1. Maruani A, Huguet G, Beggiato A, ElMaleh M, Toro R, Leblond CS, Mathieu A, Amsellem F, Lemiere N, Verloes A, Leboyer M, Gillberg C, Bourgeron T, Delorme R. {{11q24.2-25 micro-rearrangements in autism spectrum disorders: Relation to brain structures}}. {Am J Med Genet A}. 2015.
Jacobsen syndrome (JS) is characterized by intellectual disability and higher risk for autism spectrum disorders (ASD). All patients with JS are carriers of contiguous de novo deletions of 11q24.2-25, but the causative genes remain unknown. Within the critical interval, we hypothesized that haploinsufficiency of the neuronal cell adhesion molecule Neurotrimin (NTM) might increase the risk for ASD and could affect brain structure volumes. We searched for deleterious mutations affecting NTM in 1256 ASD patients and 1287 controls, using SNP arrays, and by direct sequencing of 250 ASD patients and 180 controls. We compared our results to those obtained from independent cohorts of ASD patients and controls. We identified two patients with Copy Number Variants (CNV) encompassing NTM, one with a large de novo deletion, and a clinical phenotype of JS (including macrocephaly), and a second with a paternally inherited duplication, not consistent with JS. Interestingly, no similar CNVs were observed in controls. We did not observe enrichment for deleterious NTM mutations in our cohort. We then explored if the macrocephaly in the patient with JS was associated with a homogeneous increase of brain structures volumes using automatic segmentation. Compared to subjects without NTM micro-rearrangements (n=188), the patient had an increased volume of the sub-cortical structures but a decrease of the occipital gray matter. Finally our explorations could not incriminate NTM as a susceptibility gene for ASD, but provides new information on the impact of the 11q24.2-25 deletion on brain anatomy. (c) 2015 Wiley Periodicals, Inc.
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2. Moricke E, Buitelaar JK, Rommelse NN. {{Do We Need Multiple Informants When Assessing Autistic Traits? The Degree of Report Bias on Offspring, Self, and Spouse Ratings}}. {J Autism Dev Disord}. 2015.
This study focused on the degree of report bias in assessing autistic traits. Both parents of 124 preschoolers completed the Social Communication Questionnaire and the Autism-spectrum Quotient. Acceptable agreement existed between mother and father reports of children’s mean scores of autistic traits, but interrater reliability for rank-order correlations was only fair. No evidence was found for report bias regarding parent-offspring autistic traits. However, adult autistic ratings were strongly biased: spouse-ratings were higher than self-ratings, correlations were only fair when both parents reported about the same person, and resemblance was higher for reports from the same person than for spouses’ separate self-reports. It is advisable to involve multiple informants when assessing autistic traits, and to use procedural and/or statistical remedies to control for report bias.
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3. Watanabe T, Kuroda M, Kuwabara H, Aoki Y, Iwashiro N, Tatsunobu N, Takao H, Nippashi Y, Kawakubo Y, Kunimatsu A, Kasai K, Yamasue H. {{Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism}}. {Brain}. 2015.
Autism spectrum disorder is a prevalent neurodevelopmental disorder with no established pharmacological treatment for its core symptoms. Although previous literature has shown that single-dose administration of oxytocin temporally mitigates autistic social behaviours in experimental settings, it remains in dispute whether such potentially beneficial responses in laboratories can result in clinically positive effects in daily life situations, which are measurable only in long-term observations of individuals with the developmental disorder undergoing continual oxytocin administration. Here, to address this issue, we performed an exploratory, randomized, double-blind, placebo-controlled, crossover trial including 20 high-functional adult males with autism spectrum disorder. Data obtained from 18 participants who completed the trial showed that 6-week intranasal administration of oxytocin significantly reduced autism core symptoms specific to social reciprocity, which was clinically evaluated by Autism Diagnostic Observation Scale (P = 0.034, PFDR < 0.05, Cohen's d = 0.78). Critically, the improvement of this clinical score was accompanied by oxytocin-induced enhancement of task-independent resting-state functional connectivity between anterior cingulate cortex and dorso-medial prefrontal cortex (rho = -0.60, P = 0.011), which was measured by functional magnetic resonance imaging. Moreover, using the same social-judgement task as used in our previous single-dose oxytocin trial, we confirmed that the current continual administration also significantly mitigated behavioural and neural responses during the task, both of which were originally impaired in autistic individuals (judgement tendency: P = 0.019, d = 0.62; eye-gaze effect: P = 0.03, d = 0.56; anterior cingulate activity: P = 0.00069, d = 0.97; dorso-medial prefrontal activity: P = 0.0014, d = 0.92; all, PFDR < 0.05). Furthermore, despite its longer administration, these effect sizes of the 6-week intervention were not larger than those seen in our previous single-dose intervention. These findings not only provide the evidence for clinically beneficial effects of continual oxytocin administration on the core social symptoms of autism spectrum disorder with suggesting its underlying biological mechanisms, but also highlight the necessity to seek optimal regimens of continual oxytocin treatment in future studies. Lien vers le texte intégral (Open Access ou abonnement)
4. Yu H, Liu J, Yang A, Yang G, Yang W, Lei H, Quan J, Zhang Z. {{Lack of Association Between Polymorphisms in Dopa Decarboxylase and Dopamine Receptor-1 Genes With Childhood Autism in Chinese Han Population}}. {J Child Neurol}. 2015.
Genetic factors play an important role in childhood autism. This study is to determine the association of single-nucleotide polymorphisms in dopa decarboxylase (DDC) and dopamine receptor-1 (DRD1) genes with childhood autism, in a Chinese Han population. A total of 211 autistic children and 250 age- and gender-matched healthy controls were recruited. The severity of disease was determined by Children Autism Rating Scale scores. TaqMan Probe by real-time polymerase chain reaction was used to determine genotypes and allele frequencies of single-nucleotide polymorphism rs6592961 in DDC and rs251937 in DRD1. Case-control and case-only studies were respectively performed, to determine the contribution of both single-nucleotide polymorphisms to the predisposition of disease and its severity. Our results showed that there was no significant association of the genotypes and allele frequencies of both single-nucleotide polymorphisms concerning childhood autism and its severity. More studies with larger samples are needed to corroborate their predicting roles.
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5. Zerbo O, Massolo ML, Qian Y, Croen LA. {{A Study of Physician Knowledge and Experience with Autism in Adults in a Large Integrated Healthcare System}}. {J Autism Dev Disord}. 2015.
We conducted an online survey of adult health care providers at Kaiser Permanente Northern California and semi-structured interviews with a subset of physicians. The survey assessed providers’ ability to recognize autism spectrum disorder (ASD), asked them to rate their autism knowledge, comfort level in treating affected patients, and evaluated training and resource needs. 922 providers completed the survey (response rate 25.3 %), and 9 were interviewed by telephone regarding their autism training and experiences caring for patients with autism. Most providers reported lacking skills and tools to care for this adult patient population. A high proportion of adult providers were not aware that they had patients with ASD. These findings underscore the need to educate physicians caring for adults with ASD.
