1. Anitha A, Nakamura K, Thanseem I, Matsuzaki H, Miyachi T, Tsujii M, Iwata Y, Suzuki K, Sugiyama T, Mori N. {{Downregulation of the Expression of Mitochondrial Electron Transport Complex Genes in Autism Brains}}. {Brain Pathol};2012 (Oct 23)
Mitochondrial dysfunction (MtD) and abnormal brain bioenergetics have been implicated in autism, suggesting possible candidate genes in the electron transport chain (ETC). We compared the expression of 84 ETC genes in the postmortem brains of autism patients and controls. Brain tissues from the anterior cingulate gyrus, motor cortex, and thalamus of autism patients (n=8) and controls (n=10) were obtained from Autism Tissue Program, U.S.A. Quantitative real-time PCR Arrays were used to quantify gene expression. We observed reduced expression of several ETC genes in autism brains compared to controls. 11 genes of Complex I, five genes each of Complex III and Complex IV, and seven genes of Complex V showed brain region-specific reduced expression in autism. ATP5A1 (Complex V), ATP5G3 (Complex V) and NDUFA5 (Complex I) showed consistently reduced expression in all the brain regions of autism patients. Upon silencing ATP5A1, the expression of mitogen-activated protein kinase 13 (MAPK13), a p38 MAPK responsive to stress stimuli, was upregulated in HEK 293 cells. This could have been induced by oxidative stress due to impaired ATP synthesis. We report new candidate genes involved in abnormal brain bioenergetics in autism, supporting the hypothesis that mitochondria, critical for neurodevelopment, may play a role in autism.
Lien vers le texte intégral (Open Access ou abonnement)
2. Barbeau EB, Soulieres I, Dawson M, Zeffiro TA, Mottron L. {{The Level and Nature of Autistic Intelligence III: Inspection Time}}. {J Abnorm Psychol};2012 (Oct 22)
Across the autism spectrum, level of intelligence is highly dependent on the psychometric instrument used for assessment, and there are conflicting views concerning which measures best estimate autistic cognitive abilities. Inspection time is a processing speed measure associated with general intelligence in typical individuals. We therefore investigated autism spectrum performance on inspection time in relation to two different general intelligence tests. Autism spectrum individuals were divided into autistic and Asperger subgroups according to speech development history. Compared to a typical control group, mean inspection time for the autistic subgroup but not the Asperger subgroup was significantly shorter (by 31%). However, the shorter mean autistic inspection time was evident only when groups were matched on Wechsler IQ and disappeared when they were matched using Raven’s Progressive Matrices. When autism spectrum abilities are compared to typical abilities, results may be influenced by speech development history as well as by the instrument used for intelligence matching. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
Lien vers le texte intégral (Open Access ou abonnement)
3. Gotham K, Pickles A, Lord C. {{Trajectories of Autism Severity in Children Using Standardized ADOS Scores}}. {Pediatrics};2012 (Oct 22)
OBJECTIVES:To plot longitudinal trajectories of autism spectrum disorder (ASD) severity from early childhood to early adolescence. In line with reported trajectories in toddlers, we hypothesize that a substantial minority of children will show marked changes in ASD severity over time, with « Improvers » demonstrating the highest mean baseline and rate of growth in verbal IQ (VIQ).METHODS:Patients included 345 clinic referrals and research participants with best-estimate clinical diagnoses of ASD at 1 or more time points, and repeated Autism Diagnostic Observation Schedule (ADOS), VIQ, and nonverbal IQ scores. Standardized ADOS severity scores were applied to 1026 assessments collected longitudinally between the ages of 2 and 15 (VIQ at most recent assessment: mean = 58, SD = 35). Scores were fitted for latent severity trajectory classes with and without covariates. Adaptive behavior and VIQ trajectories over time were modeled within each of the best-fit latent classes.RESULTS:A 4-class model best represented the observed data. Over 80% of participants were assigned to persistent (stable) high or moderately severe classes; 2 small classes respectively increased or decreased in severity over time. Age, gender, race, and nonverbal IQ did not predict class membership; VIQ was a significant predictor. Baseline VIQ was highest in the improving and worsening classes; it increased at the greatest rate in the improving class. Adaptive behavior declined in all but the improving class, with consistent impairment in all classes.CONCLUSIONS:If replicated, identified trajectory classes of ADOS severity may contribute to clinical prognosis and to subtyping samples for neurobiological and genetic research.
Lien vers le texte intégral (Open Access ou abonnement)
4. Hedrick A, Lee Y, Wallace GL, Greenstein D, Clasen L, Giedd JN, Raznahan A. {{Autism Risk Gene MET Variation and Cortical Thickness in Typically Developing Children and Adolescents}}. {Autism Res};2012 (Oct 24)
MET receptor tyrosine kinase (MET) has been proposed as a candidate risk gene for autism spectrum disorder (ASD) based on associations between MET polymorphisms and ASD diagnosis, as well as evidence from animal studies that MET protein may regulate early development of cortical regions implicated in the neurobiology of ASD. The relevance of differences in MET signaling for human cortical development remains unexamined, however. We sought to address this issue by relating genotype at a functional single nucleotide polymorphism within the MET promoter (rs1858830, G–>C) to in vivo measures of cortical thickness (CT) development derived from 222 healthy children and adolescents with 514 longitudinally acquired structural magnetic resonance imaging brain scans between ages 9 and 22 years. We identified a statistically significant, developmentally fixed, and stepwise CT reduction with increasing C allele dose in superior and middle temporal gyri, ventral precentral and postcentral gyri, and anterior cingulate bilaterally, and in the right frontopolar cortex. We were also able to demonstrate that mean CT within these cortical regions showed a statistically significant reduction with increasing scores on a continuous measure of autistic traits (the Social Responsiveness Scale). The cortical regions highlighted by our analyses are not only established areas of MET expression during prenatal life but are also key components of the « social brain » that have frequently shown structural and functional abnormalities in autism. Our results suggest that genetic differences in the MET gene may influence the development of cortical systems implicated in the neurobiology of ASD. Autism Res 2012, **: **-**. (c) 2012 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
5. Politi P, Emanuele E, Grassi M, Project TI. {{Development of the « Playing-in-Touch » (PiT) questionnaire: a measure of musical intouchness in people with low-functioning autism}}. {Neuro Endocrinol Lett};2012 (Oct 22);33(5):552-558.
BACKGROUND: There is accumulating evidence that people with autism have a particular affinity with music. METHODS: This study developed the « Playing-in-Touch » (PiT) questionnaire as an objective measure of musical intouchness – defined as the degree of engagement in creative exchange while playing ensemble music pieces – in persons with low-functioning autism. RESULTS: A 3-facet Rasch model supported the content and construct validity of the PiT scale. The items verified a one-dimensional hierarchical model. CONCLUSIONS: The PiT questionnaire is a convenient complement to other research methodologies exploring the attitudes of people with low-functioning autism in terms of active music making.
6. Reaven J, Blakeley-Smith A, Leuthe E, Moody E, Hepburn S. {{Facing your fears in adolescence: cognitive-behavioral therapy for high-functioning autism spectrum disorders and anxiety}}. {Autism Res Treat};2012;2012:423905.
Adolescents with high-functioning autism spectrum disorders (ASDs) are at high risk for developing psychiatric symptoms, with anxiety disorders among the most commonly cooccurring. Cognitive behavior therapies (CBTs) are considered the best practice for treating anxiety in the general population. Modified CBT approaches for youth with high-functioning ASD and anxiety have resulted in significant reductions in anxiety following intervention. The purpose of the present study was to develop an intervention for treating anxiety in adolescents with ASD based on a CBT program designed for school-aged children. The Facing Your Fears-Adolescent Version (FYF-A) program was developed; feasibility and acceptability data were obtained, along with initial efficacy of the intervention. Twenty-four adolescents, aged 13-18, completed the FYF-A intervention. Results indicated significant reductions in anxiety severity and interference posttreatment, with low rates of anxiety maintained at 3-month follow-up. In addition, nearly 46% of teen participants met criteria for a positive treatment response on primary diagnosis following the intervention. Initial findings from the current study are encouraging and suggest that modified group CBT for adolescents with high-functioning ASD may be effective in reducing anxiety symptoms. Limitations include small sample size and lack of control group. Future directions are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
7. South M, Newton T, Chamberlain PD. {{Delayed Reversal Learning and Association With Repetitive Behavior in Autism Spectrum Disorders}}. {Autism Res};2012 (Oct 24)
An important aspect of successful emotion regulation is the ability to adjust emotional responses to changing environmental cues. Difficulties with such adaptation may underlie both marked symptoms of behavioral inflexibility and frequent severe anxiety in the autism spectrum disorders (ASDs). Thirty children and adolescents diagnosed with ASD and 29 age- and intelligence quotient-matched controls completed a reversal learning paradigm following partial reinforcement Pavlovian fear conditioning, using a surprising air puff as the unconditioned stimulus. After initial reversal of cue contingencies, where a previously safe cue now predicted the air puff threat, the control group but not the ASD group responded more strongly to the new threat cue. The ASD group showed evidence for reversal learning only during later trials. Reversal learning in the ASD group was significantly negatively correlated with everyday symptoms of behavioral inflexibility but not with everyday anxiety. Understanding shared associations between inflexibility, anxiety, and autism, with regard both to clinical symptoms and neurobiological mechanisms, can provide important markers for better characterizing the substantial heterogeneity across the autism spectrum. Autism Res 2012, : -. (c) 2012 International Society for Autism Research, Wiley Periodicals, Inc.
