1. Ajram LA, Horder J, Mendez MA, Galanopoulos A, Brennan LP, Wichers RH, Robertson DM, Murphy CM, Zinkstok J, Ivin G, Heasman M, Meek D, Tricklebank MD, Barker GJ, Lythgoe DJ, Edden RAE, Williams SC, Murphy DGM, McAlonan GM. {{Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder}}. {Transl Psychiatry};2017 (May 23);7(5):e1137.
Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the ‘responsivity’ of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E-I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal ‘Inhibitory Index’-the GABA fraction within the pool of glutamate plus GABA metabolites-post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E-I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E-I flux can be ‘shifted’ with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be ‘normalised’ by targeting E-I, even in adults.
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2. Black KR, Stevenson RA, Segers M, Ncube BL, Sun SZ, Philipp-Muller A, Bebko JM, Barense MD, Ferber S. {{Linking Anxiety and Insistence on Sameness in Autistic Children: The Role of Sensory Hypersensitivity}}. {J Autism Dev Disord};2017 (May 24)
Sensory hypersensitivity and insistence on sameness (I/S) are common, co-occurring features of autism, yet the relationship between them is poorly understood. This study assessed the impact of sensory hypersensitivity on the clinical symptoms of specific phobia, separation anxiety, social anxiety and I/S for autistic and typically developing (TD) children. Parents of 79 children completed questionnaires on their child’s difficulties related to sensory processing, I/S, and anxiety. Results demonstrated that sensory hypersensitivity mediated 67% of the relationship between symptoms of specific phobia and I/S and 57% of the relationship between separation anxiety and I/S. No relationship was observed between sensory hypersensitivity and social anxiety. These mediation effects of sensory hypersensitivity were found only in autistic children, not in TD children.
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3. Cantor RM, Navarro L, Won H, Walker RL, Lowe JK, Geschwind DH. {{ASD restricted and repetitive behaviors associated at 17q21.33: genes prioritized by expression in fetal brains}}. {Mol Psychiatry};2017 (May 23)
Autism spectrum disorder (ASD) is a behaviorally defined condition that manifests in infancy or early childhood as deficits in communication skills and social interactions. Often, restricted and repetitive behaviors (RRBs) accompany this disorder. ASD is polygenic and genetically complex, so we hypothesized that focusing analyses on intermediate core component phenotypes, such as RRBs, can reduce genetic heterogeneity and improve statistical power. Applying this approach, we mined Caucasian genome-wide association studies (GWAS) data from two of the largest ASD family cohorts, the Autism Genetics Resource Exchange and Autism Genome Project (AGP). Of the 12 RRBs measured by the Autism Diagnostic Interview-Revised, seven were found to be significantly familial and substantially variable, and hence, were tested for genome-wide association in 3104 ASD-affected children from 2045 families. Using a stringent significance threshold (P<7.1 x 10-9), GWAS in the AGP revealed an association between 'the degree of the repetitive use of objects or interest in parts of objects' and rs2898883 (P<6.8 x 10-9), which resides within the sixth intron of PHB. To identify the candidate target genes of the associated single-nucleotide polymorphisms at that locus, we applied chromosome conformation studies in developing human brains and implicated three additional genes: SLC35B1, CALCOCO2 and DLX3. Gene expression, brain imaging and fetal brain expression quantitative trait locus studies prioritize SLC35B1 and PHB. These analyses indicate that GWAS of single heritable features of genetically complex disorders followed by chromosome conformation studies in relevant tissues can be successful in revealing novel risk genes for single core features of ASD.Molecular Psychiatry advance online publication, 23 May 2017; doi:10.1038/mp.2017.114. Lien vers le texte intégral (Open Access ou abonnement)
4. Cox DJ, Brown T, Ross V, Moncrief M, Schmitt R, Gaffney G, Reeve R. {{Can Youth with Autism Spectrum Disorder Use Virtual Reality Driving Simulation Training to Evaluate and Improve Driving Performance? An Exploratory Study}}. {J Autism Dev Disord};2017 (May 24)
Investigate how novice drivers with autism spectrum disorder (ASD) differ from experienced drivers and whether virtual reality driving simulation training (VRDST) improves ASD driving performance. 51 novice ASD drivers (mean age 17.96 years, 78% male) were randomized to routine training (RT) or one of three types of VRDST (8-12 sessions). All participants followed DMV behind-the-wheel training guidelines for earning a driver’s license. Participants were assessed pre- and post-training for driving-specific executive function (EF) abilities and tactical driving skills. ASD drivers showed worse baseline EF and driving skills than experienced drivers. At post-assessment, VRDST significantly improved driving and EF performance over RT. This study demonstrated feasibility and potential efficacy of VRDST for novice ASD drivers.
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5. Fischer S. {{Minibrain Storm : Cerebral Organoids Aren’t Real Brains?But They Provide a Powerful Platform for Modeling Brain Diseases Like Zika Infection, Alzheimer’s, and Even Autism}}. {IEEE Pulse};2017 (May-Jun);8(3):31-34.
Floating in a Petri dish, they look like tiny tapioca pearls in peach broth, a couple dozen in number and none much larger than the tip of a ballpoint pen. But under a microscope, dense, lumpy bodies come into focus, outlined by wispy coronas.
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6. 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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7. 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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8. 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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9. Lee S, Won J, Park S, Lee SR, Chang KT, Kim JH, Hong Y. {{Beneficial effect of interventional exercise on autistic Fragile X syndrome}}. {J Phys Ther Sci};2017 (Apr);29(4):760-762.
[Purpose] The purpose of the present review is to discuss recent published articles in the understanding of efficacy of interventional exercise on autistic Fragile X syndrome (FXS) with special emphasis on its significance in clinical application in patients. [Methods] This review article was identified scientifically and/or clinically relevant articles from PubMed that directly/indirectly met the inclusion criteria. [Results] Mutation of fragile X mental retardation 1 (fmr1) gene on the X chromosome is related with loss of fragile X mental retardation protein (FMRP) that affecting physiological and behavioral abnormalities. Autistic FXS individuals exhibit disturbed sleep and altered circadian behavior. Although the underlying molecular mechanisms are not been fully explored, interventional exercise in autistic FXS has been clinically used for the treatment of physiological and behavioral abnormalities as well as psychiatric disorder in autistic FXS. [Conclusion] This review describes beneficial efficacy of interventional exercise and its controversy in patients with autistic FXS. This review also provides interventional strategies for clinicians and scientists that the way of neurophysiological approaches according to the level of physical and behavioral abnormalities.
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10. Liu J, Mo W, Zhang Z, Yu H, Yang A, Qu F, Hu P, Liu Z, Wang S. {{Single Nucleotide Polymorphisms in SLC19A1 and SLC25A9 Are Associated with Childhood Autism Spectrum Disorder in the Chinese Han Population}}. {J Mol Neurosci};2017 (May 24)
Genetic variants have been implicated in the development of autism spectrum disorder (ASD). Recent studies suggest that solute carriers (SLCs) may play a role in the etiology of ASD. This purpose of this study was to determine the association between single nucleotide polymorphisms (SNPs) in SLC19A1 and SLC25A12 genes with childhood ASD in a Chinese Han population. A total of 201 autistic children and 200 age- and gender-matched healthy controls were recruited. A TaqMan probe-based real-time PCR approach was used to determine genotypes of SNPs corresponding to rs1023159 and rs1051266 in SLC19A1, and rs2056202 and rs2292813 in SLC25A12. Our results showed that both the T/T genotype of rs1051266 (odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.06-3.23, P = 0.0301) and the T allele (OR = 1.77, 95% CI = 1.07-2.90, P = 0.0249) of rs2292813 were significantly associated with an increased risk of childhood ASD. In addition, the G-C haplotype of rs1023159-rs1051266 in SCL19A1 (OR = 0.71, 95% CI = 0.51-0.98, P = 0.0389) and C-C haplotype of rs2056202-rs2292813 in SLC25A12 (OR = 0.58, 95% CI = 0.35-0.96, P = 0.0325) were associated with decreased risks of childhood ASD. There was no significant association between genotypes and allele frequencies with the severity of the disease. Our study suggests that these genetic variants of SLC19A1 and SLC25A12 may be associated with risks for childhood ASD.
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11. Marschik PB, Lemcke S, Einspieler C, Zhang D, Bolte S, Townend GS, Lauritsen MB. {{Early development in Rett syndrome – the benefits and difficulties of a birth cohort approach}}. {Dev Neurorehabil};2017 (May 23):1-5.
PURPOSES: Typically, early (pre-diagnostic) development in individuals later diagnosed with Rett syndrome (RTT) has been investigated retrospectively using parent reports, medical records and analysis of home videos. In recent years, prospective research designs have been increasingly applied to the investigation of early development in individuals with late phenotypical onset disorders, for example, autism spectrum disorder. METHODS: In this study, data collected by the Danish National Birth Cohort lent itself to prospective exploration of the early development of RTT, in particular early motor-, speech-language, and socio-communicative behaviors, mood, and sleep. RESULTS AND CONCLUSIONS: Despite limitations, this quasi prospective methodology proved promising. In order to add substantially to the body of knowledge, however, specific questions relating to peculiarites in early development could usefully be added to future cohort studies. As this involves considerable work, it may be more realistic to consider a set of indicators which point to a number of developmental disorders rather than to one.
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12. Quintana DS, Westlye LT, Hope S, Naerland T, Elvsashagen T, Dorum E, Rustan O, Valstad M, Rezvaya L, Lishaugen H, Stensones E, Yaqub S, Smerud KT, Mahmoud RA, Djupesland PG, Andreassen OA. {{Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial}}. {Transl Psychiatry};2017 (May 23);7(5):e1136.
The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin’s dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (eta2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.
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13. Radley KC, Dart EH, Moore JW, Lum JDK, Pasqua J. {{Enhancing appropriate and variable responding in young children with autism spectrum disorder}}. {Dev Neurorehabil};2017 (May 24):1-11.
OBJECTIVE: The present study utilized lag schedules of reinforcement, in conjunction with training multiple exemplars and provision of prompts, to promote appropriate variability of social skills. METHODS: Participants included in three children between the ages of 5 and 7 with ASD. Participants attended a social skills training program twice per week for eight weeks. A multiple probe design across target social skills was used to assess the effects of intervention. RESULTS: Findings indicate that training multiple exemplars alone did not appreciably increase appropriate and variable responding, whereas the addition of lag schedules of reinforcement and prompting to training multiple exemplars resulted in appropriate and variable responding that exceeded baseline levels. CONCLUSION: Use of lag schedule of reinforcement in conjunction with prompts was more effective than multiple exemplar training in isolation for increasing appropriate variability of social skills.
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14. Reines V, Charen K, Rosser T, Eisen A, Sherman SL, Visootsak J. {{Parental Perspectives on Pharmacological Clinical Trials: a Qualitative Study in Down Syndrome and Fragile X Syndrome}}. {J Genet Couns};2017 (May 24)
Research studies focusing on parents’ perspectives of pharmacological clinical trials have not kept pace with the number of emerging pharmacologic clinical trials in Down syndrome (DS) and Fragile X syndrome (FXS). Since individuals with DS or FXS have limited cognitive ability to make decisions about their participation in clinical trials, it is important to consider the parents’ perspectives and explore the ways in which decisions are made for their children. Using a semi-structured interview, we enrolled 9 parents of a child(ren) with FXS and 15 with a child with DS to analyze their views, experiences, and knowledge of pharmacological clinical trials. Although our study is preliminary in nature, it revealed that parents are generally supportive of pharmacological clinical trials, yet there may be concerns about safety and long-term implications and consideration for their child in the decision process. There is also parental misunderstanding of the objectives of pharmacological clinical trials; thus, it is important for pharmaceutical companies, study investigators, clinicians/medical professionals, and parent advocacy groups to collaborate to provide appropriate and up-to-date educational resources that fully explain the risks and benefits of clinical trials.
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15. Wang S, Yang C, Liu Y, Shao Z, Jackson T. {{Early and late stage processing abnormalities in autism spectrum disorders: An ERP study}}. {PLoS One};2017;12(5):e0178542.
This research assessed event-related potentials (ERPs) elicited during the processing of different kinds of visual stimuli among children with Autism Spectrum Disorder (ASD) (n = 15) and typically developing (TD) children (n = 19). Within a simple visual oddball paradigm, participating children passively viewed fruit and vegetable images that were used as standard stimuli in addition to images of these foods with their usual colors modified to create novel stimuli and cartoon depictions of these images (i.e., « deviant » stimuli). Analyses revealed significant main effect differences between the groups for P100, N100 and P300 components; ASD group children showing longer P100 latencies, weaker N100 amplitudes and larger P300 amplitudes than did the TD group. A Group x Hemisphere interaction also emerged for N400 amplitudes but differences were not significant in simple-effects analyses. Together these results suggested children with ASD may be characterized by lower attention resource allocation and engagement during early stages of processing visual stimuli. However, ERPs in later processing stages suggested children with ASD and TD children have similar neural responses in attending to visual images as stimulus presentations continue.
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16. 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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17. Yang C, Zhao W, Deng K, Zhou V, Zhou X, Hou Y. {{The association between air pollutants and autism spectrum disorders}}. {Environ Sci Pollut Res Int};2017 (May 24)
Autism spectrum disorders are a member of the pervasive developmental disorders (PDDs) that have been increasing dramatically since described by Leo Kanner in 1943. In the past decade, the number of epidemiological publications addressing air pollution exposures and autism has grown correspondingly, but the association is still unclear. Whether air pollutants play a causal role and which substances are related with autism requires further study. We systematically reviewed the literature from 2005 to 2016 in MEDLINE (National Library of Medicine), Web of Science, and PubMed and summarized the association between different air pollutants and autism. Furthermore, we further discussed the exposure time window and potential confounders that should be considered in the association analysis studies. Our objective is to summarize the association between different air pollutants and autism with literature, which has been published since 2005, and explore whether the exposure time window and potential confounders have influence on this association. These results could provide more comprehensive information about the association between air pollutants and autism and be helpful towards further validation study. Graphical abstract .
