED-RESPONSE TASKS; SEROTONIN DEFICIENCY; ANTIPSYCHOTIC ACTIVITY; PSYCHIATRIC-DISORDERS; VENTRAL HIPPOCAMPUS; ANXIETY DISORDERS; NEONATAL LESIONS; RATS; MICE; DEPRESSION AB Polymorphisms in the gene encoding the serotonin synthesis enzyme Tph2 have been identified in mental illnesses, including bipolar disorder, major depression, autism, schizophrenia, and ADHD. Deficits in cognitive flexibility and perseverative behaviors are shared common symptoms in these disorders. However, little is known about the impact of Tph2 gene variants on cognition. Mice expressing a human TPH2 variant (Tph2-KI) were used to investigate cognitive consequences of TPH2 loss of function and pharmacological treatments. We applied a recently developed behavioral assay, the automated H-maze, to study cognitive functions in Tph2-KI mice. This assay involves the consecutive discovery of three different rules: a delayed alternation task, a non-alternation task, and a delayed reversal task. Possible contribution of locomotion, reward, and sensory perception were also investigated. The expression of loss-of-function mutant Tph2 in mice was associated with impairments in reversal learning and cognitive flexibility, accompanied by perseverative behaviors similar to those observed in human clinical studies. Pharmacological restoration of 5-HT synthesis with 5-hydroxytryptophan or treatment with the 5-HT2C receptor agonist CP809.101 reduced cognitive deficits in Tph2-KI mice and abolished perseveration. In contrast, treatment with the psychostimulant methylphenidate exacerbated cognitive deficits in mutant mice. Results from this study suggest a contribution of TPH2 in the regulation of cognition. Furthermore, identification of a role for a 5-HT2 receptor agonist as a cognition-enhancing agent in mutant mice suggests a potential avenue to explore for the personalized treatment of cognitive symptoms in humans with reduced 5-HT synthesis and TPH2 polymorphisms. C1 [Del'Guidice, Thomas; Lemasson, Morgane; Manta, Stella; Etievant, Adeline; Beaulieu, Jean-Martin] Univ Laval Pavil Ferdinand Vandry, Dept Psychiat & Neurosci, Fac Med, Quebec City, PQ G1J 2G3, Canada. [Del'Guidice, Thomas; Lemay, Francis; Lemasson, Morgane; Levasseur-Moreau, Jean; Manta, Stella; Etievant, Adeline; Beaulieu, Jean-Martin] Inst Univ Sante Mentale Quebec, Quebec City, PQ, Canada. [Lemay, Francis; Dore, Francois Y.] Univ Laval Pavil FA Savard, Fac Sci Sociales, Ecole Psychol, Quebec City, PQ, Canada. [Escoffier, Guy; Roman, Francois S.] Aix Marseille Univ, CNRS, Ctr St Charles, NICN Neurobiol Proc Mnes UMR7259, Marseille, France. RP Beaulieu, JM (reprint author), Univ Laval Pavil Ferdinand Vandry, Dept Psychiat & Neurosci, Fac Med, 2601 Chemin Canardiere,Suite F-6500, Quebec City, PQ G1J 2G3, Canada. EM martin.beaulieu@crulrg.ulaval.ca FU CRCN; Natural Sciences and Engineering Research Council of Canada (NSERC); Canadian Institute of Health Research (CIHR) [NSA 93798]; NSERC discovery grant; FRSQ project for innovative strategic development FX We thank N Bouchard and K Aube for assistance maintaining mice colonies, and Hugues Dufour for assembling the H-Maze. TD is recipient of fellowships from the CRCN. FL is supported by a scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC). JMB is NARSAD Vital Projects Fund. investigator and Canada research Chair in Molecular Psychiatry. This work was supported by a Canadian Institute of Health Research (CIHR) operating grant (NSA 93798) to JMB, a NSERC discovery grant to FYD and a FRSQ project for innovative strategic development. 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[Coulon, Philippe; Pape, Hans-Christian] Univ Munster, Inst Physiol 1, D-48149 Munster, Germany. [Kiefer, Friedemann] Max Planck Inst Mol Biomed, Mammalian Cell Signalling Lab, D-48149 Munster, Germany. [Heine, Martin] Leibniz Inst Neurobiol, Mol Physiol Grp, D-39118 Magdeburg, Germany. RP Missler, M (reprint author), Univ Munster, Inst Anat & Mol Neurobiol, D-48149 Munster, Germany. EM markus.missler@uni-muenster.de FU Deutsche Forschungsgemeinschaft [SFB 629-TPB11, SFB/TRR58-TPA03]; Cells-in-Motion Cluster of Excellence [EXC 1003]; Interdisziplinares Zentrum fur Klinische Forschung Monster Mi [3/025/08]; Graduate School Cell Dynamics and Disease FX We thank G. Szabo (KOKI) for the kind gift of GAD65_GFP mice, K. Kerkhoff and D. Aschhoff for excellent technical assistance, K. Piechotta for help with molecular cloning during early stages of the project, and members of our laboratories for discussion. This work was supported by Deutsche Forschungsgemeinschaft Grant SFB 629-TPB11 (to M. M.) and Grant SFB/TRR58-TPA03 (to H.-C. P.), Cells-in-Motion Cluster of Excellence (EXC 1003 to M. M., H.-C. P., and F. K.), and the Interdisziplinares Zentrum fur Klinische Forschung Monster Mi 3/025/08 (to M. M.). S. W. is recipient of a fellowship by the Graduate School Cell Dynamics and Disease. 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Natl. Acad. Sci. U. S. A. PD APR 1 PY 2014 VL 111 IS 13 BP E1274 EP E1283 DI 10.1073/pnas.1312112111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AD9IX UT WOS:000333579700019 PM 24639499 ER PT J AU Treutlein, B Gokce, O Quake, SR Sudhof, TC AF Treutlein, Barbara Gokce, Ozgun Quake, Stephen R. Suedhof, Thomas C. TI Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE schizophrenia; neuroligin; cerebellin; LRRTM; autism ID EXCITATORY SYNAPSE FORMATION; CELL-SURFACE PROTEINS; BETA-NEUREXINS; ALPHA-NEUREXINS; ADHESION; RECEPTOR; BINDING; COMPLEX; LIGAND; GENES AB Neurexins are evolutionarily conserved presynaptic cell-adhesion molecules that are essential for normal synapse formation and synaptic transmission. Indirect evidence has indicated that extensive alternative splicing of neurexin mRNAs may produce hundreds if not thousands of neurexin isoforms, but no direct evidence for such diversity has been available. Here we use unbiased long-read sequencing of full-length neurexin (Nrxn)1 alpha, Nrxn1 beta, Nrxn2 beta, Nrxn3 alpha, and Nrxn3 beta mRNAs to systematically assess how many sites of alternative splicing are used in neurexins with a significant frequency, and whether alternative splicing events at these sites are independent of each other. In sequencing more than 25,000 full-length mRNAs, we identified a novel, abundantly used alternatively spliced exon of Nrxn1 alpha and Nrxn3 alpha (referred to as alternatively spliced sequence 6) that encodes a 9-residue insertion in the flexible hinge region between the fifth LNS (laminin-alpha, neurexin, sex hormone-binding globulin) domain and the third EGF-like sequence. In addition, we observed several larger-scale events of alternative splicing that deleted multiple domains and were much less frequent than the canonical six sites of alternative splicing in neurexins. All of the six canonical events of alternative splicing appear to be independent of each other, suggesting that neurexins may exhibit an even larger isoform diversity than previously envisioned and comprise thousands of variants. Our data are consistent with the notion that alpha-neurexins represent extracellular protein-interaction scaffolds in which different LNS and EGF domains mediate distinct interactions that affect diverse functions and are independently regulated by independent events of alternative splicing. C1 [Treutlein, Barbara; Quake, Stephen R.] Stanford Univ, Dept Bioengn, Sch Med, Stanford, CA 94305 USA. [Gokce, Ozgun; Suedhof, Thomas C.] Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA. [Treutlein, Barbara; Quake, Stephen R.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA. [Quake, Stephen R.; Suedhof, Thomas C.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA. RP Quake, SR (reprint author), Stanford Univ, Dept Bioengn, Sch Med, Stanford, CA 94305 USA. EM quake@stanford.edu; tcs1@stanford.edu FU National Institute of Mental Health [R37 MH052804]; National Institute of Neurological Disorders and Stroke [R01 NS077906] FX We thank Jody Puglisi for sharing equipment. This study was supported by Grants R37 MH052804 from the National Institute of Mental Health and R01 NS077906 from the National Institute of Neurological Disorders and Stroke (to T.C.S.). 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Natl. Acad. Sci. U. S. A. PD APR 1 PY 2014 VL 111 IS 13 BP E1291 EP E1299 DI 10.1073/pnas.1403244111 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AD9IX UT WOS:000333579700021 PM 24639501 ER PT J AU Qiao, J Gao, J Shu, Q Zhang, QL Hu, G Li, M AF Qiao, Jing Gao, Jun Shu, Qing Zhang, Qinglin Hu, Gang Li, Ming TI Long-lasting sensitization induced by repeated risperidone treatment in adolescent Sprague-Dawley rats: a possible D-2 receptor mediated phenomenon? SO PSYCHOPHARMACOLOGY LA English DT Article DE Risperidone; Conditioned avoidance response; Quinpirole; 22 kHz ultrasonic vocalization; Phencyclidine; Motor activity; Prepulse inhibition; Adolescence; Sensitization ID PHENCYCLIDINE-INDUCED HYPERLOCOMOTION; AVOIDANCE-RESPONSE MODEL; ANTIPSYCHOTIC-DRUGS; ANIMAL-MODELS; AGONIST QUINPIROLE; TIME-COURSE; OLANZAPINE; CHILDREN; AMPHETAMINE; HALOPERIDOL AB Risperidone use in children and adolescents for the treatment of various neuropsychiatric disorders (e.g., schizophrenia, autism, disruptive behavior, etc.) has increased substantially in recent decades. However, its long-term effect on the brain and behavioral functions is not well understood. The present study investigated how a short-term risperidone treatment in adolescence impacts antipsychotic response in adulthood in the conditioned avoidance response and phencyclidine (PCP)-induced hyperlocomotion tests. Male adolescent Sprague-Dawley rats (postnatal days [P] 40-44 or 43-48) were first treated with risperidone (0.3, 0.5, or 1.0 mg/kg, subcutaneously (sc)) and tested in the conditioned avoidance or PCP (3.2 mg/kg, sc)-induced hyperlocomotion model daily for five consecutive days. After they became adults (similar to P 76-80), they were challenged with risperidone (0.3 mg/kg, sc) to assess their sensitivity to risperidone reexposure. A quinpirole (a D-2/3 receptor agonist, 1.0 mg/kg, sc)-induced hyperlocomotion test was later conducted to assess the risperidone-induced functional changes in D-2 receptor. In the risperidone challenge test in adulthood, adult rats previously treated with risperidone in adolescence made significantly fewer avoidance responses and exhibited significantly lower PCP-induced hyperlocomotion than those previously treated with vehicle. They also appeared to be more hyperactive than the vehicle-pretreated ones in the quinpirole-induced hyperlocomotion test. Prepulse inhibition of acoustic startle or fear-induced 22 kHz ultrasonic vocalizations in adulthood was not altered by adolescence risperidone treatment. Adolescent risperidone exposure induces a long-term increase in behavioral sensitivity to risperidone that persists into adulthood. This long-lasting change might be due to functional upregulation of D-2-mediated neurotransmission. C1 [Qiao, Jing; Zhang, Qinglin] Southwest Univ, Inst Psychol, Minist Educ, Key Lab Cognit & Personal, Chongqing, Peoples R China. [Shu, Qing; Hu, Gang] Nanjing Med Univ, Dept Pharmacol, Jiangsu Key Lab Neurodegenerat, Nanjing, Jiangsu, Peoples R China. [Qiao, Jing; Gao, Jun; Shu, Qing; Li, Ming] Univ Nebraska, Dept Psychol, Lincoln, NE 68588 USA. RP Li, M (reprint author), Univ Nebraska, Dept Psychol, 238 Burnett Hall, Lincoln, NE 68588 USA. EM mli2@unl.edu FU Key Laboratory of Cognition and Personality and Institute of Psychology at Southwest University, China; National Institute of Mental Health [R01MH085635] FX Professor Ming Li was supported by a visiting professorship grant from the Key Laboratory of Cognition and Personality and Institute of Psychology at Southwest University, China and by National Institute of Mental Health grant R01MH085635. 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Rapp, John T. Gomes, Lindsey A. Frazer, Tammy J. Lindblad, Tracie L. TI EFFECTS OF VERBAL REPRIMANDS ON TARGETED AND UNTARGETED STEREOTYPY SO BEHAVIORAL INTERVENTIONS LA English DT Article ID VOCAL STEREOTYPY; STIMULUS-CONTROL; DEVELOPMENTAL-DISABILITIES; FUNCTIONAL-ANALYSIS; PROBLEM BEHAVIOR; YOUNG-CHILDREN; AUTISM; INTERVENTION; STIMULATION; EVENTS AB Results of brief functional analyses indicated that motor and vocal stereotypy persisted in the absence of social consequences for five participants diagnosed with autism spectrum disorder (ASD). Subsequently, effects of a stimulus control procedure involving contingent reprimands for each participant's higher probability (targeted) stereotypy were evaluated. Results indicated that contingent verbal reprimands (i) decreased the targeted stereotypy for all five participants, (ii) decreased the untargeted stereotypy for two of five participants, and (iii) increased the untargeted stereotypy for one of five participants. Although response suppression was not achieved for any participant, three participants maintained low levels of the target stereotypy with one or two reprimands during 5-min sessions. Furthermore, two of those participants maintained near-zero levels of motor and vocal stereotypy during 10-min sessions. These findings suggest that signaled verbal reprimands may be a practical intervention for reducing stereotypy in some children with ASD. Some limitations of the findings and areas of future research are briefly discussed. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Cook, Jennifer L.] St Cloud State Univ, St Cloud, MN 56301 USA. [Rapp, John T.] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. [Gomes, Lindsey A.; Frazer, Tammy J.; Lindblad, Tracie L.] Four Point Intervent Strategies Inc, Mississauga, ON L5L 5Y6, Canada. RP Rapp, JT (reprint author), Auburn Univ, Dept Psychol, 226 Thach, Auburn, AL 36849 USA. 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Intervent. PD APR PY 2014 VL 29 IS 2 BP 106 EP 124 DI 10.1002/bin.1378 PG 19 WC Psychology, Clinical SC Psychology GA AE0ZE UT WOS:000333694100002 ER PT J AU King, B Radley, KC Jenson, WR Clark, E O'Neill, RE AF King, Brian Radley, Keith C. Jenson, William R. Clark, Elaine O'Neill, Robert E. TI UTILIZATION OF VIDEO MODELING COMBINED WITH SELF-MONITORING TO INCREASE RATES OF ON-TASK BEHAVIOR SO BEHAVIORAL INTERVENTIONS LA English DT Article ID CLASSROOM INTERVENTIONS; LEARNING-DISABILITIES; IN-VIVO; CHILDREN; ACCEPTABILITY; ENGAGEMENT; STUDENTS; AUTISM; ADOLESCENTS; ACHIEVEMENT AB The study investigated the effectiveness of an intervention package consisting of self-monitoring and video modeling to increase on-task behavior during independent seatwork time in math. Four students in either the second or third grade, identified as displaying high rates of off-task behavior by their classroom teacher, were included in the study. Results showed immediate, large, and durable changes in on-task behavior for each of the four participants. At baseline, on-task behavior of the participants while working on independent math assignments was displayed in 47% of the intervals observed. During the intervention, the participants' average rate of on-task behavior increased to 85% of the intervals observed. Mean Busk and Serlin (1994) effect size for all four participants was 5.60, with a percentage of non-overlapping data points effect size of 100%. Observations of the participants 3 weeks following the termination of the study showed that the gains in on-task behavior were maintained. Both teacher and participant feedbacks concerning the use and effectiveness of the intervention package were positive. Results of the investigation suggest that the intervention package may be an effective and socially valid method for addressing off-task behaviors of students within the classroom. Copyright (c) 2014 John Wiley & Sons, Ltd. 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TI A DISCRIMINATION TRAINING PROCEDURE TO ESTABLISH CONDITIONED REINFORCERS FOR CHILDREN WITH AUTISM SO BEHAVIORAL INTERVENTIONS LA English DT Article ID SECONDARY REINFORCEMENT; PREFERENCES; DISABILITIES; BEHAVIOR AB Although conditioned reinforcers are used in many behavioral intervention programs for individuals with developmental disabilities, little research has been conducted to determine optimal methods for establishing conditioned reinforcers. An early method that has received relatively little research attention is to condition a neutral stimulus as a discriminative stimulus and then use the stimulus as a programed consequence during skill acquisition. The current study evaluated the effects of a discrimination training procedure on establishing conditioned reinforcers for three children with autism. For all participants, previously neutral stimuli reinforced behaviors after acquiring discriminative properties during discrimination training. 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Intervent. PD APR PY 2014 VL 29 IS 2 BP 157 EP 176 DI 10.1002/bin.1384 PG 20 WC Psychology, Clinical SC Psychology GA AE0ZE UT WOS:000333694100005 ER PT J AU Kappil, M Chen, J AF Kappil, Maya Chen, Jia TI Environmental exposures in utero and microRNA SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE endogenous exposures; in-utero exposures; miRNA; nutrition; xenochemicals ID TRANSMEMBRANE CONDUCTANCE REGULATOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; CONGENITAL HEART-DISEASE; ETHANOL EXPOSURE; CHINESE POPULATION; EXPRESSION PROFILE; MIRNA EXPRESSION; RNA-INTERFERENCE; EPITHELIAL-CELLS; AUTISM SPECTRUM AB Purpose of reviewUnderstanding the effects of in-utero exposures to environmental agents is of great importance as the resulting deregulation of biological processes can affect both fetal development and health outcomes that manifest later in life. Due to their established role in developmental processes and inherent stability ex vivo, microRNAs (miRNAs) have emerged as attractive candidates to explore the impact of such exposures during this critical window of susceptibility. In this review, we summarize the findings of studies assessing miRNAs as markers of in-utero environmental exposures and as candidates for the molecular basis through which these exposures exert their influence on children's health.Recent findingsTo date, miRNA expression profiles due to various in-utero environmental exposures, including xenochemicals, endogenous factors, and nutritional status, have been reported.SummaryWhile the validity of the identified exposure-specific miRNA profiles remains to be established, the findings thus far do raise interesting questions worth addressing in future studies. Gaps that remain to be addressed include linking specific in-utero exposures to subsequent health outcomes based on established miRNA expression profiles and experimentally validating putative downstream targets of the deregulated miRNAs. C1 [Kappil, Maya; Chen, Jia] Mt Sinai Sch Med, Dept Prevent Med, New York, NY 10029 USA. [Chen, Jia] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. [Chen, Jia] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Chen, Jia] Mt Sinai Sch Med, Dept Med Hematol & Med Oncol, New York, NY 10029 USA. RP Chen, J (reprint author), Mt Sinai Sch Med, Dept Prevent Med, 1468 Madison Ave, New York, NY 10029 USA. EM jia.chen@mssm.edu FU National Institutes of Health [R01 CA172460, R01HD067611/R01ES022223-01A1, U01 ES019451]; Mount Sinai Children's Environmental Health Center Pilot Fund FX This work was supported by grants from the National Institutes of Health (R01 CA172460, R01HD067611/R01ES022223-01A1, U01 ES019451) and Mount Sinai Children's Environmental Health Center Pilot Fund. 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Kurtz, Marie Panchik, Ann Pitterle, Kathleen TI 'Look at me when I am talking to you': evidence and assessment of social pragmatics interventions for children with autism and social communication disorders SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE alternative augmentative communication; autism; social skills groups; social stories; video modeling ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; MIDDLE SCHOOL; STUDENTS; SKILLS; VIDEO; IMPLEMENTATION; PRESCHOOLERS; DISABILITIES; CLASSROOM AB Purpose of reviewThis article provides an analysis of the effectiveness of commonly used interventions for social pragmatic interventions for children with autism spectrum disorder (ASD) and social communication disorders.Recent findingsSeveral evidence-based social skills interventions are emerging, including peer mentoring, social skills groups, and video modeling. Social stories are effective as supports for improved interactions but generalization is limited. Research supports the need for multimodality and individualized treatment programs. Research validates that video and visual learning is highly effective with children with ASD when utilized with specific, appropriate targets. Multiple studies have shown that picture-based communication systems are effective at improving functional communication with moderate effects on social communication. Despite limitations in research, there is strong evidence in the existing literature for the role of alternative augmentative communication in improving both functional and social communication.SummarySocial pragmatic interventions when individualized are effective for improving language, adaptive behavior and social skills. C1 [Tierney, Cheryl D.] Penn State Hershey Childrens Hosp, Div Pediat Rehabil & Dev, Hershey, PA 17033 USA. [Kurtz, Marie; Pitterle, Kathleen] Penn State Hershey Childrens Hosp, Hershey, PA 17033 USA. [Panchik, Ann] Lower Dauphin Sch Dist, South Hanover Elementary Sch, Hummelstown, PA USA. RP Tierney, CD (reprint author), Penn State Hershey Childrens Hosp, Sect Chief Behav & Dev Pediat, Div Pediat Rehabil & Dev, 500 Univ Dr,H085, Hershey, PA 17033 USA. 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J., 2003, PEER PLAY AUTISM SPE NR 38 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 EI 1531-698X J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD APR PY 2014 VL 26 IS 2 BP 259 EP 264 DI 10.1097/MOP.0000000000000075 PG 6 WC Pediatrics SC Pediatrics GA AD5JT UT WOS:000333289400020 PM 24535501 ER PT J AU Mytton, J Ingram, J Manns, S Thomas, J AF Mytton, Julie Ingram, Jenny Manns, Sarah Thomas, James TI Facilitators and Barriers to Engagement in Parenting Programs A Qualitative Systematic Review SO HEALTH EDUCATION & BEHAVIOR LA English DT Review DE parenting; evaluation; qualitative methods; family health; child health ID INTERVENTION PROGRAM; BEHAVIORAL-PROBLEMS; PRESCHOOL-CHILDREN; TRIPLE-P; PARTICIPATION; PREVENTION; SKILLS; PERSPECTIVES; AUTISM AB Parenting programs have the potential to improve the health and well-being of parents and children. A challenge for providers is to recruit and retain parents in programs. Studies researching engagement with programs have largely focused on providers', policy makers', or researchers' reflections of their experience of parents' participation. We conducted a systematic review of qualitative studies where parents had been asked why they did or did not choose to commence, or complete programs, and compared these perceptions with those of researchers and those delivering programs. We used data-mining techniques to identify relevant studies and summarized findings using framework synthesis methods. Six facilitator and five barrier themes were identified as important influences on participation, with a total of 33 subthemes. Participants focused on the opportunity to learn new skills, working with trusted people, in a setting that was convenient in time and place. Researchers and deliverers focused on tailoring the program to individuals and on the training of staff. Participants and researchers/deliverers therefore differ in their opinions of the most important features of programs that act as facilitators and barriers to engagement and retention. Program developers need to seek the views of both participants and deliverers when evaluating programs. C1 [Mytton, Julie; Manns, Sarah] Univ W England, Bristol BS16 1QY, Avon, England. [Ingram, Jenny] Univ Bristol, Bristol, Avon, England. [Thomas, James] Univ London, Inst Educ, London WC1N 1AZ, England. RP Mytton, J (reprint author), Ctr Child & Adolescent Hlth, Oakfield House, Bristol BS8 2BN, Avon, England. 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PD APR PY 2014 VL 41 IS 2 BP 127 EP 137 DI 10.1177/1090198113485755 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AC9FY UT WOS:000332841000002 PM 23640123 ER PT J AU Roizen, NJ Magyar, CI Kuschner, ES Sulkes, SB Druschel, C van Wijngaarden, E Rodgers, L Diehl, A Lowry, R Hyman, SL AF Roizen, Nancy J. Magyar, Caroline I. Kuschner, Emily S. Sulkes, Steven B. Druschel, Charlotte van Wijngaarden, Edwin Rodgers, Lisa Diehl, Alison Lowry, Richard Hyman, Susan L. TI A Community Cross-Sectional Survey of Medical Problems in 440 Children with Down Syndrome in New York State SO JOURNAL OF PEDIATRICS LA English DT Article ID HEALTH SUPERVISION; BIRTH-DEFECTS; PREVALENCE; AUTISM; QUESTIONNAIRE; ABNORMALITIES; DISORDERS AB Objective To determine the frequency of medical problems in a large population of children with Down syndrome. Study design Study population included 440 children with Down syndrome (ages 3-14 years) identified primarily through the New York Congenital Malformations Registry. Parents completed questionnaires on medical problems. Results Our study population was predominately White (92.3%), non-Hispanic (72.3%) with at least 1 college educated parent (72.3%). The prevalence of medical problems was as follows: heart disease (55%), hearing problem (39%), vision problem (39%), thyroid disease (27%), celiac disease (5%), alopecia (5%), seizures (7%), asthma/reactive airway disease (32%), diabetes (1%), and juvenile rheumatoid arthritis (0.2%). Of the children with heart disease, 58% needed surgery at a mean age of 9 months. Of the children with hearing loss, 29% were identified on newborn screening and 13% used an amplification device. Of the children with thyroid disease, 31% were diagnosed in the newborn period. Only 7% of these children with Down syndrome had no medical problem listed. Conclusion Prevalence data of medical illnesses in a large population of children with Down syndrome provide us with data to support implementation of the American Academy of Pediatrics guidelines for health supervision for children with Down syndrome. The long-term health implications of the conditions we surveyed will be important for decreasing morbidity and increasing overall health and wellness into adulthood. C1 [Roizen, Nancy J.] Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA. [Magyar, Caroline I.; Sulkes, Steven B.; Rodgers, Lisa; Diehl, Alison; Hyman, Susan L.] Univ Rochester, Sch Med, Dept Pediat, Rochester, NY 14642 USA. [Kuschner, Emily S.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. [Druschel, Charlotte] New York State Dept Hlth, New York Congenital Malformat Registry, Albany, NY USA. [Druschel, Charlotte] Univ Albany, Sch Publ Hlth, Rensselaer, NY USA. [van Wijngaarden, Edwin] Univ Rochester, Sch Med, Dept Publ Hlth, Rochester, NY USA. [Lowry, Richard] Vassar Coll, Dept Psychol, Poughkeepsie, NY 12601 USA. RP Roizen, NJ (reprint author), Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA. FU National Center on Birth Defects and Developmental Disabilities and Centers for Disease Control and Prevention [RT01 2005-I/2-18, U59/CCU321285] FX Supported by the National Center on Birth Defects and Developmental Disabilities and Centers for Disease Control and Prevention (cooperative agreements RT01 2005-I/2-18 and U59/CCU321285). The authors declare no conflict of interest. CR Amalfi A, 2006, STRONG CHILDR RES SC Cunniff C, 2001, PEDIATRICS, V107, P442 SEASHORE MR, 1994, PEDIATRICS, V93, P855 Bergholdt R, 2006, DIABETOLOGIA, V49, P1179, DOI 10.1007/s00125-006-0231-6 Berument SK, 1999, BRIT J PSYCHIAT, V175, P444, DOI 10.1192/bjp.175.5.444 Bull MJ, 2011, PEDIATRICS, V128, P393, DOI 10.1542/peds.2011-1605 Cohen W. 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Pediatr. PD APR PY 2014 VL 164 IS 4 BP 871 EP 875 DI 10.1016/j.jpeds.2013.11.032 PG 5 WC Pediatrics SC Pediatrics GA AD4YV UT WOS:000333258900041 PM 24367984 ER PT J AU El Hokayem, J Nawaz, Z AF El Hokayem, Jimmy Nawaz, Zafar TI E6AP in the Brain: One Protein, Dual Function, Multiple Diseases SO MOLECULAR NEUROBIOLOGY LA English DT Review DE E6AP; UBE3A; Nuclear hormone receptors; Ubiquitin ligase; Transcriptional coactivator; Brain; Angelman syndrome; Autism; Aging ID HUMAN-PAPILLOMAVIRUS E6; STEROID-RECEPTOR COACTIVATOR; MENTAL-RETARDATION SYNDROME; UBIQUITIN LIGASE E6-AP; ANGELMAN-SYNDROME; MOUSE MODEL; E6-ASSOCIATED PROTEIN; RETT-SYNDROME; PROTEASOMAL DEGRADATION; ALPHA-SYNUCLEIN AB E6-Associated Protein (E6AP), the founding member of the HECT (Homologus to E6AP C terminus) family of ubiquitin ligases, has been gaining increased attention from the scientific community. In addition to its ubiquitin ligase function, our laboratory has also identified steroid hormone receptor transcriptional coactivation as yet another essential function of this protein. Furthermore, it has been established that E6AP has a role in numerous diseases including cancers and neurological syndromes. In this review, we delineate genetic and biochemical knowledge of E6AP and we focus on its role in the pathobiology of neuro-developmental and neuro-aging diseases; bringing to light important gaps of knowledge related to the involvement of its well-studied ligase function versus the much less studied nuclear receptor transcriptional coactivation function in the pathogenesis of these diseases. Tackling these gaps of knowledge could reveal novel possible neuro-pathobiological mechanisms and present crucial information for the design of effective treatment modalities for devastating CNS diseases. C1 [El Hokayem, Jimmy; Nawaz, Zafar] Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA. [Nawaz, Zafar] Univ Miami, Miller Sch Med, Braman Family Breast Canc Inst, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. RP Nawaz, Z (reprint author), Univ Miami, Miller Sch Med, Braman Family Breast Canc Inst, Sylvester Comprehens Canc Ctr, BRB Bldg,Room 723 C-227,1501 NW 10th Ave, Miami, FL 33136 USA. EM znawaz@med.miami.edu FU Lois Pope LIFE Fellows Program; Foundation for Angelman Syndrome Therapeutics (FAST) FX Jimmy El Hokayem is supported by the Lois Pope LIFE Fellows Program. This work is supported by a grant from the Foundation for Angelman Syndrome Therapeutics (FAST). 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Neurobiol. PD APR PY 2014 VL 49 IS 2 BP 827 EP 839 DI 10.1007/s12035-013-8563-y PG 13 WC Neurosciences SC Neurosciences & Neurology GA AD0VX UT WOS:000332953400017 PM 24091829 ER PT J AU Moyal, WN Lord, C Walkup, JT AF Moyal, Wendy N. Lord, Catherine Walkup, John T. TI Quality of Life in Children and Adolescents with Autism Spectrum Disorders: What Is Known About the Effects of Pharmacotherapy? SO PEDIATRIC DRUGS LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; SERIOUS BEHAVIORAL-PROBLEMS; HIGH-FUNCTIONING AUTISM; PSYCHOMETRIC PROPERTIES; ASPERGER-SYNDROME; OPEN-LABEL; TRIAL; ARIPIPRAZOLE; IRRITABILITY; RISPERIDONE AB A diagnosis of autistic spectrum disorder (ASD), now estimated to affect one in 88 children, requires deficits in social communication and interactions, and restricted interests and/or repetitive behaviors. Almost all children with ASD have deficits in adaptive skills, many have intellectual disability, and others have co-occurring psychiatric disorders or symptoms. Thus, this complex disorder has shown to have a substantial impact on patients' quality of life (QoL) and that of their families. Medication treatment is considered by clinicians and families to address problems with functioning due to psychiatric problems, and, as such, one-third of children and adolescents with ASD take at least one psychotropic medication and many use complementary and alternative medicine. This paper reviews what is known about the benefits and risks of psychotropic medications on the QoL of children with ASD. Although scarce, there are studies of psychiatric medications in autistic patients that include QoL measures, such as the pediatric studies of aripiprazole for irritability and one adult study of oxytocin. The aripiprazole study showed a positive effect on QoL in treated patients, as did the oxytocin study. Several other psychotropic medications are used in the treatment of children with ASD, and although information is available on the risks and benefits of each, we do not have specific data on the QoL impact of these medications. The aripiprazole and oxytocin studies exemplify how researchers can include QoL measures and use this information to guide clinicians. Additionally, we will recommend areas of further study in pharmacotherapy and QoL research in the context of treating children with ASD. C1 [Moyal, Wendy N.; Lord, Catherine; Walkup, John T.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Lord, Catherine] NY Presbyterian Hosp, Ctr Autism & Dev Brain, Weill Cornell Med Coll, White Plains, NY 10605 USA. RP Lord, C (reprint author), NY Presbyterian Hosp, Ctr Autism & Dev Brain, Weill Cornell Med Coll, 21 Bloomingdale Rd Bard House, White Plains, NY 10605 USA. EM cal2028@med.cornell.edu FU NIMH; Tourette Syndrome Association; Center for Disease Control FX Dr. Lord receives royalties from Western Psychological Services. Dr. Walkup has received free medications and matching placebo for NIMH-funded studies involving Lily and Pfizer and is currently authoring papers on NIMH-funded studies for which he received free medication from Abbott. He has consulted to Shire once regarding a research study. Dr. Walkup has received research grants, Speaker Bureau Honoraria and travel support from the Tourette Syndrome Association for talks funded by the Center for Disease Control. He has also received royalties for books on Tourette Syndrome from Oxford and Guilford Press. Dr. Walkup is an unpaid member of the following medical or Scientific Advisory Boards: Tourette Syndrome Association, Anxiety Disorders Association of America, and the Trichotillomania Learning Center. Dr Moyal has no conflicts of interest. No sources of funding were used to assist with the preparation of this review. 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Abnormalities in the cerebellar structure have been demonstrated to produce changes in emotional, cognitive, and social behaviors resembling clinical manifestations observed in patients with autism spectrum disorders (ASD) and schizophrenia. Several animal models have been used to evaluate the effects of relevant environmental and genetic risk factors on the cerebellum development and function. However, very few models of ASD and schizophrenia selectively target the cerebellum and/or specific cell types within this structure. In this review, we critically evaluate the strength and weaknesses of these models. We will propose that the future progress in this field will require time-and cell type-specific manipulations of disease-relevant genes, not only selectively in the cerebellum, but also in frontal brain areas connected with the cerebellum. Such information can advance our knowledge of the cerebellar contribution to non-motor behaviors in mental health and disease. C1 [Shevelkin, Alexey V.; Ihenatu, Chinezimuzo; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21287 USA. [Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21287 USA. [Shevelkin, Alexey V.] PK Anokhin Res Inst Normal Physiol, Moscow 125009, Russia. [Ihenatu, Chinezimuzo] Brown Univ, Providence, RI 02912 USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. EM mpletni1@jhu.edu FU [1F05MH097457-01] FX This review was supported by the fellowship grant, 1F05MH097457-01 (AVS). 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Neurosci. PD APR PY 2014 VL 25 IS 2 BP 177 EP 194 DI 10.1515/revneuro-2013-0049 PG 18 WC Neurosciences SC Neurosciences & Neurology GA AD3YU UT WOS:000333183200001 PM 24523305 ER PT J AU Patriquin, MA Lorenzi, J Scarpa, A Bell, MA AF Patriquin, Michelle A. Lorenzi, Jill Scarpa, Angela Bell, Martha Ann TI Developmental trajectories of respiratory sinus arrhythmia: Associations with social responsiveness SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE childhood; developmental trajectory; social; respiratory sinus arrhythmia; longitudinal; autism ID CARDIAC VAGAL TONE; POLYVAGAL THEORY; AUTISTIC TRAITS; NERVOUS-SYSTEM; SAS PROCEDURE; STABILITY; PERSPECTIVE; CHILDREN; INFANTS; VARIABILITY AB The present longitudinal study examined relations between respiratory sinus arrhythmia (RSA) development and social responsiveness characteristics associated with autism spectrum disorders. Group-based developmental trajectory modeling was used to characterize RSA development patterns in 106 typically developing children across 5, 10, 24, 36, and 48 months of age. A two-group model fit of RSA development was found: a "typically" and "atypically" developing group. The typical group gradually increased in RSA across 5-48 months of age. The atypical group, however, increased in RSA from 5 to 24 months and demonstrated a plateau or "delay" in RSA development from 24 to 48 months. The atypical RSA development group also demonstrated more difficulties in parent-reported social responsiveness at 48 months. The results support current literature that identifies RSA as a marker of social functioning level. (c) 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 317-326, 2014. C1 [Patriquin, Michelle A.; Lorenzi, Jill; Scarpa, Angela; Bell, Martha Ann] Virginia Tech, Dept Psychol, Blacksburg, VA 24061 USA. 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TI The Development of end- and beginning-state comfort in a cup manipulation task SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE motor planning; motor development; end-state comfort; beginning-state comfort ID HAND PREFERENCE; YOUNG-CHILDREN; SELECTION; PERFORMANCE; HANDEDNESS; MOVEMENTS; AUTISM; ADULTS; MOTOR AB End-state comfort (ESC) is the tendency to assume comfortable postures at the end of simple object manipulation rather than at the start; and therefore has been used to assess the behavioral effects of motor planning. Adult-like patterns have been observed at age 9. Observations can extend to joint-action, such that adults consider the beginning-state comfort (BSC) of another, without sacrificing ESC; however, trends in children have yet to be delineated. This study investigated the development of ESC and BSC in a cup manipulation task. Three to 12-year-olds and adults were asked to pick up a cup and (1) pour a glass of water or (2) pass it to the researcher to pour. 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Ziviani, Jenny Dodrill, Pamela TI Features of feeding difficulty in children with Autism Spectrum Disorder SO INTERNATIONAL JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE Autism spectrum disorders; feeding difficulties; mealtime behaviours; diet; weight ID TYPICALLY DEVELOPING-CHILDREN; PERVASIVE DEVELOPMENTAL DISORDERS; BODY-MASS INDEX; FOOD SELECTIVITY; GASTROINTESTINAL SYMPTOMS; ASPERGERS-DISORDER; MEALTIME BEHAVIORS; CHILDHOOD AUTISM; EATING BEHAVIORS; DIETARY-INTAKE AB Parents of children with Autism Spectrum Disorders (ASD) commonly report concerns regarding feeding difficulties and poor nutrition. Feeding difficulties, in the form of undesirable mealtime behaviours and/or skill deficits, can cause parental concern and impact on family dynamics. Poor nutrition can have an impact on development and health outcomes. The purpose of this paper was to review recent research regarding feeding difficulties in children with ASD, in order to describe: (1) the most frequently reported undesirable mealtime behaviours and skill deficits; and (2) dietary intake and weight patterns as markers of nutrition. While the ASD population is a somewhat heterogeneous group, this literature review of 44 research studies identified a number of common issues for these children. Restricted dietary variety, food neophobia, food refusal, limiting diet based on texture, and a propensity towards being overweight were frequently reported. Gaining a better understanding of the common features of feeding difficulties experienced by children with ASD will assist in directing intervention studies. Findings from such studies have the potential to enhance developmental and nutritional outcomes for this group. Well-designed longitudinal research would be valuable in monitoring the impact of feeding difficulties for these children as they age. C1 [Marshall, Jeanne; Dodrill, Pamela] Univ Queensland, Queensland Childrens Med Res Inst, Brisbane, Qld, Australia. [Hill, Rebecca J.] Univ Queensland, Sch Med, Childrens Nutr Res Ctr, Brisbane, Qld, Australia. [Ziviani, Jenny] Univ Queensland, Sch Hlth & Rehabil Sci, Brisbane, Qld, Australia. [Ziviani, Jenny] Queensland Hlth, Brisbane, Qld, Australia. [Dodrill, Pamela] Royal Childrens Hosp, Brisbane, Qld 4029, Australia. RP Marshall, J (reprint author), Royal Childrens Hosp, Queensland Childrens Med Res Inst, Level 4,Fdn Bldg,Herston Rd, Brisbane, Qld 4029, Australia. 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J. Speech-Lang. Pathol. PD APR PY 2014 VL 16 IS 2 BP 151 EP 158 DI 10.3109/17549507.2013.808700 PG 8 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AD2AO UT WOS:000333035000007 PM 24001171 ER PT J AU Farmer, JE Clark, MJ Mayfield, WA Cheak-Zamora, N Marvin, AR Law, JK Law, PA AF Farmer, Janet E. Clark, Mary J. Mayfield, Wayne A. Cheak-Zamora, Nancy Marvin, Alison R. Law, J. Kiely Law, Paul A. TI The Relationship Between the Medical Home and Unmet Needs for Children with Autism Spectrum Disorders SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Autistic disorder; Delivery of health care; Health services; Medical home; Patient-centered care ID HEALTH-CARE NEEDS; FAMILY-CENTERED CARE; NATIONAL-SURVEY; UNITED-STATES; ACCESS; SERVICES; SATISFACTION; INSURANCE; IMPACT AB The purpose of this study was to examine the relationship between having access to a medical home and unmet needs for specialty care services for children with autism spectrum disorders (ASD). Parents of children enrolled in a national autism registry were invited to complete an online Access to Care Questionnaire. The resulting sample consisted of 371 parents-child dyads. Bivariate and hierarchical regression analyses were conducted to determine whether having a medical home was associated with the number of unmet needs for specialty care. Less than one in five children with ASD had a medical home (18.9 %). Nearly all parents reported that their child had a personal doctor or nurse as well as a usual source of care, but less than one-third received coordinated care (29.9 %) and less than one-half received family-centered care (47.1 %). Many children had unmet needs (63 %), and the highest unmet need was for behavioral therapy. Having a medical home was associated with fewer unmet specialty care needs, even after demographic, child and family characteristics were taken into account. Children with ASD who have a medical home are more likely to have adequate access to needed services. Unfortunately, relatively few children have a medical home that includes family-centered and coordinated care. Enhancements in the delivery of primary care for children with ASD may make a real difference in access to needed specialty care services, potentially improving child and family outcomes. C1 [Farmer, Janet E.] Univ Missouri, Dept Hlth Psychol, Columbia, MO 65211 USA. [Clark, Mary J.; Mayfield, Wayne A.] Univ Missouri, Thompson Ctr Autism & Neurodev Disorder, Columbia, MO 65211 USA. [Cheak-Zamora, Nancy] Univ Missouri, Dept Hlth Sci, Columbia, MO 65211 USA. [Marvin, Alison R.; Law, J. Kiely; Law, Paul A.] Kennedy Krieger Inst, Dept Med Informat, Baltimore, MD USA. [Law, J. Kiely; Law, Paul A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. RP Farmer, JE (reprint author), Univ Missouri, Dept Hlth Psychol, 421 Lewis Hall, Columbia, MO 65211 USA. 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Child Health J. PD APR PY 2014 VL 18 IS 3 BP 672 EP 680 DI 10.1007/s10995-013-1292-z PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AD1XI UT WOS:000333026600019 PM 23793533 ER PT J AU Bashir, S Al-Ayadhi, LY AF Bashir, Shahid Al-Ayadhi, Laila Y. TI Effect of camel milk on thymus and activation-regulated chemokine in autistic children: double-blind study SO PEDIATRIC RESEARCH LA English DT Article ID SPECTRUM DISORDERS; IMMUNE; SCHIZOPHRENIA; INFLAMMATION; EXPRESSION; ANTIBODIES; INFECTION; ETIOLOGY; DISEASE; PROTEIN AB BACKGROUND: This study aimed to investigate the role of the effectiveness of camel milk (CM) (raw and boiled) on thymus and activation-regulated chemokine (TARC) serum levels and childhood autism rating scale (CARS) score in subjects with autism and compared to placebo group (cow milk). METHODS: Forty-five subjects diagnosed with autism were randomly assigned to receive boiled CM for group I (n = 15), raw CM for group II (n = 15), and placebo for group III (n = 15) for 2 wk. Measures included changes in professionally completed CARS score and blood samples for TARC serum level were taken before and after milk consumption of 500 ml per day in children's regular daily diet. RESULTS: The serum levels of TARC decreased significantly (P = 0.004) in boiled CM and in raw CM group (P = 0.01) too, but no effect was observed (P = 0.68) in placebo group. Furthermore, significant improvements were observed in CARS score (P = 0.04) in raw CM group only. There were no significant relationships between the serum of TARC level and the CARS score, age, or gender for any group. CONCLUSION: CM administered for 2 wk significantly improved clinical measurements of autism severity and decreased serum level of TARC in autistic children, but subsequent studies are recommended. C1 [Bashir, Shahid; Al-Ayadhi, Laila Y.] King Saud Univ, Autism Res & Treatment Ctr, Shaik AL Amodi Autism Res Chair, Dept Physiol,Fac Med, Riyadh, Saudi Arabia. [Bashir, Shahid] Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Div Cognit Neurol,Dept Neurol,Med Sch, Boston, MA 02215 USA. RP Al-Ayadhi, LY (reprint author), King Saud Univ, Autism Res & Treatment Ctr, Shaik AL Amodi Autism Res Chair, Dept Physiol,Fac Med, Riyadh, Saudi Arabia. EM ayadh2@gmail.com FU King Abdulaziz City for Science and Technology [A-L-11-0808]; National Plane of Science and Technology Health Research program; Deanship of Scientific Research grant from King Saud University, Saudi Arabia [RGP-VPP-216] FX Work on this study was supported by grants from the King Abdulaziz City for Science and Technology (A-L-11-0808), and National Plane of Science and Technology Health Research program and Deanship of Scientific Research grant (RGP-VPP-216) from King Saud University, Saudi Arabia. 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Res. PD APR PY 2014 VL 75 IS 4 BP 559 EP 563 DI 10.1038/pr.2013.248 PG 5 WC Pediatrics SC Pediatrics GA AD3LA UT WOS:000333139400012 PM 24375082 ER PT J AU Camacho, R Anderson, A Moore, DW Furlonger, B AF Camacho, Regina Anderson, Angelika Moore, Dennis W. Furlonger, Brett TI Conducting a Function-Based Intervention in a School Setting to Reduce Inappropriate Behaviour of a Child With Autism SO BEHAVIOUR CHANGE LA English DT Article DE school; modified functional analysis; Behavior Capture; autism; problem behaviour; classroom ID SPECTRUM DISORDERS; YOUNG-CHILDREN; SOCIAL-SKILLS AB Although function-based interventions have been shown to be effective, the methods utilised to carry out functional behaviour assessments (FBA) have practical limitations. This study explored the relative utility and feasibility of three FBA methods in a school setting to inform a function-based intervention to reduce problem behaviour in a boy with autism. The study consisted of (1) indirect and direct assessments, (2) a modified functional analysis, and (3) the intervention. New video technology, Behavior Capture, was trialled to facilitate data collection in the classroom. All methods contributed to identifying the function of the problematic behaviour, though only the functional analysis provided conclusive results. A peer-mediated intervention based on these findings conducted in the school playground reduced the problem behaviours. All FBA methods could be applied in the school setting and provided useful information. Novel technology was helpful in facilitating data collection. A naturalistic intervention was successful in reducing problem behaviours and increasing play skills. C1 [Camacho, Regina; Anderson, Angelika; Moore, Dennis W.; Furlonger, Brett] Monash Univ, Melbourne, Vic 3004, Australia. RP Anderson, A (reprint author), Monash Univ, Fac Educ, Wellington Rd, Clayton, Vic 3800, Australia. 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J. Neuropsychopharmacol. PD APR PY 2014 VL 17 IS 4 BP 651 EP 673 DI 10.1017/S146114571300117X PG 23 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AC6JH UT WOS:000332627800013 PM 24229490 ER PT J AU Angkustsiri, K Goodlin-Jones, B Deprey, L Brahmbhatt, K Harris, S Simon, TJ AF Angkustsiri, Kathleen Goodlin-Jones, Beth Deprey, Lesley Brahmbhatt, Khyati Harris, Susan Simon, Tony J. TI Social Impairments in Chromosome 22q11.2 Deletion Syndrome (22q11.2DS): Autism Spectrum Disorder or a Different Endophenotype? SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; ASD; 22q11.2 deletion syndrome; Velocardiofacial syndrome ID CARDIO-FACIAL-SYNDROME; CHILDREN; SYMPTOMS; SCHIZOPHRENIA; MICRODELETION; INDIVIDUALS; COGNITION; PROFILE; THOUGHT; ADULTS AB High prevalence of autism spectrum disorders (ASD) has been reported in 22q11.2DS, although this has been based solely on parent report measures. This study describes the presence of ASD using a procedure more similar to that used in clinical practice by incorporating history (Social Communication Questionnaire) AND a standardized observation measure (Autism Diagnostic Observation Schedule) and suggests that ASD is not as common as previously reported in 22q11.2DS. Differences in methodology, along with comorbid conditions such as anxiety, likely contribute to false elevations in ASD prevalence and information from multiple sources should be included in the evaluation of ASD. C1 [Angkustsiri, Kathleen] Univ Calif Davis, Dept Pediat, Med Ctr, Sacramento, CA 95817 USA. [Angkustsiri, Kathleen; Goodlin-Jones, Beth; Deprey, Lesley; Brahmbhatt, Khyati; Harris, Susan; Simon, Tony J.] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA. [Goodlin-Jones, Beth; Brahmbhatt, Khyati; Simon, Tony J.] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. RP Angkustsiri, K (reprint author), Univ Calif Davis, MIND Inst, 2825 50th St, Sacramento, CA 95817 USA. 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Adamson, Ashley Adams, Sandra Le Couteur, Ann TI Parents' and Child Health Professionals' Attitudes Towards Dietary Interventions for Children with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; ASD; Dietary interventions; Gluten; Casein ID CASEIN-FREE DIET; INTESTINAL PERMEABILITY; YOUNG-CHILDREN; GLUTEN-FREE; COMPLEMENTARY; PREVALENCE; THERAPIES; PEPTIDES; SYMPTOMS; BLIND AB Parents of children with autism spectrum disorders (ASD) use a wide range of interventions including poorly evidenced dietary interventions. To investigate parents' and professionals' experience of dietary interventions and attitudes towards a proposed trial to evaluate the gluten free casein free diet (GFCFD). Survey of UK parents of children with ASD, and professionals. 258 parents and 244 professionals participated. 83 % of children had received a range of dietary manipulations; three quarters of professionals have been asked for advice about GFCFD. Respondents identified an inadequate evidence base for dietary interventions in ASD and suggested modifications to a proposed trial design. Both parents and professionals supported the need for further evaluation of dietary interventions in ASD. C1 [Winburn, Elizabeth] Solent NHS Trust, Southampton SO16 9QX, Hants, England. [Charlton, Jenna] Newcastle Univ, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [McConachie, Helen; Le Couteur, Ann] Newcastle Univ, Inst Hlth & Soc, Sir James Spence Inst, Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [McColl, Elaine] Newcastle Univ, Sch Med, Newcastle Clin Trials Unit, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Parr, Jeremy] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [O'Hare, Anne; Wilson, David C.] Univ Edinburgh, Edinburgh EH9 1UW, Midlothian, Scotland. [Baird, Gillian; Gringras, Paul] Guys & Thomas NHS Fdn Trust, London SE1 7EH, England. [Adamson, Ashley] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Adamson, Ashley] Newcastle Univ, Human Nutr Res Ctr, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Adams, Sandra] North Tyneside Gen Hosp, Dept Nutr & Dietet, North Shields, Tyne & Wear, England. RP Le Couteur, A (reprint author), Newcastle Univ, Inst Hlth & Soc, Sir James Spence Inst, Royal Victoria Infirm, 3rd Floor, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. 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Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 747 EP 757 DI 10.1007/s10803-013-1922-8 PG 11 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900002 PM 23996225 ER PT J AU Young, RL Rodi, ML AF Young, Robyn L. Rodi, Melissa L. TI Redefining Autism Spectrum Disorder Using DSM-5: The Implications of the Proposed DSM-5 Criteria for Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Diagnosis; DSM-IV; DSM-5 ID PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC-CRITERIA; ASPERGER-SYNDROME; CHILDREN; PHENOTYPE; QUOTIENT; VALIDITY AB A number of changes were made to pervasive developmental disorders (PDDs) in the recently released diagnostic and statistical manual of mental disorders (APA, Diagnostic and statistical manual of mental disorders, American Psychiatric Publishing, Arlington, VA, 2013). Of the 210 participants in the present study who met DSM-IV-TR criteria for a PDD [i.e., autistic disorder, Asperger's disorder and pervasive developmental disorder-not otherwise specified (PDD-NOS)], only 57.1 % met DSM-5 criteria (specificity = 1.0) for autism spectrum disorder when criteria were applied concurrently during diagnostic assessment. High-functioning individuals (i.e., Asperger's disorder and PDD-NOS) were less likely to meet DSM-5 criteria than those with autistic disorder. A failure to satisfy all three criteria in the social-communication domain was the most common reason for exclusion (39 %). The implications of these results are discussed. C1 [Young, Robyn L.; Rodi, Melissa L.] Flinders Univ South Australia, Adelaide, SA 5001, Australia. RP Young, RL (reprint author), Flinders Univ South Australia, GPO BOX 2100, Adelaide, SA 5001, Australia. 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Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 758 EP 765 DI 10.1007/s10803-013-1927-3 PG 8 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900003 PM 24057130 ER PT J AU Xu, GF Jing, J Bowers, K Liu, BY Bao, W AF Xu, Guifeng Jing, Jin Bowers, Katherine Liu, Buyun Bao, Wei TI Maternal Diabetes and the Risk of Autism Spectrum Disorders in the Offspring: A Systematic Review and Meta-Analysis SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Diabetes; Pregnancy ID COMPREHENSIVE METAANALYSIS; AUTOIMMUNE-DISEASES; LIPID-PEROXIDATION; OXIDATIVE STRESS; NEONATAL FACTORS; PREGNANCY; COMPLICATIONS; POPULATION; PREVALENCE; MELLITUS AB We performed a systematic literature search regarding maternal diabetes before and during pregnancy and the risk of autism spectrum disorders (ASD) in the offspring. Of the 178 potentially relevant articles, 12 articles including three cohort studies and nine case-control studies were included in the meta-analysis. Both the meta-analyses of cohort studies and case-control studies showed significant associations. The pooled relative risk and 95 % confidence interval (CI) among cohort studies was 1.48 (1.25-1.75, p < 0.001). For case-control studies, the pooled odds ratio and 95 % CI was 1.72 (1.24-2.41, p = 0.001). No indication of significant heterogeneity across studies or publication bias was observed. In conclusion, maternal diabetes was significantly associated with a greater risk of ASD in the offspring. C1 [Xu, Guifeng; Jing, Jin; Liu, Buyun] Sun Yat Sen Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Guangzhou 510080, Guangdong, Peoples R China. [Bowers, Katherine] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Coll Med, Cincinnati, OH 45229 USA. 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Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 766 EP 775 DI 10.1007/s10803-013-1928-2 PG 10 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900004 PM 24057131 ER PT J AU Orellana, LM Martinez-Sanchis, S Silvestre, FJ AF Orellana, Lorena M. Martinez-Sanchis, Sonia Silvestre, Francisco J. TI Training Adults and Children with an Autism Spectrum Disorder to be Compliant with a Clinical Dental Assessment Using a TEACCH-Based Approach SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Oral assessment; TEACCH-based training program; Compliance ID BEHAVIOR; MANAGEMENT; NEEDS AB The specific neuropsychological and sensory profile found in persons with autism spectrum disorders complicate dental procedures and as a result of this, most are treated under general anesthesia or unnecessary sedation. The main goal of the present study was to evaluate the effectiveness of a short treatment and education of autistic and related communication-handicapped children-based intervention program (five sessions) to facilitate a 10-component oral assessment in children (n = 38, aged 4-9 years) and adults (n = 34, aged 19-41) with autism spectrum disorder (with or without associated intellectual disability). The assessment ranges from entering into the examination room to the evaluation of the dental occlusion. There were statistically significant differences in the number of components reached and in compliance before and after the training program. C1 [Orellana, Lorena M.; Silvestre, Francisco J.] Univ Valencia, Dept Stomatol, Valencia 46010, Spain. [Martinez-Sanchis, Sonia] Univ Valencia, Fac Psychol, Dept Psychobiol, Valencia 46010, Spain. [Martinez-Sanchis, Sonia] Univ Valencia, Neurodev Disorders Res Unit, Valencia 46010, Spain. 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PD APR PY 2014 VL 44 IS 4 BP 776 EP 785 DI 10.1007/s10803-013-1930-8 PG 10 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900005 PM 24002415 ER PT J AU Sappok, T Budczies, J Dziobek, I Bolte, S Dosen, A Diefenbacher, A AF Sappok, Tanja Budczies, Jan Dziobek, Isabel Boelte, Sven Dosen, Anton Diefenbacher, Albert TI The Missing Link: Delayed Emotional Development Predicts Challenging Behavior in Adults with Intellectual Disability SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Intellectual disability; Autism spectrum disorders; Adults; Emotional development; Challenging behavior ID AUTISM SPECTRUM DISORDER; OVERT AGGRESSION SCALE; DIAGNOSTIC OBSERVATION SCHEDULE; EARLY INTERVENTION PROGRAM; SELF-INJURIOUS-BEHAVIOR; PSYCHOTROPIC MEDICATION; PSYCHIATRIC-ASSESSMENT; ADAPTIVE-BEHAVIOR; MENTAL-HEALTH; RISK MARKERS AB Individuals with intellectual disability (ID) show high rates of challenging behavior (CB). The aim of this retrospective study was to assess the factors underlying CB in an adult, clinical ID sample (n = 203). Low levels of emotional development (ED), as measured by the Scheme of Appraisal of ED, predicted overall CB, specifically irritability and self-injury, high unemployment and low occupation rates, while severity of ID controlled for ED did not. Autism was the only mental disorder associated with overall CB, stereotypy, lethargy, and predicted antipsychotic drug usage. Given the persistence and clinical significance of CB, evaluation of autism and ED may suggest priority areas for diagnostics and therapy, to provide the prerequisites for participation in society and living up one's potentials. C1 [Sappok, Tanja; Diefenbacher, Albert] Univ Affiliated Hosp Charite, Konigin Elisabeth Herzberge Hosp, Dept Psychiat Psychotherapy & Psychosomat, D-10365 Berlin, Germany. [Budczies, Jan] Charite, Dept Pathol, D-10117 Berlin, Germany. [Dziobek, Isabel] Free Univ Berlin, Cluster Excellence Languages Emot, D-14195 Berlin, Germany. [Boelte, Sven] Karolinska Inst KIND, Dept Womens & Childrens Hlth, Ctr Neurodev Disorders, S-17176 Stockholm, Sweden. [Dosen, Anton] Radboud Univ Nijmegen, Univ Hosp, Dept Psychiat, NL-6525 HP Nijmegen, Netherlands. RP Sappok, T (reprint author), Univ Affiliated Hosp Charite, Konigin Elisabeth Herzberge Hosp, Dept Psychiat Psychotherapy & Psychosomat, Herzbergstr 79, D-10365 Berlin, Germany. 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PD APR PY 2014 VL 44 IS 4 BP 786 EP 800 DI 10.1007/s10803-013-1933-5 PG 15 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900006 PM 24002416 ER PT J AU Evers, K Panis, S Torfs, K Steyaert, J Noens, I Wagemans, J AF Evers, Kris Panis, Sven Torfs, Katrien Steyaert, Jean Noens, Ilse Wagemans, Johan TI Disturbed Interplay Between Mid- and High-Level Vision in ASD? Evidence from a Contour Identification Task with Everyday Objects SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder (ASD); Visual perception; Object identification; Weak central coherence theory; Enhanced perceptual functioning hypothesis; Bottom-up versus top-down; Gabor; Local versus global processing ID AUTISM SPECTRUM DISORDERS; TOP-DOWN FACILITATION; VISUAL-PERCEPTION; CATEGORY-SPECIFICITY; OUTLINE VERSIONS; WEAK COHERENCE; CHILDREN; RECOGNITION; INTEGRATION; CONNECTIVITY AB Atypical visual processing in children with autism spectrum disorder (ASD) does not seem to reside in an isolated processing component, such as global or local processing. We therefore developed a paradigm that requires the interaction between different processes-an identification task with Gaborized object outlines-and applied this to two age groups of 6-to-10 and 10-to-14 year old children with and without ASD. Event history analyses demonstrated an identification disadvantage in the ASD group, which remained quite stable during the temporal unfolding of the outline. The typically developing group particularly outperformed the ASD group when more complex contours were shown. Together, our results suggest that the interplay between local and global processes and between bottom-up and top-down processes is disturbed in ASD. C1 [Evers, Kris; Panis, Sven; Torfs, Katrien; Wagemans, Johan] Katholieke Univ Leuven, Expt Psychol Lab, B-3000 Louvain, Belgium. [Evers, Kris; Steyaert, Jean] UPC KU Leuven, Dept Child Psychiat, Louvain, Belgium. [Evers, Kris; Steyaert, Jean; Noens, Ilse; Wagemans, Johan] Katholieke Univ Leuven, Leuven Autism Res LAuRes, B-3000 Louvain, Belgium. [Steyaert, Jean] Univ Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands. [Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, B-3000 Louvain, Belgium. 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Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 801 EP 815 DI 10.1007/s10803-013-1931-7 PG 15 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900007 PM 24037639 ER PT J AU Koegel, RL Bradshaw, JL Ashbaugh, K Koegel, LK AF Koegel, Robert L. Bradshaw, Jessica L. Ashbaugh, Kristen Koegel, Lynn Kern TI Improving Question-Asking Initiations in Young Children with Autism Using Pivotal Response Treatment SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Initiations; Early intervention; Motivation; Question-asking; Autism spectrum disorder; Pivotal response treatment ID JOINT ATTENTION; NONVERBAL-COMMUNICATION; TEACHING-CHILDREN; INTERVENTION; ACQUISITION; SPECTRUM; BEHAVIOR; DISORDERS; ABILITIES; DEFICITS AB Social initiations make up a core deficit for children with autism spectrum disorder (ASD). In particular, initiated questions during social interactions are often minimal or absent in this population. In the context of a multiple baseline design, the efficacy of using the motivational procedures of Pivotal Response Treatment to increase social question-asking for three young children with autism was assessed. Results indicated that participants initiated a greater number of targeted questions following intervention. Additionally, all children exhibited increases in initiation of untargeted questions during social interaction in novel settings. Furthermore, post intervention data revealed collateral gains in communication and adaptive behavior. Theoretical implications of incorporating motivational strategies into intervention to improve social initiations in young children with ASD are discussed. C1 [Koegel, Robert L.; Bradshaw, Jessica L.; Ashbaugh, Kristen; Koegel, Lynn Kern] Univ Calif Santa Barbara, Counseling Clin & Sch Psychol Dept, Koegel Autism Ctr, Grad Sch Educ, Santa Barbara, CA 93106 USA. RP Koegel, RL (reprint author), Univ Calif Santa Barbara, Counseling Clin & Sch Psychol Dept, Koegel Autism Ctr, Grad Sch Educ, Santa Barbara, CA 93106 USA. EM koegel@education.ucsb.edu; jbradshaw@education.ucsb.edu CR Bellugi U., 1965, DEV LANGUAGE FUNCTIO, P103 Brownell R., 2000, EXPRESSIVE RECEPTIVE Carr E. G., 1994, COMMUNICATION BASED, Vxxiii Frea W. D., 1995, TEACHING CHILDREN AU, P53 Harper CB, 2008, J AUTISM DEV DISORD, V38, P815, DOI 10.1007/s10803-007-0449-2 HUNG DW, 1977, J BEHAV THER EXP PSY, V8, P237, DOI 10.1016/0005-7916(77)90061-1 Kanne SM, 2011, J AUTISM DEV DISORD, V41, P1007, DOI 10.1007/s10803-010-1126-4 Klin A, 2007, J AUTISM DEV DISORD, V37, P748, DOI 10.1007/s10803-006-0229-4 Koegel L. 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PD APR PY 2014 VL 44 IS 4 BP 816 EP 827 DI 10.1007/s10803-013-1932-6 PG 12 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900008 PM 24014174 ER PT J AU Davidson, MM Weismer, SE AF Davidson, Meghan M. Weismer, Susan Ellis TI Characterization and Prediction of Early Reading Abilities in Children on the Autism Spectrum SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Emergent literacy; Reading; Language; Comprehension; Autism spectrum disorder ID EMERGENT LITERACY SKILLS; PARENT VERBAL RESPONSIVENESS; LANGUAGE IMPAIRMENT; ORAL LANGUAGE; PRESCHOOL-CHILDREN; COMPREHENSION DIFFICULTIES; COMMUNICATIVE DEVELOPMENT; DEVELOPMENTAL DISORDERS; INDIVIDUAL-DIFFERENCES; EXPRESSIVE LANGUAGE AB Many children with autism spectrum disorder (ASD) have reading profiles characterized by higher decoding skills and lower reading comprehension. This study assessed whether this profile was apparent in young children with ASD and examined concurrent and longitudinal predictors of early reading. A discrepant profile of reading (higher alphabet and lower meaning) was found in 62 % of this sample. Concurrent analyses revealed that reading proficiency was associated with higher nonverbal cognition and expressive language, and that social ability was negatively related to alphabet knowledge. Nonverbal cognition and expressive language at mean age 2A1/2 years predicted later reading performance at mean age 5A1/2 years. These results support the importance of early language skills as a foundation for reading in children with ASD. C1 [Davidson, Meghan M.; Weismer, Susan Ellis] Univ Wisconsin, Dept Commun Sci & Disorders, Waisman Ctr, Madison, WI 53706 USA. RP Davidson, MM (reprint author), Univ Wisconsin, Dept Commun Sci & Disorders, Waisman Ctr, Goodnight Hall,1975 Willow Dr, Madison, WI 53706 USA. 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Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 846 EP 859 DI 10.1007/s10803-013-1935-3 PG 14 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900010 PM 24005986 ER PT J AU Ziv, Y Hadad, BS Khateeb, Y Terkel-Dawer, R AF Ziv, Yair Hadad, Bat Sheva Khateeb, Yasmine Terkel-Dawer, Ruth TI Social Information Processing in Preschool Children Diagnosed with Autism Spectrum Disorder (vol 44, pg 846, 2014) SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Correction C1 [Ziv, Yair; Khateeb, Yasmine] Univ Haifa, Dept Counseling & Human Dev, IL-31905 Haifa, Israel. [Hadad, Bat Sheva] Univ Haifa, Dept Special Educ, IL-31905 Haifa, Israel. [Khateeb, Yasmine; Terkel-Dawer, Ruth] Clalit Hlth Serv, Inst Pediat Neurol & Child Dev, Haifa, Israel. RP Ziv, Y (reprint author), Univ Haifa, Dept Counseling & Human Dev, IL-31905 Haifa, Israel. EM yziv@edu.haifa.ac.il CR Ziv Y, 2014, J AUTISM DEV DISORD, V44, P846, DOI 10.1007/s10803-013-1935-3 NR 1 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 860 EP 860 DI 10.1007/s10803-013-1998-1 PG 1 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900011 ER PT J AU Adams, RE Fredstrom, BK Duncan, AW Holleb, LJ Bishop, SL AF Adams, Ryan E. Fredstrom, Bridget K. Duncan, Amie W. Holleb, Lauren J. Bishop, Somer L. TI Using Self- and Parent-Reports to Test the Association Between Peer Victimization and Internalizing Symptoms in Verbally Fluent Adolescents with ASD SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Peer victimization; Adolescence; Internalizing ID AUTISM SPECTRUM DISORDERS; PSYCHOSOCIAL ADJUSTMENT; PSYCHIATRIC-DISORDERS; ASPERGER-SYNDROME; CHILDREN; DEPRESSION; PREVALENCE; ANXIETY; HEALTH; YOUTH AB The current study tested the associations between peer victimization and internalizing symptoms in 54 verbally fluent adolescent males with a diagnosis of autism spectrum disorder. Adolescent- and parent-reports of multiple types of peer victimization and internalizing symptoms were used. First, the validity and reliability of the adolescent-report measure of peer victimization were successfully tested, with some exceptions. Then, structural equation models showed that adolescent-reports of peer victimization were associated with a latent construct of internalizing symptoms even after controlling for parent-reports of peer victimization. Discussion focuses on the importance of considering adolescent-reports of negative peer experience, such as peer victimization, rather than relying exclusively on parent reports. C1 [Adams, Ryan E.; Fredstrom, Bridget K.; Duncan, Amie W.; Holleb, Lauren J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Bishop, Somer L.] Weill Cornell Med Coll, White Plains, NY 10605 USA. RP Adams, RE (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave,MLC 4002, Cincinnati, OH 45229 USA. EM ryan.adams@cchmc.org CR Achenbach T. M., 2001, CHILD BEHAV CHECKLIS Achenbach T. 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Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 861 EP 872 DI 10.1007/s10803-013-1938-0 PG 12 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900012 PM 24005987 ER PT J AU Emberti Gialloreti, L Pardini, M Benassi, F Marciano, S Amore, M Mutolo, MG Porfirio, MC Curatolo, P AF Gialloreti, Leonardo Emberti Pardini, Matteo Benassi, Francesca Marciano, Sara Amore, Mario Mutolo, Maria Giulia Porfirio, Maria Cristina Curatolo, Paolo TI Reduction in Retinal Nerve Fiber Layer Thickness in Young Adults with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Retinal nerve fiber layer thickness; Optical coherence tomography (OCT); White matter ID OPTICAL COHERENCE TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS; ABNORMALITIES; REPRODUCIBILITY; METAANALYSIS; SENSITIVITY; CHILDREN; GLAUCOMA AB Recent years have seen an increase in the use of retinal nerve fiber layer (RNFL) evaluation as an easy-to-use, reproducible, proxy-measure of brain structural abnormalities. Here, we evaluated RNFL thickness in a group of subjects with high functioning autism (HFA) or with Asperger Syndrome (AS) to its potential as a tool to study autism pathophysiology. All subjects underwent high-resolution spectral domain optical coherence tomography to evaluate RNFL thickness. HFA subjects presented with reduced global RNFL thickness compared both to AS subjects and controls. AS subjects showed a reduced nasal quadrant RNFL thickness compared to controls. Verbal-IQ/performance-IQ discrepancy correlated with RNFL thickness. Our data suggest that RNFL evaluation could help in the development of biological markers of autism pathophysiology. C1 [Gialloreti, Leonardo Emberti] Univ Roma Tor Vergata, Dept Biomed & Prevent, I-00133 Rome, Italy. [Gialloreti, Leonardo Emberti; Pardini, Matteo; Benassi, Francesca] Ctr Commun & Neurorehabil Res CNAPP, Rome, Italy. [Pardini, Matteo; Amore, Mario] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet & Maternal, Genoa, Italy. [Pardini, Matteo] Univ Genoa, Dept Magnet Resonance, Res Ctr Nervous Syst Dis, Genoa, Italy. [Marciano, Sara; Porfirio, Maria Cristina; Curatolo, Paolo] Tor Vergata Univ Hosp, Dept Syst Med, Pediat Neurosci Unit, Rome, Italy. [Mutolo, Maria Giulia] Univ Roma La Sapienza, Dept Ophthalmol, SantAndrea Hosp, I-00185 Rome, Italy. RP Emberti Gialloreti, L (reprint author), Univ Roma Tor Vergata, Dept Biomed & Prevent, Via Montpellier 1, I-00133 Rome, Italy. 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PD APR PY 2014 VL 44 IS 4 BP 883 EP 893 DI 10.1007/s10803-013-1941-5 PG 11 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900014 PM 24146130 ER PT J AU Nichols, CM Ibanez, LV Foss-Feig, JH Stone, WL AF Nichols, Caitlin McMahon Ibanez, Lisa V. Foss-Feig, Jennifer H. Stone, Wendy L. TI Social Smiling and Its Components in High-Risk Infant Siblings Without Later ASD Symptomatology SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; High-risk siblings; Infants; Social smiling ID AUTISM SPECTRUM DISORDERS; JOINT ATTENTION; CHILDREN; COMMUNICATION; MOTHERS; FACE; PHENOTYPE; DIAGNOSIS; TODDLERS; LANGUAGE AB Impaired affective expression, including social smiling, is common in children with autism spectrum disorder (ASD), and may represent an early marker for ASD in their infant siblings (Sibs-ASD). Social smiling and its component behaviors (eye contact and non-social smiling) were examined at 15 months in Sibs-ASD who demonstrated later ASD symptomatology (Sibs-ASD/AS), those who did not (Sibs-ASD/NS), and low-risk controls (Sibs-TD). Both Sibs-ASD subgroups demonstrated lower levels of social smiling than Sibs-TD, suggesting that early social smiling may reflect elevated genetic vulnerability rather than a specific marker for ASD. Only the Sibs-ASD/AS demonstrated less eye contact and non-social smiling than Sibs-TD, suggesting that different processes, threshold effects, or protective factors may underlie social smiling development in the two Sibs-ASD subgroups. C1 [Nichols, Caitlin McMahon; Foss-Feig, Jennifer H.; Stone, Wendy L.] Vanderbilt Univ, Dept Psychol & Human Dev, Nashville, TN 37235 USA. [Ibanez, Lisa V.] Univ Miami, Dept Psychol, Miami, FL USA. [Stone, Wendy L.] Vanderbilt Univ, Dept Pediat, Nashville, TN USA. 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Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 894 EP 902 DI 10.1007/s10803-013-1944-2 PG 9 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900015 PM 24057094 ER PT J AU Timberlake, MT Leutz, WN Warfield, ME Chiri, G AF Timberlake, Maria T. Leutz, Walter N. Warfield, Marji Erickson Chiri, Giuseppina TI "In the Driver's Seat": Parent Perceptions of Choice in a Participant-Directed Medicaid Waiver Program for Young Children with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Participant direction; Choice; Medicaid home and community-based services; Autism waiver ID CARE; SERVICES; CASH AB This study investigated families' experience of choice within a participant-directed Medicaid waiver program for young children with autism. Fourteen parents or grandparents participated in in-depth interviews about their experience of choosing personnel, directing in-home services, and managing the $25,000 annual allocation. Key findings included families' preference to hire providers with whom they have a prior relationship, parent empowerment and differences of opinion about parents as teachers. Professionals implementing participant directed service models could benefit from understanding the strong value parents' placed on the personalities and interpersonal skills of providers. Parents' descriptions of directing rather than merely accepting autism services revealed increased confidence in their ability to choose and manage the multiple components of their children's HCBS autism waiver program. C1 [Timberlake, Maria T.; Warfield, Marji Erickson; Chiri, Giuseppina] Brandeis Univ, Heller Sch Social Policy & Management, Starr Ctr Intellectual & Dev Disabil, Waltham, MA 02454 USA. [Timberlake, Maria T.] Care of Warfield ME, Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA 02454 USA. [Leutz, Walter N.] Brandeis Univ, Heller Sch Social Policy & Management, Schneider Inst Hlth Policy, Waltham, MA 02454 USA. RP Timberlake, MT (reprint author), SUNY Coll Cortland, Fdn & Social Advocacy Dept, Cortland, NY 13045 USA. 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R., 2001, J DISABIL POLICY STU, V12, P133, DOI DOI 10.1177/104420730101200302 Valentine K, 2010, SOC SCI MED, V71, P950, DOI 10.1016/j.socscimed.2010.06.010 NR 33 TC 2 Z9 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 903 EP 914 DI 10.1007/s10803-013-1942-4 PG 12 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900016 PM 24057132 ER PT J AU Ausderau, K Sideris, J Furlong, M Little, LM Bulluck, J Baranek, GT AF Ausderau, Karla Sideris, John Furlong, Melissa Little, Lauren M. Bulluck, John Baranek, Grace T. TI National Survey of Sensory Features in Children with ASD: Factor Structure of the Sensory Experience Questionnaire (3.0) SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Factor analysis; Sensory processing ID AUTISM SPECTRUM DISORDERS; DEVELOPMENTAL DELAYS; ADAPTIVE-BEHAVIOR; YOUNG-CHILDREN; DISABILITIES; TODDLERS; PERCEPTION; ATTENTION; PATTERNS; STIMULI AB This national online survey study characterized sensory features in 1,307 children with autism spectrum disorder (ASD) ages 2-12 years using the Sensory Experiences Questionnaire Version 3.0 (SEQ-3.0). Using the SEQ-3.0, a confirmatory factor analytic model with four substantive factors of hypothesized sensory response patterns (i.e., hyporesponsiveness; hyperresponsiveness; sensory interests, repetitions and seeking behaviors; enhanced perception), five method factors of sensory modalities (i.e., auditory, visual, tactile, gustatory/olfactory, vestibular/proprioceptive), and one of social context were tested with good model fit. Child and family characteristics associated with the sensory response patterns were explored. The effect of sensory response patterns on autism severity was tested, controlling for key child and family characteristics. The SEQ-3.0 demonstrates an empirically valid factor structure specific to ASD that considers sensory response patterns, modalities, and social context. C1 [Ausderau, Karla; Little, Lauren M.; Bulluck, John; Baranek, Grace T.] Univ N Carolina, Div Occupat Sci, Dept Allied Hlth Sci, Chapel Hill, NC USA. [Ausderau, Karla] Univ Wisconsin, Occupat Therapy Program, Dept Kinesiol, Med Sci Ctr 3195, Madison, WI 53706 USA. [Sideris, John] Univ N Carolina, Frank Porter Graham Child Dev Inst, Chapel Hill, NC USA. [Furlong, Melissa] Univ N Carolina, Dept Epidemiol, UNC Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Little, Lauren M.] Univ Kansas, Med Ctr, Dept Occupat Therapy, Kansas City, MO USA. RP Ausderau, K (reprint author), Univ Wisconsin, Occupat Therapy Program, Dept Kinesiol, Med Sci Ctr 3195, 1300 Univ Ave, Madison, WI 53706 USA. EM kausderau@wisc.edu CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT American Psychiatric Association, 2012, PROP AUT SPECTR DIS Baio Jon, 2012, Morbidity and Mortality Weekly Report, V61, P1 Baranek G. 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K., 2010, MPLUS USERS GUIDE O'Donnell S, 2012, AM J OCCUP THER, V66, P586, DOI 10.5014/ajot.2012.004168 Parush S., 2006, OCCUPATIONAL THERAPY, V3, P274, DOI 10.1002/oti.41 Pine E, 2006, AUTISM, V10, P344, DOI 10.1177/1362361306064434 Qualtrics Labs Inc, 2011, VERS 21269 QUALTR RE Rogers SJ, 2003, J AUTISM DEV DISORD, V33, P631, DOI 10.1023/B:JADD.0000006000.38991.a7 Rogers SJ, 2005, J CHILD PSYCHOL PSYC, V46, P1255, DOI 10.1111/j.1469-7610.2005.01431.x Schoen Sarah A, 2009, Front Integr Neurosci, V3, P29, DOI 10.3389/neuro.07.029.2009 Schumacker RE, 2004, BEGINNERS GUIDE STRU, V2nd Talay-Ongan A., 2000, INT J DISABIL DEV ED, V47, P201, DOI DOI 10.1080/713671112 Wallace GL, 2009, PHILOS T R SOC B, V364, P1425, DOI 10.1098/rstb.2008.0330 Watling RL, 2001, AM J OCCUP THER, V55, P416 Watson LR, 2011, J SPEECH LANG HEAR R, V54, P1562, DOI 10.1044/1092-4388(2011/10-0029) Wetherby A, 2006, SOCIAL COMMUNICATION, P3 NR 54 TC 3 Z9 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 915 EP 925 DI 10.1007/s10803-013-1945-1 PG 11 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900017 PM 24097141 ER PT J AU Smith, J Hand, L Dowrick, PW AF Smith, Jemma Hand, Linda Dowrick, Peter W. TI Video Feedforward for Rapid Learning of a Picture-Based Communication System SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Communication systems; Rapid learning; VSM; Self modeling; Feedforward; Autism; Down syndrome ID AUTISM SPECTRUM DISORDERS; SPECIAL-EDUCATION; YOUNG-CHILDREN; SINGLE-SUBJECT; DOWN-SYNDROME; PECS; INTERVENTIONS; DISABILITIES; METAANALYSIS; SPEECH AB This study examined the efficacy of video self modeling (VSM) using feedforward, to teach various goals of a picture exchange communication system (PECS). The participants were two boys with autism and one man with Down syndrome. All three participants were non-verbal with no current functional system of communication; the two children had long histories of PECS failure. A series of replications, with different length baselines, was used to examine whether video self modeling could replace the PECS method of teaching to achieve the same goals. All three participants showed rapid learning of their target behavior when introduced to their self modeling videos, and effects generalized without the need for further intervention. We conclude that VSM, using feedforward, can provide a fast, simple way of teaching the use of a picture-based communication system without the need for prompts or intensive operant conditioning. VSM may provide an accessible, easy-to-use alternative to common methods of teaching augmentative and alternative communication systems. C1 [Smith, Jemma; Hand, Linda; Dowrick, Peter W.] Univ Auckland, Dept Psychol, Auckland, New Zealand. 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A., 1989, P AM COLL SPORTS MED, P1 Wert BY, 2003, J POSIT BEHAV INTERV, V5, P30, DOI 10.1177/10983007030050010501 Whitlow C. K., 2003, J RES SPECIAL ED NEE, V3, DOI [10.1111/j.1471-3802.2003.00183.x, DOI 10.1111/J.1471-3802.2003.00183.X] NR 53 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 926 EP 936 DI 10.1007/s10803-013-1946-0 PG 11 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900018 PM 24068486 ER PT J AU Holm, MB Baird, JM Kim, YJ Rajora, KB D'Silva, D Podolinsky, L Mazefsky, C Minshew, N AF Holm, Margo B. Baird, Joanne M. Kim, Young Joo Rajora, Kuwar B. D'Silva, Delma Podolinsky, Lin Mazefsky, Carla Minshew, Nancy TI Therapeutic Horseback Riding Outcomes of Parent-Identified Goals for Children with Autism Spectrum Disorder: An ABA' Multiple Case Design Examining Dosing and Generalization to the Home and Community SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Single subject design; Home; Community ID ABERRANT BEHAVIOR CHECKLIST; GROSS MOTOR FUNCTION; CEREBRAL-PALSY; SPECIAL-EDUCATION; HIPPOTHERAPY; PROGRAM; METAANALYSIS; HEALTH; TRIAL AB We examined whether different doses of therapeutic riding influenced parent-nominated target behaviors of children with autism spectrum disorder (ASD) (a) during the session (b) at home, and (c) in the community. We used a single subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5 times/week. Three boys with ASD, 6-8 years of age participated, and counts of target behaviors were collected in each setting and phase of the study. Compared to Baseline, 70 % of the target behaviors were better during Intervention and improvement was retained in 63 % of the behaviors during Withdrawal. Increased doses of therapeutic riding were significant for magnitude of change, and the effect of the therapeutic riding sessions generalized to home and community. C1 [Holm, Margo B.; Baird, Joanne M.; Kim, Young Joo; Rajora, Kuwar B.; D'Silva, Delma] Univ Pittsburgh, Dept Occupat Therapy, Sch Hlth & Rehabil Sci SHRS, Pittsburgh, PA 15260 USA. [Podolinsky, Lin] Nickers N Neighs, Acme, PA 15610 USA. [Mazefsky, Carla] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15213 USA. [Mazefsky, Carla; Minshew, Nancy] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Minshew, Nancy] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. 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Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 937 EP 947 DI 10.1007/s10803-013-1949-x PG 11 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900019 PM 24091469 ER PT J AU Hirota, T Veenstra-VanderWeele, J Hollander, E Kishi, T AF Hirota, Tomoya Veenstra-VanderWeele, Jeremy Hollander, Eric Kishi, Taro TI Antiepileptic Medications in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Antiepileptic; Mood stabilizer; Anticonvulsant; Autism; Pervasive developmental disorder ID BORDERLINE PERSONALITY-DISORDER; PLACEBO-CONTROLLED TRIAL; PERVASIVE DEVELOPMENTAL DISORDERS; DOUBLE-BLIND; DIVALPROEX SODIUM; CHILDREN; AGGRESSION; ADOLESCENTS; LEVETIRACETAM; IRRITABILITY AB Electroencephalogram-recorded epileptiform activity is common in children with autism spectrum disorder (ASD), even without clinical seizures. A systematic literature search identified 7 randomized, placebo-controlled trials of antiepileptic drugs (AEDs) in ASD (total n = 171), including three of valproate, and one each of lamotrigine, levetiracetam, and topiramate. Meta-analysis revealed no significant difference between medication and placebo in four studies targeting irritability/agitation and three studies investigating global improvement, although limitations include lack of power and different medications with diverse actions. Across all seven studies, there was no significant difference in discontinuation rate between two groups. AEDs do not appear to have a large effect size to treat behavioral symptoms in ASD, but further research is needed, particularly in the subgroup of patients with epileptiform abnormalities. C1 [Hirota, Tomoya; Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Dept Psychiat, Med Ctr, Nashville, TN 37212 USA. [Hollander, Eric] Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10467 USA. 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Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 948 EP 957 DI 10.1007/s10803-013-1952-2 PG 10 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900020 PM 24077782 ER PT J AU Erickson, CA Veenstra-Vanderweele, JM Melmed, RD McCracken, JT Ginsberg, LD Sikich, L Scahill, L Cherubini, M Zarevics, P Walton-Bowen, K Carpenter, RL Bear, M Wang, P King, B AF Erickson, Craig A. Veenstra-Vanderweele, Jeremy M. Melmed, Raun D. McCracken, James T. Ginsberg, Lawrence D. Sikich, Linmarie Scahill, Lawrence Cherubini, Maryann Zarevics, Peter Walton-Bowen, Karen Carpenter, Randall L. Bear, Mark F. Wang, Paul P. King, Bryan H. TI STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE STX209; Arbaclofen; Gamma-aminobutyric acid (GABA); Autism spectrum disorder; Clinical trial ID PERVASIVE DEVELOPMENTAL DISORDERS; FRAGILE-X-SYNDROME; GABA(B) RECEPTORS; CHILDREN; EXCITATION/INHIBITION; COMMUNICATION; DYSFUNCTION; MEDICINE; GENETICS; TRIAL AB STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32 children and adolescents with either Autistic Disorder or Pervasive Developmental Disorder-Not Otherwise Specified, and a score a parts per thousand yen17 on the Aberrant Behavior Checklist (ABC)-Irritability subscale. STX209 was generally well-tolerated. The most common adverse events were agitation and irritability, which typically resolved without dose changes, and were often felt to represent spontaneous variation in underlying symptoms. Improvements were observed on several outcome measures in this exploratory trial, including the ABC-Irritability (the primary endpoint) and the Lethargy/Social Withdrawal subscales, the Social Responsiveness Scale, the CY-BOCS-PDD, and clinical global impression scales. Placebo-controlled study of STX209 is warranted. C1 [Erickson, Craig A.] Cincinnati Childrens Hosp Med Ctr, Div Child & Adolescent Psychiat, Cincinnati, OH 45229 USA. [Veenstra-Vanderweele, Jeremy M.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. [Melmed, Raun D.] Southwest Autism Res & Resource Ctr, Scottsdale, AZ USA. [McCracken, James T.] Univ Calif Los Angeles, NPI Semel Inst, Los Angeles, CA USA. [Ginsberg, Lawrence D.] Red Oak Psychiat Associates, Houston, TX USA. [Sikich, Linmarie] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Scahill, Lawrence] Emory Univ, Marcus Autism Ctr, Atlanta, GA 30322 USA. [Cherubini, Maryann; Zarevics, Peter; Walton-Bowen, Karen; Carpenter, Randall L.; Wang, Paul P.] Seaside Therapeut Inc, Cambridge, MA 02139 USA. [Bear, Mark F.] MIT, Dept Brain & Cognit Sci, Howard Hughes Med Inst, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [King, Bryan H.] Univ Washington, Dept Psychiat & Behav Sci, Seattle Childrens Hosp, Seattle, WA 98195 USA. RP Wang, P (reprint author), Seaside Therapeut Inc, 840 Mem Dr, Cambridge, MA 02139 USA. 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TI Brief Report: An Evaluation of TAGteach Components to Decrease Toe-Walking in a 4-Year-Old Child with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Toe-walking; TAGteach; Autism; Conditioned reinforcement AB The current study evaluated the effectiveness of using a modified TAGteach (TM) procedure and correction to decrease toe-walking in a 4-year-old boy with autism. Two conditions were analyzed: correction alone and correction with an audible conditioned reinforcing stimulus. Correction alone produced minimal and inconsistent decreases in toe-walking but correction with an audible conditioned stimulus proved most effective in reducing this behavior. This has implications for decreasing toe-walking in other children with autism and may be easily used by teachers and parents. C1 [Persicke, Angela; Jackson, Marianne; Adams, Amanda N.] Calif State Univ Fresno, Fresno, CA 93740 USA. 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PD APR PY 2014 VL 44 IS 4 BP 965 EP 968 DI 10.1007/s10803-013-1934-4 PG 4 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900022 PM 24008838 ER PT J AU Ozsivadjian, A Hibberd, C Hollocks, MJ AF Ozsivadjian, Ann Hibberd, Charlotte Hollocks, Matthew J. TI Brief Report: The Use of Self-Report Measures in Young People with Autism Spectrum Disorder to Access Symptoms of Anxiety, Depression and Negative Thoughts SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Affective disorders; Anxiety disorders; Cognition; Cognitive behavioral therapy; Emotion; Neurodevelopmental disorders ID CONTROLLED-TRIAL; CHILDREN; PARENT; ADOLESCENTS; SAMPLE; YOUTH AB The aims of this study were two-fold; firstly, to investigate whether self-report measures are useful and reflect parent-reported psychiatric symptoms in children with autism spectrum disorder (ASD), and secondly, to investigate whether children with ASD are able to access and report their cognitions, a prerequisite skill for cognitive behavior therapies. Thirty children with ASD and 21 comparison children without ASD completed the Spence Children's Anxiety Scale and the Children's Depression Inventory, with parents completing the parent version of both questionnaires. Intraclass correlations revealed that there was good agreement between ASD children and their parents on both measures, but only on the depression measure in non-ASD children. The children in both groups also completed the Children's Automatic Thoughts Questionnaires; multiple regression analyses indicated that within the ASD group, child-rated scores on the CATS questionnaire were positively related to increased self-reported symptoms of anxiety and depression, but not in the comparison group, suggesting that children with ASD are able to accurately report their anxious and depressed cognitions. The implications of these results for both the practice and theory of CBT for children with ASD are discussed. C1 [Ozsivadjian, Ann] St Thomas Hosp, Newcomen St Thomas, Childrens Neurosci Dept, London SE1 7EH, England. [Hibberd, Charlotte] St Thomas Hosp, Newcomen St Thomas, London SE1 7EH, England. 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PD APR PY 2014 VL 44 IS 4 BP 969 EP 974 DI 10.1007/s10803-013-1937-1 PG 6 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900023 PM 24014195 ER PT J AU Esposito, G Rostagno, MD Venuti, P Haltigan, JD Messinger, DS AF Esposito, Gianluca Rostagno, Maria del Carmen Venuti, Paola Haltigan, John D. Messinger, Daniel S. TI Brief Report: Atypical Expression of Distress During the Separation Phase of the Strange Situation Procedure in Infant Siblings at High Risk for ASD SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Cry; Autism spectrum disorders; Fundamental frequency; Strange situation; Behavior ID TYPICAL DEVELOPMENT; SPECTRUM DISORDER; AUTISTIC DISORDER; YOUNG-CHILDREN; EMOTION; CRY; RESPONSES; LANGUAGE; DELAY; AGE AB Previous studies have provided preliminary evidence that disruptions in cry acoustics may be part of an atypical vocal signature of autism early in life. We examined the acoustic characteristics of cries extracted from the separation phase of the strange situation procedure in a sample of toddler of younger siblings of a child with autism spectrum disorder-autism spectrum disorders (ASD) (high risk, HR) and a low risk (LR) group. Cry samples derived from vocal recordings of 15-month-old HR (n = 13) and LR infants (n = 14) were subjected to acoustic analyses. HR toddlers, compared to those with LR, produced cries that were shorter and had a higher fundamental frequency (F0). Three HR toddlers later classified with an ASD at 36 months (autistic disorder in all cases) produced cries that had among the highest F0 and shortest durations. Taken together these results indicate that toddlers at high risk for ASD (and those with an ASD) express atypical patterns of distress in response a social stressor. Implications for early diagnosis and parenting are discussed. C1 [Esposito, Gianluca] RIKEN Brain Sci Inst, Unit Affiliat Social Behav, Saitama, Japan. [Esposito, Gianluca; Rostagno, Maria del Carmen; Venuti, Paola] Univ Trento, Dept Psychol & Cognit Sci, Trento, Italy. [Haltigan, John D.] Univ N Carolina, Greensboro, NC 27412 USA. [Messinger, Daniel S.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Messinger, Daniel S.] Univ Miami, Dept Pediat, Coral Gables, FL 33124 USA. [Messinger, Daniel S.] Univ Miami, Dept Elect & Comp Engn, Coral Gables, FL 33124 USA. RP Esposito, G (reprint author), RIKEN Brain Sci Inst, Unit Affiliat Social Behav, Saitama, Japan. EM gesposito@brain.riken.jp CR Ainsworth M. D., 1969, DETERMINANTS INFANT, V4, P113 Ainsworth M. D. 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Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 975 EP 980 DI 10.1007/s10803-013-1940-6 PG 6 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900024 PM 24026913 ER PT J AU Erickson, CA Wink, LK Early, MC Stiegelmeyer, E Mathieu-Frasier, L Patrick, V McDougle, CJ AF Erickson, Craig A. Wink, Logan K. Early, Maureen C. Stiegelmeyer, Elizabeth Mathieu-Frasier, Lauren Patrick, Vanessa McDougle, Christopher J. TI Brief Report: Pilot Single-Blind Placebo Lead-In Study of Acamprosate in Youth with Autistic Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Acamprosate; Autism spectrum disorder; Glutamate; Gamma-aminobutyric acid ID FRAGILE-X-SYNDROME; PERVASIVE DEVELOPMENTAL DISORDERS; MGLUR5 ANTAGONIST MPEP; DIAGNOSTIC INTERVIEW; GLUTAMATE RECEPTORS; MENTAL-RETARDATION; GABA(A) RECEPTOR; RATING-SCALE; MOUSE MODEL; OPEN-LABEL AB Rationale An excitatory/inhibitory (E:I) imbalance marked by enhanced glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission may contribute to the pathophysiology of autism spectrum disorders (ASD). We report on the first single-blind placebo lead-in trial of acamprosate, a drug with putative mechanisms restoring E:I imbalance, in twelve youth with ASD. We conducted a 12-week single-blind, placebo lead-in study of acamprosate in youth age 5-17 years with autistic disorder. Six of nine subjects who received active drug treatment were deemed treatment responders (defined by a score at final visit of "very much improved" or "much improved" on the Clinical Global Impressions Improvement scale) and a parts per thousand yen25 % improvement on the Aberrant Behavior Checklist Social Withdrawal subscale. Future larger-scale dose finding studies of acamprosate in ASD may be warranted given this preliminary indication of benefit. C1 [Erickson, Craig A.; Wink, Logan K.; Early, Maureen C.; Stiegelmeyer, Elizabeth; Mathieu-Frasier, Lauren; Patrick, Vanessa; McDougle, Christopher J.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Erickson, Craig A.; Wink, Logan K.; Early, Maureen C.; Stiegelmeyer, Elizabeth; Mathieu-Frasier, Lauren; Patrick, Vanessa; McDougle, Christopher J.] James Whitcomb Riley Hosp Children, Christian Sarkine Autism Treatment Ctr, Indianapolis, IN 46202 USA. RP Erickson, CA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Child & Adolescent Psychiat, 3333 Burnet Ave,MLC 4002, Cincinnati, OH 45215 USA. 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Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 981 EP 987 DI 10.1007/s10803-013-1943-3 PG 7 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900025 PM 24052275 ER PT J AU Anderson, GM Stahl, SS AF Anderson, George M. Stahl, Sherin S. TI Two Proposed Early Biomarker Tests of ASD: More Harm Than Good SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Letter ID TROPHOBLAST INCLUSIONS; AUTISM; CHILDREN; BRAIN C1 [Anderson, George M.; Stahl, Sherin S.] Yale Univ, Sch Med, Yale Child Study Ctr, Dept Child Psychiat, New Haven, CT 06519 USA. [Anderson, George M.] Yale Univ, Sch Med, Yale Child Study Ctr, Dept Lab Med, New Haven, CT 06519 USA. [Stahl, Sherin S.] Yale Univ, Sch Med, Yale Child Study Ctr, Dept Pediat, New Haven, CT 06519 USA. RP Anderson, GM (reprint author), Yale Univ, Sch Med, Yale Child Study Ctr, Dept Child Psychiat, 230 S Frontage Rd, New Haven, CT 06519 USA. EM george.anderson@yale.edu CR Anderson GM, 2007, BIOL PSYCHIAT, V61, P487, DOI 10.1016/j.biopsych.2006.03.068 Bauman MD, 2013, TRANSL PSYCHIAT, V3, DOI 10.1038/tp.2013.47 Braunschweig D, 2013, TRANSL PSYCHIAT, V3, DOI 10.1038/tp.2013.50 Walker CK, 2013, BIOL PSYCHIAT, V74, P204, DOI 10.1016/j.biopsych.2013.03.006 Wingate M., 2012, MMWR SURVEILL SUMM, V61, P1 NR 5 TC 1 Z9 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD APR PY 2014 VL 44 IS 4 BP 988 EP 989 DI 10.1007/s10803-013-1981-x PG 2 WC Psychology, Developmental SC Psychology GA AC7EB UT WOS:000332688900026 PM 24174282 ER PT J AU Al Jabery, MA Arabiat, DH Al Khamra, HA Betawi, IA Jabbar, SKA AF AL Jabery, Mohammad A. Arabiat, Diana H. AL Khamra, Hatem A. Betawi, Iman Amy Jabbar, Sinaria Kamil Abdel TI Parental Perceptions of Services Provided for Children with Autism in Jordan SO JOURNAL OF CHILD AND FAMILY STUDIES LA English DT Article DE Autism; Parents' satisfaction; Special education; Parent's perceptions; Services in Jordan ID SPECTRUM DISORDERS; EDUCATION; DISABILITIES; CARE; COMPLEMENTARY; SATISFACTION; VOICES; ACCESS; VIEWS; NEEDS AB Providing formal support for children with autism and their parents is important and mandatory to improve children's abilities and enhance the capabilities of parents. The present study attempted to investigate the perceptions of parents of children with autism regarding the services provided in Jordan. A questionnaire consisting of five sections was designed and distributed to a sample of 60 parents of children with autism (5-18 years old) among four special education institutions in Jordan. The questionnaire addressed five domains: demographics, type and number of received services, methods and difficulties of obtaining services, parents' satisfaction, and parents' perceived needed services. The results revealed that the service delivery system with which parents interacted was composed of multiple places and providers, but had several difficulties. Parents participating in this study expressed an average satisfaction with the received services. Issues pertaining to the cost of services, parents-professional partnerships, and overall quality of services were seen by parents as sources of low satisfaction. On the other hand, parents expressed the need for early intervention, family counseling, and community awareness services. Further suggestions and implications are presented in the study. C1 [AL Jabery, Mohammad A.; AL Khamra, Hatem A.] Univ Jordan, Dept Counseling & Special Educ, Fac Educ Sci, Amman 11942, Jordan. [Arabiat, Diana H.] Univ Jordan, Dept Maternal & Child Hlth Nursing, Fac Nursing, Amman 11942, Jordan. [Betawi, Iman Amy; Jabbar, Sinaria Kamil Abdel] Univ Jordan, Dept Curriculum & Instruct, Fac Educ Sci, Amman 11942, Jordan. RP Al Jabery, MA (reprint author), Univ Jordan, Dept Counseling & Special Educ, Fac Educ Sci, Amman 11942, Jordan. EM m.algabery@ju.edu.jo CR Al Khatib F., 2008, J INT ASS SPECIAL ED, V9, P109 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Batten A., 2006, MAKE SCH MAKE SENSE Bitterman A, 2008, J AUTISM DEV DISORD, V38, P1509, DOI 10.1007/s10803-007-0531-9 Brewin BJ, 2008, FOCUS AUTISM DEV DIS, V23, P242, DOI 10.1177/1088357608322997 Crabtree SA, 2007, DISABIL SOC, V22, P49, DOI 10.1080/09687590601056618 Goin-Kochel RP, 2009, RES AUTISM SPECT DIS, V3, P528, DOI 10.1016/j.rasd.2008.11.001 Green VA, 2006, RES DEV DISABIL, V27, P70, DOI 10.1016/j.ridd.2004.12.002 Green VA, 2007, J DEV PHYS DISABIL, V19, P91, DOI 10.1007/s10882-007-9035-y Hess KL, 2008, J AUTISM DEV DISORD, V38, P961, DOI 10.1007/s10803-007-0470-5 Higher Council for Affairs of Persons with Disabilities (HCAPD), 2007, LAW RIGHTS PERS DIS Higher Council for Affairs of Persons with Disabilities (HCAPD), 2010, IND SPEC ED I ED PER Jarbrink K, 2003, J AUTISM DEV DISORD, V33, P395, DOI 10.1023/A:1025058711465 Kohelr F., 1999, FOCUS AUTISM OTHER D, V3, P150 Krauss MW, 2003, MENT RETARD, V41, P329, DOI 10.1352/0047-6765(2003)41<329:ATSMCF>2.0.CO;2 Liptak Gregory S, 2006, J Pediatr Health Care, V20, P245, DOI 10.1016/j.pedhc.2005.12.008 Mackintosh V. 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M., 2008, EFFECTIVE PRACTICES, P111 Wong HHL, 2006, J AUTISM DEV DISORD, V36, P901, DOI 10.1007/s10803-006-0131-0 NR 36 TC 0 Z9 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1062-1024 EI 1573-2843 J9 J CHILD FAM STUD JI J. Child Fam. Stud. PD APR PY 2014 VL 23 IS 3 BP 475 EP 486 DI 10.1007/s10826-012-9703-0 PG 12 WC Family Studies; Psychology, Developmental; Psychiatry SC Family Studies; Psychology; Psychiatry GA AC6RE UT WOS:000332651300002 ER PT J AU Hwang, YS Kearney, P AF Hwang, Yoon-Suk Kearney, Patrick TI Mindful and Mutual Care for Individuals with Developmental Disabilities: A Systematic Literature Review SO JOURNAL OF CHILD AND FAMILY STUDIES LA English DT Review DE Mindfulness; Care; Stress; Developmental disabilities; Autism Spectrum Disorders ID PARENTING DECREASES AGGRESSION; INTELLECTUAL DISABILITIES; CHILDREN; STAFF; CAREGIVERS; BEHAVIOR; AUTISM; REDUCE AB Parental and professional caregivers of individuals with developmental disabilities (DD) often experience stress and hardship associated with their role, placing them in real danger of burnout and affecting their quality of care. Mindfulness practice is currently being applied to address these issues. We conducted a systematic literature review to explore the effects of mindfulness practice and analyse the intervention and methodological features used for eliciting these effects. An initial search produced 386 publications. Of these, seven met the selection criteria of intervention studies that applied mindfulness to parental and professional caregivers of individuals with DD. We found, from analysis of seven studies, direct effects of mindfulness practice for practitioners (i.e., parental and professional caregivers) and crossover effects for individuals with whom these practitioners interacted (i.e., their children and care recipients). The studies under review collectively suggest that the practice of mindfulness in everyday life over significant periods of time can both improve the experience of care providers and support them in providing a better standard of care for care recipients. 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V., 2002, MINDFULNESS BASED CO Singh NN, 2006, J EMOT BEHAV DISORD, V14, P169, DOI 10.1177/10634266060140030401 Singh NN, 2007, BEHAV MODIF, V31, P749, DOI 10.1177/0145445507300924 Singh NN, 2009, J APPL RES INTELLECT, V22, P194, DOI 10.1111/j.1468-3148.2008.00488.x Singh NN, 2004, RES DEV DISABIL, V25, P207, DOI 10.1016/j.ridd.2003.05.001 Singh NN, 2006, RES DEV DISABIL, V27, P545, DOI 10.1016/j.ridd.2005.07.002 Weiss JA, 2011, J CHILD FAM STUD, V20, P521, DOI 10.1007/s10826-010-9419-y NR 22 TC 1 Z9 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1062-1024 EI 1573-2843 J9 J CHILD FAM STUD JI J. Child Fam. Stud. PD APR PY 2014 VL 23 IS 3 BP 497 EP 509 DI 10.1007/s10826-012-9707-9 PG 13 WC Family Studies; Psychology, Developmental; Psychiatry SC Family Studies; Psychology; Psychiatry GA AC6RE UT WOS:000332651300004 ER PT J AU Ghanizadeh, A Sahraeizadeh, A Berk, M AF Ghanizadeh, Ahmad Sahraeizadeh, Aliakbar Berk, Michael TI A Head-to-Head Comparison of Aripiprazole and Risperidone for Safety and Treating Autistic Disorders, a Randomized Double Blind Clinical Trial SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE Autism; Treatment; Aripiprazole; Risperidone; Clinical trial; Randomized ID PLACEBO-CONTROLLED TRIAL; PEDIATRIC-PATIENTS; ABERRANT BEHAVIOR; CHILDREN; IRRITABILITY; ADOLESCENTS AB Aripiprazole and risperidone are the only FDA approved medications for treating irritability in autistic disorder, however there are no head-to-head data comparing these agents. This is the first prospective randomized clinical trial comparing the safety and efficacy of these two medications in patients with autism spectrum disorders. Fifty nine children and adolescents with autism spectrum disorders were randomized to receive either aripiprazole or risperidone for 2 months. The primary outcome measure was change in Aberrant Behavior Checklist (ABC) scores. Adverse events were assessed. Aripiprazole as well as risperidone lowered ABC scores during 2 months. The rates of adverse effects were not significantly different between the two groups. The safety and efficacy of aripiprazole (mean dose 5.5 mg/day) and risperidone (mean dose 1.12 mg/day) were comparable. The choice between these two medications should be on the basis of clinical equipoise considering the patient's preference and clinical profile. C1 [Ghanizadeh, Ahmad; Sahraeizadeh, Aliakbar] Shiraz Univ Med Sci, Sch Med, Res Ctr Psychiat & Behav Sci, Shiraz, Iran. [Ghanizadeh, Ahmad; Sahraeizadeh, Aliakbar] Shiraz Univ Med Sci, Sch Med, Dept Psychiat, Shiraz, Iran. [Berk, Michael] Deakin Univ, Sch Med, Geelong, Vic 3217, Australia. [Berk, Michael] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Orygen Res Ctr, Dept Psychiat, Melbourne, Vic, Australia. RP Ghanizadeh, A (reprint author), Shiraz Univ Med Sci, Sch Med, Res Ctr Psychiat & Behav Sci, Shiraz, Iran. 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Hum. Dev. PD APR PY 2014 VL 45 IS 2 BP 185 EP 192 DI 10.1007/s10578-013-0390-x PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AB8YS UT WOS:000332076700006 PM 23801256 ER PT J AU Wu, MS McGuire, JF Arnold, EB Lewin, AB Murphy, TK Storch, EA AF Wu, Monica S. McGuire, Joseph F. Arnold, Elysse B. Lewin, Adam B. Murphy, Tanya K. Storch, Eric A. TI Psychometric Properties of the Children's Yale-Brown Obsessive Compulsive Scale in Youth with Autism Spectrum Disorders and Obsessive-Compulsive Symptoms SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE Obsessive-compulsive disorder; Autism spectrum disorder; Children; Assessment; Reliability ID PERVASIVE DEVELOPMENTAL DISORDERS; COGNITIVE-BEHAVIORAL THERAPY; HIGH-FUNCTIONING AUTISM; MULTIDIMENSIONAL ANXIETY SCALE; DIAGNOSTIC INTERVIEW; CONTROLLED-TRIAL; PARENT VERSIONS; ADOLESCENTS; RELIABILITY; DIMENSIONS AB The psychometric properties of the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) were investigated in 46 treatment-seeking youth, 7-15 years of age, who were diagnosed with an autism spectrum disorder (ASD) and exhibited obsessive-compulsive symptoms. The CY-BOCS Total score exhibited good internal consistency, with differing internal consistencies observed on the Obsession Severity scale (alpha = 0.86) and Compulsion Severity scale (alpha = 0.59). Good to excellent inter-rater reliability was observed for the CY-BOCS Total score and both Severity scales. Convergent and divergent validity of the CY-BOCS Total score and both Severity scales were satisfactory. Insight into obsessive-compulsive symptoms was moderately associated with the CY-BOCS Total score. The CY-BOCS demonstrated treatment sensitivity, demonstrating significant changes in obsessive-compulsive symptoms within a subsample of youth receiving cognitive-behavioral treatment. Overall, the CY-BOCS demonstrated adequate psychometric properties and utility in assessing obsessive-compulsive symptoms in youth with ASD and clinically significant obsessive-compulsive symptoms. C1 [Wu, Monica S.] Univ S Florida, Rothman Ctr Neuropsychiat, Dept Pediat, St Petersburg, FL 33701 USA. [Wu, Monica S.; McGuire, Joseph F.; Storch, Eric A.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. [McGuire, Joseph F.; Arnold, Elysse B.; Lewin, Adam B.; Murphy, Tanya K.; Storch, Eric A.] Univ S Florida, Dept Pediat, Morsani Coll Med, Tampa, FL 33620 USA. [Lewin, Adam B.; Murphy, Tanya K.; Storch, Eric A.] Univ S Florida, Dept Psychiat & Behav Neurosci, Morsani Coll Med, Tampa, FL USA. RP Wu, MS (reprint author), Univ S Florida, Rothman Ctr Neuropsychiat, Dept Pediat, 880 6th St South,Suite 460,Box 7523, St Petersburg, FL 33701 USA. 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PD APR PY 2014 VL 45 IS 2 BP 201 EP 211 DI 10.1007/s10578-013-0392-8 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AB8YS UT WOS:000332076700008 PM 23827959 ER PT J AU Ahmadlou, M Adeli, A Bajo, R Adeli, H AF Ahmadlou, Mehran Adeli, Anahita Bajo, Ricardo Adeli, Hojjat TI Complexity of functional connectivity networks in mild cognitive impairment subjects during a working memory task SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Complexity of functional connectivity networks; Efficiency Complexity; Graph Index Complexity; Magneto encephalography; Mild cognitive impairment; Working memory ID FUZZY SYNCHRONIZATION LIKELIHOOD; AUTISM SPECTRUM DISORDER; EEG-BASED DIAGNOSIS; GRAY-MATTER LOSS; ALZHEIMERS-DISEASE; GENERALIZED SYNCHRONIZATION; THETA OSCILLATIONS; WEIGHTED NETWORKS; EPISODIC MEMORY; BRAIN DYNAMICS AB Objectives: The objective is to study the changes of brain activity in patients with mild cognitive impairment (MCI). Using magneto-encephalogram (MEG) signals, the authors investigate differences of complexity of functional connectivity network between MCI and normal elderly subjects during a working memory task. Methods: MEGs are obtained from 18 right handed patients with MCI and 19 age-matched elderly participants without cognitive impairment used as the control group. The brain networks' complexities are measured by Graph Index Complexity (C-r) and Efficiency Complexity (C-e). Results: The results obtained by both measurements show complexity of functional networks involved in the working memory function in MCI subjects is reduced at alpha and theta bands compared with subjects with control subjects, and at the theta band this reduction is more pronounced in the whole brain and intra left hemisphere. Conclusions: Ce would be a better measurement for showing the global differences between normal and MCI brains compared with Cr. Significance: The high accuracy of the classification shows Ce at theta band can be used as an index for assessing deficits associated with working memory, a good biomarker for diagnosis of MCI. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Ahmadlou, Mehran] Netherlands Inst Neurosci, Amsterdam, Netherlands. [Adeli, Anahita] Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA. [Bajo, Ricardo] Ctr Biomed Technol CTB, Lab Cognit & Computat Neurosci UCM UPM, Madrid 28223, Spain. [Adeli, Hojjat] Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA. [Adeli, Hojjat] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA. [Adeli, Hojjat] Ohio State Univ, Dept Civil Environm & Geodet Engn, Columbus, OH 43210 USA. [Adeli, Hojjat] Ohio State Univ, Dept Elect & Comp Engn, Columbus, OH 43210 USA. [Adeli, Hojjat] Ohio State Univ, Dept Neurol Surg, Columbus, OH 43210 USA. [Adeli, Hojjat] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA. RP Adeli, H (reprint author), Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA. 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Neurophysiol. PD APR PY 2014 VL 125 IS 4 BP 694 EP 702 DI 10.1016/j.clinph.2013.08.033 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AC3FH UT WOS:000332400300009 PM 24405905 ER PT J AU Blackman, JA Conaway, MR AF Blackman, James A. Conaway, Mark R. TI Adolescents With Cerebral Palsy: Transitioning to Adult Health Care Services SO CLINICAL PEDIATRICS LA English DT Article DE cerebral palsy; adolescents; transition; disability; developmental pediatrics; behavior ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; QUALITY-OF-LIFE; BEHAVIORAL-PROBLEMS; YOUNG-ADULTS; CHILDREN; PAIN; COORDINATION; AGREEMENT; PARENT; FATIGUE AB Data from the 2009-2010 US National Survey of Children with Special Health Care Needs were examined to determine the health, developmental and behavioral status of adolescents with cerebral palsy (CP) and to assess how well pediatric health care providers were preparing them for transition to adult health care services. Adolescents with CP had no higher rates of attention deficit hyperactivity disorder, depression, anxiety, oppositional or conduct disorders, or autism spectrum than a comparison group. However, those with CP participated less in sports, clubs, or other organized activities (P < .001). Neither group reported much help in coordinating health services or preparing for transition to adult health care services. Inadequate adult health care services have a direct and unsatisfactory impact on the adult life span. Physicians and other health care providers who include adolescents with CP in their practices should begin discussion and planning for transition to adult health care early in adolescence. C1 [Blackman, James A.; Conaway, Mark R.] Univ Virginia, Charlottesville, VA USA. [Blackman, James A.] Cerebral Palsy Int Res Fdn, Princeton Jct, NJ 08550 USA. RP Blackman, JA (reprint author), Cerebral Palsy Int Res Fdn, 186 Princeton Hightstown Roa, Princeton Jct, NJ 08550 USA. EM jblackman@cpirf.org FU US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [R40 MC 20610] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by grant number R40 MC 20610 from the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program. 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Pediatr. PD APR PY 2014 VL 53 IS 4 BP 356 EP 363 DI 10.1177/0009922813510203 PG 8 WC Pediatrics SC Pediatrics GA AC0SU UT WOS:000332205900009 PM 24275216 ER PT J AU Alessandrini, A Cappelletti, A Zancanaro, M AF Alessandrini, Andrea Cappelletti, Alessandro Zancanaro, Massimo TI Audio-augmented paper for therapy and educational intervention for children with autistic spectrum disorder SO INTERNATIONAL JOURNAL OF HUMAN-COMPUTER STUDIES LA English DT Article DE Autism spectrum disorder; Social competence; Social story; Audio-augmented paper; Interaction design; Tangible user interface ID YOUNG-CHILDREN AB Autism affects children's learning and social development. Commonly used rehabilitative treatments are aimed at stimulating the social skills of children with autism. In this article, we present a prototype and a pilot study on an audio-augmented paper to support the therapy of children with autism spectrum disorder (ASD). The prototype supports audio recording with standard sheets of paper by using tangible tools that can be shared between the therapist and the child. The prototype is a tool for the therapist to engage the child in a storytelling activity. We use a progressive design method based on a dynamic process that merges concept generation, technology benchmarking and activity design into continuously enriching actions. The paper highlights the qualities and benefits of using tangible audio-augmented artefacts for therapy and educational intervention for children with ASD. The work describes three main qualities of our prototype: from building cooperation to attention control, flow control, and using the children's own voices to foster attention. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Alessandrini, Andrea] Univ Dundee, Coll Art Sci & Engn, Dundee DD1 4HN, Scotland. RP Alessandrini, A (reprint author), Univ Dundee, Coll Art Sci & Engn, Dundee DD1 4HN, Scotland. EM a.alessandrini@dundee.ac.uk FU European Commission through the COSPATIAL Project (FP7) [231266] FX This work has been partially funded by the European Commission through the COSPATIAL Project (FP7, Grant agreement no. 231266). We would like to thank the children, their families and the therapists of the Associazione Genitori Soggetti Autistici del Trentino (A.G.S.A.T.) education centre in Trento, Italy. CR Alessandrini A., 2013, P HUM FACT COMP SYST, P505 Antle A. N., 2009, P 8 INT C INT DES CH, P80, DOI 10.1145/1551788.1551803 Antle AN, 2007, P 1 INT C TANG EMB I, P195, DOI 10.1145/1226969.1227010 Back M., 2001, P SIGCHI C HUM FACT, P23, DOI 10.1145/365024.365031 Carroll J. 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Stavarache, Mihaela Kaplitt, Michael Bonci, Antonello Powell, Craig M. TI PTEN Knockdown Alters Dendritic Spine/Protrusion Morphology, not Density SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE dendrite; spine; amygdale; dentate gyrus; AKT; mTOR; PTEN ID AUTISM SPECTRUM DISORDERS; LHERMITTE-DUCLOS-DISEASE; TUMOR-SUPPRESSOR GENE; BEHAVIORAL-TEST BATTERIES; RILEY-RUVALCABA-SYNDROME; GERMLINE MUTATIONS; MICROSCOPY IMAGES; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; PHOSPHATASE GENE AB Mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) are implicated in neuropsychiatric disorders including autism. Previous studies report that PTEN knockdown in neurons in vivo leads to increased spine density and synaptic activity. To better characterize synaptic changes in neurons lacking PTEN, we examined the effects of shRNA knockdown of PTEN in basolateral amygdala neurons on synaptic spine density and morphology by using fluorescent dye confocal imaging. Contrary to previous studies in the dentate gyrus, we find that knockdown of PTEN in basolateral amygdala leads to a significant decrease in total spine density in distal dendrites. Curiously, this decreased spine density is associated with increased miniature excitatory postsynaptic current frequency and amplitude, suggesting an increase in number and function of mature spines. These seemingly contradictory findings were reconciled by spine morphology analysis demonstrating increased mushroom spine density and size with correspondingly decreased thin protrusion density at more distal segments. The same analysis of PTEN conditional deletion in the dentate gyrus demonstrated that loss of PTEN does not significantly alter total density of dendritic protrusions in the dentate gyrus, but does decrease thin protrusion density and increases density of more mature mushroom spines. These findings suggest that, contrary to previous reports, PTEN knockdown may not induce de novo spinogenesis, but instead may increase synaptic activity by inducing morphological and functional maturation of spines. Furthermore, behavioral analysis of basolateral amygdala PTEN knockdown suggests that these changes limited only to the basolateral amygdala complex may not be sufficient to induce increased anxiety-related behaviors. J. Comp. Neurol. 522:1171-1190, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Haws, Michael E.; Jaramillo, Thomas C.; Espinosa, Felipe; Widman, Allie J.; Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Haws, Michael E.; Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Neurosci Grad Program, Dallas, TX 75390 USA. [Russo, Scott J.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Parada, Luis F.] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA. [Stavarache, Mihaela; Kaplitt, Michael] Weill Cornell Med Coll, Dept Neurol Surg, New York, NY 10065 USA. [Bonci, Antonello] Natl Inst Drug Abuse, Intramural Res Program, Bethesda, MD 21224 USA. [Stuber, Garret D.; Sparta, Dennis R.; Tye, Kay M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Bonci, Antonello] Johns Hopkins Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21287 USA. [Bonci, Antonello] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21287 USA. [Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. RP Powell, CM (reprint author), 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM craig.powell@utsouthwestern.edu FU National Institute of Mental Health, National Institutes of Health [MH081164]; National Institute of Child Health and Human Development, National Institutes of Health [HD069560]; Autism Speaks; Lowe Foundation; Crystal Charity Ball; Hartwell Foundation FX Grant sponsor: National Institute of Mental Health, National Institutes of Health; Grant number: MH081164 (to C. M. P.); Grant sponsor: National Institute of Child Health and Human Development, National Institutes of Health; Grant number: HD069560 (to C. M. P.); Grant sponsor: Autism Speaks (to C. M. P.); Grant sponsor: Lowe Foundation (to C. M. P.); Grant sponsor: Crystal Charity Ball (to C. M. P.); Grant sponsor: The Hartwell Foundation (to C.M.P.). 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Comp. Neurol. PD APR 1 PY 2014 VL 522 IS 5 BP 1171 EP 1190 DI 10.1002/cne.23488 PG 20 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA AA3QF UT WOS:000331006700010 PM 24264880 ER PT J AU Stores, RJ Stores, G AF Stores, R. J. Stores, G. TI The significance of aspects of screening for obstructive sleep apnoea in children with Down syndrome SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE Down syndrome; obstructive sleep apnoea; screening ID ABERRANT BEHAVIOR CHECKLIST; YOUNG-CHILDREN; ADOLESCENTS; DISORDERS; DISTURBANCE; ACTIGRAPHY; VALIDITY; MEDICINE; AUTISM; IMPACT AB BackgroundThe sleep problems of children with intellectual disabilities remains a relatively neglected topic in spite of the consistent reports that such problems are common, often severe and persistent with potentially serious consequences for the children and their families. Children with Down syndrome (DS) are a case in point. They often suffer from obstructive sleep apnoea (OSA), early detection of which is recommended because of its potentially adverse effects on development. This study is concerned with aspects of assessment that have been considered important in helping to recognise OSA in children with DS. The relationships between different objective measures, and between these measures and parental reports of their child's sleep and daytime behaviour, were explored. MethodOvernight recordings were carried out on a group of children with DS (n=31) involving video and audio recording, oximetry and activity monitoring during sleep. Parents also completed questionnaires concerning their child's sleep and daytime behaviour. Results Parents' reports of restless sleep and noisy breathing were supported by objective measures of activity during sleep and audio recording respectively. No significant association was found between objective measures of restlessness during sleep and snoring' (see later for definition), nor were objective measures of restlessness related to reductions in overnight blood oxygen levels. However, the objective measure of snoring was significantly associated with reductions in overnight blood oxygen levels. All three of the objective measures were significantly associated with parental reports of various types of disturbed daytime behaviour. ConclusionsThe findings have implications for aspects of screening for OSA in children with DS and for the interpretation of the relevance of the results to the children's daytime behaviour. C1 [Stores, R. J.] Univ Portsmouth, Sch Hlth Sci & Social Work, Portsmouth PO1 2FR, Hants, England. [Stores, G.] Univ Oxford, Oxford, England. RP Stores, RJ (reprint author), Univ Portsmouth, Sch Hlth Sci & Social Work, 2 King Richard 1st Rd, Portsmouth PO1 2FR, Hants, England. 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B. M., 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0021879 Wiggs L., 2005, INT J BEHAV CONSULT, V1, P165 NR 38 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-2633 EI 1365-2788 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD APR PY 2014 VL 58 IS 4 BP 381 EP 392 DI 10.1111/jir.12033 PG 12 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA AA7PO UT WOS:000331289600007 PM 23489956 ER PT J AU Englund, JA Decker, SL Allen, RA Roberts, AM AF Englund, Julia A. Decker, Scott L. Allen, Ryan A. Roberts, Alycia M. TI Common Cognitive Deficits in Children With Attention-Deficit/Hyperactivity Disorder and Autism: Working Memory and Visual-Motor Integration SO JOURNAL OF PSYCHOEDUCATIONAL ASSESSMENT LA English DT Article DE assessment; ADHD; autism; working memory; intelligence ID EXECUTIVE FUNCTION DEFICITS; SPECTRUM DISORDERS; NEURODEVELOPMENTAL DISORDERS; HYPERACTIVITY DISORDER; CONSTRUCT-VALIDITY; DOPAMINE THEORY; FRONTAL-LOBE; ADHD; IMPAIRMENTS; INTELLIGENCE AB Cognitive deficits in working memory (WM) are characteristic features of Attention-Deficit/Hyperactivity Disorder (ADHD) and autism. However, few studies have investigated cognitive deficits using a wide range of cognitive measures. We compared children with ADHD (n = 49) and autism (n = 33) with a demographically matched control group (n = 79) on a multidimensional battery of cognitive ability. Results confirmed previous research that both groups were characterized by deficits in WM. However, results also suggest verbal WM measures were better predictors than nonverbal WM measures. In addition, measures of visual-motor integration are equally discriminating of children with ADHD and autism from a matched control group. In all, 81% discrimination accuracy was obtained using only WM and visual-motor integration measures. Demonstrated shared deficits in WM and visual-motor integration are explained based on proposed neurological mechanisms common across the two disorders. Clinical implications are discussed. C1 [Englund, Julia A.; Decker, Scott L.; Roberts, Alycia M.] Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. [Allen, Ryan A.] John Carroll Univ, University Hts, OH USA. RP Englund, JA (reprint author), Univ S Carolina, Dept Psychol, 1512 Pendleton St, Columbia, SC 29208 USA. 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PD APR PY 2014 VL 32 IS 2 BP 95 EP 106 DI 10.1177/0734282913505074 PG 12 WC Psychology, Educational SC Psychology GA AB2JB UT WOS:000331617900001 ER PT J AU Klubnik, C Murphy, L Campbell, JM Reed, CB Warner-Metzger, CM AF Klubnik, Cynthia Murphy, Laura Campbell, Jonathan M. Reed, Colby B. Warner-Metzger, Christina M. TI Assessing Understanding of Social Awareness Concepts in Children With Intellectual Disability and Autism Spectrum Disorder Using the Bracken Basic Concept Scale-Third Edition SO JOURNAL OF PSYCHOEDUCATIONAL ASSESSMENT LA English DT Article DE autism spectrum disorders (ASD); preschool; social awareness; school readiness ID ADAPTIVE-BEHAVIOR; MIND; ADOLESCENTS; SKILLS; INDIVIDUALS; RECOGNITION; DYSFUNCTION; DIAGNOSIS; PATTERNS AB Authors contrasted Bracken Basic Concept Scale: Receptive, Third Edition (BBCS: R-3) test performance between 57 children with intellectual disability (ID) and 76 children with autism spectrum disorder (ASD) and ID. BBCS: R-3 School Readiness Composite (SRC) and Self-/Social Awareness subtests were analyzed. Multivariate analysis of covariance revealed no differences between groups on SRC performance; however, children with ID demonstrated better mastery of self-/social awareness concepts when compared to children with ASD. Within the group of children with ASD, mastery of school-based concepts exceeded mastery of self-/social awareness concepts. Findings suggest relatively greater delays in mastery of self-/social awareness concepts for young children with ASDs when compared to mastery of other concepts. C1 [Klubnik, Cynthia] Pediat Therapy Profess Inc, Philomath, OR USA. [Murphy, Laura] Univ Tennessee, Dept Psychiat, Hlth Sci Ctr, Memphis, TN 38105 USA. [Murphy, Laura; Reed, Colby B.; Warner-Metzger, Christina M.] Univ Tennessee, Boling Ctr Dev Disabil, Hlth Sci Ctr, Memphis, TN 38105 USA. [Campbell, Jonathan M.] Univ Kentucky, Lexington, KY USA. 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Meta-analysis of oxytocin receptor genotype effects in humans SO PSYCHIATRIC GENETICS LA English DT Review DE rs2254298; prosocial; autism; oxytocin receptor gene; rs53576; OXTR; meta-analysis ID OXTR GENE; DIFFERENTIAL SUSCEPTIBILITY; INFANT ATTACHMENT; SOCIAL-BEHAVIOR; 5-HTT GENES; ASSOCIATION; POLYMORPHISMS; AUTISM; CHILDHOOD; ENVIRONMENT AB Variation in the oxytocin receptor (OXTR) gene may partly explain individual differences in oxytocin-related social behavior. Two single nucleotide polymorphisms (SNPs) have been suggested as promising candidates: rs53576 and rs2254298, although the results of studies were not consistent. We carried out meta-analyses for these two SNPs, covering five domains of outcomes: (a) biology, (b) personality, (c) social behavior, (d) psychopathology, and (e) autism, on the basis of 82 pertinent effect sizes, 48 for OXTR rs53576 (N=17 559) and 34 for OXTR rs2254298 (N=13 547). Combined effect sizes did not differ from zero in any of the domains, nor for all domains combined. Clinical status, age, and sex did not moderate the effect sizes. Minor allele frequency was related to ethnicity, with significantly lower minor allele frequencies in samples with predominantly Caucasian participants. The domain of biological functioning seemed most promising, but comprised few studies. We conclude that so far two of the most intensively studied OXTR SNPs (rs53576 and rs2254298) failed to explain a significant part of human social behavior. C1 [Bakermans-Kranenburg, Marian J.; van IJzendoorn, Marinus H.] Leiden Univ, Ctr Child & Family Studies, NL-2300 RB Leiden, Netherlands. RP Bakermans-Kranenburg, MJ (reprint author), Leiden Univ, Ctr Child & Family Studies, POB 9555, NL-2300 RB Leiden, Netherlands. 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Genet. PD APR PY 2014 VL 24 IS 2 BP 45 EP 51 DI 10.1097/YPG.0b013e3283643684 PG 7 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AC0TY UT WOS:000332209400001 PM 23921259 ER PT J AU Takayama, Y Hashimoto, R Tani, M Kanai, C Yamada, T Watanabe, H Ono, T Kato, N Iwanami, A AF Takayama, Yuko Hashimoto, Ryuichiro Tani, Masayuki Kanai, Chieko Yamada, Takashi Watanabe, Hiromi Ono, Taisei Kato, Nobumasa Iwanami, Akira TI Standardization of the Japanese version of the Glasgow Sensory Questionnaire (GSQ) SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Sensory sensitivity; Glasgow Sensory Questionnaire; Autism spectrum quotient ID AUTISM SPECTRUM DISORDERS; DEVELOPMENTAL DISORDERS; QUOTIENT AQ; TODDLERS; PERCEPTION; TRAITS; ADULTS; TWIN AB Individuals with autism spectrum disorders (ASD) often have sensory processing abnormalities. However, limited measures that assess these problems in adults with ASD have been developed till date, particularly in Japan. Robertson and Simmons (2012) developed a self-rating scale to investigate sensory sensitivity: the Glasgow Sensory Questionnaire (GSQ). In the present study, we developed a Japanese version of GSQ and investigated sensory abnormalities in adults with ASD. We compared results of the Japanese version of GSQ in adults between an ASD group (n = 64) and a control group (n = 70). In addition, we also administered these individuals with the autism spectrum quotient (AQ), which is a questionnaire for assessing autistic traits. The Japanese version of GSQ scores was significantly higher in the ASD group than that in the control group. The total GSQ score and each sensory subscale showed a positive correlation with AQ in the total study sample. These results indicate that individuals with pronounced autistic traits have more frequent and extreme sensory processing problems compared with that in individuals with less pronounced autistic traits. We also assessed validity of the new test. Cronbach's alpha of the questionnaire was calculated, and its high value indicates that the Japanese version of GSQ has high reliability. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Takayama, Yuko; Hashimoto, Ryuichiro; Tani, Masayuki; Kanai, Chieko; Yamada, Takashi; Watanabe, Hiromi; Ono, Taisei; Kato, Nobumasa; Iwanami, Akira] Showa Univ, Karasuyama Hosp, Dept Psychiat, Setagaya Ku, Tokyo 1578577, Japan. [Hashimoto, Ryuichiro] Tokyo Metropolitan Univ, Grad Sch Humanities, Dept Language Sci, Hachioji, Tokyo 1920364, Japan. [Hashimoto, Ryuichiro; Kato, Nobumasa] CREST, Japan Sci & Technol Agcy, Tokyo, Japan. RP Hashimoto, R (reprint author), Showa Univ, Karasuyama Hosp, Dept Psychiat, Setagaya Ku, 6-11-11 Kitakarasuyama, Tokyo 1578577, Japan. 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Autism Spectr. Disord. PD APR PY 2014 VL 8 IS 4 BP 347 EP 353 DI 10.1016/j.rasd.2013.12.017 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AC3NS UT WOS:000332429100001 ER PT J AU Mannion, A Leader, G AF Mannion, Arlene Leader, Geraldine TI Epilepsy in autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Review DE Autism spectrum disorders; Epilepsy; Seizures; Comorbidity; Treatment ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; DRUG-REFRACTORY EPILEPSY; COMMITMENT THERAPY; CHILDHOOD EPILEPSY; EEG ABNORMALITIES; CHILDREN; ACCEPTANCE; DEPRESSION; IMPACT AB The purpose of this review is to provide an overview of the research on epilepsy in autism spectrum disorder (ASD). Topics explored are the prevalence of epilepsy in ASD, the importance of studying epilepsy, as well as the questionnaire measures used to assess epilepsy side-effects. Research on the relationships between epilepsy and parental stress and psychological distress, developmental regression, language and communication, adaptive behavior, social skills, autism severity, challenging behavior, comorbid psychopathology, gastrointestinal symptoms, sleep problems, sensory issues and quality of life are also discussed. Finally, recommendations for treatment are given as well as areas where future research is needed. (C) 2014 Published by Elsevier Ltd. C1 [Mannion, Arlene; Leader, Geraldine] Natl Univ Ireland, Galway, Ireland. RP Leader, G (reprint author), Natl Univ Ireland, Sch Psychol, Irish Ctr Autism & Neurodev Res, Galway, Ireland. 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J., 2013, J AUTISM DI IN PRESS Zeber JE, 2007, EPILEPSY BEHAV, V10, P539, DOI 10.1016/j.yebeh.2007.02.008 NR 49 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD APR PY 2014 VL 8 IS 4 BP 354 EP 361 DI 10.1016/j.rasd.2013.12.012 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AC3NS UT WOS:000332429100002 ER PT J AU Sappok, T Gaul, I Bergmann, T Dziobek, I Bolte, S Diefenbacher, A Heinrich, M AF Sappok, Tanja Gaul, Isabell Bergmann, Thomas Dziobek, Isabel Bolte, Sven Diefenbacher, Albert Heinrich, Manuel TI The Diagnostic Behavioral Assessment for autism spectrum disorder-Revised: A screening instrument for adults with intellectual disability suspected of autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Intellectual disability; Diagnostics; Psychometric properties; Adults ID PERVASIVE DEVELOPMENTAL DISORDERS; OVERT AGGRESSION SCALE; QUALITY-OF-LIFE; CHALLENGING BEHAVIOR; PSYCHOTROPIC MEDICATION; MENTAL-RETARDATION; ASD-DA; PREVALENCE; CHILDREN; QUESTIONNAIRE AB Given the strong association between intellectual disability (ID) and autism spectrum disorder (ASD), standardized instruments for the assessment of ASD in adults with ID are desirable. The Diagnostic Behavioral Assessment for ASD - Revised (DiBAS-R) is a DSM-5/ICD-10 based caregiver-report screening tool that consists of 19 Likert-scaled items. This study evaluated the item-validities, item-difficulties, item-variances, part-whole corrected item total-correlations, reliability, and the factorial, diagnostic, and convergent/discriminant validities of the DiBAS-R in a clinical, adult ID sample (N = 219). Factor analysis yielded two consistent dimensions; i.e., social interaction/communication and stereotypy/rigidity/sensory abnormalities. The diagnostic validity was adequate, as reflected by an area under the curve of 0.89 and balanced sensitivity and specificity values of 81%. The DiBAS-R total scores were significantly correlated with the Social Communication Questionnaire (r = 0.52), the Scale for Pervasive Developmental Disorders in Mentally Retarded Persons (r = 0.50), and the Autism-Checklist (r = 0.59), while no significant correlation with the Modified Overt Aggression Scale was observed. The interrater reliability was excellent (ICC = 0.88). These findings indicate that the DiBAS-R is a promising and psychometrically sound instrument for ASD screening of adults with ID. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Sappok, Tanja; Gaul, Isabell; Bergmann, Thomas; Diefenbacher, Albert; Heinrich, Manuel] Evangel Krankenhaus Konigin Elisabeth Herzberge, Abt Psychiat Psychotherapie & Psychosomat, D-10365 Berlin, Germany. [Dziobek, Isabel] Free Univ Berlin, Cluster Excellence Languages Emot, D-14195 Berlin, Germany. [Bolte, Sven] Karolinska Inst, Ctr Neurodev Disorders, Dept Womens & Childrens Hlth, SE-17177 Stockholm, Sweden. RP Sappok, T (reprint author), Evangel Krankenhaus Konigin Elisabeth Herzberge, Abt Psychiat Psychotherapie & Psychosomat, Herzbergstr 79, D-10365 Berlin, Germany. 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Autism Spectr. Disord. PD APR PY 2014 VL 8 IS 4 BP 362 EP 375 DI 10.1016/j.rasd.2013.12.016 PG 14 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AC3NS UT WOS:000332429100003 ER PT J AU Stasolla, F Damiani, R Caffo, AO AF Stasolla, Fabrizio Damiani, Rita Caffo, Alessandro O. TI Promoting constructive engagement by two boys with autism spectrum disorders and high functioning through behavioral interventions SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Behavioral interventions; Constructive engagement; Stereotyped behaviors; Multi-elements baseline design ID SOCIAL-SKILLS INTERVENTIONS; SCANNING KEYBOARD EMULATOR; MOTOR DISABILITIES; MULTIPLE DISABILITIES; ADAPTIVE BEHAVIORS; YOUNG-CHILDREN; INDIVIDUALS; TECHNOLOGY; SEVERITY; STUDENTS AB We assessed a behavioral intervention-based strategy to promote constructive engagement and to reduce stereotyped behaviors by two boys with autism spectrum disorders and high functioning. The program included two functional activities for each participant (i.e. coloring and using a personal computer with a multimedia software for reading and writing) according to a multi-elements baseline design, during classroom. Both participants showed a preference for the computer activity during the choice phase. Results showed an increasing of constructive engagement, according to both functional activities, and a reduction of stereotyped behaviors during intervention phases for both participants. Psychological as well as practical implications of the findings are discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Stasolla, Fabrizio] Lega del Filo dOro Res Ctr, Molfetta, Italy. [Damiani, Rita; Caffo, Alessandro O.] Univ Bari, Dept Educ Sci, I-70121 Bari, Italy. RP Stasolla, F (reprint author), Lega del Filo dOro Res Ctr, Molfetta, Italy. EM f.stasolla@psico.uniba.it CR Barlow D. 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Autism Spectr. Disord. PD APR PY 2014 VL 8 IS 4 BP 376 EP 380 DI 10.1016/j.rasd.2013.12.020 PG 5 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AC3NS UT WOS:000332429100004 ER PT J AU Tsai, PH Chen, MH Su, TP Chen, YS Hsu, JW Huang, KL Chang, WH Chen, TJ Bai, YM AF Tsai, Po-Hsin Chen, Mu-Hong Su, Tung-Ping Chen, Ying-Sheue Hsu, Ju-Wei Huang, Kai-Lin Chang, Wen-Han Chen, Tzeng-Ji Bai, Ya-Mei TI Increased risk of autism spectrum disorder among early life asthma patients: An 8-year nationwide population-based prospective study SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Allergy; Asthma; Wheezing ID HEALTH-CARE USE; 1ST 6 YEARS; DEVELOPMENTAL-DISABILITIES; AUTOIMMUNE-DISEASES; CHILDHOOD AUTISM; MATERNAL SMOKING; CHILDREN; PREVALENCE; COHORT; ADOLESCENCE AB Previous research has suggested an association between autism spectrum disorder (ASD) and allergic disorders, but epidemiological evidence regarding asthma remains limited. We conducted a nationwide population-based prospective cohort study (1:4 case:control patients, age- and gender-matched), hypothesizing that asthma in infancy or toddlerhood increased the risk of ASD. The participants comprised 2134 asthmatic infants and children and 8536 controls aged 0-3 years in 2002. We identified cases of ASD that occurred near the end of the follow-up period (December 31, 2010), determining that asthmatic infants and children exhibited a higher accumulative incidence rate of ASD than did the controls (1.3% vs 0.7%, P = .007). After adjusting for age at enrollment, gender, level of urbanization, and comorbid allergic diseases (i.e., allergic rhinitis and atopic dermatitis), asthmatic infants and children exhibited an elevated risk of developing ASD (hazard ratio: 2.01, 95% confidence interval: 1.19-3.40). This prospective study indicated a temporal relation between asthma and subsequent ASD diagnosis, supporting the immune hypothesis of ASD pathogenesis. Further studies are required to clarify the probable interactional effects between these disorders and define a homogenous ASD subgroup. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Tsai, Po-Hsin] Chang Gung Mem Hosp, Dept Psychiat, Keelung 204, Taiwan. [Chen, Mu-Hong; Su, Tung-Ping; Chen, Ying-Sheue; Hsu, Ju-Wei; Huang, Kai-Lin; Chang, Wen-Han; Bai, Ya-Mei] Taipei Vet Gen Hosp, Dept Psychiat, Taipei 112, Taiwan. [Su, Tung-Ping; Bai, Ya-Mei] Natl Yang Ming Univ, Coll Med, Dept Psychiat, Taipei 112, Taiwan. [Chen, Tzeng-Ji] Taipei Vet Gen Hosp, Dept Family Med, Taipei 112, Taiwan. [Chen, Tzeng-Ji] Natl Yang Ming Univ, Inst Hosp & Hlth Care Adm, Taipei 112, Taiwan. RP Bai, YM (reprint author), Taipei Vet Gen Hosp, Dept Psychiat, 201,Sect 2,Shipai Rd, Taipei 112, Taiwan. 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PD APR PY 2014 VL 8 IS 4 BP 381 EP 386 DI 10.1016/j.rasd.2013.12.022 PG 6 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AC3NS UT WOS:000332429100005 ER PT J AU Hoppenbrouwers, M Vandermosten, M Boets, B AF Hoppenbrouwers, Margot Vandermosten, Maaike Boets, Bart TI Autism as a disconnection syndrome: A qualitative and quantitative review of diffusion tensor imaging studies SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Review DE Autism spectrum disorder; Diffusion tensor imaging; Review; Brain connectivity; Fibre tracking ID HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; MATTER FRACTIONAL ANISOTROPY; CEREBRAL WHITE-MATTER; SPECTRUM DISORDER; NEURAL SYSTEMS; SPATIAL-STATISTICS; BRAIN CONNECTIVITY; CORPUS-CALLOSUM; FRONTAL-LOBE AB This review aims at evaluating the leading hypothesis of lower long-range and greater short-range cortical connectivity in individuals with autism spectrum disorder (ASD) by the available literature on diffusion tensor imaging (DTI) studies. DTI, coupled with tractography, assesses the structural connections between cortical regions and quantifies their white matter integrity. First, we provide an extensive qualitative overview of DTI findings in ASD. Next, to reveal convergence between studies, results are quantitatively analyzed using Activation Likelihood Estimation (ALE) and fibre tracking is performed to visualize the white matter tracts running through the obtained ALE clusters. Finally, findings from DTI research are related to specific symptoms characteristic of ASD. Overall, the qualitative analysis yields a widespread disruption of white matter integrity in the brain of individuals with ASD as compared to typically developing controls. This is the case for both the long-range and the local short-range connections, partially contradicting the leading hypothesis. However, several studies investigating very young children with ASD report greater structural connectivity, suggesting a developmental switch in white matter integrity in the ASD brain. Based on the combined qualitative and quantitative analysis, the corpus callosum and the ventral tracts emerge as particularly affected connections in individuals with ASD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Hoppenbrouwers, Margot; Boets, Bart] Univ Leuven KU Leuven, B-3000 Louvain, Belgium. [Vandermosten, Maaike] Univ Leuven KU Leuven, Ctr Parenting Child Welf & Disabil, B-3000 Louvain, Belgium. [Boets, Bart] Univ Leuven KU Leuven, Leuven Autism Res Consortium, B-3000 Louvain, Belgium. RP Boets, B (reprint author), Univ Leuven KU Leuven, Herestraat 49,Box 7003, B-3000 Louvain, Belgium. 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PD APR PY 2014 VL 8 IS 4 BP 387 EP 412 DI 10.1016/j.rasd.2013.12.018 PG 26 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AC3NS UT WOS:000332429100006 ER PT J AU Strauss, K Esposito, M Polidori, G Vicari, S Valeri, G Fava, L AF Strauss, Kristin Esposito, Marco Polidori, Giorgia Vicari, Stefano Valeri, Giovanni Fava, Leonardo TI Facilitating play, peer engagement and social functioning in a peer group of young autistic children: Comparing highly structured and more flexible behavioral approaches SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Play; Engagement; Social functioning ID PERVASIVE DEVELOPMENTAL DISORDERS; JOINT ATTENTION; SYMBOLIC PLAY; PRETEND PLAY; SKILLS; IMITATION; LANGUAGE; SPECTRUM; PRESCHOOL; SYMPTOMS AB This study examined the differential effect of a highly structured adult-directed behavioral treatment condition and a more flexible child-oriented blending of behavioral and developmental treatment strategies in a clinical group setting with autistic children. The children with autism following the more flexible child-oriented treatment condition engaged significantly more in higher-order play activities allowing for peer proximity and demonstrated better social functioning during activities with other autistic peers. A relation of child-oriented teaching utilizing less intrusive prompting to more developmentally appropriate play as well as social functioning was found. The findings suggest that child-oriented play and social skill interventions in the clinical context, although being applied in a group of autistic children, may facilitate social functioning and engagement. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Strauss, Kristin; Esposito, Marco; Fava, Leonardo] Autism Treatment & Res Ctr Una Breccia Nel Muro, Rome, Italy. [Strauss, Kristin] Ernst Moritz Arndt Univ Greifswald, Dept Hlth & Prevent, Greifswald, Germany. [Polidori, Giorgia] Univ Roma La Sapienza, Dept Psychol, I-00185 Rome, Italy. 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PD APR PY 2014 VL 8 IS 4 BP 413 EP 423 DI 10.1016/j.rasd.2014.01.002 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AC3NS UT WOS:000332429100007 ER PT J AU Katagiri, M Miya, K Matsui, M AF Katagiri, Masatoshi Miya, Kazushi Matsui, Mie TI Difficulty of crossmodal processing in individuals with autism spectrum disorders: An audio-visual gap/overlap paradigm study SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Gap/overlap task; Crossmodal processing; Attention ID HIGH-FUNCTIONING AUTISM; GAP OVERLAP TASK; ASPERGERS-DISORDER; MULTISENSORY INTEGRATION; SPEECH INTEGRATION; SHIFTING ATTENTION; SPATIAL ATTENTION; NO EVIDENCE; CHILDREN; LEVEL AB Evidence suggests that individuals with autism spectrum disorders (ASD) exhibit difficulty in integrating crossmodal information. However, few previous studies have investigated crossmodal attention switching in individuals with ASD. The present study investigates whether children with ASD have difficulty in crossmodal processing across auditory and visual modalities. For this study, we observed 10 children with ASD and 11 IQ-, age-, and gender-matched, healthy, control children. We used a modified gap/overlap task that required the simultaneous allocation of attention to auditory and visual stimuli (audiovisual gap/overlap task). In addition, the visual-only gap/overlap task used a classical gap/overlap procedure. In the visual-only gap/overlap task, children with ASD exhibited the same performance as control children. In contrast, in the audio-visual condition, children with ASD were significantly slower to respond than control children in both the gap and overlap tasks. 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Autism Spectr. Disord. PD APR PY 2014 VL 8 IS 4 BP 424 EP 431 DI 10.1016/j.rasd.2014.01.001 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AC3NS UT WOS:000332429100008 ER PT J AU Mannion, A Leader, G AF Mannion, Arlene Leader, Geraldine TI Attention-deficit/hyperactivity disorder (AD/HD) in autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Review DE Autism spectrum disorders; Attention-deficit/hyperactivity disorder (AD/HD); Comorbidity; Treatment ID DEFICIT HYPERACTIVITY DISORDER; COMORBID ASD; PHARMACOLOGICAL-TREATMENT; PEDIATRIC-PATIENTS; TANTRUM BEHAVIOR; SLEEP PROBLEMS; ADHD SYMPTOMS; CHILDREN; METAANALYSIS; PROFILES AB The purpose of this review is to provide an overview of the research on attention-deficit/hyperactivity disorder (AD/HD) in individuals with autism spectrum disorder (ASD). Topics explored are the prevalence of AD/HD, the importance of studying AD/HD, as well as the questionnaire measures used to measure AD/HD in individuals with ASD. Research on the relationship between AD/HD in ASD and parental stress and psychological distress, developmental regression, language and communication, adaptive behavior, social skills, autism severity, challenging behavior, comorbid psychopathology, gastrointestinal symptoms, sleep problems, epilepsy, sensory issues, motor difficulties, and quality of life are also discussed. Research on cardiac reactivity and executive functioning are also explored. Finally, recommendations for treatment are given as well as areas where future research is needed. (C) 2014 Published by Elsevier Ltd. C1 [Mannion, Arlene; Leader, Geraldine] Natl Univ Ireland, Galway, Ireland. RP Leader, G (reprint author), Natl Univ Ireland, Irish Ctr Autism & Neurodev Res, Galway, Ireland. 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J., 2014, J AUTISM DE IN PRESS van Steijn DJ, 2013, J AUTISM DEV DISORD, V43, P1935, DOI 10.1007/s10803-012-1746-y NR 55 TC 1 Z9 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD APR PY 2014 VL 8 IS 4 BP 432 EP 439 DI 10.1016/j.rasd.2013.12.021 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AC3NS UT WOS:000332429100009 ER PT J AU Lee, R Sturmey, P AF Lee, Ronald Sturmey, Peter TI The effects of script-fading and a Lag-1 schedule on varied social responding in children with autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Response variability; Scripting; Social skills; Autism ID INTERACTION SKILLS; VARIABILITY; OPERANT; DISABILITIES AB This study investigated the effects of a script-fading procedure and a Lag-1 reinforcement schedule with repeated trials contingent on repeated responses on varied responding during brief conversations by one girl and two boys with autism. The experiment used a multiple-baseline-across-participants design. During baseline (Lag-0), the experimenter reinforced appropriate responding during a brief three-turn conversation. During scripting and script-fading, the experimenter gave participants audio taped models to imitate in response to experimenter-delivered antecedents in the conversation. During Lag-1 with repeated trials, the experimenter delivered reinforcement contingent on appropriate and varied responding in any part of the social conversation. During the Lag-0, participants emitted low levels of appropriate and varied responding. During scripting the participants emitted increased appropriate and varied responding. This systematically decreased to baseline levels during the return to Lag-0. During Lag-1 with repeated trials, participants increased varied and appropriate responding to levels similar to that seen during scripting. Generalization of varied responding to different settings, people, and conversations did not occur. These results are discussed in terms of extinction-induced variability and stimulus control. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Lee, Ronald; Sturmey, Peter] Queens Coll, Flushing, NY USA. [Lee, Ronald; Sturmey, Peter] CUNY Grad Sch & Univ Ctr, New York, NY USA. RP Lee, R (reprint author), QSAC Day Sch, 12-10 150th St, Whitestone, NY 11357 USA. 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Autism Spectr. Disord. PD APR PY 2014 VL 8 IS 4 BP 440 EP 448 DI 10.1016/j.rasd.2014.01.003 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AC3NS UT WOS:000332429100010 ER PT J AU Deckers, A Roelofs, J Muris, P Rinck, M AF Deckers, Anne Roelofs, Jeffrey Muris, Peter Rinck, Mike TI Desire for social interaction in children with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Children; Desire for social interaction; Approach and avoidance tendencies ID PERVASIVE DEVELOPMENTAL DISORDERS; HIGH-FUNCTIONING CHILDREN; PSYCHOPATHOLOGY; INTERVENTIONS; MOTIVATION AB In this experimental clinical study, a first attempt was made to examine the desire for social interaction in children with autism spectrum disorders (ASD). Children with ASD and typically developing (TD) children completed both an explicit measure (self-report) and an implicit measure (Face Turn Approach-Avoidance Task) of the desire for social interaction. On the explicit assessment, children with ASD clearly displayed lower scores reflecting less desire for social interaction than TO children. On the implicit assessment, children with ASD showed a stronger tendency to pull both social and non-social stimuli towards them, which indicates a general automatic tendency towards approach, as compared to the TO children. Possible reasons for this dissociation between the explicit and implicit desire for social interaction are discussed and directions for future research are provided. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Deckers, Anne; Roelofs, Jeffrey; Muris, Peter] Maastricht Univ, Fac Psychol & Neurosci, RIAGG Maastricht Child & Youth Care, NL-6200 MD Maastricht, Netherlands. [Deckers, Anne; Roelofs, Jeffrey; Muris, Peter] Maastricht Univ, Fac Psychol & Neurosci, Dept Clin Psychol Sci, NL-6200 MD Maastricht, Netherlands. [Rinck, Mike] Radboud Univ Nijmegen, Inst Behav Sci, NL-6525 ED Nijmegen, Netherlands. RP Deckers, A (reprint author), Maastricht Univ, Fac Psychol & Neurosci, Dept Clin Psychol Sci, Postbox 616, NL-6200 MD Maastricht, Netherlands. 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PD APR PY 2014 VL 8 IS 4 BP 449 EP 453 DI 10.1016/j.rasd.2013.12.019 PG 5 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AC3NS UT WOS:000332429100011 ER PT J AU McConnell, D Savage, A Breitkreuz, R AF McConnell, David Savage, Amber Breitkreuz, Rhonda TI Resilience in families raising children with disabilities and behavior problems SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Family; Disabilities; Resilience; Social ecology; Behavior problems ID AUTISM SPECTRUM DISORDER; MATERNAL SOCIAL SUPPORT; DOUBLE ABCX MODEL; QUALITY-OF-LIFE; INTELLECTUAL DISABILITIES; MENTAL-HEALTH; DEVELOPMENTAL-DISABILITIES; YOUNG-CHILDREN; PRESCHOOL-CHILDREN; DISABLED-CHILDREN AB The purpose of this study was to investigate the resilience displayed by families raising children with disabilities and behavior problems. The question is why do some families do well when others, exposed to similar stressors, struggle to keep their family life running? A stratified (by child age group) random sample of 538 families raising children with disabilities in Alberta, Canada took part. Participants completed the Family Life Survey, which incorporated measures of child behavior problems, social-ecological resources and family-level 'outcomes'. Families raising children with disabilities and behavior problems 'do well' under conditions of high social support and low financial hardship. In contrast, families with low levels of social support and high levels of financial hardship typically struggle, even when the number or intensity of child behavior problems is low. The study findings are consistent with the view that 'resilience' has more to do with the availability and accessibility of culturally relevant resources than with intrinsic, individual or family factors. 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PD APR PY 2014 VL 35 IS 4 BP 833 EP 848 DI 10.1016/j.ridd.2014.01.015 PG 16 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AC3NK UT WOS:000332428300009 PM 24491480 ER PT J AU Meral, BF Fidan, A AF Meral, Bekir Fatih Fidan, Ahmet TI Psychometric properties of the screening tool of feeding problems (STEP) in Turkish children with ASD SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Screening tool of feeding problems (STEP); Children with autism spectrum disorders (ASD); Feeding problems; Confirmatory factor analysis; Validity; Reliability ID AUTISM SPECTRUM DISORDERS; CONFIRMATORY FACTOR-ANALYSIS; OF-FIT INDEXES; INTELLECTUAL DISABILITIES; MEALTIME BEHAVIOR; FOOD SELECTIVITY; SAMPLE-SIZE; ASSOCIATION; CHILDHOOD; SYMPTOMS AB The purpose of this study is to determine the psychometric properties of the screening tool of feeding problems (STEP) in Turkish children with autism spectrum disorders (ASD). After providing linguistic equivalence of the scale, STEP was applied to 360 mothers on behalf of their children with ASD in order to determine the associated feeding problems. The scale which has 5 sub-domains and 3 Likert-type questions originally consisted of 23 items. Item-total correlations of the scale were acceptable, with the exception of item 8 and the differences between the item averages of the upper 27% and the lower 27% groups were significant (p < 0.001). The internal consistency coefficient (alpha = 0.81) and the splithalf reliability (Spearman's rho = 0.69**) were high. The STEP achieved criterion-related validity. The results of Confirmatory Factor Analysis (X-2/df = 3.2, RMSEA = 0.08, SRMR= 0.08, GFI= 0.85, AGFI= 0.81, CFI = 0.86) showed that the scale has an acceptable goodness of fit. This study suggests that the Turkish version of the STEP could be a useful assessment tool when it comes to measuring feeding problems in children with ASD. (c) 2014 Elsevier Ltd. 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Dev. Phys. Disabil. PD APR PY 2014 VL 26 IS 2 BP 123 EP 134 DI 10.1007/s10882-013-9348-y PG 12 WC Rehabilitation SC Rehabilitation GA AB7LL UT WOS:000331971400001 ER PT J AU Beighley, JS Matson, JL Rieske, RD Cervantes, PE Goldin, R Jang, J AF Beighley, Jennifer S. Matson, Johnny L. Rieske, Robert D. Cervantes, Paige E. Goldin, Rachel Jang, Jina TI Differences in Stereotypic Behavior in Adults Diagnosed with Autism Spectrum Disorders Using the DSM-IV-TR and the DSM-5 SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Autism; Stereotypic behavior; Stereotypy; DSM-5 ID PERVASIVE DEVELOPMENTAL DISORDER; PROFOUND MENTAL-RETARDATION; SEVERELY HANDICAPPED DASH; SELF-INJURIOUS-BEHAVIOR; PROPOSED DSM-5; ASPERGERS SYNDROME; CHILDREN; CRITERIA; SYMPTOMS; INFANTS AB The purpose of the current study was to investigate differences in the frequency of stereotypic behavior (e.g., engaging in repetitive activities; repetitive body movements such as rocking, spinning, handflapping; repetition of words or sounds; and perseveration on specific topics) using a psychometrically sound measure, the Diagnostic Assessment for the Severely Handicapped, second edition (DASH-II). The sample investigated included 261 adults with severe or profound intellectual disability (ID), 51 of whom met criteria for ASD according to the DSM-5; 84 of whom met criteria for the DSM-IV-TR, but no longer qualify for an ASD diagnosis with the new criteria; and a control group of 126 adults who did not qualify for an ASD diagnosis according to either version of the DSM. The DSM-5 captured a more impaired population in terms of stereotypies, though a significant difference remains between those who no longer meet criteria and a control group with ID who did not meet criteria for ASD under either version of the DSM. Highlights aEuro cent Approximately 38 % of adults with ID currently meeting criteria for autism under the DSM-IV-TR did not meet the DSM-5 criteria. aEuro cent Those who continued to meet criteria for ASD had higher scores on the DASH-II stereotypy subscale. aEuro cent People meeting DSM-IV but not DSM-5 criteria had significantly more stereotypic behavior than adults without ASD. C1 [Beighley, Jennifer S.; Matson, Johnny L.; Rieske, Robert D.; Cervantes, Paige E.; Goldin, Rachel; Jang, Jina] Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. RP Beighley, JS (reprint author), Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. 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PD APR PY 2014 VL 26 IS 2 BP 193 EP 202 DI 10.1007/s10882-013-9356-y PG 10 WC Rehabilitation SC Rehabilitation GA AB7LL UT WOS:000331971400007 ER PT J AU Leaf, JB Leaf, R Taubman, M McEachin, J Delmolino, L AF Leaf, Justin B. Leaf, Ronald Taubman, Mitchell McEachin, John Delmolino, Lara TI Comparison of Flexible Prompt Fading to Error Correction for Children with Autism Spectrum Disorder SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Autism; Discrete trial teaching; Error correction; Flexible prompt fading; Prompting ID CONSTANT-TIME DELAY; DISCRIMINATION; PREFERENCE; STUDENTS AB This study compared flexible prompt fading to an error correction procedure involving feedback and remedial trials for teaching four children with Autism Spectrum Disorder. 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Jakobsen, Tanya Kingstone, Alan TI The influence of personality on social attention SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Personality; Social cognition; Big Five; Social attention; Eye-tracking ID SPECTRUM QUOTIENT AQ; 5-FACTOR MODEL; BIG 5; INDIVIDUAL-DIFFERENCES; GAZE; AUTISM; SCENES; EYES; BEHAVIOR; FEATURES AB The intersection between personality psychology and the study of social attention has been relatively untouched. We present an initial study that investigates the influence of the Big Five personality traits on eye movement behaviour towards social stimuli. By combining a free-viewing eye-tracking paradigm with canonical correlation and regression analyses, we discover that personality relates to fixations towards eye regions. Specifically, Extraversion and Agreeableness were related to greater gaze selection. while Openness to Experience was related to diminished gaze selection. 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TI Individual differences predict eyewitness identification performance SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Eyewitness identification; Simultaneous and sequential lineups; Working memory; Facial recognition ability; Autism Spectrum; Need for Cognition ID SEQUENTIAL LINEUP ADVANTAGE; FACE RECOGNITION; WORKING-MEMORY; DISTINCTIVENESS; RECOLLECTION; COGNITION; AUTISM; NEED AB A great deal of research has focused on eyewitness identification performance as a function of sequential versus simultaneous lineup presentation methods. We examined if individual differences in cognitive ability influence eyewitness identification, and whether these factors lead to performance differences as a function of lineup presentation method. We found that individual differences in facial recognition ability, working memory capacity, and levels of autistic traits, did result in differential performance. Differences in lineup performance are due to the interaction of individual differences and presentation method, signaling that it is possible to enhance the accuracy of eyewitness identifications by tailoring a lineup presentation method to the capabilities of an individual eyewitness. (C) 2013 Elsevier Ltd, All rights reserved. C1 [Andersen, Shannon M.; Gronlund, Scott D.] Univ Oklahoma, Norman, OK 73019 USA. [Carlson, Curt A.; Carlson, Maria A.] Texas A&M Univ Commerce, Commerce, TX 75429 USA. RP Andersen, SM (reprint author), Univ Oklahoma, Dept Psychol, 455 W Lindsey St,Dale Hall Tower,Room 705, Norman, OK 73019 USA. EM Shannon.M.Andersen-1@ou.edu; curt.carlson@tamuc.edu; Maria.carlson@tamuc.edu; sgronlund@ou.edu CR Baron-Cohen S, 2001, J AUTISM DEV DISORD, V31, P5, DOI 10.1023/A:1005653411471 CACIOPPO JT, 1984, J PERS ASSESS, V48, P306, DOI 10.1207/s15327752jpa4803_13 Cacioppo JT, 1996, PSYCHOL BULL, V119, P197, DOI 10.1037/0033-2909.119.2.197 Carlson CA, 2011, MEMORY, V19, P916, DOI 10.1080/09658211.2011.613846 Clark SE, 2012, PERSPECT PSYCHOL SCI, V7, P238, DOI 10.1177/1745691612439584 Cohen J., 1988, STAT POWER ANAL BEHA, V2nd Craik FIM, 1996, J EXP PSYCHOL GEN, V125, P159, DOI 10.1037/0096-3445.125.2.159 Darling S, 2009, PERS INDIV DIFFER, V47, P369, DOI 10.1016/j.paid.2009.04.010 Duchaine B, 2006, NEUROPSYCHOLOGIA, V44, P576, DOI 10.1016/j.neuropsychologia.2005.07.001 Gronlund S. D., CURRENT DIR IN PRESS Gronlund S. 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Individ. Differ. PD APR PY 2014 VL 60 BP 36 EP 40 DI 10.1016/j.paid.2013.12.011 PG 5 WC Psychology, Social SC Psychology GA AB0TA UT WOS:000331503800009 ER PT J AU Durdiakova, J Warrier, V Baron-Cohen, S Chakrabarti, B AF Durdiakova, Jaroslava Warrier, Varun Baron-Cohen, Simon Chakrabarti, Bhismadev TI Single nucleotide polymorphism rs6716901 in SLC25A12 gene is associated with Asperger syndrome SO MOLECULAR AUTISM LA English DT Article DE SLC25A12; Asperger syndrome; Association study; Single nucleotide polymorphisms ID AUTISM SPECTRUM DISORDERS; ASPARTATE-GLUTAMATE; ABNORMALITIES; MITOCHONDRIA; DEFICIENCY; VARIANTS; BEHAVIOR; LINKAGE; TRAITS; CITRIN AB Background: Autism Spectrum Conditions (ASC) are a group of developmental conditions which affect communication, social interactions and behaviour. Mitochondrial oxidative dysfunction has been suggested as a mechanism of autism based on the results of multiple genetic association and expression studies. SLC25A12 is a gene encoding a calcium-binding carrier protein that localizes to the mitochondria and is involved in the exchange of aspartate for glutamate in the inner membrane of the mitochondria regulating the cytosolic redox state. rs2056202 SNP in this gene has previously been associated with ASC. SNPs rs6716901 and rs3765166 analysed in this study have not been previously explored in association with AS. Methods: We genotyped three SNPs (rs2056202, rs3765166, and rs6716901) in SLC25A12 in n = 117 individuals with Asperger syndrome (AS) and n = 426 controls, all of Caucasian ancestry. Results: rs6716901 showed significant association with AS (P = 0.008) after correcting for multiple testing. We did not replicate the previously identified association between rs2056202 and AS in our sample. Similarly, rs3765166 (P = 0.11) showed no significant association with AS. Conclusion: The present study, in combination with previous studies, provides evidence for SLC25A12 as involved in the etiology of AS. Further cellular and molecular studies are required to elucidate the role of this gene in ASC. C1 [Durdiakova, Jaroslava; Warrier, Varun; Baron-Cohen, Simon; Chakrabarti, Bhismadev] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. [Baron-Cohen, Simon] Cambridgeshire & Peterborough NHS Fdn Trust CPFT, CLASS Clin, Cambridge CB21 5EF, England. [Chakrabarti, Bhismadev] Univ Reading, Sch Psychol & Clin Language Sci, Ctr Integrat Neurosci & Neurodynam, Reading RG6 6AL, Berks, England. RP Baron-Cohen, S (reprint author), Univ Cambridge, Dept Psychiat, Autism Res Ctr, 18b Trumpington Rd, Cambridge CB2 8AH, England. EM sb205@cam.ac.uk; b.chakrabarti@reading.ac.uk FU Target Autism Genome (TAG); Autism Research Trust (ART); MRC UK; Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands FX This study was funded by grants to SBC by Target Autism Genome (TAG), the Autism Research Trust (ART), the MRC UK, and the Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands. We are grateful to Lindsey Kent, Jonathan Breidbord, Allen Chan, Laura Murphy, Agnese Di Napoli, Simon Fisher, Sally Wheelwright, Carrie Allison, Grant Hill-Cawthorne, Vicky Harris for help with various stages of the project. CR Bacchelli E, 2003, MOL PSYCHIATR, V8, P916, DOI 10.1038/sj.mp.4001340 Baron-Cohen S, 2001, J AUTISM DEV DISORD, V31, P5, DOI 10.1023/A:1005653411471 Chakrabarti B, 2009, AUTISM RES, V2, P157, DOI 10.1002/aur.80 Chelala C, 2009, BIOINFORMATICS, V25, P655, DOI 10.1093/bioinformatics/btn653 Chien WH, 2010, PROG NEURO-PSYCHOPH, V34, P189, DOI 10.1016/j.pnpbp.2009.11.004 Correia C, 2006, J AUTISM DEV DISORD, V36, P1137, DOI 10.1007/s10803-006-0138-6 KANNER L, 1968, ACTA PAEDOPSYCHIATR, V35, P100 Kim SJ, 2011, MOL AUTISM, V2, DOI 10.1186/2040-2392-2-8 Lee PH, 2009, BIOINFORMATICS, V25, P1048, DOI 10.1093/bioinformatics/btp103 Lepagnol-Bestel AM, 2008, MOL PSYCHIATR, V13, P385, DOI 10.1038/sj.mp.4002120 Lombard J, 1998, MED HYPOTHESES, V50, P497, DOI 10.1016/S0306-9877(98)90270-5 Napolioni V, 2011, MOL NEUROBIOL, V44, P83, DOI 10.1007/s12035-011-8192-2 Palmieri L, 2010, MOL PSYCHIATR, V15, P38, DOI 10.1038/mp.2008.63 Palmieri L, 2001, EMBO J, V20, P5060, DOI 10.1093/emboj/20.18.5060 Persico AM, 2013, BEHAV BRAIN RES, V251, P95, DOI 10.1016/j.bbr.2013.06.012 Pons R, 2004, J PEDIATR-US, V144, P81, DOI 10.1016/j.jpeds.2003.10.023 Purcell S, 2007, AM J HUM GENET, V81, P559, DOI 10.1086/519795 Rabionet Raquel, 2006, Am J Psychiatry, V163, P929, DOI 10.1176/appi.ajp.163.5.929 Ramoz N, 2008, AM J MED GENET B, V147B, P1152, DOI 10.1002/ajmg.b.30739 Ramoz N, 2004, AM J PSYCHIAT, V161, P662, DOI 10.1176/appi.ajp.161.4.662 Rosenberg RE, 2009, ARCH PEDIAT ADOL MED, V163, P907, DOI 10.1001/archpediatrics.2009.98 Saheki T, 2002, J HUM GENET, V47, P333, DOI 10.1007/s100380200046 Satrustegui J, 2007, J NEUROSCI RES, V85, P3359, DOI 10.1002/jnr.21299 Segurado R, 2005, AM J PSYCHIAT, V162, P2182, DOI 10.1176/appi.ajp.162.11.2182 Silverman JM, 2008, AM J MED GENET B, V147B, P408, DOI 10.1002/ajmg.b.30614 Turunen JA, 2008, AUTISM RES, V1, P189, DOI 10.1002/aur.25 Ward LD, 2012, NUCLEIC ACIDS RES, V40, pD930, DOI 10.1093/nar/gkr917 Wibom R, 2009, NEW ENGL J MED, V361, P489, DOI 10.1056/NEJMoa0900591 Woodbury-Smith MR, 2005, J AUTISM DEV DISORD, V35, P331, DOI 10.1007/s10803-005-3300-7 Woodbury-Smith MR, 2009, EUR CHILD ADOLES PSY, V18, P2, DOI 10.1007/s00787-008-0701-0 NR 30 TC 3 Z9 3 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 MAR 31 PY 2014 VL 5 AR 25 DI 10.1186/2040-2392-5-25 PG 5 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AF4YA UT WOS:000334719300001 PM 24679184 ER PT J AU Terrien, S Stefaniak, N Blondel, M Mouras, H Morvan, Y Besche-Richard, C AF Terrien, Sarah Stefaniak, Nicolas Blondel, Marine Mouras, Harold Morvan, Yannick Besche-Richard, Chrystel TI Theory of mind and hypomanic traits in general population SO PSYCHIATRY RESEARCH LA English DT Article DE Hypomanic personality; Theory of mind; Gender effect; Vulnerability ID NATIONAL COMORBIDITY SURVEY; EUTHYMIC BIPOLAR DISORDER; HIGH-FUNCTIONING AUTISM; PSYCHOTIC SYMPTOMS; GENDER-DIFFERENCES; SOCIAL COMPETENCE; IMPAIRED THEORY; NORMAL ADULTS; DEPRESSION; DEFICITS AB Theory of Mind (TOM) is the ability to assign a set of mental states to yourself and others. In bipolar disorders, alteration of social relationship can be explained by the impairment of the functioning of ToM. Deficit in ToM could be a trait marker of bipolar disorder and people in the general population with high hypomanic personality scores would be more likely to develop bipolar disorders. This study examined 298 participants. Measures of hypomanic personality were evaluated using the Hypomanic Personality Scale. ToM was explored using the Yoni task. Participants also completed the BDI-II. Forward multiple regressions were performed to examine the effect of components of the HPS on the total score in the ToM task. In the women's group, no subscales of the HPS were included in the model. Conversely, the analyses performed on men revealed that the mood vitality and excitement subscale was a significant predictor of TOM abilities. Our study is the first to show the impact of certain dimensions of hypomanic personality on performance in ToM in a male sample. This result supports the idea that deficits in ToM can be a trait marker of bipolar disorder in a healthy male population. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Terrien, Sarah; Stefaniak, Nicolas; Blondel, Marine; Besche-Richard, Chrystel] Univ Reims, Lab Cognit Sante Socialisat C2S, EA6291, F-51096 Reims, France. [Terrien, Sarah; Stefaniak, Nicolas; Blondel, Marine; Besche-Richard, Chrystel] Univ Reims, SFR CAP Sante, F-51096 Reims, France. [Mouras, Harold] Univ Picardie Jules Verne, Lab Cognit Psychisme Org, EA 7273, Amiens, France. [Morvan, Yannick] Univ Paris 05, Ctr Psychiat & Neurosci, INSERM, LPMP,U894, Paris, France. [Morvan, Yannick] Univ Paris Ouest Nanterre Def, Lab CLIPSYD, Nanterre, France. [Besche-Richard, Chrystel] Inst Univ France, Paris, France. RP Besche-Richard, C (reprint author), Univ Reims, Lab Cognit Sante Socialisat C2S, EA6291, 57 Rue Pierre Taittinger, F-51096 Reims, France. EM chrystel.bekhe@univ-reims.fr FU Institut Universitaire de France (IUF), Ministere de l'Enseignement Superieur et de la Recherche, Paris, France FX Funding support for this study was awarded to Chrystel Besche-Richard by the Institut Universitaire de France (IUF), Ministere de l'Enseignement Superieur et de la Recherche, Paris, France. The IUF had no influence on data collection, data entry, data analyses, the interpretation of the data, the writing or submission of the manuscript, or on the choice of journal for possible publication. We would like to thank Maude Cabouillet and Candice Zimmermann for their assistance with data collection, and Simone Shamay-Tsoory for her authorization to adapt the Yoni task in French. 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TI Impaired Theory of Mind and psychosocial functioning among pediatric patients with Type I versus Type II bipolar disorder SO PSYCHIATRY RESEARCH LA English DT Article DE Pediatric bipolar disorder; Theory of mind; Psychosocial functioning ID EMOTION LABELING DEFICITS; RATING-SCALE; EUTHYMIC PATIENTS; CHILDREN; SCHIZOPHRENIA; AUTISM; EYES; PSYCHOPATHY; ADOLESCENTS; RELIABILITY AB Deficits in Theory of Mind (ToM) have been documented among pediatric patients with Bipolar Disorder (BD). However, fewer studies have directly examined differences between type I and type II patients and whether or not ToM deficits are related to psychosocial difficulties. Therefore, the aim of this study was to compare type I versus type II pediatric bipolar patients and matched Healthy Controls (HC) on TOM and interpersonal functioning tasks. All participants completed the Revised Mind in the Eyes Task (MET), the Cognitive and Emotional Perspective Taking Task (CEPTT), and the Index of Peer Relations (IPR). Type I BD patients reported greater peer difficulties on the IPR compared to HC, and also performed more poorly on the MET and the cognitive condition of the CEPTT, but did not differ significantly on the emotional condition. There were no significant group differences between type II BD patients and HC. More impaired ToM performance was associated with poorer interpersonal functioning. Type IBD patients show deficits in the ability to understand another's mental state, irrespective of emotional valence. Deficits in understanding others' mental states could be an important treatment target for type I pediatric patients with BD. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Schenkel, Lindsay S.; Chamberlain, Todd F.; Towne, Terra L.] Rochester Inst Technol, Dept Psychol, Rochester, NY 14623 USA. 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PD MAR 30 PY 2014 VL 215 IS 3 BP 740 EP 746 DI 10.1016/j.psychres.2013.10.025 PG 7 WC Psychiatry SC Psychiatry GA AE2AU UT WOS:000333776500038 PM 24461271 ER PT J AU Miellet, S Caldara, R Gillberg, C Raju, M Minnis, H AF Miellet, Sebastien Caldara, Roberto Gillberg, Christopher Raju, Monika Minnis, Helen TI Disinhibited reactive attachment disorder symptoms impair social judgements from faces SO PSYCHIATRY RESEARCH LA English DT Article DE Reactive attachment disorder; Indiscriminate friendliness; Eye tracking; Appraisal of faces ID AUTISM SPECTRUM DISORDERS; PSYCHOPHYSICS TOOLBOX; INFORMATION USE; PATTERNS; TRUST; FIXATION; INDIVIDUALS; RECOGNITION; COMPETENCE; CHILDHOOD AB Typically developing adults and children can rapidly reach consensus regarding the trustworthiness of unfamiliar faces. Maltreated children can have problems with trusting others, yet those with the disinhibited form of reactive attachment disorder (dRAD) can be indiscriminately friendly. Whether children with dRAD symptoms appraise and conform to typical judgements about trustworthiness of faces is still unknown. We recorded eye movements of 10 maltreated dRAD children and 10 age and gender matched typically developing control children while they made social judgements from faces. Children were presented with a series of pairs of faces previously judged by adults to have high or low attractiveness or trustworthiness ratings. Typically developing children reached a consensus regarding which faces were the most trustworthy and attractive. There was less agreement among the children with dRAD symptoms. judgments from the typically developing children showed a strong correlation between the attractiveness and trustworthiness tasks. This was not the case for the dRAD group, who showed less agreement and no significant correlation between trustworthiness and attractiveness judgments. Finally, both groups of children sampled the eye region to perform social judgments. Our data offer a unique insight in children with dRAD symptoms, providing novel and important knowledge for their rehabilitation. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Miellet, Sebastien; Caldara, Roberto] Univ Fribourg, Dept Psychol, CH-1700 Fribourg, Switzerland. [Miellet, Sebastien; Caldara, Roberto] Univ Fribourg, Fribourg Ctr Cognit, CH-1700 Fribourg, Switzerland. [Raju, Monika] NHS Greater Glasgow & Clyde, Yorkhill Hosp, Glasgow G3 8SJ, Lanark, Scotland. [Gillberg, Christopher; Minnis, Helen] Univ Glasgow, Inst Hlth & Wellbeing, Yorkhill Hosp, Glasgow G3 8SJ, Lanark, Scotland. RP Minnis, H (reprint author), Univ Glasgow, Inst Hlth & Wellbeing, Yorkhill Hosp, Caledonia House, Glasgow G3 8SJ, Lanark, Scotland. EM helen.minnis@glasgow.ac.uk FU National Center of Competence in Research (NCCR) Affective sciences; Swiss National Science Foundation [51NF40-104897]; Weir Bequest for Child and Adolescent Psychiatric Research FX RC was supported by the National Center of Competence in Research (NCCR) Affective sciences financed by the Swiss National Science Foundation (no 51NF40-104897). We are grateful to all participating families, to Mrs. Fiona Lettice from Adoption UK for facilitating recruitment of our adoptive sample and to Dr. Jasmeet Bindra, Dr. Lisa Collin, Kay Foreman and Junpeng Lao for their help with data collection. The funding for the study came from the Weir Bequest for Child and Adolescent Psychiatric Research. 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Pettygrove, Sydney Cunniff, Chris Schulz, Eldon Ghosh, Tista Robinson, Cordelia Lee, Li-Ching Landa, Rebecca Constantino, John Fitzgerald, Robert Zahorodny, Walter Daniels, Julie Nicholas, Joyce Charles, Jane McMahon, William Bilder, Deborah Durkin, Maureen Baio, Jon Christensen, Deborah Van, Kim Braun, Naarden Clayton, Heather Goodman, Alyson Doernberg, Nancy Yeargin-Allsopp, Marshalyn CA Autism Dev Disabilities Monitoring TI Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2010 SO MMWR SURVEILLANCE SUMMARIES LA English DT Article ID IDENTIFICATION; PREDICTORS; HEALTH; RISK AB Problem/Condition: Autism spectrum disorder (ASD). Period Covered: 2010. Description of System: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system in the United States that provides estimates of the prevalence of ASD and other characteristics among children aged 8 years whose parents or guardians live in 11 ADDM sites in the United States. ADDM surveillance is conducted in two phases. The first phase consists of screening and abstracting comprehensive evaluations performed by professional providers in the community. Multiple data sources for these evaluations include general pediatric health clinics and specialized programs for children with developmental disabilities. In addition, most ADDM Network sites also review and abstract records of children receiving special education services in public schools. The second phase involves review of all abstracted evaluations by trained clinicians to determine ASD surveillance case status. A child meets the surveillance case definition for ASD if a comprehensive evaluation of that child completed by a qualified professional describes behaviors consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for any of the following conditions: autistic disorder, pervasive developmental disorder-not otherwise specified (including atypical autism), or Asperger disorder. This report provides updated prevalence estimates for ASD from the 2010 surveillance year. In addition to prevalence estimates, characteristics of the population of children with ASD are described. Results: For 2010, the overall prevalence of ASD among the ADDM sites was 14.7 per 1,000 (one in 68) children aged 8 years. Overall ASD prevalence estimates varied among sites from 5.7 to 21.9 per 1,000 children aged 8 years. ASD prevalence estimates also varied by sex and racial/ethnic group. Approximately one in 42 boys and one in 189 girls living in the ADDM Network communities were identified as having ASD. Non-Hispanic white children were approximately 30% more likely to be identified with ASD than non-Hispanic black children and were almost 50% more likely to be identified with ASD than Hispanic children. Among the seven sites with sufficient data on intellectual ability, 31% of children with ASD were classified as having IQ scores in the range of intellectual disability (IQ <= 70), 23% in the borderline range (IQ = 71-85), and 46% in the average or above average range of intellectual ability (IQ > 85). The proportion of children classified in the range of intellectual disability differed by race/ethnicity. Approximately 48% of non-Hispanic black children with ASD were classified in the range of intellectual disability compared with 38% of Hispanic children and 25% of non-Hispanic white children. The median age of earliest known ASD diagnosis was 53 months and did not differ significantly by sex or race/ethnicity. Interpretation: These findings from CDC's ADDM Network, which are based on 2010 data reported from 11 sites, provide updated population-based estimates of the prevalence of ASD in multiple communities in the United States. Because the ADDM Network sites do not provide a representative sample of the entire United States, the combined prevalence estimates presented in this report cannot be generalized to all children aged 8 years in the United States population. Consistent with previous reports from the ADDM Network, findings from the 2010 surveillance year were marked by significant variations in ASD prevalence by geographic area, sex, race/ethnicity, and level of intellectual ability. The extent to which this variation might be attributable to diagnostic practices, underrecognition of ASD symptoms in some racial/ethnic groups, socioeconomic disparities in access to services, and regional differences in clinical or school-based practices that might influence the findings in this report is unclear. Public Health Action: ADDM Network investigators will continue to monitor the prevalence of ASD in select communities, with a focus on exploring changes within these communities that might affect both the observed prevalence of ASD and population-based characteristics of children identified with ASD. Although ASD is sometimes diagnosed by 2 years of age, the median age of the first ASD diagnosis remains older than age 4 years in the ADDM Network communities. Recommendations from the ADDM Network include enhancing strategies to address the need for 1) standardized, widely adopted measures to document ASD severity and functional limitations associated with ASD diagnosis; 2) improved recognition and documentation of symptoms of ASD, particularly among both boys and girls, children without intellectual disability, and children in all racial/ethnic groups; and 3) decreasing the age when children receive their first evaluation for and a diagnosis of ASD and are enrolled in community-based support systems. C1 [Wingate, Martha] Univ Alabama, Tuscaloosa, AL 35487 USA. [Kirby, Russell S.] Univ S Florida, Tampa, FL USA. [Pettygrove, Sydney; Cunniff, Chris] Univ Arizona, Tucson, AZ USA. [Schulz, Eldon] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Ghosh, Tista] Colorado Dept Publ Hlth & Environm, Denver, CO USA. [Robinson, Cordelia] Univ Colorado Denver, Denver, CO USA. [Lee, Li-Ching] Johns Hopkins Univ, Baltimore, MD USA. [Landa, Rebecca] Kennedy Krieger Inst, Baltimore, MD USA. [Constantino, John; Fitzgerald, Robert] Washington Univ, St Louis, MO 63130 USA. [Zahorodny, Walter] Rutgers State Univ, New Jersey Med Sch, Newark, NJ USA. [Daniels, Julie] Univ N Carolina, Chapel Hill, NC USA. [Nicholas, Joyce; Charles, Jane] Med Univ S Carolina, Charleston, SC USA. [McMahon, William; Bilder, Deborah] Univ Utah, Salt Lake City, UT USA. [Durkin, Maureen] Univ Wisconsin, Madison, WI 53706 USA. [Baio, Jon; Christensen, Deborah; Van, Kim; Braun, Naarden; Clayton, Heather; Goodman, Alyson; Doernberg, Nancy; Yeargin-Allsopp, Marshalyn] CDC, Natl Ctr Birth Defects & Dev Disabil, Div Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. RP Baio, J (reprint author), CDC, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. 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On-site synthesis confers novel signaling properties to a protein and helps to maintain local proteome homeostasis. Local translation plays particularly important roles in distal neuronal compartments, and dysregulated RNA localization and translation cause defects in neuronal wiring and survival. Here, we discuss key findings in this area and possible implications of this adaptable and swift mechanism for spatial control of gene function. C1 [Jung, Hosung] Yonsei Univ, Coll Med, Brain Res Inst, Dept Anat, Seoul 120752, South Korea. [Jung, Hosung] Yonsei Univ, Coll Med, Brain Korea PLUS Project Med Sci 21, Seoul 120752, South Korea. [Gkogkas, Christos G.] Univ Edinburgh, Ctr Integrat Physiol, Patrick Wild Ctr, Edinburgh EH8 9XD, Midlothian, Scotland. [Sonenberg, Nahum] McGill Univ, Dept Biochem, Montreal, PQ H3A 1A3, Canada. [Sonenberg, Nahum] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3A 1A3, Canada. [Holt, Christine E.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3DY, England. RP Sonenberg, N (reprint author), McGill Univ, Dept Biochem, Montreal, PQ H3A 1A3, Canada. EM nahum.sonenberg@mcgill.ca; ceh33@cam.ac.uk FU Basic Science Research Program [2013R1A1A1009625]; Bio and Medical Technology Development Program through NRF [2010-0020232]; Korean government (MSIP); Autism Speaks [7109]; Canadian Institutes of Health Research [MOP114994]; Wellcome Trust Programme [085314/Z/08/Z]; ERC [322817] FX We thank A. Bellon for comments on the manuscript. This work was supported by Basic Science Research Program (2013R1A1A1009625) and Bio and Medical Technology Development Program (2010-0020232) funded through NRF by the Korean government (MSIP) (H.J.), Autism Speaks (C.G.G.; 7109), Canadian Institutes of Health Research (N.S.;MOP114994), Wellcome Trust Programme Grant (C.E.H.; 085314/Z/08/Z) and ERC Advanced Grant (C.E.H.; 322817). 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State, Matthew W. TI Psychiatric Disorders: Diagnosis to Therapy SO CELL LA English DT Review ID DE-NOVO MUTATIONS; TRANSCRANIAL MAGNETIC STIMULATION; AUTISM SPECTRUM DISORDERS; OBSESSIVE-COMPULSIVE DISORDER; TERM-FOLLOW-UP; BRAIN-STIMULATION; RECEPTOR ANTAGONIST; RESONANCE-SPECTROSCOPY; COCAINE DEPENDENCE; EXPOSURE THERAPY AB Recent findings in a range of scientific disciplines are challenging the conventional wisdom regarding the etiology, classification, and treatment of psychiatric disorders. This Review focuses on the current state of the psychiatric diagnostic nosology and recent progress in three areas: genomics, neuroimaging, and therapeutics development. The accelerating pace of novel and unexpected findings is transforming the understanding of mental illness and represents a hopeful sign that the approaches and models that have sustained the field for the past 40 years are yielding to a flood of new data and presaging the emergence of a new and more powerful scientific paradigm. C1 [Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. [Krystal, John H.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA. [Krystal, John H.] VA Connecticut Healthcare Syst, VA Natl Ctr PTSD, West Haven, CT 06516 USA. [State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [State, Matthew W.] Univ Calif San Francisco, Langley Porter Psychiat Inst, San Francisco, CA 94143 USA. RP Krystal, JH (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. EM john.krystal@yale.edu; matthew.state@ucsf.edu FU Department of Veterans Affairs; VA National Center for PTSD; Coalition to Alleviate PTSD; National Institute on Alcohol Abuse and Alcoholism [3P50AA012870]; National Institute of Mental Health (FAST-PS) [R01 MH092289-01A1, R01 MH081754, U01 MH100239]; National Center for Advancing Translational Science [UH2TR000960-01]; Clinical and Translational Science Award; UL1 RR024139; State of Connecticut Department of Mental Health and Addiction Services; Abraham Ribicoff Research Facilities of the Connecticut Mental Health Center; Simons Foundation Autism Research Initiative and the Overlook International Fund FX We gratefully acknowledge the Department of Veterans Affairs, the VA National Center for PTSD and its joint funding (with the Department of Defense) of the Coalition to Alleviate PTSD (to J.H.K.), the National Institute on Alcohol Abuse and Alcoholism (3P50AA012870 to J.H.K.), the National Institute of Mental Health (FAST-PS to J.H.K. and R01 MH092289-01A1, R01 MH081754, and U01 MH100239 to M. W. S.), the National Center for Advancing Translational Science (UH2TR000960-01; Clinical and Translational Science Award Grant No. UL1 RR024139 to J.H.K.), the State of Connecticut Department of Mental Health and Addiction Services for its support of the Abraham Ribicoff Research Facilities of the Connecticut Mental Health Center (to J.H.K.), and the Simons Foundation Autism Research Initiative and the Overlook International Fund (to M.W.S.). J.H.K. has served as a scientific consultant to the following companies with compensation in the past year of more than $5,000: Novartis Pharma AG, Janssen Research and Development LLC, AbbVie, Inc., Eli Lilly Corporation, and Naurex, Inc. He holds stock in Biohaven Medical Sciences. He also has the following patents and inventions: (1) dopamine and noradrenergic reuptake inhibitors in treatment of schizophrenia, patent no. 5447948, 5 September 1995; (2) a pending patent for glutamatergic treatments for neuropsychiatric disorders (PCTWO06108055A1); and (3) a pending patent for some applications of ketamine to the treatment of depression. 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CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD MAR 27 PY 2014 VL 157 IS 1 BP 201 EP 214 DI 10.1016/j.cell.2014.02.042 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AE4QW UT WOS:000333968900017 PM 24679536 ER PT J AU Stoner, R Chow, ML Boyle, MP Sunkin, SM Mouton, PR Roy, S Wynshaw-Boris, A Colamarino, SA Lein, ES Courchesne, E AF Stoner, Rich Chow, Maggie L. Boyle, Maureen P. Sunkin, Susan M. Mouton, Peter R. Roy, Subhojit Wynshaw-Boris, Anthony Colamarino, Sophia A. Lein, Ed S. Courchesne, Eric TI Patches of Disorganization in the Neocortex of Children with Autism SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SPECTRUM DISORDER; BRAIN OVERGROWTH; CORTEX; CONNECTIVITY; PATTERNS; NUMBER; SIZE; LIFE AB BackgroundAutism involves early brain overgrowth and dysfunction, which is most strongly evident in the prefrontal cortex. As assessed on pathological analysis, an excess of neurons in the prefrontal cortex among children with autism signals a disturbance in prenatal development and may be concomitant with abnormal cell type and laminar development. MethodsTo systematically examine neocortical architecture during the early years after the onset of autism, we used RNA in situ hybridization with a panel of layer- and cell-type-specific molecular markers to phenotype cortical microstructure. We assayed markers for neurons and glia, along with genes that have been implicated in the risk of autism, in prefrontal, temporal, and occipital neocortical tissue from postmortem samples obtained from children with autism and unaffected children between the ages of 2 and 15 years. ResultsWe observed focal patches of abnormal laminar cytoarchitecture and cortical disorganization of neurons, but not glia, in prefrontal and temporal cortical tissue from 10 of 11 children with autism and from 1 of 11 unaffected children. We observed heterogeneity between cases with respect to cell types that were most abnormal in the patches and the layers that were most affected by the pathological features. No cortical layer was uniformly spared, with the clearest signs of abnormal expression in layers 4 and 5. Three-dimensional reconstruction of layer markers confirmed the focal geometry and size of patches. ConclusionsIn this small, explorative study, we found focal disruption of cortical laminar architecture in the cortexes of a majority of young children with autism. Our data support a probable dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages. (Funded by the Simons Foundation and others.) Molecular analysis of postmortem samples of brain tissue obtained from 11 children with autism showed that the prefrontal and temporal cortexes in 10 of these children had patches of neuronal disorganization. Autism is, in part, a heritable developmental disorder involving macroscopic early brain overgrowth in the majority of cases(1)-(7) and dysfunction(8) that affects several cortical and subcortical regions mediating autistic symptoms, including prefrontal and temporal cortexes.(4),(9)-(11) The underlying cortical defects remain uncertain. Despite the early diagnosable onset, in more than 40 studies, the average age of patients with autism in postmortem analyses was 22 years.(4) Three previous case studies that evaluated Nissl-stained sections of brains obtained from patients with autism ranging in age from 4 to 60 years described individual instances of heterotopias, slight focal laminar disorganization,(12), ... C1 [Stoner, Rich; Chow, Maggie L.; Boyle, Maureen P.; Courchesne, Eric] Univ Calif San Diego, Autism Ctr Excellence, La Jolla, CA 92037 USA. [Stoner, Rich; Chow, Maggie L.; Boyle, Maureen P.; Roy, Subhojit; Courchesne, Eric] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92037 USA. [Roy, Subhojit] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92037 USA. [Boyle, Maureen P.; Sunkin, Susan M.; Lein, Ed S.] Allen Inst Brain Sci, Seattle, WA USA. [Mouton, Peter R.] Univ S Florida, Sch Med, Dept Pathol & Cell Biol, Tampa, FL 33620 USA. [Mouton, Peter R.] Alzheimers Inst, Tampa, FL USA. [Mouton, Peter R.] Res Ctr, Tampa, FL USA. [Wynshaw-Boris, Anthony] Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, Cleveland, OH 44106 USA. [Colamarino, Sophia A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. RP Courchesne, E (reprint author), Univ Calif San Diego, Sch Med, Autism Ctr Excellence, Dept Neurosci, 8110 La Jolla Shores Dr, La Jolla, CA 92037 USA. EM ecourchesne@ucsd.edu FU Simons Foundation; Peter Emch Family Foundation; Cure Autism Now/Autism Speaks; Thursday Club Juniors; Allen Institute for Brain Science; University of California, San Diego, Autism Center of Excellence [P50-MH081755] FX Supported by grants from the Simons Foundation (to Drs. Courchesne and Wynshaw-Boris), the Peter Emch Family Foundation (to Dr. Cour-chesne), Cure Autism Now/Autism Speaks (to Dr. Courchesne), the Thursday Club Juniors (to Dr. Courchesne), the Allen Institute for Brain Science (to Drs. Lein, Sunkin, and Boyle), and the University of California, San Diego, Autism Center of Excellence (P50-MH081755, to Dr. Courchesne). Tissue for this study was provided by the National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders (Baltimore) (N01-HD-4-3368 and N01-HD-4-3383), the Brain and Tissue Bank for Developmental Disorders (Miami), Autism Tissue Program (Princeton, NJ), and Harvard Brain Tissue Resource Center (Belmont, MA). 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Engl. J. Med. PD MAR 27 PY 2014 VL 370 IS 13 BP 1209 EP 1219 DI 10.1056/NEJMoa1307491 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AD7EW UT WOS:000333426000008 PM 24670167 ER PT J AU Abekhoukh, S Bardoni, B AF Abekhoukh, Sabiha Bardoni, Barbara TI CYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE autism; intellectual disability; Fragile X; CYFIP family proteins; WAVE complex; F-actin; dendritic spines ID MENTAL-RETARDATION PROTEIN; PRADER-WILLI-SYNDROME; SYNDROME MOUSE MODEL; MESSENGER-RNA; DENDRITIC SPINE; WAVE COMPLEX; TRANSLATING POLYRIBOSOMES; RECURRENT MICRODELETIONS; NEURONAL CONNECTIVITY; SYNAPTIC PLASTICITY AB Intellectual disability (ID) and autism spectrum disorders (ASDs) have in common alterations in some brain circuits and brain abnormalities, such as synaptic transmission and dendritic spines morphology. Recent studies have indicated a differential expression for specific categories of genes as a cause for both types of disease, while an increasing number of genes is recognized to produce both disorders. An example is the Fragile X mental retardation gene 1 (FMR1), whose silencing causes the Fragile X syndrome, the most common form of ID and autism, also characterized by physical hallmarks. Fragile X mental retardation protein (FMRP), the protein encoded by FMR1, is an RNA-binding protein with an important role in translational control. Among the interactors of FMRP CYFIP1/2 (cytoplasmic FMRP interacting protein) proteins are good candidates for ID and autism, on the bases of their genetic implication and functional properties, even if the precise functional significance of the CYFIP/FMRP interaction is not understood yet. CYFIP1 and CYFIP2 represent a link between Rac1, the WAVE (WAS protein family member) complex and FMRP favoring the cross talk between actin polymerization and translational control. C1 [Abekhoukh, Sabiha; Bardoni, Barbara] CNRS, Inst Mol & Cellular Pharmacol, UMR 7275, F-06560 Valbonne, France. [Abekhoukh, Sabiha; Bardoni, Barbara] Univ Nice Sophia Antipolis, F-06189 Nice, France. [Abekhoukh, Sabiha; Bardoni, Barbara] CNRS, Int Associated Labs NEOGENEX, F-06560 Valbonne, France. RP Bardoni, B (reprint author), CNRS, Inst Mol & Cellular Pharmacol, UMR7275, 660 Route Lucioles, F-06560 Valbonne, France. EM bardoni@ipmc.cnrs.fr RI Bardoni, Barbara/F-9918-2013 FU INSERM; CNRS LIA NEOGENEX; Agence Nationale de la Recherche [ANR-11-LABX-0028-01, SVSE4-2012, SVSE8-2012]; ARC (Fondation ARC pour la Recherche Sur le Cancer) fellowship FX The authors are grateful to Dr, F. Lalli for critical reading of the manuscript, Prof, F. Askenazy for discussion and to Frank Aguila for graphics. 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Behav. Neurosci. PD MAR 27 PY 2014 VL 8 AR 104 DI 10.3389/fnbeh.2014.00104 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AD7BM UT WOS:000333416000001 PM 24723866 ER PT J AU Jerng, HH Pfaffinger, PJ AF Jerng, Henry H. Pfaffinger, Paul J. TI Modulatory mechanisms and multiple functions of somatodendritic A-type K+ channel auxiliary subunits SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE somatodendritic A-type current; potassium channel; auxiliary subunit; Kv channel-interacting protein; dipeptidyl peptidase-like protein; N-terminal variant; modulatory mechanism; excitability ID AMYOTROPHIC-LATERAL-SCLEROSIS; CEREBELLAR GRANULE CELLS; HIPPOCAMPAL PYRAMIDAL NEURONS; CLOSED-STATE INACTIVATION; CELLULAR PRION PROTEIN; PEPTIDASE-LIKE PROTEIN; DIPEPTIDYL AMINOPEPTIDASE FAMILY; TRANSIENT OUTWARD CURRENTS; AUTISM SPECTRUM DISORDER; KV4.2 POTASSIUM CHANNELS AB Auxiliary subunits are non-conducting, modulatory components of the multi-protein ion channel complexes that underlie normal neuronal signaling. They interact with the pore-forming alpha-subunits to modulate surface distribution, ion conductance, and channel gating properties. For the somatodendritic subthreshold A-type potassium (I-SA) channel based on Kv4 alpha-subunits, two types of auxiliary subunits have been extensively studied: Kv channel-interacting proteins (KChIPs) and dipeptidyl peptidase-like proteins (DPLPs). KChIPs are cytoplasmic calcium-binding proteins that interact with intracellular portions of the Kv4 subunits, whereas DPLPs are type II transmembrane proteins that associate with the Kv4 channel core. Both KChIPs and DPLPs genes contain multiple start sites that are used by various neuronal populations to drive the differential expression of functionally distinct N-terminal variants. In turn, these N-terminal variants generate tremendous functional diversity across the nervous system. Here, we focus our review on (1) the molecular mechanism underlying the unique properties of different N-terminal variants, (2) the shaping of native I-SA properties by the concerted actions of KChIPs and DPLP variants, and (3) the surprising ways that KChIPs and DPLPs coordinate the activity of multiple channels to fine-tune neuronal excitability. Unlocking the unique contributions of different auxiliary subunit N-terminal variants may provide an important opportunity to develop novel targeted therapeutics to treat numerous neurological disorders. C1 [Jerng, Henry H.; Pfaffinger, Paul J.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. RP Jerng, HH (reprint author), Baylor Coll Med, Dept Neurosci, One Baylor Plaza,S630, Houston, TX 77030 USA. 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Cell. Neurosci. PD MAR 27 PY 2014 VL 8 AR 82 DI 10.3389/fncel.2014.00082 PG 20 WC Neurosciences SC Neurosciences & Neurology GA AD7BR UT WOS:000333416600001 PM 24723849 ER PT J AU Wassink, TH Hazlett, HC Davis, LK Reiss, AL Piven, J AF Wassink, Thomas H. Hazlett, Heather C. Davis, Lea K. Reiss, Allan L. Piven, Joseph TI Testing for association of the monoamine oxidase A promoter polymorphism with brain structure volumes in both autism and the fragile X syndrome SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Fragile X syndrome; Brain structure; Monoamine oxidase A; Polymorphism ID SEROTONIN TRANSPORTER GENE; ROBUST PEDIGREE ANALYSIS; FUNCTIONAL POLYMORPHISM; NEUROPSYCHIATRIC DISORDERS; SPECTRUM DISORDERS; MENTAL-RETARDATION; INBRED STRAINS; NORRIE-DISEASE; MAOA GENOTYPE; BEHAVIOR AB Background: Autism and the fragile X syndrome (FXS) are related to each other genetically and symptomatically. A cardinal biological feature of both disorders is abnormalities of cerebral cortical brain volumes. We have previously shown that the monoamine oxidase A (MAOA) promoter polymorphism is associated with cerebral cortical volumes in children with autism, and we now sought to determine whether the association was also present in children with FXS. Methods: Participants included 47 2-year-old Caucasian boys with FXS, some of whom also had autism, as well as 34 2-year-old boys with idiopathic autism analyzed in a previous study. The MAOA promoter polymorphism was genotyped and tested for relationships with gray and white matter volumes of the cerebral cortical lobes and cerebro-spinal fluid volume of the lateral ventricles. Results: MAOA genotype effects in FXS children were the same as those previously observed in idiopathic autism: the low activity MAOA promoter polymorphism allele was associated with increased gray and white matter volumes in all cerebral lobes. The effect was most pronounced in frontal lobe gray matter and all three white matter regions: frontal gray, F = 4.39, P = 0.04; frontal white, F = 5.71, P = 0.02; temporal white, F = 4.73, P = 0.04; parieto-occipital white, F = 5.00, P = 0.03. Analysis of combined FXS and idiopathic autism samples produced P values for these regions <0.01 and effect sizes of approximately 0.10. Conclusions: The MAOA promoter polymorphism is similarly associated with brain structure volumes in both idiopathic autism and FXS. These data illuminate a number of important aspects of autism and FXS heritability: a genetic effect on a core biological trait of illness, the specificity/generalizability of the genetic effect, C1 [Wassink, Thomas H.] Univ Iowa Carver Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. [Hazlett, Heather C.; Piven, Joseph] Univ N Carolina, Neurodev Disorders Res Ctr, Chapel Hill, NC USA. [Hazlett, Heather C.; Piven, Joseph] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. 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PD MAR 26 PY 2014 VL 6 AR 6 DI 10.1186/1866-1955-6-6 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AF7EQ UT WOS:000334876800001 PM 24669826 ER PT J AU Pignatelli, M Piccinin, S Molinaro, G Di Menna, L Riozzi, B Cannella, M Motolese, M Vetere, G Catania, MV Battaglia, G Nicoletti, F Nistico, R Bruno, V AF Pignatelli, Marco Piccinin, Sonia Molinaro, Gemma Di Menna, Luisa Riozzi, Barbara Cannella, Milena Motolese, Marta Vetere, Gisella Catania, Maria Vincenza Battaglia, Giuseppe Nicoletti, Ferdinando Nistico, Robert Bruno, Valeria TI Changes in mGlu5 Receptor-Dependent Synaptic Plasticity and Coupling to Homer Proteins in the Hippocampus of Ube3A Hemizygous Mice Modeling Angelman Syndrome SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Angelman syndrome; hippocampus; Homer proteins; LTD; metabotropic glutamate receptors ID LONG-TERM DEPRESSION; FRAGILE-X-SYNDROME; METABOTROPIC GLUTAMATE RECEPTORS; UBIQUITIN-PROTEASOME SYSTEM; MENTAL-RETARDATION; MOUSE MODEL; IP3 RECEPTORS; TRANSLATION; ACTIVATION; INDUCTION AB Angelman syndrome (AS) is caused by the loss of Ube3A, an ubiquitin ligase that commits specific proteins to proteasomal degradation. How this defect causes autism and other pathological phenotypes associated with AS is unknown. Long-term depression (LTD) of excitatory synaptic transmission mediated by type 5 metabotropic glutamate (mGlu5) receptors was enhanced in hippocampal slices of Ube3A(m-/p+) mice, which model AS. No changes were found in NMDA-dependent LTD induced by low-frequency stimulation. mGlu5 receptor-dependent LTD in AS mice was sensitive to the protein synthesis inhibitor anisomycin, and relied on the same signaling pathways as in wild-type mice, e. g., the mitogen-activated protein kinase (MAPK) pathway, the phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycine pathway, and protein tyrosine phosphatase. Neither the stimulation of MAPK and PI3K nor the increase in Arc (activity-regulated cytoskeleton-associated protein) levels in response to mGlu5 receptor activation were abnormal in hippocampal slices from AS mice compared with wild-type mice. mGlu5 receptor expression and mGlu1/5 receptor-mediated polyphosphoinositide hydrolysis were also unchanged in the hippocampus of AS mice. In contrast, AS mice showed a reduced expression of the short Homerprotein isoformHomer 1a, and an increased coupling of mGlu5 receptors to Homer 1b/c proteins in the hippocampus. These findings support the link between Homer proteins and monogenic autism, and lay the groundwork for the use of mGlu5 receptor antagonists in AS. C1 [Pignatelli, Marco; Piccinin, Sonia; Nicoletti, Ferdinando; Nistico, Robert; Bruno, Valeria] Univ Roma La Sapienza, Dept Physiol & Pharmacol, I-00185 Rome, Italy. [Pignatelli, Marco; Piccinin, Sonia] European Brain Res Inst, Pharmacol Synapt Plast Unit, I-00143 Rome, Italy. [Molinaro, Gemma; Di Menna, Luisa; Riozzi, Barbara; Cannella, Milena; Motolese, Marta; Battaglia, Giuseppe; Nicoletti, Ferdinando; Bruno, Valeria] Ist Ricovero & Cura Carattere Sci IRCCS Neuromed, I-86077 Pozzilli, Italy. [Vetere, Gisella; Nistico, Robert] IRCCS Fdn Santa Lucia, I-00143 Rome, Italy. [Vetere, Gisella] CNR, Inst Cell Biol & Neurobiol, I-00143 Rome, Italy. [Catania, Maria Vincenza] CNR, Inst Neurol Sci, I-95126 Catania, Italy. [Catania, Maria Vincenza] IRCCS Oasi Maria SS, I-94018 Troina, Italy. RP Bruno, V (reprint author), Dept Physiol & Pharmacol, Piazzale Aldo Moro 5, I-00185 Rome, Italy. 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Neurosci. PD MAR 26 PY 2014 VL 34 IS 13 BP 4558 EP 4566 DI 10.1523/JNEUROSCI.1846-13.2014 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AE0RP UT WOS:000333674200012 PM 24672001 ER PT J AU Barth, L Sutterlin, R Nenniger, M Vogt, KE AF Barth, Lydia Suetterlin, Rosmarie Nenniger, Markus Vogt, Kaspar E. TI Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE Rett syndrome; stem cell-derived neurons; neurodevelopment; electrophysiology; excitability; synaptic activity ID CPG-BINDING PROTEIN-2; MOUSE MODEL; MECP2-DEFICIENT MICE; DELAYED MATURATION; NEURAL DEVELOPMENT; PYRAMIDAL NEURONS; MECP2; DEFICIENCY; DYSFUNCTION; EXPRESSION AB Neurodevelopmental diseases such as the Rett syndrome (RTT) have received renewed attention, since the mechanisms involved may underlie a broad range of neuropsychiatric disorders such as schizophrenia and autism. In vertebrates early stages in the functional development of neurons and neuronal networks are difficult to study. Embryonic stem cell-derived neurons provide an easily accessible tool to investigate neuronal differentiation and early network formation. We used in vitro cultures of neurons derived from murine embryonic stem cells missing the methyl-CpG-binding protein 2 (MECP2) gene (MeCP2-/y) and from wild type cells of the corresponding background. Cultures were assessed using whole-cell patch-clamp electrophysiology and immunofluorescence. We studied the functional maturation of developing neurons and the activity of the synaptic connections they formed. Neurons exhibited minor differences in the developmental patterns for their intrinsic parameters, such as resting membrane potential and excitability; with the MeCP2-/y cells showing a slightly accelerated development, with shorter action potential half-widths at early stages. There was no difference in the early phase of synapse development, but as the cultures matured, significant deficits became apparent, particularly for inhibitory synaptic activity. MeCP2-/y embryonic stem cell-derived neuronal cultures show clear developmental deficits that match phenotypes observed in slice preparations and thus provide a compelling tool to further investigate the mechanisms behind RTT pathophysiology. C1 [Barth, Lydia; Suetterlin, Rosmarie; Nenniger, Markus; Vogt, Kaspar E.] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland. RP Vogt, KE (reprint author), Univ Basel, Biozentrum, Klingelbergstr 50-70, CH-4056 Basel, Switzerland. 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Here we show that for chromosomes # 1, 2 and 22 the actual number of miRNA loci affected by de novo CNVs in patients was found significantly higher than that estimated by Monte Carlo simulation of random CNV events. Out of 24 miRNA genes over-represented in CNVs from these three chromosomes only hsa-mir-4436b-1 and hsa-mir-4436b-2 have not been detected in CNVs from non-autistic subjects as reported in the Database of Genomic Variants. Altogether the results reported in this study represent a first step towards a full understanding of how a dysregulated expression of the 24 miRNAs genes affect neurodevelopment in autism. We also propose that the procedure used in this study can be effectively applied to CNVs/miRNA genes association data in other genomic disorders beyond autism. C1 [Marrale, Maurizio; Albanese, Nadia Ninfa; Romano, Valentino] Univ Palermo, Dipartimento Fis & Chim, Palermo, Italy. [Cali, Francesco; Romano, Valentino] Assoc Oasi Maria SS IRCCS, UOC Genet Med Lab Genet Mol, Troina, Italy. RP Romano, V (reprint author), Univ Palermo, Dipartimento Fis & Chim, Palermo, Italy. EM valentino.romano@unipa.it RI MARRALE, MAURIZIO/I-9926-2014 OI MARRALE, MAURIZIO/0000-0002-0091-3243 FU University of Palermo; Italian Ministry of Health FX The authors acknowledge funding from University of Palermo and from the Italian Ministry of Health: "Ricerca corrente 2013" entitled: "Ritardo mentale, epilessia e autismo: studio genetico, clinico e neurofisiologico". 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 typically developed subjects, such coupling occurs at the right posterior temporal sulcus (pSTS) for frequencies below 1 Hz, and reflects the neural processing of sentence-level rhythmic prosody at the prelexical level. Methods: Cortical neuromagnetic signals were recorded with MEG (Elekta Oy, Finland) while seven right-handed and native French-speaking ASD subjects (six males, one female, range: 13-20 years) listened to live (Live) or recorded (Recorded) voices continuously reading a text in French for five minutes. Coherence was computed between the reader's voice time-course and ASD subjects' MEG signals. Coherent neural sources were subsequently reconstructed using a beamformer. Key findings: Significant coupling was found at 0.5 Hz in all ASD subjects in Live and in six subjects in Recorded. Coherent sources were located close to the right pSTS in both conditions. No significant difference was found in coherence levels between Live and Recorded, and between ASD subjects and ten typically developed subjects (right-handed, native French-speaking adults, 5 males, 5 females, age range: 21-38 years) included in a previous study. Significance: This study discloses a preserved coupling between the reader's voice and ASD subjects' cortical activity at the right pSTS. These findings support the existence of preserved neural processing of sentence-level rhythmic prosody in ASD. The preservation of early cortical processing of prosodic elements in verbal language might be exploited in therapeutic interventions in ASD. C1 [Clumeck, Catherine; Garcia, Sarah Suarez; Bourguignon, Mathieu; Wens, Vincent; Op de Beeck, Marc; Marty, Brice; Goldman, Serge; Van Bogaert, Patrick; De Tiege, Xavier] Univ Libre Brussels, UNI ULB Neurosci Inst, Lab Cartog Fonct Cerveau, Brussels, Belgium. [Clumeck, Catherine] Univ Libre Brussels, UNI ULB Neurosci Inst, Lab Rech Psychiat, Brussels, Belgium. [Deconinck, Nicolas; Soncarrieu, Marie-Vincianne] Hop Univ Enfants Reine Fabiola, Ctr Reference Troubles Envahissants Dev & Trouble, Brussels, Belgium. [Jousmaki, Veikko] Aalto Univ, Brain Res Unit, OV Lounasmaa Lab, Espoo, Finland. [Jousmaki, Veikko] Aalto Univ, MEG Core, Espoo, Finland. RP De Tiege, X (reprint author), Univ Libre Brussels, UNI ULB Neurosci Inst, Lab Cartog Fonct Cerveau, Brussels, Belgium. EM xdetiege@ulb.ac.be RI Bourguignon, Mathieu/I-6967-2012 OI Bourguignon, Mathieu/0000-0003-1694-5087 FU Fonds de la Recherche Scientifique (FRS-FNRS, Belgium); FRS-FNRS [J.0021.13] FX Catherine Clumeck (Research Fellow) and Xavier De Tiege (Postdoctorate Clinical Master Specialist) benefit of a research grant form the Fonds de la Recherche Scientifique (FRS-FNRS, Belgium). This study was supported by a research grant from the FRS-FNRS (research project: J.0021.13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Ahmad, Eizaaz Li, Hongyan Crawford, Dorota A. TI Prostaglandin E2 alters Wnt-dependent migration and proliferation in neuroectodermal stem cells: implications for autism spectrum disorders SO CELL COMMUNICATION AND SIGNALING LA English DT Article DE Prostaglandin E2; Wnt signalling; Neuroectodermal stem cells; Cell motility; Proliferation; Autism ID HEPATOCELLULAR-CARCINOMA CELLS; CYCLIN D1 GENE; BETA-CATENIN; PROSTANOID RECEPTORS; HISTONE H3; MATRIX METALLOPROTEINASES; NEURONAL DIFFERENTIATION; CHROMOSOME CONDENSATION; CORTICAL DEVELOPMENT; SIGNALING PATHWAY AB Prostaglandin E2 (PGE(2)) is a natural lipid-derived molecule that is involved in important physiological functions. Abnormal PGE(2) signalling has been associated with pathologies of the nervous system. Previous studies provide evidence for the interaction of PGE(2) and canonical Wnt signalling pathways in non-neuronal cells. Since the Wnt pathway is crucial in the development and organization of the brain, the main goal of this study is to determine whether collaboration between these pathways exists in neuronal cell types. We report that PGE(2) interacts with canonical Wnt signalling through PKA and PI-3K in neuroectodermal (NE-4C) stem cells. We used time-lapse microscopy to determine that PGE(2) increases the final distance from origin, path length travelled, and the average speed of migration in Wnt-activated cells. Furthermore, PGE(2) alters distinct cellular phenotypes that are characteristic of Wnt-induced NE-4C cells, which corresponds to the modified splitting behaviour of the cells. We also found that in Wnt-induced cells the level of beta-catenin protein was increased and the expression levels of Wnt-target genes (Ctnnb1, Ptgs2, Ccnd1, Mmp9) was significantly upregulated in response to PGE(2) treatment. This confirms that PGE(2) activated the canonical Wnt signalling pathway. Furthermore, the upregulated genes have been previously associated with ASD. Our findings show, for the first time, evidence for cross-talk between PGE(2) and Wnt signalling in neuronal cells, where PKA and PI-3K might act as mediators between the two pathways. Given the importance of PGE(2) and Wnt signalling in prenatal development of the nervous system, our study provides insight into how interaction between these two pathways may influence neurodevelopment. C1 [Wong, Christine T.; Li, Hongyan; Crawford, Dorota A.] York Univ, Sch Kinesiol & Hlth Sci, Toronto, ON M3J 1P3, Canada. [Wong, Christine T.; Crawford, Dorota A.] York Univ, Neurosci Grad Diploma Program, Toronto, ON M3J 1P3, Canada. [Ahmad, Eizaaz; Crawford, Dorota A.] York Univ, Fac Hlth, Dept Biol, Toronto, ON M3J 1P3, Canada. RP Crawford, DA (reprint author), York Univ, Sch Kinesiol & Hlth Sci, 4700 Keele St, Toronto, ON M3J 1P3, Canada. EM dakc@yorku.ca FU Natural Sciences and Engineering Research Council of Canada (NSERC) FX This research work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC). 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Signal. PD MAR 23 PY 2014 VL 12 AR 19 DI 10.1186/1478-811X-12-19 PG 18 WC Cell Biology SC Cell Biology GA AF3UY UT WOS:000334639000001 PM 24656144 ER PT J AU Smith, RG Fernandes, C Kember, R Schalkwyk, LC Buxbaum, J Reichenberg, A Mill, J AF Smith, Rebecca G. Fernandes, Cathy Kember, Rachel Schalkwyk, Leonard C. Buxbaum, Joseph Reichenberg, Abraham Mill, Jonathan TI Transcriptomic changes in the frontal cortex associated with paternal age SO MOLECULAR AUTISM LA English DT Article DE Autism; Advanced paternal age; Gene expression; Transcriptome; Inflammation; Immune response; Brain ID AUTISM SPECTRUM DISORDERS; DE-NOVO MUTATIONS; LARGE GENE LISTS; DIFFERENTIAL REGULATION; NEUROTROPHIC FACTOR; EXPRESSION; BRAIN; MICROARRAY; PATHWAYS; PROTEIN AB Background: Advanced paternal age is robustly associated with several human neuropsychiatric disorders, particularly autism. The precise mechanism(s) mediating the paternal age effect are not known, but they are thought to involve the accumulation of de novo (epi)genomic alterations. In this study we investigate differences in the frontal cortex transcriptome in a mouse model of advanced paternal age. Findings: Transcriptomic profiling was undertaken for medial prefrontal cortex tissue dissected from the male offspring of young fathers (2 month old, 4 sires, n = 16 offspring) and old fathers (10 month old, 6 sires, n = 16 offspring) in a mouse model of advancing paternal age. We found a number of differentially expressed genes in the offspring of older fathers, many previously implicated in the aetiology of autism. Pathway analysis highlighted significant enrichment for changes in functional networks involved in inflammation and inflammatory disease, which are also implicated in autism. Conclusions: We observed widespread alterations to the transcriptome associated with advanced paternal age with an enrichment of genes associated with inflammation, an interesting observation given previous evidence linking the immune system to several neuropsychiatric disorders including autism. C1 [Smith, Rebecca G.; Fernandes, Cathy; Kember, Rachel; Schalkwyk, Leonard C.; Reichenberg, Abraham; Mill, Jonathan] Kings Coll London, Inst Psychiat, London SE5 8AF, England. [Buxbaum, Joseph; Reichenberg, Abraham] Mt Sinai Sch Med, New York, NY 10029 USA. [Mill, Jonathan] Univ Exeter, Sch Med, Exeter EX1 2LU, Devon, England. RP Mill, J (reprint author), Kings Coll London, Inst Psychiat, De Crespigny Pk,Denmark Hill, London SE5 8AF, England. EM j.mill@exeter.ac.uk RI Smith, Rebecca/C-1978-2012; Fernandes, Cathy/F-3422-2011; Schalkwyk, Leonard/A-2150-2010; Mill, Jonathan/B-3276-2010 OI Schalkwyk, Leonard/0000-0001-7030-5756; Mill, Jonathan/0000-0003-1115-3224 FU Beatrice and Samuel A Seaver Foundation; British Medical Association Margaret Temple Award; National Institute of Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service Foundation Trust; Institute of Psychiatry, King's College London FX This study was supported by the Beatrice and Samuel A Seaver Foundation, by a British Medical Association Margaret Temple Award, and the National Institute of Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service Foundation Trust and the Institute of Psychiatry, King's College London, Pilot Award to Drs Jonathan Mill and Abraham (Avi) Reichenberg. 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Autism PD MAR 23 PY 2014 VL 5 AR 24 DI 10.1186/2040-2392-5-24 PG 7 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AF8LE UT WOS:000334966500001 PM 24655730 ER PT J AU Makin, S AF Makin, Simon TI Environment linked to autism rise once again SO NEW SCIENTIST LA English DT News Item NR 0 TC 0 Z9 0 PU REED BUSINESS INFORMATION LTD PI SUTTON PA QUADRANT HOUSE THE QUADRANT, SUTTON SM2 5AS, SURREY, ENGLAND SN 0262-4079 J9 NEW SCI JI New Sci. PD MAR 22 PY 2014 VL 221 IS 2961 BP 11 EP 11 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AD7WB UT WOS:000333476500006 ER PT J AU Smith, CM Walker, AW Hosken, IT Chua, BE Zhang, C Haidar, M Gundlach, AL AF Smith, Craig M. Walker, Andrew W. Hosken, Ihaia T. Chua, Berenice E. Zhang, Cary Haidar, Mouna Gundlach, Andrew L. TI Relaxin-3/RXFP3 networks: an emerging target for the treatment of depression and other neuro psychiatric diseases? SO FRONTIERS IN PHARMACOLOGY LA English DT Review DE relaxin-3; RXFP3; neuropeptide; arousal; stress; mood and depression; autism spectrum disorders; eating disorders ID CORTICOTROPIN-RELEASING-FACTOR; HIPPOCAMPAL-THETA-RHYTHM; CENTRAL-NERVOUS-SYSTEM; INTERGENICULATE LEAFLET NEURONS; RELAXIN FAMILY PEPTIDES; RECEPTOR MESSENGER-RNA; DORSAL RAPHE NUCLEUS; MALE WISTAR RATS; NEUROPEPTIDE-Y; STRIA TERMINALIS AB Animal and clinical studies of gene-environment interactions have helped elucidate the mechanisms involved in the pathophysiology of several mental illnesses including anxiety, depression, and schizophrenia; and have led to the discovery of improved treatments. The study of neuropeptides and their receptors is a parallel frontier of neuropsychopharmacology research and has revealed the involvement of several peptide systems in mental illnesses and identified novel targets for their treatment. Relaxin-3 is a newly discovered neuropeptide that binds, and activates the G-protein coupled receptor, RXFP3. Existing anatomical and functional evidence suggests relaxin-3 is an arousal transmitter which is highly responsive to environmental stimuli, particularly neurogenic stressors, and in turn modulates behavioral responses to these stressors and alters key neural processes, including hippocampal theta rhythm and associated learning and memory. Here, we review published experimental data on relaxin-3/RXFP3 systems in rodents, and attempt to highlight aspects that are relevant and/or potentially translatable to the etiology and treatment of major depression and anxiety. Evidence pertinent to autism spectrum and metabolism/eating disorders, or related psychiatric conditions, is also discussed. We also nominate some key experimental studies required to better establish the therapeutic potential of this intriguing neuromodulatory signaling system, including an examination of the impact of RXFP3 agonists and antagonists on the overall activity of distinct or common neural substrates and circuitry that are identified as dysfunctional in these debilitating brain diseases. C1 [Smith, Craig M.; Walker, Andrew W.; Hosken, Ihaia T.; Chua, Berenice E.; Zhang, Cary; Haidar, Mouna; Gundlach, Andrew L.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Neuropeptides Div, Peptide Neurobiol Lab, Parkville, Vic 3052, Australia. [Smith, Craig M.; Walker, Andrew W.; Hosken, Ihaia T.; Zhang, Cary; Haidar, Mouna; Gundlach, Andrew L.] Univ Melbourne, Florey Dept Neurosci & Mental Hlth, Melbourne, Vic 3010, Australia. [Gundlach, Andrew L.] Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic 3052, Australia. RP Smith, CM (reprint author), Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Neuropeptides Div, Peptide Neurobiol Lab, 30 Royal Parade, Parkville, Vic 3052, Australia. EM craig.smith@florey.edu.au; andrew.gundlach@florey.edu.au FU National Health and Medical Research Council (NHMRC) of Australia [509246, 1005988, 1024885]; Pratt Foundation; Besen Foundation; Victorian Government Strategic Investment FX The research in the authors' laboratory reviewed here was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (509246, 1005988, and 1024885) and the Pratt and Besen Foundations, and by the Victorian Government Strategic Investment. Andrew L. Gundlach is an NHMRC (Australia) Senior Research Fellow and a Brain & Behavior Research Foundation (USA) NARSAD Independent Investigator. The authors acknowledge the contribution of their current and former colleagues to the relaxin-3 related research reviewed. 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Pharmacol. PD MAR 21 PY 2014 VL 5 AR 46 DI 10.3389/fphar.2014.00046 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AX6WS UT WOS:000347059600001 PM 24711793 ER PT J AU Tavassoli, T Kolevzon, A Wang, AT Curchack-Lichtin, J Halpern, D Schwartz, L Soffes, S Bush, L Grodberg, D Cai, GQ Buxbaum, JD AF Tavassoli, Teresa Kolevzon, Alexander Wang, A. Ting Curchack-Lichtin, Jocelyn Halpern, Danielle Schwartz, Lily Soffes, Sarah Bush, Lauren Grodberg, David Cai, Guiqing Buxbaum, Joseph D. TI De novo SCN2A splice site mutation in a boy with Autism spectrum disorder SO BMC MEDICAL GENETICS LA English DT Article DE DSM-5; autism spectrum disorder; de novo SCN2A splice site mutation ID SENSORY OVER-RESPONSIVITY; INFANTILE SEIZURES; YOUNG-CHILDREN; SCN3A GENES; EPILEPSY; SCN1A; ABNORMALITIES; PROFILE; RETARDATION; DUPLICATION AB Background: SCN2A is a gene that codes for the alpha subunit of voltage-gated, type II sodium channels, and is highly expressed in the brain. Sodium channel disruptions, such as mutations in SCN2A, may play an important role in psychiatric disorders. Recently, de novo SCN2A mutations in autism spectrum disorder (ASD) have been identified. The current study characterizes a de novo splice site mutation in SCN2A that alters mRNA and protein products. Case presentation: We describe results from clinical and genetic characterizations of a seven-year-old boy with ASD. Psychiatric interview and gold standard autism diagnostic instruments (ADOS and ADI-R) were used to confirm ASD diagnosis, in addition to performing standardized cognitive and adaptive functioning assessments (Leiter-R and Vineland Adaptive Behavior Scale), and sensory reactivity assessments (Sensory Profile and Sensory Processing Scales). Genetic testing by whole exome sequencing revealed four de novo events, including a splice site mutation c.476 + 1G > A in SCN2A, a missense mutation (c.2263G > A) causing a p.V755I change in the TLE1 gene, and two synonymous mutations (c.2943A > G in the BUB1 gene, and c.1254 T > A in C10orf68 gene). The de novo SCN2A splice site mutation produced a stop codon 10 amino acids downstream, possibly resulting in a truncated protein and/or a nonsense-mediated mRNA decay. The participant met new DSM-5 criteria for ASD, presenting with social and communication impairment, repetitive behaviors, and sensory reactivity issues. The participant's adaptive and cognitive skills fell in the low range of functioning. Conclusion: This report indicates that a splice site mutation in SCN2A might be contributing to the risk of ASD. Describing the specific phenotype associated with SCN2A mutations might help to reduce heterogeneity seen in ASD. C1 [Tavassoli, Teresa; Kolevzon, Alexander; Wang, A. Ting; Curchack-Lichtin, Jocelyn; Halpern, Danielle; Schwartz, Lily; Soffes, Sarah; Bush, Lauren; Grodberg, David; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Tavassoli, Teresa; Kolevzon, Alexander; Wang, A. Ting; Curchack-Lichtin, Jocelyn; Grodberg, David; Buxbaum, Joseph D.] Dept Psychiat, New York, NY USA. [Cai, Guiqing; Buxbaum, Joseph D.] Dept Genet & Genom Sci, New York, NY USA. [Cai, Guiqing; Buxbaum, Joseph D.] Dept Neurosci, New York, NY USA. [Wang, A. Ting; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY USA. [Wang, A. Ting; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY USA. [Kolevzon, Alexander; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA. RP Tavassoli, T (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. EM teresa.tavassoli@mssm.edu FU Beatrice and Samuel A. Seaver Foundation; Wallace Research Foundation; Seaver Foundation; Autism Science Foundation; NIH; Hofmann-LaRoche FX This work was supported by grants from the Beatrice and Samuel A. Seaver Foundation. TT received funding from the Wallace Research Foundation, the Seaver Foundation and the Autism Science Foundation during the period of this work. A. K. received research support from the NIH, the Autism Science Foundation, the Seaver Foundation, and Hofmann-LaRoche. 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Genet. PD MAR 20 PY 2014 VL 15 AR 35 DI 10.1186/1471-2350-15-35 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AF2JO UT WOS:000334538600001 PM 24650168 ER PT J AU Shaw, AD Tiwari, Y Kaplan, W Heath, A Mitchell, PB Schofield, PR Fullerton, JM AF Shaw, Alex D. Tiwari, Yash Kaplan, Warren Heath, Anna Mitchell, Philip B. Schofield, Peter R. Fullerton, Janice M. TI Characterisation of Genetic Variation in ST8SIA2 and Its Interaction Region in NCAM1 in Patients with Bipolar Disorder SO PLOS ONE LA English DT Article ID CELL-ADHESION MOLECULE; DNA-SEQUENCING DATA; GENOME-WIDE SCAN; POLYSIALIC-ACID; PSA-NCAM; HUMAN POLYSIALYLTRANSFERASE; SUSCEPTIBILITY LOCUS; PREFRONTAL CORTEX; SCHIZOPHRENIA; EXPRESSION AB Alpha-2,8-sialyltransferase 2 (ST8SIA2) is an enzyme responsible for the transfer of polysialic acid (PSA) to glycoproteins, principally the neuronal cell adhesion molecule (NCAM1), and is involved in neuronal plasticity. Variants within ST8SIA2 have previously shown association with bipolar disorder, schizophrenia and autism. In addition, altered PSA-NCAM expression in brains of patients with schizophrenia or bipolar disorder indicates a functional dysregulation of glycosylation in mental illness. To explore the role of sequence variation affecting PSA-NCAM formation, we conducted a targeted re-sequencing study of a similar to 100 kb region - including the entire ST8SIA2 gene and its region of interaction with NCAM1 - in 48 Caucasian cases with bipolar disorder using the Roche 454 platform. We identified over 400 DNA variants, including 47 putative novel variants not described in dbSNP. Validation of a subset of variants via Sequenom showed high reliability of Roche 454 genotype calls (97% genotype concordance, with 80% of novel variants independently verified). We did not observe major loss-of-function mutations that would affect PSA-NCAM formation, either by ablating ST8SIA2 function or by affecting the ability of NCAM1 to be glycosylated. However, we identified 13 SNPs in the UTRs of ST8SIA2, a synonymous coding SNP in exon 5 (rs2305561, P207P) and many additional non-coding variants that may influence splicing or regulation of ST8SIA2 expression. We calculated nucleotide diversity within ST8SIA2 on specific haplotypes, finding that the diversity on the specific "risk" and "protective" haplotypes was lower than other non-disease-associated haplotypes, suggesting that putative functional variation may have arisen on a spectrum of haplotypes. We have identified common and novel variants (rs11074064, rs722645, 15:92961050) that exist on a spectrum of haplotypes, yet are plausible candidates for conferring the effect of risk and protective haplotypes via multiple enhancer elements. A Galaxy workflow/pipeline for sequence analysis used herein is available at: https://main.g2.bx.psu.edu/u/a-shaw-neura/p/next-generation-resources. C1 [Shaw, Alex D.; Tiwari, Yash; Heath, Anna; Schofield, Peter R.; Fullerton, Janice M.] Neurosci Res Australia, Sydney, NSW, Australia. [Shaw, Alex D.; Tiwari, Yash; Schofield, Peter R.; Fullerton, Janice M.] Schizophrenia Res Inst, Sydney, NSW, Australia. [Tiwari, Yash; Schofield, Peter R.; Fullerton, Janice M.] Univ New S Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia. [Kaplan, Warren] Garvan Inst, Peter Wills Bioinformat Ctr, Sydney, NSW, Australia. [Mitchell, Philip B.] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. [Mitchell, Philip B.] Black Dog Inst, Sydney, NSW, Australia. RP Fullerton, JM (reprint author), Neurosci Res Australia, Sydney, NSW, Australia. EM j.fullerton@neura.edu.au FU Australian National Medical and Health Research Council [630574, 510135, 1037196]; Schizophrenia Research Institute; NSW Health; Australian National Health and Medical Research Council [401184]; Cancer Institute NSW [11/REG/1-10]; Australian Postgraduate Award FX This work was supported by the Australian National Medical and Health Research Council (project grant 630574, and program grants 510135 and 1037196) and by the Schizophrenia Research Institute, utilizing infrastructure funding from NSW Health. Genetic Repositories Australia is supported by an Australian National Health and Medical Research Council (Grant # 401184). The authors used Garvan Galaxy, funded by a Cancer Institute NSW grant (11/REG/1-10). Mr Yash Tiwari was supported by an Australian Postgraduate 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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Santamaria, Enrique TI Applying mass spectrometry-based qualitative proteomics to human amygdaloid complex SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE brain; amygdala; proteomics; mass spectrometry; bioinformatics ID CEREBROSPINAL-FLUID; RAT-BRAIN; QUADRUPOLE-TIME; 2-D DIGE; PROTEINS; CHROMATOGRAPHY; TRANSCRIPTOME; EXPRESSION; MOLECULES; IDENTIFICATION AB The amygdaloid complex is a key brain structure involved in the expression of behaviors and emotions such as learning, fear, and anxiety. Brain diseases including depression, epilepsy, autism, schizophrenia, and Alzheimer's disease, have been associated with amygdala dysfunction. For several decades, neuroanatomical, neurophysiological, volumetric, and cognitive approaches have been the gold standard techniques employed to characterize the amygdala functionality. However, little attention has been focused specifically on the molecular composition of the human amygdala from the perspective of proteomics. We have performed a global proteome analysis employing protein and peptide fractionation methods followed by nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS), detecting expression of at least 1820 protein species in human amygdala, corresponding to 1814 proteins which represent a nine-fold increase in proteome coverage with respect to previous proteomic profiling of the rat amygdala. Gene ontology analysis were used to determine biological process represented in human amygdala highlighting molecule transport, nucleotide binding, and oxidoreductase and GTPase activities. Bioinformatic analyses have revealed that nearly 4% of identified proteins have been previously associated to neurodegenerative syndromes, and 26% of amygdaloid proteins were also found to be present in cerebrospinal fluid (CSF). In particular, a subset of amygdaloid proteins was mainly involved in axon guidance, synaptic vesicle release, L1CAM interactome, and signaling pathways transduced by NGF and NCAM1. Taken together, our data contributes to the repertoire of the human brain proteome, serving as a reference library to provide basic information for understanding the neurobiology of the human amygdala. C1 [Fernandez-Irigoyen, Joaquin; Santamaria, Enrique] Fdn Miguel Servet, Navarrabiomed, Clin Neuroprote Grp, Prote Unit, Pamplona 31008, Spain. [Zelaya, Maria V.] Fdn Miguel Servet, Navarrabiomed, Neurol Tissue Bank, Pamplona 31008, Spain. RP Santamaria, E (reprint author), Fdn Miguel Servet, Navarrabiomed, Clin Neuroprote Grp, Prote Unit, Irunlarrea St, Pamplona 31008, Spain. EM esantamma@navarra.es FU Fundacion Miguel Servet (Government of Navarra); PRB2-ISCIII [PT13/0001] FX We are very grateful to the tissue donors and their families. We thank the Neurological Tissue Bank of Navarrabiomed for immunohistochemical analysis of the brains and for providing us the amygdala specimens. We are grateful to Teresa Tunon and Federico Garcia-Bragado from Pathological Anatomy Department of Navarra Health Service for sharing experiences on human brain processing. This work was supported by Fundacion Miguel Servet (Government of Navarra). Navarrabiomed Proteomics Unit belongs to Proteored, PRB2-ISCIII, supported by grant PT13/0001 and is member of the Spanish Human Proteome Project (SpHPP) (Chromosome 16 Consortium). 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Cell. Neurosci. PD MAR 20 PY 2014 VL 8 AR 80 DI 10.3389/fncel.2014.00080 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AD2SM UT WOS:000333085500001 PM 24688456 ER PT J AU Mishra, A Traut, MH Becker, L Klopstock, T Stein, V Klein, R AF Mishra, Archana Traut, Matthias H. Becker, Lore Klopstock, Thomas Stein, Valentin Klein, Ruediger TI Genetic Evidence for the Adhesion Protein IgSF9/Dasm1 to Regulate Inhibitory Synapse Development Independent of its Intracellular Domain SO JOURNAL OF NEUROSCIENCE LA English DT Article ID CELL-ADHESION; DENDRITE ARBORIZATION; SEIZURE SUSCEPTIBILITY; MATURATION-1 DASM1; IG SUPERFAMILY; FAMILY-MEMBER; NEUROLIGIN 2; IN-VIVO; TURTLE; DIFFERENTIATION AB Normal brain function requires balanced development of excitatory and inhibitory synapses. An imbalance in synaptic transmission underlies many brain disorders such as epilepsy, schizophrenia, and autism. Compared with excitatory synapses, relatively little is known about the molecular control of inhibitory synapse development. We used a genetic approach in mice to identify the Ig superfamily member IgSF9/Dasm1 as a candidate homophilic synaptic adhesion protein that regulates inhibitory synapse development. IgSF9 is expressed in pyramidal cells and subsets of interneurons in the CA1 region of hippocampus. Electrophysiological recordings of acute hippocampal slices revealed that genetic inactivation of the IgSF9 gene resulted in fewer functional inhibitory synapses; however, the strength of the remaining synapses was unaltered. These physiological abnormalities were correlated with decreased expression of inhibitory synapse markers in IgSF9(-/-) mice, providing anatomical evidence for a reduction in inhibitory synapse numbers, whereas excitatory synapse development was normal. Surprisingly, knock-in mice expressing a mutant isoform of IgSF9 lacking the entire cytoplasmic domain (IgSF9(Delta C/Delta C) mice) had no defects in inhibitory synapse development, providing genetic evidence that IgSF9 regulates synapse development via ectodomain interactions rather than acting itself as a signaling receptor. Further, we found that IgSF9 mediated homotypic binding and cell aggregation, but failed to induce synapse formation, suggesting that IgSF9 acts as a cell adhesion molecule (CAM) to maintain synapses. Juvenile IgSF9(-/-) mice exhibited increased seizure susceptibility indicative of an imbalance in synaptic excitation and inhibition. These results provide genetic evidence for a specific role of IgSF9 in inhibitory synapse development/maintenance, presumably by its CAM-like activity. C1 [Mishra, Archana; Traut, Matthias H.; Klein, Ruediger] Max Planck Inst Neurobiol, Dept Mol Signaling Dev, D-82152 Martinsried, Germany. [Traut, Matthias H.; Stein, Valentin] Max Planck Inst Neurobiol, Synapt Receptor Trafficking Grp, D-82152 Martinsried, Germany. [Becker, Lore; Klopstock, Thomas] German Res Ctr Environm & Hlth, Helmholtz Zentrum Munchen, Inst Expt Genet, German Mouse Clin, D-85764 Neuherberg, Germany. [Becker, Lore; Klopstock, Thomas] Univ Munich, Friedrich Baur Inst, Dept Neurol, D-80336 Munich, Germany. [Klopstock, Thomas; Klein, Ruediger] Munich Cluster Syst Neurol SyNergy, D-80336 Munich, Germany. [Stein, Valentin] Univ Bonn, Dept Physiol 2, D-53115 Bonn, Germany. RP Klein, R (reprint author), Max Planck Inst Neurobiol, Dept Mol Signaling Dev, D-82152 Martinsried, Germany. EM valentin.stein@ukb.uni-bonn.de; rklein@neuro.mpg.de RI Klein, Ruediger/C-6147-2008; Becker, Lore/E-3717-2010 OI Klein, Ruediger/0000-0002-3109-0163; FU Max-Planck Society; German Federal Ministry of Education and Research [01GS0850, 01E00901, 01KX1012]; European Union (EUMODIC) FX This work was supported by the Max-Planck Society. L.B. and T.K. received funding from the German Federal Ministry of Education and Research (Grants 01GS0850, 01E00901, and 01KX1012) and the European Union (EUMODIC). We thank Marianne Braun for technical assistance with electron microscopy and Gonul Seyit-Bremer for generating Igsf9/9b antibodies and recombinant proteins. 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Neurosci. PD MAR 19 PY 2014 VL 34 IS 12 BP 4187 EP 4199 DI 10.1523/JNEUROSCI.3671-13.2014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AD4WX UT WOS:000333253300008 PM 24647940 ER PT J AU Han, S Tai, C Jones, CJ Scheuer, T Catterall, WA AF Han, Sung Tai, Chao Jones, Christina J. Scheuer, Todd Catterall, William A. TI Enhancement of Inhibitory Neurotransmission by GABA(A) Receptors Having alpha(2,3)-Subunits Ameliorates Behavioral Deficits in a Mouse Model of Autism SO NEURON LA English DT Article ID MICE; BENZODIAZEPINES; DYSFUNCTION; WITHDRAWAL; TOLERANCE; GENETICS; SUBTYPES; EXCITATION/INHIBITION; NEUROBIOLOGY; PHARMACOLOGY AB Autism spectrum disorder (ASD) may arise from increased ratio of excitatory to inhibitory neurotransmission in the brain. Many pharmacological treatments have been tested in ASD, but only limited success has been achieved. Here we report that BTBR T+ Itpr3(tf)/J (BTBR) mice, a model of idiopathic autism, have reduced spontaneous GABAergic neurotransmission. Treatment with low nonsedating/nonanxiolytic doses of benzodiazepines, which increase inhibitory neurotransmission through positive allosteric modulation of postsynaptic GABA(A) receptors, improved deficits in social interaction, repetitive behavior, and spatial learning. Moreover, negative allosteric modulation of GABA(A) receptors impaired social behavior in C57BL/6J and 129SvJ wild-type mice, suggesting that reduced inhibitory neurotransmission may contribute to social and cognitive deficits. The dramatic behavioral improvement after low-dose benzodiazepine treatment was subunit specific-the alpha(2,3)-subunit-selective positive allosteric modulator L-838,417 was effective, but the alpha(1)-subunit-selective drug zolpidem exacerbated social deficits. Impaired GABAergic neurotransmission may contribute to ASD, and alpha(2,3)-subunit-selective positive GABA(A) receptor modulation may be an effective treatment. C1 [Han, Sung; Tai, Chao; Jones, Christina J.; Scheuer, Todd; Catterall, William A.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. RP Catterall, WA (reprint author), Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. EM wcatt@u.washington.edu FU Simons Foundation; National Institute of Child Health and Human Development [P30HD02274]; National Institute of Neurological Disorders and Stroke of the National Institutes of Health [R01NS25704] FX Research reported in this publication was supported by the Simons Foundation, the National Institute of Child Health and Human Development under award number P30HD02274, and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number R01NS25704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 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TI Impaired holistic and analytic face processing in congenital prosopagnosia: Evidence from the eye-contingent mask/window paradigm SO VISUAL COGNITION LA English DT Article DE Holistic perception; Prosopagnosia; Face processing ID DEFICIT HYPERACTIVITY DISORDER; DEVELOPMENTAL PROSOPAGNOSIA; ACQUIRED PROSOPAGNOSIA; DETAILED EXPLORATION; FUNCTIONING AUTISM; GAZE-CONTINGENCY; NEURAL BASES; PERCEPTION; RECOGNITION; INVERSION AB There is abundant evidence that face recognition, in comparison to the recognition of other objects, is based on holistic processing rather than analytic processing. One line of research that provides evidence for this hypothesis is based on the study of people who experience pronounced difficulties in visually identifying conspecifics on the basis of their face. Earlier, we developed a behavioural paradigm to directly test analytic vs. holistic face processing. In comparison to a to be remembered reference face stimulus, one of two test stimuli was either presented in full view, with an eye-contingently moving window (only showing the fixated face feature, and therefore only affording analytic processing), or with an eye-contingently moving mask or scotoma (masking the fixated face feature, but still allowing holistic processing). In the present study we use this paradigm (that we used earlier in acquired prosopagnosia) to study face perception in congenital prosopagnosia (people having difficulties recognizing faces from birth on, without demonstrable brain damage). We observe both holistic and analytic face processing deficits in people with congenital prosopagnosia. Implications for a better understanding, both of congenital prosopagnosia and of normal face perception, are discussed. C1 [Verfaillie, K.; Huysegems, S.; De Graef, P.; Van Belle, G.] Katholieke Univ Leuven, Expt Psychol Lab, B-3000 Leuven, Belgium. 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L., 1844, NEW VIEW INSANITY DU YIN RK, 1969, J EXP PSYCHOL, V81, P141, DOI 10.1037/h0027474 YOUNG AW, 1987, PERCEPTION, V16, P747, DOI 10.1068/p160747 NR 86 TC 1 Z9 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1350-6285 EI 1464-0716 J9 VIS COGN JI Vis. Cogn. PD MAR 16 PY 2014 VL 22 IS 3-4 SI SI BP 503 EP 521 DI 10.1080/13506285.2014.881446 PG 19 WC Psychology, Experimental SC Psychology GA AE6AH UT WOS:000334070000014 ER PT J AU Alvaro-Gonzalez, LC AF Alvaro-Gonzalez, Luis C. TI Neuroethics (II): moral pathways in disordered brain SO REVISTA DE NEUROLOGIA LA Spanish DT Article DE Autism; Frontotemporal dementias; Neuroethics; Parkinson's disease; Psychopathies; Sociopathies ID PARKINSONS-DISEASE; ORBITOFRONTAL CORTEX; DOPAMINE AGONISTS; RESPONSE REVERSAL; REWARD; COGNITION; EMOTION; PSYCHOPATHY; AGGRESSION; MECHANISMS AB Introduction. Morality is made out of rules and values that guide human behavior. They barely change among different cultures and result in top social accomplishments. Specific moral pathways are available for this purpose in the brain. Their lesion or dysfunction will produce changes or alterations in moral behavior. Aim. To describe the process and mechanisms of moral dysfunctions under different lesions and neurological disorders. Development. Moral pathologies are the result of either different structural lesions (destructive of the prefrontal cortex; microscopic involvement of the amygdala/prefrontal cortex in psychopathies), or neurochemical involvement (dopaminergic hyperfunction in Parkinson patients under certain treatments, or in some drug-dependences) or genetic alterations (point mutations of COMT or MAO enzymes in certain psychopathies). This activity is due to excitatory, inhibitory or mixed mechanisms. They operate at different levels of the moral circuits, as much emotional (temporal lobe) as cognitive ones (prefrontal lobe). The underlying topography and operating mechanisms can explain the different clinical expressivity. Conclusions. The knowledge of the disordered moral behaviors improves the background of information about the moral circuits that operate in healthy control groups, in anatomical and also in physiological terms. By this means, ethical variations among different cultures might be elucidated. This contribution is also paramount for the huge current progress of neuroethics, which is highly complex and influenced by distinct areas of the neuroculture. C1 [Alvaro-Gonzalez, Luis C.] Hosp Univ Basurto, Serv Neurol, E-48013 Bilbao, Vizcaya, Spain. [Alvaro-Gonzalez, Luis C.] Hosp Univ Basurto, Com Bioet Asistencial, E-48013 Bilbao, Vizcaya, Spain. [Alvaro-Gonzalez, Luis C.] Univ Basque Country, Dept Neurociencias, Bilbao, Vizcaya, Spain. RP Alvaro-Gonzalez, LC (reprint author), Hosp Univ Basurto, Serv Neurol, Avda Montevideo 18, E-48013 Bilbao, Vizcaya, Spain. 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Neurologia PD MAR 16 PY 2014 VL 58 IS 6 BP 268 EP 276 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AD4YR UT WOS:000333258500005 PM 24610694 ER PT J AU Teixeira, S Machado, S Velasques, B Sanfim, A Minc, D Peressutti, C Bittencourt, J Budde, H Cagy, M Anghinah, R Basile, LF Piedade, R Ribeiro, P Diniz, C Cartier, C Gongora, M Silva, F Manaia, F Silva, JG AF Teixeira, Silmar Machado, Sergio Velasques, Bruna Sanfim, Antonio Minc, Daniel Peressutti, Caroline Bittencourt, Juliana Budde, Henning Cagy, Mauricio Anghinah, Renato Basile, Luis F. Piedade, Roberto Ribeiro, Pedro Diniz, Claudia Cartier, Consuelo Gongora, Mariana Silva, Farmy Manaia, Femanda Silva, Julio Guilherme TI Integrative parietal cortex processes: Neurological and psychiatric aspects SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Review DE Parietal cortex; Sensorimotor integration; Hand movement control; Neurological and psychiatric aspects; Neuroanatomy; Movement observation ID SACCADIC EYE-MOVEMENTS; TRANSCRANIAL MAGNETIC STIMULATION; PARKINSONS-DISEASE; SOMATOSENSORY CORTEX; OPTIC ATAXIA; BIPOLAR DISORDER; VISUAL-ATTENTION; MACAQUE MONKEY; DIFFERENTIAL ACTIVATION; PARIETOOCCIPITAL CORTEX AB For many decades the parietal cortex (PC) has been considered the key area in tasks which involve the integration of different stimuli. PC is fundamental to determine spatial sense, information navigation and integration, and is involved in several aspects of the complex motor repertoire and in neurological and psychiatric disorders. In this review, we focus on seven different aspects of PC: (i) neuroanatomy of the parietal cortex; (ii) sensory motor integration processes; iii) hand movement control: reaching, grasping, and pointing; (iv) saccadic eye movements; (v) movement observation; (vi) neurological aspects: ataxia, autism and Parkinson's disease; and (vii) psychiatric aspects: schizophrenia, bipolar disorder and depression. Among these, we related the perspectives which involve the functions of the parietal cortex and mirror neurons and that seem to play a fundamental role in action prediction, planning, observation and execution. Furthermore, we focused on the relationship between posterior parietal cortex (PPC) and hand-guided movements. For this review, we conducted an academic paper search which fulfilled the objective of the study. We conclude that the PC has great participation in different motor functions and neurological/psychiatric disorders. (C) 2013 Elsevier B.V. All rights reserved. C1 [Teixeira, Silmar; Machado, Sergio; Velasques, Bruna; Sanfim, Antonio; Minc, Daniel; Peressutti, Caroline; Bittencourt, Juliana; Piedade, Roberto; Ribeiro, Pedro; Diniz, Claudia; Cartier, Consuelo; Gongora, Mariana; Silva, Farmy; Manaia, Femanda; Silva, Julio Guilherme] Fed Univ Rio de Janeiro IPUB UFRJ, Inst Psychiat, Rio De Janeiro, Brazil. [Ribeiro, Pedro; Gongora, Mariana] Biosci Dept EEFD UFRJ, Sch Phys Educ, Rio De Janeiro, Brazil. [Cagy, Mauricio] Fed Fluminense Univ UFF, Inst Hlth Community, Div Epidemiol & Biostat, Rio De Janeiro, Brazil. [Anghinah, Renato; Basile, Luis F.] Univ Sao Paulo Med Sch, Div Neurosurg, Sao Paulo, Brazil. [Basile, Luis F.] Univ Metodista Sao Paulo, Lab Psychophysiol Psychol & Speech Therapy, Sao Bernardo Do Campo, SP, Brazil. [Velasques, Bruna; Peressutti, Caroline; Ribeiro, Pedro] Inst Appl Neurosci INA, Rio De Janeiro, Brazil. [Budde, Henning] Humboldt Univ, Inst Sport Sci, Dept Movement & Training Sci, Berlin, Germany. [Machado, Sergio; Velasques, Bruna; Sanfim, Antonio; Minc, Daniel; Ribeiro, Pedro] Fed Univ Rio de Janeiro IPUB UFRJ, Lab Neurophysiol & Neuropsychol Attent, Rio De Janeiro, Brazil. [Teixeira, Silmar] Univ Veiga de Almeida, Rio De Janeiro, Brazil. RP Teixeira, S (reprint author), Rua Condessa Pereira Cameiro 36-103, Rio De Janeiro, RJ, Brazil. 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PD MAR 15 PY 2014 VL 338 IS 1-2 BP 12 EP 22 DI 10.1016/j.jns.2013.12.025 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AE3NO UT WOS:000333883400003 PM 24398346 ER PT J AU Foley, AG Cassidy, AW Regan, CM AF Foley, Andrew G. Cassidy, Andrew W. Regan, Ciaran M. TI Penty1-4-yn-VPA, a histone deacetylase inhibitor, ameliorates deficits in social behavior and cognition in a rodent model of autism spectrum disorders SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Social cognition; SAHA; VPA; H3K9ac ID VALPROIC ACID; DEVELOPMENTAL ANOMALIES; MOTION PERCEPTION; MEMORY FORMATION; IN-VITRO; ACETYLATION; RATS; ANTICONVULSANT; TERATOGENICITY; CONSOLIDATION AB In utero exposure of rodents to valproic acid (VPA) has been proposed to induce an adult phenotype with behavioural characteristics reminiscent of those observed in autism spectrum disorder (ASD). Our previous studies have demonstrated the social cognition deficits observed in this model, a major core symptom of ASD, to be ameliorated following chronic administration of histone deacetylase (HDAC) inhibitors. Using this model, we now demonstrate pentyl-4-yn-VPA, an analogue of valproate and HDAC inhibitor, to significantly ameliorate deficits in social cognition as measured using the social approach avoidance paradigm as an indicator of social reciprocity and spatial teaming to interrogate dorsal stream cognitive processing. The effects obtained with penty1-4-yn-VPA were found to be similar to those obtained with SAHA, a pan-specific HDAC inhibitor. Histones isolated from the cerebellar cortex and immunoblottecl with antibodies recognising lysine-specific modification revealed SAHA and pentyl-4-yn-VPA to enhance the acetylation status of H4K8. Additionally, the action of penty1-4-yn-VPA, could be differentiated from that of SAHA by its ability to decrease H3K9 acetylation and enhance H3K14 acetylation. The histone modifications mediated by penty1-4-yn-VPA are suggested to act cooperatively through differential acetylation of the promoter and transcription regions of active genes. (C) 2014 Elsevier B.V. All rights reserved. C1 [Foley, Andrew G.; Cassidy, Andrew W.] Univ Coll Dublin, NovaUCD, Berand Neuropharmacol, Dublin 4, Ireland. [Regan, Ciaran M.] Univ Coll Dublin, UCD Conway Inst, Sch Biomol & Biomed Sci, Dublin 4, Ireland. RP Regan, CM (reprint author), Univ Coll Dublin, UCD Conway Inst, Sch Biomol & Biomed Sci, Dublin 4, Ireland. EM ciaran.regan@ucd.ie FU Berand Neuropharmacology FX Berand Neuropharmacology provided financial support for the conduct of the research and in the preparation of the article. 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J. Pharmacol. PD MAR 15 PY 2014 VL 727 BP 80 EP 86 DI 10.1016/j.ejphar.2014.01.050 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AC8EY UT WOS:000332767500011 PM 24486700 ER PT J AU Zhu, L Wang, XM Li, XL Towers, A Cao, XY Wang, P Bowman, R Yang, HN Goldstein, J Li, YJ Jiang, YH AF Zhu, Li Wang, Xiaoming Li, Xin-Lei Towers, Aaron Cao, Xinyu Wang, Ping Bowman, Rachel Yang, Hyuna Goldstein, Jennifer Li, Yi-Ju Jiang, Yong-Hui TI Epigenetic dysregulation of SHANK3 in brain tissues from individuals with autism spectrum disorders SO HUMAN MOLECULAR GENETICS LA English DT Article ID SCAFFOLDING PROTEIN SHANK3; 22Q13 DELETION SYNDROME; DNA METHYLATION; MOLECULAR CHARACTERIZATION; PRENATAL NUTRITION; CPG ISLANDS; MICE; DUPLICATION; MUTATIONS; SCHIZOPHRENIA AB The molecular basis for the majority of cases of autism spectrum disorders (ASD) remains unknown. We tested the hypothesis that ASD have an epigenetic cause by performing DNA methylation profiling of five CpG islands (CGI-1 to CGI-5) in the SHANK3 gene in postmortem brain tissues from 54 ASD patients and 43 controls. We found significantly increased overall DNA methylation (epimutation) in three intragenic CGIs (CGI-2, CGI-3 and CGI-4). The increased methylation was clustered in the CGI-2 and CGI-4 in similar to 15% of ASD brain tissues. SHANK3 has an extensive array of mRNA splice variants resulting from combinations of five intragenic promoters and alternative splicing of coding exons. Altered expression and alternative splicing of SHANK3 isoforms were observed in brain tissues with increased methylation of SHANK3 CGIs in ASD brain tissues. A DNA methylation inhibitor modified the methylation of CGIs and altered the isoform-specific expression of SHANK3 in cultured cells. This study is the first to find altered methylation patterns in SHANK3 in ASD brain samples. Our finding provides evidence to support an alternative approach to investigating the molecular basis of ASD. The ability to alter the epigenetic modification and expression of SHANK3 by environmental factors suggests that SHANK3 may be a valuable biomarker for dissecting the role of gene and environment interaction in the etiology of ASD. C1 [Zhu, Li; Wang, Xiaoming; Li, Xin-Lei; Cao, Xinyu; Wang, Ping; Bowman, Rachel; Goldstein, Jennifer; 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. [Towers, Aaron; Jiang, Yong-Hui] Duke Univ, Sch Med, Program Genet & Genom, Durham, NC 27710 USA. [Jiang, Yong-Hui] Duke Univ, Sch Med, Program Cell & Mol Biol, Durham, NC 27710 USA. [Jiang, Yong-Hui] Duke Univ, Sch Med, Duke Inst Brain Sci, Durham, NC 27710 USA. [Yang, Hyuna; Li, Yi-Ju] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC 27710 USA. RP Jiang, YH (reprint author), Duke Univ, Sch Med, Div Med Genet, Dept Pediat & Neurobiol, Durham, NC 27710 USA. EM yong-hui.jiang@duke.edu RI wang, xiaoming/I-2158-2013 OI wang, xiaoming/0000-0002-7763-690X FU Autism Speaks grant; National Institute of Health [R01MH098114-01]; Phelan-McDermid syndrome foundation FX We thank Yoonji Lee, Xiaodong Zhai, Zhiqing Huang and Richard Person for technical assistance. We also thank Catherine Rehder for assisting CNV analysis. We would like to acknowledge the Autism Tissue Program, Harvard Brain Tissue Bank and NICHD Brain Tissue Bank for providing the brain tissues for this study. We also thank Jane Picket from the Autism Tissue Program and Robert Johnson from NICHD brain tissue bank for their assistance. We thank David Goldstein, Jan Bressler and Susan Murphy for critical reading of the manuscript. Y.H.J. is supported by an Autism Speaks grant and National Institute of Health grant R01MH098114-01. X. 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Mol. Genet. PD MAR 15 PY 2014 VL 23 IS 6 BP 1563 EP 1578 DI 10.1093/hmg/ddt547 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AB8MK UT WOS:000332044300014 PM 24186872 ER PT J AU Brodkin, J Frank, D Grippo, R Hausfater, M Gulinello, M Achterholt, N Gutzen, C AF Brodkin, Jesse Frank, Dana Grippo, Ryan Hausfater, Michal Gulinello, Maria Achterholt, Nils Gutzen, Christian TI Validation and implementation of a novel high-throughput behavioral phenotyping instrument for mice SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Automated detection; Neurobehavioral assessment; Behavioral screening; Ethological analysis; Grooming; Video analysis ID T PLUS TF/J; INFLAMMATORY PAIN; MOUSE MODEL; AUTISM; CLASSIFICATION; C57BL/6J; RODENTS; STRESS; DRUGS AB Background: Behavioral assessment of mutant mouse models and novel candidate drugs is a slow and labor intensive process. This limitation produces a significant impediment to CNS drug discovery. New method: By combining video and vibration analysis we created an automated system that provides the most detailed description of mouse behavior available. Our system (The Behavioral Spectrometer) allowed for the rapid assessment of behavioral abnormalities in the BTBR model of Autism, the restraint model of stress and the irritant model of inflammatory pain. Results: We found that each model produced a unique alteration of the spectrum of behavior emitted by the mice. BTBR mice engaged in more grooming and less rearing behaviors. Prior restraint stress produced dramatic increases in grooming activity at the expense of locomotor behavior. Pain produced profound decreases in emitted behavior that were reversible with analgesic treatment. Comparison with existing method(s): We evaluated our system through a direct comparison on the same subjects with the current "gold standard" of human observation of video recordings. Using the same mice evaluated over the same range of behaviors, the Behavioral Spectrometer produced a quantitative categorization of behavior that was highly correlated with the scores produced by trained human observers (r = 0.97). Conclusions: Our results show that this new system is a highly valid and sensitive method to characterize behavioral effects in mice. As a fully automated and easily scalable instrument the Behavioral Spectrometer represents a high-throughput behavioral tool that reduces the time and labor involved in behavioral research. (C) 2013 Elsevier B.V. All rights reserved. C1 [Brodkin, Jesse; Frank, Dana] Behav Instruments, Hillsborough, NJ 08844 USA. [Grippo, Ryan; Hausfater, Michal] Rutgers State Univ, Dept Psychol, Piscataway, NJ 08854 USA. [Gulinello, Maria] Yeshiva Univ, Albert Einstein Coll Med, Rose F Kennedy Ctr, Dominick P Putpura Dept Neurosci,Behav Core Facil, Bronx, NY 10461 USA. [Achterholt, Nils; Gutzen, Christian] BIOBSERVE GmbH, D-53757 St Augustin, Germany. RP Brodkin, J (reprint author), Behav Instruments, 5 Jill Court Unit 1, Hillsborough, NJ 08844 USA. 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Neurosci. Methods PD MAR 15 PY 2014 VL 224 BP 48 EP 57 DI 10.1016/j.jneumeth.2013.12.010 PG 10 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AB5TB UT WOS:000331850500005 PM 24384067 ER PT J AU Varlinskaya, EI Mooney, SM AF Varlinskaya, Elena I. Mooney, Sandra M. TI Acute exposure to ethanol on gestational day 15 affects social motivation of female offspring SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Adolescence; Autism; Fetal alcohol syndrome; Sex difference ID REPEATED RESTRAINT; ADULT RATS; BEHAVIOR; ADOLESCENT; PUBERTY; ANXIETY; CONSEQUENCES; ALCOHOL; BRAIN; PLAY AB Alterations in social behavior are a hallmark of many neurodevelopmental disorders in humans. In rodents, social behavior is affected by prenatal insults. The outcomes are dependent on the timing of the insult as well as the sex and age of the animal tested. The limbic system is particularly important for social behavior, and a peak of neurogenesis within this system occurs on gestational day (G)15. Neurons appear particularly vulnerable to ethanol insult around the time they become post-mitotic. We tested the hypothesis that acute exposure to ethanol on G15 would result in significant social behavior deficits. Accordingly, Long Evans pregnant females were injected with ethanol (2.9 g/kg) or an equivalent volume of saline on G15. Offspring were assessed in a modified social interaction test on postnatal day (P) 28, P42, or P75, i.e., during early adolescence, late adolescence, or young adulthood. Prenatal ethanol exposure decreased social investigation in P28 females and transformed social preference into social avoidance in 75-day-old females. Contact behavior, play fighting, and locomotor activity differed as a function of age, but were not significantly affected by ethanol exposure. Males demonstrated significantly more contact behavior and play fighting at P42 than at P28 or P70, whereas there were no age-related changes in females. Adult females showed more locomotor activity than adult males. Overall, prenatal ethanol exposure on G15 enhanced social anxiety in females, with these effects seen in adulthood only. (C) 2013 Elsevier B.V. All rights reserved. C1 [Varlinskaya, Elena I.] SUNY Binghamton, Dept Psychol, Ctr Dev & Behav Neurosci, Binghamton, NY 13902 USA. [Varlinskaya, Elena I.; Mooney, Sandra M.] Dev Exposure Alcohol Res Ctr, Baltimore, MD 21201 USA. [Varlinskaya, Elena I.; Mooney, Sandra M.] Dev Exposure Alcohol Res Ctr, Binghamton, NY 13902 USA. [Varlinskaya, Elena I.; Mooney, Sandra M.] Dev Exposure Alcohol Res Ctr, Cortland, NY 13054 USA. [Varlinskaya, Elena I.; Mooney, Sandra M.] Dev Exposure Alcohol Res Ctr, Syracuse, NY 13210 USA. [Mooney, Sandra M.] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. [Mooney, Sandra M.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Mooney, SM (reprint author), Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. EM varlinsk@binghamton.edu; smooney@peds.umaryland.edu FU National Institute of Alcohol Abuse and Alcoholism [AA018693, AA0178231, AA012453]; Autism Speaks FX The authors thank Renee Mezza, Wendi Burnette, Terri Novak, and Bill Bondi for technical assistance. This research was supported by the National Institute of Alcohol Abuse and Alcoholism (AA018693 and AA0178231 to SMM; AA012453 to EIV) and Autism Speaks (SMM). None of the funding sources had any role in study design, data collection, analysis or interpretation, in the writing of the report; or in the decision to submit the article for publication. The authors have no conflicts of interest to disclose. CR Bayer S. 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Brain Res. PD MAR 15 PY 2014 VL 261 BP 106 EP 109 DI 10.1016/j.bbr.2013.12.016 PG 4 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AB0QK UT WOS:000331497000015 PM 24355753 ER PT J AU de Theije, CGM Wu, JB Koelink, PJ Korte-Bouws, GAH Borre, Y Kas, MJH da Silva, SL Korte, SM Olivier, B Garssen, J Kraneveld, AD AF de Theije, Caroline G. M. Wu, Jiangbo Koelink, Pim J. Korte-Bouws, Gerdien A. H. Borre, Yuliya Kas, Martien J. H. da Silva, Sofia Lopes Korte, S. Mechiel Olivier, Berend Garssen, Johan Kraneveld, Aletta D. TI Autistic-like behavioural and neurochemical changes in a mouse model of food allergy SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Autism spectrum disorders; Food allergy; Social behaviour; Repetitive behaviour; Monoamines; Neuronal activation ID IRRITABLE-BOWEL-SYNDROME; SEROTONIN TRANSPORTER FUNCTION; FRONTAL-LOBE DAMAGE; C-FOS EXPRESSION; SPECTRUM DISORDERS; PREFRONTAL CORTEX; MESOCORTICOLIMBIC DOPAMINE; SPONTANEOUS-ALTERNATION; SOCIAL INTERACTIONS; 5-HT3 RECEPTORS AB Food allergy has been suggested to contribute to the expression of psychological and psychiatric traits, including disturbed social behaviour and repetitive behaviour inherent in autism spectrum disorders (ASD). Most research in this field receives little attention, since fundamental evidence showing direct effects of food allergic immune responses on social behaviour is very limited. In the present study, we show that a food allergic reaction to cow's milk protein, induced shortly after weaning, reduced social behaviour and increased repetitive behaviour in mice. This food allergic reaction increased levels of serotonin (5-hydroxytryptamine; 5-HT) and the number of 5-HT positive cells, and decreased levels of 5-hydroxyindoleacetic acid (5-HIAA) in the intestine. Behavioural changes in food allergic mice were accompanied by reduced dopaminergic activity in the prefrontal cortex. Furthermore, neuronal activation (c-Fos expression) was increased in the prefrontal cortex and reduced in the paraventricular nucleus of the hypothalamus after exposure to a social target. We hypothesize that an intestinal allergic response regulates complex, but critical, neuroimmune interactions, thereby affecting brain circuits involved in social interaction, repetitive behaviour and cognition. Together witha genetic predisposition and multiple environmental factors, these effects of allergic immune activation may exacerbate behavioural abnormalities in patients with ASD. (C) 2013 Elsevier B.V. All-rights reserved. C1 [de Theije, Caroline G. M.; Wu, Jiangbo; Koelink, Pim J.; Korte-Bouws, Gerdien A. H.; Borre, Yuliya; da Silva, Sofia Lopes; Korte, S. Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D.] Univ Utrecht, Div Pharmacol, Fac Sci, Utrecht Inst Pharmaceut Sci, NL-3584 CG Utrecht, Netherlands. [Kas, Martien J. H.] Univ Med Ctr Utrecht, Dept Translat Neurosci, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. [da Silva, Sofia Lopes; Garssen, Johan] Nutricia Res, Utrecht, Netherlands. RP de Theije, CGM (reprint author), Univ Utrecht, Div Pharmacol, Univ Weg 99, NL-3584 CG Utrecht, Netherlands. EM c.g.m.detheije@uu.nl FU Nutricia Research FX This study is part of the Utrecht University 'Focus en Massa' program and financially supported by Nutricia Research. Dr. S. Lopes da Silva and Prof. Dr. J. Garssen are employees of Nutricia Research and therefore declare potential conflicts of interest. All other authors report no biomedical financial interest or potential conflicts of interest. 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Brain Res. PD MAR 15 PY 2014 VL 261 BP 265 EP 274 DI 10.1016/j.bbr.2013.12.008 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AB0QK UT WOS:000331497000033 PM 24333575 ER PT J AU LaSarge, CL Danzer, SC AF LaSarge, Candi L. Danzer, Steve C. TI Mechanisms regulating neuronal excitability and seizure development following mTOR pathway hyperactivation SO FRONTIERS IN MOLECULAR NEUROSCIENCE LA English DT Review DE granule cells; epilepsy; mTOR; neurogenesis; PTEN; TSC; hippocampus; autism ID TUBEROUS SCLEROSIS COMPLEX; TEMPORAL-LOBE EPILEPSY; LONG-TERM DEPRESSION; DENTATE GRANULE CELLS; RAPAMYCIN SIGNALING PATHWAY; TUMOR-SUPPRESSOR GENE; INDUCED STATUS EPILEPTICUS; AUTISM SPECTRUM DISORDERS; LHERMITTE-DUCLOS-DISEASE; FOCAL CORTICAL DYSPLASIA AB The phosphatidylinositol-3-kinase/phosphatase and tensin homolog (PTEN)-mammalian target of rapamycin (mTOR) pathway regulates a variety of neuronal functions, including cell proliferation, survival, growth, and plasticity. Dysregulation of the pathway is implicated in the development of both genetic and acquired epilepsies. Indeed, several causal mutations have been identified in patients with epilepsy, the most prominent of these being mutations in PTEN and tuberous sclerosis complexes 1 and 2 (TSC1, TSC2). These genes act as negative regulators of mTOR signaling, and mutations lead to hyperactivation of the pathway. Animal models deleting PTEN, TSC1, and TSC2 consistently produce epilepsy phenotypes, demonstrating that increased mTOR signaling can provoke neuronal hyperexcitability. Given the broad range of changes induced by altered mTOR signaling, however, the mechanisms underlying seizure development in these animals remain uncertain. In transgenic mice, cell populations with hyperactive mTOR have many structural abnormalities that support recurrent circuit formation, including somatic and dendrite hypertrophy, aberrant basal dendrites, and enlargement of axon tracts. At the functional level, mTOR hyperactivation is commonly, but not always, associated with enhanced synaptic transmission and plasticity. Moreover, these populations of abnormal neurons can affect the larger network, inducing secondary changes that may explain paradoxical findings reported between cell and network functioning in different models or at different developmental time points. Here, we review the animal literature examining the link between mTOR hyperactivation and epileptogenesis, emphasizing the impact of enhanced mTOR signaling on neuronal form and function. C1 [LaSarge, Candi L.; Danzer, Steve C.] Cincinnati Childrens Hosp Med Ctr, Dept Anesthesia, Cincinnati, OH 45229 USA. [Danzer, Steve C.] Univ Cincinnati, Dept Anesthesia, Cincinnati, OH USA. [Danzer, Steve C.] Univ Cincinnati, Dept Pediat, Cincinnati, OH USA. RP Danzer, SC (reprint author), Cincinnati Childrens Hosp Med Ctr, Dept Anesthesia, 3333 Burnet Ave,ML 2001, Cincinnati, OH 45229 USA. EM steve.danzer@cchmc.org FU National Institute of Neurological Disorders and Stroke [R01NS065020, R01NS062806, NRSA F32NS083239] FX This work was supported by the National Institute of Neurological Disorders and Stroke (SCD, Award Numbers R01NS065020 and R01NS062806; CLL, NRSA F32NS083239). 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. We would also like to thank Keri Kaeding for useful comments on earlier versions of this manuscript and Victor R. Santos, Raymund Y. K. Pun, and Isaiah Rolle for contributing images for figures. 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Molec. Neurosci. PD MAR 14 PY 2014 VL 7 AR 18 DI 10.3389/fnmo1.2014.00018 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AZ0WN UT WOS:000347962900001 PM 24672426 ER PT J AU Cauda, F Geminiani, GC Vercelli, A AF Cauda, Franco Geminiani, Giuliano Carlo Vercelli, Alessandro TI Evolutionary appearance of von Econorno's neurons in the mammalian cerebral cortex SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Review DE insula; cingulate cortex; salience network; self-awareness; prediction; development ID ANTERIOR CINGULATE CORTEX; INTRINSIC FUNCTIONAL CONNECTIVITY; VARIANT FRONTOTEMPORAL DEMENTIA; DEFAULT-MODE NETWORKS; ECONOMO NEURONS; PHYSIOLOGICAL CONDITION; FRONTOINSULAR CORTEX; CORTICAL NETWORKS; CORPUS-CALLOSUM; MACAQUE MONKEY AB von Economo's neurons (VENs) are large, spindle-shaped projection neurons in layer V of the frontoinsular (El) cortex, and the anterior cingulate cortex. During human ontogenesis, the VENs can first be differentiated at late stages of gestation, and increase in number during the first eight postnatal months. VENs have been identified in humans, chimpanzee, bonobos, gorillas, orangutan and, more recently, in the macaque. Their distribution in great apes seems to correlate with human-like social cognitive abilities and self-awareness. VENs are also found in whales, in a number of different cetaceans, and in the elephant. This phylogenetic distribution may suggest a correlation among the VENs, brain size and the "social brain." VENs may be involved in the pathogenesis of specific neurological and psychiatric diseases, such as autism, callosal agenesis and schizophrenia. VENs are selectively affected in a behavioral variant of frontotemporal dementia in which empathy, social awareness and self-control are seriously compromised, thus associating VENs with the social brain. However, the presence of VENs has also been related to special functions such as mirror self-recognition. Areas containing VENs have been related to motor awareness or sense-of-knowing, discrimination between self and other, and between self and the external environment. Along this line, VENs have been related to the "global Workspace" architecture: in accordance the VENs have been correlated to emotional and interoceptive signals by providing fast connections (large axons = fast communication) between salience-related insular and cingulate and other widely separated brain areas. Nevertheless, the lack of a characterization of their physiology and anatomical connectivity allowed only to infer their functional role based on their location and on the functional magnetic resonance imaging data. The recent finding of VENs in the anterior insula of the macaque opens the way to new insights and experimental investigations. C1 [Cauda, Franco; Geminiani, Giuliano Carlo] Univ Turin, CCS fMRI Koelliker Hosp, I-10043 Turin, Italy. [Cauda, Franco; Geminiani, Giuliano Carlo] Univ Turin, Dept Psychol, I-10043 Turin, Italy. [Vercelli, Alessandro] Univ Turin, Dept Neurosci, Neurosci Inst Cavalieri Ottolenghi, I-10043 Turin, Italy. RP Vercelli, A (reprint author), Univ Turin, Dept Neurosci, Neurosci Inst Cavalieri Ottolenghi, Reg Gonzole 10, I-10043 Turin, Italy. EM alessandro.vercelli@unito.it FU Italian Ministry of University FX Supported by grants of the Italian Ministry of University and Research to Giuliano Carlo Geminiani and Alessandro Vercelli. 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Hum. Neurosci. PD MAR 14 PY 2014 VL 8 AR 104 DI 10.3389/fnhum.2014.00104 PG 11 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AC8DY UT WOS:000332764500001 PM 24672457 ER PT J AU Bartholomew, AJ Cirulli, ET AF Bartholomew, Alex J. Cirulli, Elizabeth T. TI Individual Variation in Contagious Yawning Susceptibility Is Highly Stable and Largely Unexplained by Empathy or Other Known Factors SO PLOS ONE LA English DT Article ID COGNITIVE TESTS; CHIMPANZEES; SCALE; PERFORMANCE; SLEEPINESS; IMITATION; AGE AB The contagious aspect of yawning is a well-known phenomenon that exhibits variation in the human population. Despite the observed variation, few studies have addressed its intra-individual reliability or the factors modulating differences in the susceptibility of healthy volunteers. Due to its obvious biological basis and impairment in diseases like autism and schizophrenia, a better understanding of this trait could lead to novel insights into these conditions and the general biological functioning of humans. We administered 328 participants a 3-minute yawning video stimulus, a cognitive battery, and a comprehensive questionnaire that included measures of empathy, emotional contagion, circadian energy rhythms, and sleepiness. Individual contagious yawning measurements were found to be highly stable across testing sessions, both in a lab setting and if administered remotely online, confirming that certain healthy individuals are less susceptible to contagious yawns than are others. Additionally, most individuals who failed to contagiously yawn in our study were not simply suppressing their reaction, as they reported not even feeling like yawning in response to the stimulus. In contrast to previous studies indicating that empathy, time of day, or intelligence may influence contagious yawning susceptibility, we found no influence of these variables once accounting for the age of the participant. Participants were less likely to show contagious yawning as their age increased, even when restricting to ages of less than 40 years. However, age was only able to explain 8% of the variability in the contagious yawn response. The vast majority of the variability in this extremely stable trait remained unexplained, suggesting that studies of its inheritance are warranted. C1 [Bartholomew, Alex J.; Cirulli, Elizabeth T.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27706 USA. RP Cirulli, ET (reprint author), Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27706 USA. EM etc3@duke.edu FU National Institute of Mental Health of the National Institutes of Health [K01MH098126]; Ellison Medical Foundation [AG-NS-0441-08] FX Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award number K01MH098126 and the Ellison Medical Foundation New Scholar award AG-NS-0441-08. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Alterations in Early and Late Visually Evoked EEG Potentials in Asperger Observers SO PLOS ONE LA English DT Article ID FUNCTIONING AUTISM; PERCEPTION; ATTENTION; QUOTIENT; BRAIN; P300; RECOGNITION; DISORDERS; CHILDREN; P3B AB Background: Asperger Autism is a lifelong psychiatric condition with highly circumscribed interests and routines, problems in social cognition, verbal and nonverbal communication, and also perceptual abnormalities with sensory hypersensitivity. To objectify both lower-level visual and cognitive alterations we looked for differences in visual event-related potentials (EEG) between Asperger observers and matched controls while they observed simple checkerboard stimuli. Methods: In a balanced oddball paradigm checkerboards of two checksizes (0.6 degrees and 1.2 degrees) were presented with different frequencies. Participants counted the occurrence times of the rare fine or rare coarse checkerboards in different experimental conditions. 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The lateralization of the P3b signal might be a compensatory consequence of the compromised early checksize effect. Higher-level analytical information processing units may need to compensate for difficulties in low-level signal analysis. C1 [Kornmeier, Juergen] Inst Frontier Areas Psychol & Mental Hlth, Freiburg, Germany. [Kornmeier, Juergen; Bach, Michael] Univ Freiburg, Ctr Eye, D-79106 Freiburg, Germany. [Woerner, Rike] PPD Germany GmbH & Co Kg, Karlsruhe, Germany. [Riedel, Andreas; van Elst, Ludger Tebartz] Univ Freiburg, Sect Expt Neuropsychiat, Clin Psychiat & Psychotherapy, D-79106 Freiburg, Germany. RP Kornmeier, J (reprint author), Inst Frontier Areas Psychol & Mental Hlth, Freiburg, Germany. EM juergen.kornmeier@uni-freiburg.de RI Bach, Michael/A-6637-2010 OI Bach, Michael/0000-0003-2028-535X FU Deutsche Forschungsgemeinschaft [KO 4764/1-1, TE 280/8-1] FX This study was supported by the Deutsche Forschungsgemeinschaft (KO 4764/1-1 & TE 280/8-1). 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F. Logan, David J. Saulnier, Jessica Lam, Daniel Johnson, Caroline Root, David E. Carpenter, Anne E. Sabatini, Bernardo L. TI High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons SO PLOS ONE LA English DT Article ID PSYCHIATRIC-DISORDERS; BETA-CATENIN; RAT-BRAIN; EXPRESSION; PROTEINS; SCHIZOPHRENIA; SYNAPSE; FAMILY; AUTISM; SCALE AB The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders. C1 [Nieland, Thomas J. F.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA. [Lam, Daniel; Root, David E.] Broad Inst Harvard & MIT, RNAi Platform, Cambridge, MA USA. [Logan, David J.; Carpenter, Anne E.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Saulnier, Jessica; Johnson, Caroline; Sabatini, Bernardo L.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Nieland, TJF (reprint author), Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA. EM tnieland@broadinstitute.org; bernardo_sabatini@hms.harvard.edu RI Carpenter, Anne/C-4982-2008 OI Carpenter, Anne/0000-0003-1555-8261 FU National Institutes of Health [MH095096, R01 GM089652] FX Grants supported by National Institutes of Health (MH095096 to BLS and R01 GM089652 to AEC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Various strategies are used, but research and debate on their efficacy have remained limited to a specific area and have rarely reached the general medical community. Objective: To systematically evaluate outcomes of AAC interventions in children with limited speech or language skills. Methods: Searches were conducted (up to December 2012) in the MEDLINE, EMBASE, PsycINFO, CINAHL, DARE, and Cochrane Library databases. Furthermore, relevant journals were searched by hand. References from identified studies were examined. Only RCTs were considered. Trial quality was assessed according to a standardized and validated set of criteria. Results: Fourteen of 1661 retrieved papers met inclusion criteria. A total of 666 children were included in the review and 7 papers involved only children <5 years old. Papers were of average quality and all but one had been published during the previous 10 years by one of 8 research groups, 5 of which from the United States. Seven studies directly addressed AAC use by children with different disabilities. Seven studies enrolled typically developing children: 5 evaluated the use of AAC technologies by children without disabilities in order to obtain results that could be used to improve interventions in peers with disabilities, and 2 evaluated peers' attitudes towards children who used AAC. Both interventions and outcome measures varied widely between studies. Overall findings demonstrate the effectiveness of the AAC interventions considered, but the focus on RCTs alone appears too restrictive. Conclusions: Solid evidence of the positive effects of AAC interventions in children with severe communication disorders must be generated, and different methods are needed besides RCTs. Moreover, it is important that knowledge, research, and debate extend to the medical community in order to ensure clinically effective AAC provision for these children (and their parents). 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The objectives of this study are to evaluate the basic profile of acoustic startle response, including peak startle latency and startle magnitude to weaker stimuli, in children with ASD and typical development (TD), and to evaluate their relationship to ASD characteristics. Methods: We investigated acoustic startle response with weak and strong acoustic stimuli in 12 children with ASD and 28 children with TD, analyzing the relationship between startle measures and quantitative autistic traits assessed with the Social Responsiveness Scale (SRS). The electromyographic activity of the left orbicularis oculi muscle to acoustic stimuli of 65 to 115 dB sound pressure level (SPL), in increments of 5 dB, was measured to evaluate acoustic startle response. The average eyeblink magnitude for each acoustic stimuli intensity and the average peak startle latency of acoustic startle response were evaluated. Results: The magnitude of the acoustic startle response to weak stimuli (85 dB or smaller) was greater in children with ASD. The peak startle latency was also prolonged in individuals with ASD. The average magnitude of the acoustic startle response for stimulus intensities greater than 85 dB was not significantly larger in the ASD group compared with the controls. Both greater startle magnitude in response to weak stimuli (particularly at 85 dB) and prolonged peak startle latency were significantly associated with total scores, as well as several subscales of the SRS in the whole sample. We also found a significant relationship between scores on the social cognition subscale of the SRS and the average magnitude of the acoustic startle response for stimulus intensities of 80 and 85 dB in the TD group. Conclusions: Children with ASD exhibited larger startle magnitude to weak stimuli and prolonged peak startle latency. These startle indices were related to several characteristics of ASD. A comprehensive investigation of acoustic startle response, including the magnitude of startle responses to weak stimuli and peak startle latency, might further our understanding of the neurophysiological impairments underlying ASD. C1 [Takahashi, Hidetoshi; Nakahachi, Takayuki; Komatsu, Sahoko; Ogino, Kazuo; Iida, Yukako; Kamio, Yoko] Natl Ctr Neurol & Psychiat, Natl Inst Mental Hlth, Dept Child & Adolescent Mental Hlth, Kodaira, Tokyo 1878553, Japan. RP Takahashi, H (reprint author), Natl Ctr Neurol & Psychiat, Natl Inst Mental Hlth, Dept Child & Adolescent Mental Hlth, 4-1-1 Ogawahigashicho, Kodaira, Tokyo 1878553, Japan. EM htakahashi@ncnp.go.jp FU Japanese Ministry of Education, Culture, Sports, Science and Technology [23890257, 24591739]; Intramural Research Grant for Neurological and Psychiatric Disorders of the National Center of Neurology and Psychiatry (NCNP) [23-1]; Japanese Ministry of Health, Labour and Welfare [H19-KOKORO-006, H20-KOKORO-004] FX The authors wish to thank all the subjects who participated in this study and their parents. This study was supported by Grants-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology (23890257, 24591739), Intramural Research Grant (23-1) for Neurological and Psychiatric Disorders of the National Center of Neurology and Psychiatry (NCNP), and research grants from the Japanese Ministry of Health, Labour and Welfare (H19-KOKORO-006 and H20-KOKORO-004). 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Autism PD MAR 12 PY 2014 VL 5 AR 23 DI 10.1186/2040-2392-5-23 PG 8 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AF4XU UT WOS:000334718700001 PM 24618368 ER PT J AU Connelly, JJ Golding, J Gregory, SP Ring, SM Davis, JM Smith, GD Harris, JC Carter, CS Pembrey, M AF Connelly, Jessica J. Golding, Jean Gregory, Steven P. Ring, Susan M. Davis, John M. Smith, George Davey Harris, James C. Carter, C. Sue Pembrey, Marcus TI Personality, Behavior and Environmental Features Associated with OXTR Genetic Variants in British Mothers SO PLOS ONE LA English DT Article ID OXYTOCIN RECEPTOR GENE; CHILDREN ALSPAC; EXPOSOME; PARENTS; SAMPLE; PSYCHOPATHOLOGY; VASOPRESSIN; METABOLISM; HEALTH; AUTISM AB Background: It is assumed that the oxytocin receptor gene (OXTR) is associated with factors that are related to features of reproduction as well as the currently emerging fields of mood and emotional response. Methods: We analysed data from over 8000 mothers who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC). We determined reproductive, emotional and personality differences related to the two SNPs rs53576 and rs2254298 of the oxytocin receptor gene to determine whether there was evidence in this population for: (i) associations with emotional and personality differences, and (ii) behavioural or environmental links with these SNPs using a hypothesis free approach with over 1000 types of exposure. Results: Our analyses of 7723 women showed that there were no differences in 11 mood, social or relationship characteristics associated with the rs2254298, and just one with rs53576 (with emotional loneliness) - one statistically significant out of 22 tests is no more than would be expected by chance. There were no interactions with childhood abuse. Using a hypothesis-free approach we found few indicators of environmental or behavioural differences associated with rs2254298, but there was an excess of associations with eating habits with rs53576. The findings included an association with dieting to lose weight, and habits typical of bulimia for the women with GG. The nutrition of the women also showed negative associations of the GG genotype with 13 nutrients, including vitamins D, B-12 and retinol, and intake of calcium, potassium and iodine. Conclusions: We conclude that this large database of pregnant women was unable to provide confirmation of the types of personality associated with these two OXTR SNPs, but we have shown some evidence of eating differences in those with GG on rs53576. Confirmation of our hypothesis free associations using other data sets is important. C1 [Connelly, Jessica J.] Univ Virginia, Dept Med, Div Cardiovasc Med, Charlottesville, VA 22903 USA. [Connelly, Jessica J.] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA USA. [Golding, Jean; Gregory, Steven P.; Pembrey, Marcus] Univ Bristol, Ctr Child & Adolescent Hlth, Sch Social & Community Med, Bristol, Avon, England. [Ring, Susan M.; Smith, George Davey] Univ Bristol, Sch Social & Community Med, Avon Longitudinal Study Parents & Children, Bristol, Avon, England. [Davis, John M.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Harris, James C.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Carter, C. Sue] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Carter, C. Sue] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Pembrey, Marcus] UCL, Inst Child Hlth, London, England. RP Connelly, JJ (reprint author), Univ Virginia, Dept Med, Div Cardiovasc Med, Charlottesville, VA 22903 USA. EM jessica.connelly@virginia.edu RI Davey Smith, George/A-7407-2013 OI Davey Smith, George/0000-0002-1407-8314 FU Medical Research Council [G1100226]; Fetzer Institute [3091.00] FX The UK Medical Research Council (MRC), the Wellcome Trust and the University of Bristol currently provide core support for ALSPAC. The statistical analyses for this project were undertaken with funding from the Medical Research Council [grant no. G1100226]. Genotyping to confirm imputation of rs2254298 was funded through the Fetzer Institute (Project #3091.00). 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 Brain Activity of Adolescents with High Functioning Autism in Response to Emotional Words and Facial Emoticons SO PLOS ONE LA English DT Article ID FUSIFORM FACE AREA; COMPUTER-MEDIATED COMMUNICATION; NONVERBAL-COMMUNICATION; SPECTRUM DISORDERS; BIOLOGICAL MOTION; JOINT ATTENTION; PERCEPTION; CHILDREN; COMPREHENSION; LANGUAGE AB Studies of social dysfunction in patients with autism spectrum disorder (ASD) have generally focused on the perception of emotional words and facial affect. Brain imaging studies have suggested that the fusiform gyrus is associated with both the comprehension of language and face recognition. We hypothesized that patients with ASD would have decreased ability to recognize affect via emotional words and facial emoticons, relative to healthy comparison subjects. In addition, we expected that this decreased ability would be associated with altered activity of the fusiform gyrus in patients with ASD. Ten male adolescents with ASDs and ten age and sex matched healthy comparison subjects were enrolled in this case-control study. The diagnosis of autism was further evaluated with the Autism Diagnostic Observation Schedule. Brain activity was assessed using functional magnetic resonance imaging (fMRI) in response to emotional words and facial emoticon presentation. Sixty emotional words (45 pleasant words +15 unpleasant words) were extracted from a report on Korean emotional terms and their underlying dimensions. Sixty emoticon faces (45 pleasant faces +15 unpleasant faces) were extracted and modified from on-line sites. Relative to healthy comparison subjects, patients with ASD have increased activation of fusiform gyrus in response to emotional aspects of words. In contrast, patients with ASD have decreased activation of fusiform gyrus in response to facial emoticons, relative to healthy comparison subjects. We suggest that patients with ASD are more familiar with word descriptions than facial expression as depictions of emotion. C1 [Han, Doug Hyun] Chung Ang Univ Hosp, Dept Psychiat, Seoul, South Korea. [Yoo, Hee Jeong] Seoul Natl Bundang Hosp, Dept Psychiat, Seoul, South Korea. [Kim, Bung Nyun] Seoul Natl Hosp, Dept Psychiat, Seoul, South Korea. [McMahon, William] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Renshaw, Perry F.] Univ Utah, Inst Brain, Salt Lake City, UT USA. RP Han, DH (reprint author), Chung Ang Univ Hosp, Dept Psychiat, Seoul, South Korea. EM hduk@yahoo.com FU Korean Game Culture Foundation; Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A120013] FX This work was supported by Korean Game Culture Foundation and a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A120013). 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 Soy Infant Formula and Seizures in Children with Autism: A Retrospective Study SO PLOS ONE LA English DT Article ID FED BREAST-MILK; FRAGILE-X-SYNDROME; SPECTRUM DISORDERS; FEBRILE SEIZURES; EPILEPSY; PHYTOESTROGENS; MANAGEMENT; EXPOSURE; BEHAVIOR; DISEASE AB Seizures are a common phenotype in many neurodevelopmental disorders including fragile X syndrome, Down syndrome and autism. We hypothesized that phytoestrogens in soy-based infant formula were contributing to lower seizure threshold in these disorders. Herein, we evaluated the dependence of seizure incidence on infant formula in a population of autistic children. Medical record data were obtained on 1,949 autistic children from the SFARI Simplex Collection. An autism diagnosis was determined by scores on the ADI-R and ADOS exams. The database included data on infant formula use, seizure incidence, the specific type of seizure exhibited and IQ. Soy-based formula was utilized in 17.5% of the study population. Females comprised 13.4% of the subjects. There was a 2.6-fold higher rate of febrile seizures [4.2% versus 1.6%, OR = 2.6, 95% CI = 1.3-5.3], a 2.1-fold higher rate of epilepsy comorbidity [3.6% versus 1.7%, OR = 2.2, 95% CI = 1.1-4.7] and a 4-fold higher rate of simple partial seizures [1.2% versus 0.3%, OR = 4.8, 95% CI = 1.0-23] in the autistic children fed soy-based formula. No statistically significant associations were found with other outcomes including: IQ, age of seizure onset, infantile spasms and atonic, generalized tonic clonic, absence and complex partial seizures. Limitations of the study included: infant formula and seizure data were based on parental recall, there were significantly less female subjects, and there was lack of data regarding critical confounders such as the reasons the subjects used soy formula, age at which soy formula was initiated and the length of time on soy formula. 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MeCP2 is previously known as a transcriptional repressor by binding to methylated DNA and recruiting histone deacetylase complex (HDAC). Here, we report that MeCP2 regulates gene expression posttranscriptionally by suppressing nuclear microRNA processing. We found that MeCP2 binds directly to DiGeorge syndrome critical region 8 (DGCR8), a critical component of the nuclear microRNA-processing machinery, and interferes with the assembly of Drosha and DGCR8 complex. Protein targets of MeCP2-suppressed microRNAs include CREB, LIMK1, and Pumilio2, which play critical roles in neural development. Gain of function of MeCP2 strongly inhibits dendritic and spine growth, which depends on the interaction of MeCP2 and DGCR8. Thus, control of microRNA processing via direct interaction with DGCR8 represents a mechanism for MeCP2 regulation of gene expression and neural development. C1 [Cheng, Tian-Lin; Liao, Qiuming; Zhu, Ying; Qiu, Zilong] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China. [Wang, Zhizhi; Xu, Wenqing] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. [Zhou, Wen-Hao] Fudan Univ, Childrens Hosp, Dept Neonatol, Shanghai 201102, Peoples R China. [Cheng, Tian-Lin] Univ Chinese Acad Sci, Beijing 100049, Peoples R China. RP Qiu, ZL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China. EM zqiu@ion.ac.cn FU 973 Program Grant [2011CBA00400]; CAS Hundreds of Talents Program; Strategic Priority Research Program of the Chinese Academy of Science [XDB02050400] FX We thank Dr. Mu-ming Poo for his critical comments on the manuscript. We thank Dr. Adrian Bird for providing rat MeCP2 cDNA. This work was supported by the 973 Program Grant 2011CBA00400, CAS Hundreds of Talents Program, Strategic Priority Research Program of the Chinese Academy of Science Grant XDB02050400 to Z.Q. 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Cell PD MAR 10 PY 2014 VL 28 IS 5 BP 547 EP 560 DI 10.1016/j.devcel.2014.01.032 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA AD6XU UT WOS:000333405600009 PM 24636259 ER PT J AU Wilson, C AF Wilson, Clare TI Girls shielded from mutations linked to autism SO NEW SCIENTIST LA English DT News Item NR 0 TC 0 Z9 0 PU REED BUSINESS INFORMATION LTD PI SUTTON PA QUADRANT HOUSE THE QUADRANT, SUTTON SM2 5AS, SURREY, ENGLAND SN 0262-4079 J9 NEW SCI JI New Sci. PD MAR 8 PY 2014 VL 221 IS 2959 BP 12 EP 12 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AC8AO UT WOS:000332755600010 ER PT J AU Lai, MC Lombardo, MV Baron-Cohen, S AF Lai, Meng-Chuan Lombardo, Michael V. Baron-Cohen, Simon TI Autism SO LANCET LA English DT Article ID DE-NOVO MUTATIONS; RANDOMIZED CONTROLLED-TRIAL; SPECTRUM DISORDERS; CHILDHOOD AUTISM; WHITE-MATTER; COMPREHENSIVE METAANALYSIS; PSYCHIATRIC COMORBIDITY; BRAIN CONNECTIVITY; ASPERGER SYNDROME; ALE METAANALYSIS AB Autism is a set of heterogeneous neurodevelopmental conditions, characterised by early-onset difficulties in social communication and unusually restricted, repetitive behaviour and interests. The worldwide population prevalence is about 1%. Autism affects more male than female individuals, and comorbidity is common (>70% have concurrent conditions). Individuals with autism have atypical cognitive profiles, such as impaired social cognition and social perception, executive dysfunction, and atypical perceptual and information processing. These profiles are underpinned by atypical neural development at the systems level. Genetics has a key role in the aetiology of autism, in conjunction with developmentally early environmental factors. Large-effect rare mutations and small-effect common variants contribute to risk. Assessment needs to be multidisciplinary and developmental, and early detection is essential for early intervention. Early comprehensive and targeted behavioural interventions can improve social communication and reduce anxiety and aggression. Drugs can reduce comorbid symptoms, but do not directly improve social communication. Creation of a supportive environment that accepts and respects that the individual is different is crucial. C1 [Lai, Meng-Chuan; Lombardo, Michael V.; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. [Lai, Meng-Chuan] Natl Taiwan Univ, Coll Med, Dept Psychiat, Taipei 10764, Taiwan. [Lombardo, Michael V.] Univ Cyprus, Dept Psychol, Nicosia, Cyprus. [Baron-Cohen, Simon] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England. RP Lai, MC (reprint author), Univ Cambridge, Dept Psychiat, Autism Res Ctr, Douglas House,18B Trumpington Rd, Cambridge CB2 8AH, England. EM mcl45@cam.ac.uk FU European Autism Interventions-A Multicentre Study for Developing New Medications; Innovative Medicines Initiative [115300]; European Union's Seventh Framework Programme [FP7]; European Federation of Pharmaceutical Industries and Associations companies; Autism Speaks; Wolfson College (University of Cambridge, UK); British Academy and Jesus College (University of Cambridge, UK); Wellcome Trust; UK Medical Research Council; National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough NHS Foundation Trust; Autism Research Trust; European Union ASC-Inclusion Project; Target Autism Genome FX All authors are supported by the European Autism Interventions-A Multicentre Study for Developing New Medications (which receives support from the Innovative Medicines Initiative Joint Undertaking [grant agreement 115300], resources of which are composed of financial contribution from the European Union's Seventh Framework Programme [FP7/2007-2013], European Federation of Pharmaceutical Industries and Associations companies, and Autism Speaks). M-CL is supported by Wolfson College (University of Cambridge, UK). MVL is supported by the British Academy and Jesus College (University of Cambridge, UK). SB-C is supported by the Wellcome Trust, the UK Medical Research Council, the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough NHS Foundation Trust, the Autism Research Trust, the European Union ASC-Inclusion Project, and Target Autism Genome. We thank Wei-Tsuen Soong and Digby Tantam for valuable discussions. 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We would like to thank Catherine Kraper, Marisa Biondi and the members of the UMass Boston Baby Lab for their help with data collection. 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Putz, S. Russell, R. Boeckers, T. M. Liebau, S. TI THE KV beta 2 SUBUNIT OF VOLTAGE-GATED POTASSIUM CHANNELS IS INTERACTING WITH PROSAP2/SHANK3 IN THE PSD SO NEUROSCIENCE LA English DT Article DE kv-channel; Kv beta 2; beta-subunit; ProSAP2/Shank3; PSD; interaction ID AXON INITIAL SEGMENT; BETA-SUBUNITS; ION CHANNELS; POSTSYNAPTIC DENSITY; K+ CHANNELS; ARCHITECTURAL FRAMEWORK; SCAFFOLDING PROTEINS; EXCITATORY SYNAPSES; CORTICAL-NEURONS; MAMMALIAN BRAIN AB The postsynaptic density is an electron dense meshwork composed of a variety of molecules facilitating neuronal signal transmission. ProSAP2/Shank3 represents a crucial player at postsynaptic sites, assembling large multimeric platforms and anchoring numerous other molecules, thereby linking the functional synapse with the cytoskeleton. ProSAP2/Shank3 is also implicated in the pathogenesis of numerous diseases, including autism spectrum disorders. KvBeta2 (Kv beta 2) on the other hand serves as a regulatory subunit of voltage-gated potassium channels. Kv beta 2 is located at various sites in the neuron including the axon (binding to Kv1.2), the dendrites (binding to Kv4.2) and the synapse. Binding of Kv beta 2 to either Kv1.2 or Kv4 modulates not only the channel conformation but directs targeting of the channel protein complex to distinct loci within the cell. Thus an interaction between ProSAP2 and Kv beta 2 could have important roles at diverse cellular compartments and moreover during maturation stages. We report here on the direct protein-protein interaction of the postsynaptic density anchoring molecule ProSAP2 and the potassium channel subunit Kv beta 2, initially identified in a yeast-two-hybridscreen. Furthermore, we characterize this interaction at synapses using primary hippocampal neurons in vitro. (C) 2014 Published by Elsevier Ltd. on behalf of IBRO. C1 [Proepper, C.; Putz, S.; Boeckers, T. M.; Liebau, S.] Univ Ulm, Inst Anat & Cell Biol, D-89069 Ulm, Germany. [Russell, R.] Ulm Univ Hosp, Dept Internal Med 1, Ulm, Germany. [Liebau, S.] Univ Tubingen, Inst Neuroanat, D-72074 Tubingen, Germany. RP Liebau, S (reprint author), Univ Tubingen, Inst Neuroanat, Oesterbergstr 3, D-72074 Tubingen, Germany. EM stefan.liebau@uni-tuebungen.de FU Deutsche Forschungsgemeinschaft (DFG) [BO1718/4-1]; German Foundation for Heart Research [F/34/11]; Boehringer-Ingelheim BIU [N5]; Helmholtz Gesellschaft [VH-VI-510]; Else-Kroner-Fresenius-Stiftung [2011_A200]; BMBF (German MND-Net ) FX The authors thank Ursula Pika-Hartlaub and Sabine Seltenheim for excellent technical assistance, This study was funded by the Deutsche Forschungsgemeinschaft (DFG, SL & TMB BO1718/4-1), the German Foundation for Heart Research (F/34/11; to S.L.), Boehringer-Ingelheim BIU (N5 to S.L.), the Helmholtz Gesellschaft (VH-VI-510 to TMB and S.L.), the Else-Kroner-Fresenius-Stiftung (2011_A200; to S.L.) and BMBF (German MND-Net to TMB and S.L.). 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Willsey, Arthur Jeremy Kou, Yan Cicek, Abdullah Ercument Klei, Lambertus Lu, Cong He, Xin Li, Mingfeng Muhle, Rebecca A. Ma'ayan, Avi Noonan, James P. Sestan, Nenad McFadden, Kathryn A. State, Matthew W. Buxbaum, Joseph D. Devlin, Bernie Roeder, Kathryn TI DAWN: a framework to identify autism genes and subnetworks using gene expression and genetics SO MOLECULAR AUTISM LA English DT Article DE Autism; Risk prediction; Gene discovery; Weighted gene co-expression network analysis; Network; Hidden Markov random field; Neurite extension; Neuronal arborization ID DE-NOVO MUTATIONS; SPECTRUM DISORDERS; NEURITE OUTGROWTH; LARGE-SCALE; PROTEIN; NEURONS; RISK; ABNORMALITIES; DATABASE; NETWORKS AB Background: De novo loss-of-function (dnLoF) mutations are found twofold more often in autism spectrum disorder (ASD) probands than their unaffected siblings. Multiple independent dnLoF mutations in the same gene implicate the gene in risk and hence provide a systematic, albeit arduous, path forward for ASD genetics. It is likely that using additional non-genetic data will enhance the ability to identify ASD genes. Methods: To accelerate the search for ASD genes, we developed a novel algorithm, DAWN, to model two kinds of data: rare variations from exome sequencing and gene co-expression in the mid-fetal prefrontal and motor-somatosensory neocortex, a critical nexus for risk. The algorithm casts the ensemble data as a hidden Markov random field in which the graph structure is determined by gene co-expression and it combines these interrelationships with node-specific observations, namely gene identity, expression, genetic data and the estimated effect on risk. Results: Using currently available genetic data and a specific developmental time period for gene co-expression, DAWN identified 127 genes that plausibly affect risk, and a set of likely ASD subnetworks. Validation experiments making use of published targeted resequencing results demonstrate its efficacy in reliably predicting ASD genes. DAWN also successfully predicts known ASD genes, not included in the genetic data used to create the model. Conclusions: Validation studies demonstrate that DAWN is effective in predicting ASD genes and subnetworks by leveraging genetic and gene expression data. The findings reported here implicate neurite extension and neuronal arborization as risks for ASD. Using DAWN on emerging ASD sequence data and gene expression data from other brain regions and tissues would likely identify novel ASD genes. DAWN can also be used for other complex disorders to identify genes and subnetworks in those disorders. C1 [Liu, Li; Lei, Jing; Lu, Cong; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Sanders, Stephan J.; Willsey, Arthur Jeremy; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Sanders, Stephan J.; Willsey, Arthur Jeremy; Muhle, Rebecca A.; Noonan, James P.; State, Matthew W.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Kou, Yan; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY USA. [Kou, Yan; Ma'ayan, Avi] Icahn Sch Med Mt Sinai, Dept Pharmacol, New York, NY USA. [Kou, Yan; Ma'ayan, Avi] Icahn Sch Med Mt Sinai, Syst Therapeut & Syst Biol Ctr New York, New York, NY USA. [Cicek, Abdullah Ercument; He, Xin; Roeder, Kathryn] Carnegie Mellon Univ, Ray & Stephanie Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. [Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Li, Mingfeng; Muhle, Rebecca A.; Noonan, James P.; Sestan, Nenad] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT USA. [Li, Mingfeng; Sestan, Nenad; State, Matthew W.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Muhle, Rebecca A.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. [McFadden, Kathryn A.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [State, Matthew W.] Yale Univ, Sch Med, Program Neurogenet, New Haven, CT USA. [State, Matthew W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Psychiat, New York, NY USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Neurosci, New York, NY USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Genet & Genom Sci, New York, NY USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Mindisch Child Hlth & Dev Inst, New York, NY USA. RP Roeder, K (reprint author), Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. EM roeder@stat.cmu.edu RI Liu, Li/G-1897-2015 FU National Institute of Mental Health [MH057881, MH100233]; Overlook International Foundation; Simons Foundation; Seaver Foundation FX This work was supported by National Institute of Mental Health grants MH057881, MH100233, a gift from the Overlook International Foundation, a grant from the Simons Foundation, and a grant from the Seaver Foundation. We thank the members of the Devlin and Roeder labs for thought-provoking discussion of the ideas presented here. 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Autism PD MAR 6 PY 2014 VL 5 AR 22 DI 10.1186/2040-2392-5-22 PG 18 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AF8LB UT WOS:000334966200001 PM 24602502 ER PT J AU Trent, S Fry, JP Ojarikre, OA Davies, W AF Trent, Simon Fry, Jonathan P. Ojarikre, Obah A. Davies, William TI Altered brain gene expression but not steroid biochemistry in a genetic mouse model of neurodevelopmental disorder SO MOLECULAR AUTISM LA English DT Article DE Acetylserotonin O-methyltransferase; COUMATE; Steroid sulphatase; 39; (XO)-O-Y* ID DEFICIT HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; SULFATASE INHIBITOR COUMATE; MESSENGER-RNA EXPRESSION; COPY NUMBER VARIATIONS; ATTENTION-DEFICIT; NEUROACTIVE STEROIDS; AGGRESSIVE-BEHAVIOR; MELATONIN SYNTHESIS; REGRESSIVE AUTISM AB Background: The 39, X-Y* O mouse, which lacks the orthologues of the ADHD and autism candidate genes STS (steroid sulphatase) and ASMT (acetylserotonin O-methyltransferase), exhibits behavioural phenotypes relevant to developmental disorders. The neurobiology underlying these phenotypes is unclear, although there is evidence for serotonergic abnormalities in the striatum and hippocampus. Methods: Using microarray and quantitative gene expression analyses, and gas chromatography-mass spectrometry, we compared brain gene expression and steroid biochemistry in wildtype (40, XY) and 39, XY* O adult mice to identify non-obvious genetic and endocrine candidates for between-group differences in behaviour and neurochemistry. We also tested whether acute STS inhibition by COUMATE in wildtype (40, XY) adult male mice recapitulated any significant gene expression or biochemical findings from the genetic comparison. Data were analysed by unpaired t-test or Mann Whitney U-test depending on normality, with a single factor of KARYOTYPE. Results: Microarray analysis indicated seven robust gene expression differences between the two groups (Vmn2r86, Sfil, Pisd-ps1, Tagap1, C1qc, Metap1d, Erdr1); Erdr1 and C1qc expression was significantly reduced in the 39, XY* O striatum and hippocampus, whilst the expression of Dhcr7 (encoding 7-dehydrocholesterol reductase, a modulator of serotonin system development), was only reduced in the 39, X-Y* O hippocampus. None of the confirmed gene expression changes could be recapitulated by COUMATE administration. We detected ten free, and two sulphated steroids in 40, XY and 39, XY* O brain; surprisingly, the concentrations of all of these were equivalent between groups. Conclusions: Our data demonstrate that the mutation in 39, X-Y* O mice: i) directly disrupts expression of the adjacent Erdr1 gene, ii) induces a remarkably limited suite of downstream gene expression changes developmentally, with several of relevance to associated neurobehavioural phenotypes and iii) does not elicit large changes in brain steroid biochemistry. It is possible that individuals with STS/ASMT deficiency exhibit a similarly specific pattern of gene expression changes to the 39, X-Y* O mouse, and that these contribute towards their abnormal neurobiology. Future work may focus on whether complement pathway function, mitochondrial metabolism and cholesterol biosynthesis pathways are perturbed in such subjects. C1 [Trent, Simon; Davies, William] Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff CF10 3AX, S Glam, Wales. [Fry, Jonathan P.] UCL, Dept Neurosci Physiol & Pharmacol, London, England. [Ojarikre, Obah A.] Natl Inst Med Res, MRC, London NW7 1AA, England. [Davies, William] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales. [Davies, William] Cardiff Univ, Sch Psychol, Cardiff CF10 3AT, S Glam, Wales. RP Davies, W (reprint author), Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff CF10 3AX, S Glam, Wales. EM daviesw4@cardiff.ac.uk RI Trent, Simon/B-4228-2010 OI Trent, Simon/0000-0001-9563-4281 FU Medical Research Council United Kingdom (MRC UK) New Investigator Research [G0900636]; Research Councils UK Fellowship [U117532009] FX The work was supported by a Medical Research Council United Kingdom (MRC UK) New Investigator Research Grant to WD (G0900636), by a Research Councils UK Fellowship to WD, and by MRC UK funding to OAO (U117532009). The funding bodies had no role in the design, collection, analysis or interpretation of data, nor in the writing of the manuscript, nor in the decision to submit the manuscript for publication. COUMATE was a kind gift to JPF from Dr Laurent Nicolas. 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Autism PD MAR 6 PY 2014 VL 5 DI 10.1186/2040-2392-5-21 PG 11 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AF4XR UT WOS:000334718400001 PM 24602487 ER PT J AU Jacquemont, S Coe, BP Hersch, M Duyzend, MH Krumm, N Bergmann, S Beckmann, JS Rosenfeld, JA Eichler, EE AF Jacquemont, Sebastien Coe, Bradley P. Hersch, Micha Duyzend, Michael H. Krumm, Niklas Bergmann, Sven Beckmann, Jacques S. Rosenfeld, Jill A. Eichler, Evan E. TI A Higher Mutational Burden in Females Supports a "Female Protective Model" in Neurodevelopmental Disorders SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID COPY-NUMBER VARIATION; AUTISM SPECTRUM DISORDERS; DE-NOVO MUTATIONS; CLINICAL-SIGNIFICANCE; CNVS; IDENTIFICATION; MICRODELETION; VARIANTS; CHILDREN; BEHAVIOR AB Increased male prevalence has been repeatedly reported in several neurodevelopmental disorders (NDs), leading to the concept of a "female protective model." We investigated the molecular basis of this sex-based difference in liability and demonstrated an excess of deleterious autosomal copy-number variants (CNVs) in females compared to males (odds ratio [OR] = 1.46, p = 8 x 10(-10)) in a cohort of 15,585 probands ascertained for NDs. In an independent autism spectrum disorder (ASD) cohort of 762 families, we found a 3-fold increase in deleterious autosomal CNVs (p = 7 x 10(-4)) and an excess of private deleterious single-nucleotide variants (SNVs) in female compared to male probands (OR = 1.34, p = 0.03). We also showed that the deleteriousness of autosomal SNVs was significantly higher in female probands (p = 0.0006). A similar bias was observed in parents of probands ascertained for NDs. Deleterious CNVs (>400 kb) were maternally inherited more often (up to 64%, p = 10(-15)) than small CNVs < 400 kb (OR = 1.45, p = 0.0003). In the ASD cohort, increased maternal transmission was also observed for deleterious CNVs and SNVs. Although ASD females showed higher mutational burden and lower cognition, the excess mutational burden remained, even after adjustment for those cognitive differences. These results strongly suggest that females have an increased etiological burden unlinked to rare deleterious variants on the X chromosome. Carefully phenotyped and genotyped cohorts will be required for identifying the symptoms, which show gender-specific liability to mutational burden. C1 [Jacquemont, Sebastien] Univ Lausanne, Univ Lausanne Hosp, Serv Med Genet, CH-1011 Lausanne, Switzerland. [Coe, Bradley P.; Duyzend, Michael H.; Krumm, Niklas; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Hersch, Micha; Bergmann, Sven] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland. [Hersch, Micha; Bergmann, Sven; Beckmann, Jacques S.] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland. [Rosenfeld, Jill A.] PerkinElmer Inc, Signature Genom Labs LLC, Spokane, WA 99207 USA. [Eichler, Evan E.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Jacquemont, S (reprint author), Univ Lausanne, Univ Lausanne Hosp, Serv Med Genet, CH-1011 Lausanne, Switzerland. EM sebastien.jacquemont@chuv.ch; eee@gs.washington.edu RI Beckmann, Jacques/A-9772-2008 OI Beckmann, Jacques/0000-0002-9741-1900 FU Fond de Releve Academique, Universitede Lausanne; Swiss National Science Foundation [PP00P3_144902]; Simons Foundation Autism Research Initiative [137578, 191889]; National Institutes of Health [MH101221]; Novartis Pharma AG FX This work was supported by the Fond de Releve Academique, Universitede Lausanne (S.J.), Swiss National Science Foundation (PP00P3_144902), Simons Foundation Autism Research Initiative (137578 and 191889 to E. E. E.), and National Institutes of Health MH101221 (E. E. E.). E. E. E. is an investigator of the Howard Hughes Medical Institute, is on the scientific advisory board (SAB) of SynapDx Corp., and was an SAB member of Pacific Biosciences Inc. (2009-2013) and DNAnexus Inc. (2011-2013). J.R. is an employee of Signature Genomic Laboratories, a subsidiary of PerkinElmer Inc. S.J. has acted as a consultant for Novartis Pharma AG and has received grants for the clinical investigation of mavoglurant. We thank all families at the participating Simons Simplex Collection (SSC) sites and the principal investigators (A. Beaudet, R. B., J. Constantino, E. Cook, E. Fombonne, D. Geschwind, E. Hanson, D. Grice, A. Klin, R. Kochel, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, Z. Warren, and E. Wijsman). We acknowledge M. State and the SSC Genetics Consortium for providing Illumina genotyping and T. Lehner and the Autism Sequencing Consortium for data exchange among the participating groups. This study used data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to data generation is available at http://www.wtccc.org.uk/. We are grateful for manuscript preparation from T. Brown and helpful discussion from M. Kircher and Eichler lab members. 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E., 2014, J CHILD PSYCHOL PSYC, DOI [10.1111/jcpp.12210, DOI 10.1111/JCPP.12210.[] NR 71 TC 2 Z9 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD MAR 6 PY 2014 VL 5 AR 193 DI 10.3389/fpsyg.2014.00193 PG 9 WC Psychology, Multidisciplinary SC Psychology GA AC8KU UT WOS:000332782700001 PM 24639664 ER PT J AU Kim, YR Kim, CH Park, JH Pyo, J Treasure, J AF Kim, Youl-Ri Kim, Chan-Hyung Park, Jin Hong Pyo, Jimin Treasure, Janet TI The Impact of Intranasal Oxytocin on Attention to Social Emotional Stimuli in Patients with Anorexia Nervosa: A Double Blind within-Subject Cross-over Experiment SO PLOS ONE LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; EATING-DISORDERS; FACIAL EXPRESSIONS; BODY DISSATISFACTION; ANGER; METAANALYSIS; FACES; ANXIETY; AUTISM; THREAT AB Background and aim: Social factors may be of importance causally and act as maintenance factors in patients with anorexia nervosa. Oxytocin is a neuromodulatory hormone involved in social emotional processing associated with attentional processes. This study aimed to examine the impact of oxytocin on attentional processes to social faces representing anger, disgust, and happiness in patients with anorexia nervosa. Method: A double-blind, placebo-controlled within-subject crossover design was used. Intranasal oxytocin or placebo followed by a visual probe detection task with faces depicting anger, disgust, and happiness was administered to 64 female subjects: 31 patients with anorexia nervosa and 33 control students. Results: Attentional bias to the disgust stimuli was observed in both groups under the placebo condition. The attentional bias to disgust was reduced under the oxytocin condition (a moderate effect in the patient group). Avoidance of angry faces was observed in the patient group under the placebo condition and vigilance was observed in the healthy comparison group; both of these information processing responses were moderated by oxytocin producing an increase in vigilance in the patients. Happy/smiling faces did not elicit an attentional response in controls or the patients under either the placebo or oxytocin conditions. Conclusion: Oxytocin attenuated attentional vigilance to disgust in patients with anorexia nervosa and healthy controls. On the other hand, oxytocin changed the response to angry faces from avoidance to vigilance in patients but reduced vigilance to anger in healthy controls. We conclude that patients with anorexia nervosa appear to use different strategies/circuits to emotionally process anger from their healthy counterparts. C1 [Kim, Youl-Ri; Park, Jin Hong; Pyo, Jimin] Inje Univ, Seoul Paik Hosp, Dept Neuropsychiat, Seoul, South Korea. [Kim, Chan-Hyung] Yonsei Univ, Severance Mental Hosp, Dept Psychiat, Coll Med, Gyeonggi Do, South Korea. [Park, Jin Hong] Carleton Coll, Dept Psychol, Northfield, MN 55057 USA. [Treasure, Janet] Kings Coll London, Dept Psychol Med, Sect Eating Disorders, Inst Psychiat, London WC2R 2LS, England. RP Kim, YR (reprint author), Inje Univ, Seoul Paik Hosp, Dept Neuropsychiat, Seoul, South Korea. EM youlri.kim@paik.ac.kr FU National Research Foundation of Korea [2011-0030914]; National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London; National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at Maudsley National Health Service (NHS) Foundation Trust; National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at King's College London FX This study was supported under the framework of the international cooperation program managed by the National Research Foundation of Korea (2011-0030914) to Youl-Ri Kim. Janet Treasure is in part funded by the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London, and Maudsley National Health Service (NHS) Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. In addition the Swiss Anorexia Foundation contributed to this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Messier, Claude TI 2-Methyl-6-(phenylethynyl) pyridine( MPEP) reverses maze learning and PSD-95 deficits in Fmr1 knock-out mice SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE fragile X syndrome; Hebb-Williams mazes; 2-methyl-6-(phenylethynyl) pyridine; post-synaptic density-95; Western blot ID FRAGILE-X-SYNDROME; MENTAL-RETARDATION PROTEIN; RECEPTOR-DEPENDENT TRANSLATION; MGLUR5 ANTAGONIST MPEP; MOUSE MODEL; AMPA RECEPTOR; SYNAPTIC PLASTICITY; MESSENGER-RNAS; SPATIAL MEMORY; PHARMACOLOGICAL RESCUE AB Fragile X Syndrome (FXS) is caused by the lack of expression of the fragile X mental retardation protein (FMRP), which results in intellectual disability and other debilitating symptoms including impariment of visual-spatial functioning. FXS is the only single-gene disorder that is highly co-morbid with autism spectrum disorder and can therefore provide insight into its pathophysiology. Lack of FMRP results in altered group I metabotropic glutamate receptor (mGluR) signaling, which is a target for putative treatments. The Hebb-Williams (H-W) mazes are a set of increasingly complex spatial navigation problems that depend on intact hippocampal and thus mGluR-5 functioning. In the present investigation, we examined whether an antagonist of mGluR-5 would reverse previously described behavioral deficits in fragile X mental retardation 1 knock-out (Fmr1 KO) mice. Mice were trained on a subset of the H-W mazes and then treated with either 20 mg/kg of an mGluR-5 antagonist, 2-Methyl-6(phenylethynyl) pyridine (MPEP; n = 11) or an equivalent dose of salline (n = 1) prior of running test mazes. Latency and errors were dependent variables recorded during the test phase. Immediately after completing each test, marble-burying behavior was assessed, which confirmed that the drug treatment was pharmacologically active during maze learning. Although latency was not statistically different between the groups, MPEP treated Fmr1 KO mice made significantly fewer errors on mazes deemed more difficult suggesting a reversal of the behavioral deficit. MPEP treated mice were also less perseverative and impulsive when navigating mazes. Furthermore, MPEP treatment reversed post-synaptic density-95 (PSD-95) protein deficits in Fmr1 KO treated mice, whereas levels of a control protein (beta-tubulin) remained unchanted. These data further valildate MPEP as a potentially beneficial treatment for FXS. Our findings also suggest that adapted H-W mazes may be a useful tool to document alternations in behavioral functioning following pharmacological intervention in FXS. C1 [Gandhi, Reno M.; Kogan, Cary S.; Messier, Claude] Univ Ottawa, Sch Psychol, Ottawa, ON K1N 6N5, Canada. RP Kogan, CS (reprint author), Univ Ottawa, Sch Psychol, Vanier Bldg,136 Jean Jacques Lussier Pvt, Ottawa, ON K1N 6N5, Canada. EM ckogan@uottawa.ca RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU Natural Sciences and Engineering Research Council of Canada (NSERC); Canadian Institutes of Health Research (CIHR); University of Ottawa FX This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) grant to Cary S. Kogan, a Doctoral Research Award to Reno M. Gandhi by the Canadian Institutes of Health Research (CIHR) and the University of Ottawa. The authors would like to thank Drs. Dwayne Schindler and Lindsey Macleod for their advice regarding statistical analyses and recording of the behavioral data, respectively. 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