1. {{Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia}}. {Mol Autism};2017;8:21.
BACKGROUND: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15). METHODS: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). RESULTS: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 x 10-6). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. CONCLUSIONS: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4. Lien vers le texte intégral (Open Access ou abonnement)
2. Ahmadlou M, Adeli H. {{Complexity of weighted graph: A new technique to investigate structural complexity of brain activities with applications to aging and autism}}. {Neurosci Lett};2017 (May 22);650:103-108.
In recent years complexity of the brain structure in healthy and disordered subjects has been studied increasingly. But to the best of the authors’ knowledge, researchers so far have investigated the structural complexity only in the context of two restricted networks known as Small-World and Scale-free networks; whereas other aspects of the structural complexity of brain activities may be affected by aging and neurodegenerative disorders such as the Alzheimer’s disease and autism spectrum disorder. In this study, two general complexity metrics of graphs, Graph Index Complexity and Offdiagonal Complexity are proposed as general measures of complexity, not restricted to SWN only. They are adopted to measure the structural complexity of the weighted graphs instead of the common binary graphs. Fuzzy Synchronization Likelihood is applied to the EEGs and their sub-bands, as a functional connectivity metric of the brain, to construct the functional connectivity graphs. Two applications are used to evaluate the efficacy of the complexity measures: diagnosis of autism and aging, both based on EEG. It was discovered that the Graph Index Complexity of gamma band is discriminative in distinguishing autistic children from non-autistic children. Also, Offdiagonal Complexity of theta band in young subjects was observed to be significantly different than old subjects. This study shows that changes in the structure of functional connectivity of brain in disorders and different healthy states can be revealed by unrestricted metrics of graph complexity. While the applications presented in this paper are based on EEG, the approach is general and can be used with other modalities such as fMRI, MEG, etc. Further, it can be used to study every other neurological and psychiatric disorder.
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3. Casarrubea M, Faulisi F, Cudia A, Cancemi D, Cardaci M, Magnusson MS, Crescimanno G. {{Discovery of recurring behavioural sequences in Wistar rat social activity: possible support to studies on Autism Spectrum Disorders}}. {Neurosci Lett};2017 (May 17)
This study was undertaken to investigate whether, in rat interactive activities, recurring sequences of behavioural events might be identified and how and to what extent each component of the pair is involved. To this aim, the multivariate temporal-pattern (t-pattern) analysis was applied to the social interactions of 9 pairs of male Wistar rats tested in open field. Interactive activities were classified into intra- and inter-subjects. Quantitative evaluations showed that intra-subject behavioural elements represented 62.37% and inter-subject ones 37.63% of the comprehensive behaviour. T-pattern analysis revealed the presence of 221 different t-patterns organized in four different categories: containing exclusively inter-subject elements; containing both inter- and intra-subject elements; consisting of rat 1 and rat 2 intra-subject elements and, finally, consisting of intra-subject elements carried out by one of the two subjects. Results show that the activity of two interacting Wistar rats is structured on the basis of several recurring temporal sequences. Moreover, social interactions appear to be expressed also by t-patterns where the behavioural elements are carried out by animals seemingly not interacting. A support of t-pattern analysis to studies on Autism Spectrum Disorders is proposed.
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4. H OM, Sampaio A, Martinez-Regueiro R, Gomez-Guerrero L, Lopez-Doriga CG, Gomez S, Carracedo A, Fernandez-Prieto M. {{Touch Processing and Social Behavior in ASD}}. {J Autism Dev Disord};2017 (May 22)
Abnormal patterns of touch processing have been linked to core symptoms in ASD. This study examined the relation between tactile processing patterns and social problems in 44 children and adolescents with ASD, aged 6-14 (M = 8.39 +/- 2.35). Multiple linear regression indicated significant associations between touch processing and social problems. No such relationships were found for social problems and autism severity. Within touch processing, patterns of hyper-responsiveness and hypo-responsiveness best predicted social problems, whereas sensory-seeking did not. These results support that atypical touch processing in individuals with ASD might be contributing to the social problems they present. Moreover, it the need to explore more in depth the contribution of sensory features to the ASD phenotype.
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5. Ito H, Morishita R, Nagata KI. {{Autism spectrum disorder-associated genes and the development of dentate granule cells}}. {Med Mol Morphol};2017 (May 22)
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by severe clinical symptoms such as the deficiency of the social communication, repetitive and stereotyped behaviors, and restricted interests. Although complex genetic and environmental factors are thought to contribute to the development of ASD, the precise etiologies are largely unknown. Neuroanatomical observations have been made of developmental abnormalities in different brain regions, including dentate gyrus of hippocampus, which is widely accepted as the center for learning and memory. However, little is known about what roles ASD-associated genes play in the development of hippocampal dentate granule cells. In this article, we summarized functions and pathophysiological significance of 6 representative ASD-associated genes, SEMA5A, PTEN, NLGN, EN-2, FMR1, and MECP2, by focusing on the development of dentate gyrus. We then introduced a recently developed gene transfer method directed to neonatal dentate granule cells. This new method will be useful for elucidating physiological as well as pathophysiological significance of ASD-associated genes in the development of hippocampal formation.
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6. Kuschner ES, Morton HE, Maddox BB, de Marchena A, Anthony LG, Reaven J. {{The BUFFET Program: Development of a Cognitive Behavioral Treatment for Selective Eating in Youth with Autism Spectrum Disorder}}. {Clin Child Fam Psychol Rev};2017 (May 22)
Selective eating (often referred to as « picky » eating) is common in individuals with autism spectrum disorder (ASD) across the lifespan. Behavioral interventions are widely used to treat selective eating; however, most of these programs are time intensive, have not been evaluated for use in outpatient settings, and do not typically include youth beyond early childhood. Despite the functional impact and risk for negative outcomes associated with selective eating, there are no empirically supported treatments available for older children, adolescents, or adults, either with or without ASD. To address this treatment gap, we developed BUFFET: the Building Up Food Flexibility and Exposure Treatment program. BUFFET is a 14-week, multi-family group cognitive behavioral treatment for selective eating in children (8-12 years) with ASD. In this paper, we will (1) discuss the theoretical conceptualization of BUFFET, (2) describe the treatment content and structure, (3) present feasibility data from the initial pilot trial, and (4) consider next steps in treatment development.
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7. Smith IM, MacDonald NE. {{Countering evidence denial and the promotion of pseudoscience in autism spectrum disorder}}. {Autism Res};2017 (May 22)
This commentary introduces a framework within which clinical and research experts in autism spectrum disorder (ASD) can address public instances of evidence denial and promotion of pseudoscience related to ASD. This is a generalized extension of work by a World Health Organization (WHO) group dedicated to reducing the influence of Vocal Vaccine Deniers through educating advocates in how to effectively defuse their arguments. The WHO guidelines were informed by conceptual work on the « denialism » phenomenon, and by studies in psychology, communication, vaccine science, and public health. Our goal is to introduce these ideas to, and encourage discussion within, the ASD research community. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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8. Viktorin A, Uher R, Reichenberg A, Levine SZ, Sandin S. {{Autism risk following antidepressant medication during pregnancy}}. {Psychol Med};2017 (May 22):1-10.
BACKGROUND: Previous studies have examined if maternal antidepressant medication during pregnancy increase the risk of autism spectrum disorder (ASD) in the offspring, but the results have been conflicting. METHODS: In a population-based cohort of 179 007 children born in 2006 and 2007 and followed through 2014 when aged 7 and 8, we estimated relative risks (RRs) of ASD and 95% confidence intervals (CIs) from Cox regression in children exposed to any antidepressant medication during pregnancy, and nine specific antidepressant drugs. Analyses were adjusted for potential confounders and were conducted in the full population sample, and in a clinically relevant sub-sample of mothers with at least one diagnosis of depression or anxiety during life. RESULTS: The adjusted RR of ASD in children of mothers who used antidepressant medication during pregnancy was estimated at 1.23 (95% CI 0.96-1.57), and at 1.07 (95% CI 0.80-1.43) in women with a history of depression or anxiety. Analyses of specific antidepressants initially revealed increased RRs of offspring ASD confined to citalopram and escitalopram (RR: 1.47; 95% CI 0.92-2.35) and clomipramine (RR: 2.86; 95% CI 1.04-7.82). CONCLUSION: Medication with antidepressants during pregnancy does not appear to be causally associated with an increased risk of ASD in the offspring. Instead, the results suggest that the association is explained by factors related to the underlying susceptibility to psychiatric disorders. Based on these findings, the risk of ASD in the offspring should not be a consideration to withhold treatment with commonly used antidepressant drugs from pregnant women.
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9. Warren LR, Rao PA, Paton DC. {{A Pilot Observational Study of an Acupressure/Acupuncture Intervention in Children with Autism Spectrum Disorder}}. {J Altern Complement Med};2017 (May 22)
OBJECTIVES: To determine whether children with autism spectrum disorder (ASD) would tolerate an acupressure/acupuncture intervention and whether parents would adhere to a twice-weekly, 8-week intervention protocol. Second, to further understand best measures to use to capture impact of intervention on behavioral and regulatory functions. DESIGN: This is an observational pilot study with pre-, mid-, and postintervention measures. SETTINGS/LOCATION: The intervention was carried out in a private practice office in a large metropolitan area. SUBJECTS: A total of 10 children of ages 3-10 years with ASD and one of their parents participated. INTERVENTIONS: A total of 16 biweekly treatment sessions of acupressure and/or acupuncture were carried out by a licensed acupuncturist, and a daily home-based acupressure intervention was carried out by a parent. OUTCOME MEASURES: Attendance, tolerance of intervention, parent compliance with home program, and parent compliance in completing daily diary and five standardized measures of behavioral and regulatory functions pre-, mid-, and postintervention were recorded. RESULTS: The 10 children in this observational study, collectively, tolerated the intervention and parents adhered to the 16 sessions, biweekly protocol, and home protocol, as well as completing daily diary and five standardized measures at three different time intervals. The five measurements appeared to be sensitive to behavioral and regulatory functions that may improve with this type of intervention. CONCLUSIONS: The results of this observational pilot study suggest that acupressure/acupuncture is a feasible intervention for children with ASD that merits rigorous evaluation through a randomized controlled trial.
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10. Xie Y, Yuan H, Wang M, Zhong L, Zhou J, Song B, Yin Q, Sun X. {{Copy Number Variations independently induce Autism Spectrum Disorder}}. {Biosci Rep};2017 (May 22)
The examination of copy number variation (CNV) is critical to understanding the etiology of the CNV-related autism spectrum disorders (ASD). DNA samples were obtained from 64 ASD probands, which were genotyped on an Affymetrix CytoScan HD platform. qPCR or FISH were used as a validation for some novel recurrent CNVs. We further compared the clinical phenotypes of the genes in the DECIPHER database with these overlapping genes. Using vast, readily available databases with previously reported clinically relevant CNVs from human populations, the genes were evaluated using Enrichment Analysis and GO Slim Classification. By using the Ploysearch2 software, we identified the interaction relationship between significant genes and known ASD genes.A total of 29 CNVs, overlapping with 520 genes, including 315 OMIM genes, were identified. Additionally, MEF2C with two cases of CNV overlap were also identified. Enrichment analysis showed that the 520 genes are most likely related to membrane components with protein binding functions involved in metabolic processes. In the interaction network of those genes, the known ASD genes are mostly at the core position and the significant genes found in our samples are closely related to the known ASD genes.CNVs should be an independent factor to induce autism. With the strategy of our study, we could find the ASDs candidate genes by CNVs data and review certain pathogenesis of this disorder. Those CNVs were associated with ASD and they may contribute to ASD by affecting the ASD-related genes.
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11. Zander E, Willfors C, Berggren S, Coco C, Holm A, Jifalt I, Kosieradzki R, Linder J, Nordin V, Olafsdottir K, Bolte S. {{The Interrater Reliability of the Autism Diagnostic Interview-Revised (ADI-R) in Clinical Settings}}. {Psychopathology};2017 (May 20)
BACKGROUND: The Autism Diagnostic Interview-Revised (ADI-R) is considered a first choice assessment tool in autism spectrum disorder. Nevertheless, despite its wide use in psychiatric practice and recommendations by various clinical guidelines, its interrater reliability has predominantly been confirmed in research settings by specially trained, research reliability interviewers. The reliability of ADI-R assessments among clinicians has not yet been established. Therefore, this study examined the spontaneous interrater reliability of the ADI-R in a naturalistic clinical multicenter setting. SAMPLING AND METHODS: Ten video-recorded ADI-R administrations were rated by 5 different raters each from a pool of 11 raters affiliated to 8 different clinical sites. RESULTS: The interrater reliability for the 12 diagnostic criteria operationalizing autism spectrum disorders according to DSM-IV/ICD-10 in the ADI-R algorithms ranged between G(q,k) (analogous to intraclass correlations) = 0.96 and 0.99 for reciprocal social interaction, 0.96 and 1.00 for communication, and 0.91 and 0.97 for repetitive and restricted behavior. Reliability of diagnostic classification was kCohen 0.83. CONCLUSIONS: The findings endorse the psychometric properties of ADI-R in terms of interrater reliability previously reported from research settings and support their generalization to common clinical settings. Limitations of this study include an unbalanced sample composition.
