1. Bag O, Alsen Guney S, Cevher Binici N, Tuncel T, Sahin A, Berksoy E, Ecevit C. {{Is it Infant colic or early symptom of autistic spectrum disorder?}}. {Pediatrics international : official journal of the Japan Pediatric Society}. 2018.
OBJECTIVE: Gastrointestinal disorders (GI) are common in autistic spectrum disorder (ASD). Infant colic (IC), the functional GI disorder of infancy, has not been evaluated in this patient group. The aim of this study is to determine the rate of IC in ASD and investigate a possible association between ASD and IC. METHODS: The study group included patient group (ASD) and healthy controls. The parents were questioned with Diagnostic Criteria for Infant Colic for clinical research purposes defined in Rome IV to diagnose IC, retrospectively. The sample size was estimated by considering a maximum type I error probability of 5% (alpha) and a type II error of 20%. RESULTS: The study consisted of 100 ASD patients (mean age: 6.6+/-3.5 years) and 100 healthy controls (mean age: 5.3+/-2.8 years). The rate of IC was 16% and 17% in ASD group and control group, respectively (p>0.05). A group of infants with excessive crying was observed with late-onset, long duration and was described as persistent crying infants. The rate of persistent crying infants was significantly higher in ASD group than controls (32% vs 9%, p<0.001). The relative risk of persistent crying was 4.40 in ASD. The rate of being misdiagnosed as IC in this group was 78%. CONCLUSION: The rate of IC is not increased in patients with ASDs. But infants with excessive crying should be well evaluated before being diagnosed with IC. Especially late onset and long duration of an infant crying may be a risk factor for developing ASD. This article is protected by copyright. All rights reserved. Lien vers le texte intégral (Open Access ou abonnement)
2. Hertz-Picciotto I, Schmidt RJ, Krakowiak P. {{Understanding environmental contributions to autism: Causal concepts and the state of science}}. {Autism Res}. 2018.
The complexity of neurodevelopment, the rapidity of early neurogenesis, and over 100 years of research identifying environmental influences on neurodevelopment serve as backdrop to understanding factors that influence risk and severity of autism spectrum disorder (ASD). This Keynote Lecture, delivered at the May 2016 annual meeting of the International Society for Autism Research, describes concepts of causation, outlines the trajectory of research on nongenetic factors beginning in the 1960s, and briefly reviews the current state of this science. Causal concepts are introduced, including root causes; pitfalls in interpreting time trends as clues to etiologic factors; susceptible time windows for exposure; and implications of a multi-factorial model of ASD. An historical background presents early research into the origins of ASD. The epidemiologic literature from the last fifteen years is briefly but critically reviewed for potential roles of, for example, air pollution, pesticides, plastics, prenatal vitamins, lifestyle and family factors, and maternal obstetric and metabolic conditions during her pregnancy. Three examples from the case-control CHildhood Autism Risks from Genes and the Environment Study are probed to illustrate methodological approaches to central challenges in observational studies: capturing environmental exposure; causal inference when a randomized controlled clinical trial is either unethical or infeasible; and the integration of genetic, epigenetic, and environmental influences on development. We conclude with reflections on future directions, including exposomics, new technologies, the microbiome, gene-by-environment interaction in the era of -omics, and epigenetics as the interface of those two. As the environment is malleable, this research advances the goal of a productive and fulfilling life for all children, teen-agers and adults. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This Keynote Lecture, delivered at the 2016 meeting of the International Society for Autism Research, discusses evidence from human epidemiologic studies of prenatal factors contributing to autism, such as pesticides, maternal nutrition and her health. There is no single cause for autism. Examples highlight the features of a high-quality epidemiology study, and what comprises a compelling case for causation. Emergent research directions hold promise for identifying potential interventions to reduce disabilities, enhance giftedness, and improve lives of those with ASD.
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3. Noel JP, Stevenson RA, Wallace MT. {{Atypical Audiovisual Temporal Function in Autism and Schizophrenia: Similar Phenotype, Different Cause}}. {Eur J Neurosci}. 2018.
Binding across sensory modalities yields substantial perceptual benefits, including enhanced speech intelligibility. The coincidence of sensory inputs across time is a fundamental cue for this integration process. Recent work has suggested that individuals with diagnoses of Schizophrenia (SZ) and Autism Spectrum Disorder (ASD) will characterize auditory and visual events as synchronous over larger temporal disparities than their neurotypical counterparts. Namely, these clinical populations possess an enlarged temporal binding window (TBW). Although SZ and ASD patients share aspects of their symptomatology, phenotypic similarities may result from distinctly etiologies. To examine similarities and variances in audiovisual temporal function in these two populations, individuals diagnosed with ASD (n=46; controls n=40) and SZ (n=16, controls=16) completed an audiovisual simultaneity judgment task. In addition to standard psychometric analyses, synchrony judgments were assessed using Bayesian causal inference modeling. This approach permits distinguishing between distinct causes of an enlarged TBW: an a priori bias to bind sensory information and poor fidelity in the sensory representation. Findings indicate that both ASD and SZ populations show deficits in multisensory temporal acuity. Importantly, results suggest that while the wider TBWs in ASD most prominently results from atypical priors, the wider TBWs in SZ results from a trend toward changes in prior and weaknesses in the sensory representations. Results are discussed in light of current ASD and SZ theories and highlight that different perceptual training paradigms focused on improving multisensory integration may be most effective in these two clinical populations and emphasize that similar phenotypes may emanate from distinct mechanistic causes. This article is protected by copyright. All rights reserved.
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4. Rose DR, Yang H, Serena G, Sturgeon C, Ma B, Careaga M, Hughes HK, Angkustsiri K, Rose M, Hertz-Picciotto I, Van de Water J, Hansen RL, Ravel J, Fasano A, Ashwood P. {{Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms}}. {Brain, behavior, and immunity}. 2018.
OBJECTIVES: Many studies have reported the increased presence of gastrointestinal (GI) symptoms in children with autism spectrum disorders (ASD). Altered microbiome profiles, pro-inflammatory responses and impaired intestinal permeability have been observed in children with ASD and co-morbid GI symptoms, yet few studies have compared these findings to ASD children without GI issues or similarly aged typical developing children. The aim of this study was to determine whether there are biological signatures in terms of immune dysfunction and microbiota composition in children with ASD with GI symptoms. METHODS: Children were enrolled in one of four groups: ASD and GI symptoms of irregular bowel habits (ASD(GI)), children with ASD but without current or previous GI symptoms (ASD(NoGI)), typically developing children with GI symptoms (TD(GI)) and typically developing children without current or previous GI symptoms (TD(NoGI)). Peripheral blood mononuclear cells (PBMC) were isolated from the blood, stimulated and assessed for cytokine production, while stool samples were analyzed for microbial composition. RESULTS: Following Toll-Like receptor (TLR)-4 stimulation, the ASD(GI) group produced increased levels of mucosa-relevant cytokines including IL-5, IL-15 and IL-17 compared to ASD(NoGI). The production of the regulatory cytokine TGFbeta1 was decreased in the ASD(GI) group compared with both the ASD(NoGI) and TD(NoGI) groups. Analysis of the microbiome at the family level revealed differences in microbiome composition between ASD and TD children with GI symptoms; furthermore, a predictive metagenome functional content analysis revealed that pathways were differentially represented between ASD and TD subjects, independently of the presence of GI symptoms. The ASD(GI) also showed an over-representation of the gene encoding zonulin, a molecule regulating gut permeability, compared to the other groups. CONCLUSIONS: Overall our findings suggest that children with ASD who experience GI symptoms have an imbalance in their immune response, possibly influenced by or influencing metagenomic changes, and may have a propensity to impaired gut barrier function which may contribute to their symptoms and clinical outcome.
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5. Woodbury-Smith M, Scherer SW. {{Progress in the genetics of autism spectrum disorder}}. {Dev Med Child Neurol}. 2018.
A genetic basis for autism spectrum disorder (ASD) is now well established, and with the availability of high-throughput microarray and sequencing platforms, major advances have been made in our understanding of genetic risk factors. Rare, often de novo, copy number and single nucleotide variants are both implicated, with many ASD-implicated genes showing pleiotropy and variable penetrance. Additionally, common variants are also known to play a role in ASD’s genetic etiology. These new insights into the architecture of ASD’s genetic etiology offer opportunities for the identification of molecular targets for novel interventions, and provide new insight for families seeking genetic counselling. WHAT THE PAPER ADDS: A number of rare genetic variants are implicated in autism spectrum disorder (ASD), with some showing recurrence. Common genetic variants are also important and a number of loci are now being uncovered. Genetic testing for individuals with ASD offers the opportunity to identify relevant genetic etiology.
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6. Zhao H, Jiang YH, Zhang YQ. {{Modeling autism in non-human primates: Opportunities and challenges}}. {Autism Res}. 2018.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and restricted, repetitive patterns of behavior. For more than a decade, genetically-modified, risk factor-induced, as well as naturally occurring rodent models for ASD have been used as the most predominant tools to dissect the molecular and circuitry mechanisms underlying ASD. However, the apparent evolutionary differences in terms of social behavior and brain anatomy between rodents and humans have become an issue of debate regarding the translational value of rodent models for studying ASD. More recently, genome manipulation of non human primates using lentivirus-based gene expression, TALEN and CRISPR/Cas9 mediated gene editing techniques, has been reported. Genetically modified non-human primate models for ASD have been produced and characterized. While the feasibility, value, and exciting opportunities provided by the non-human primate models have been clearly demonstrated, many challenges still remain. Here, we review current progress, discuss the remaining challenges, and highlight the key issues in the development of non-human primate models for ASD research and drug development. Autism Res 2018,. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Over the last two decades, genetically modified rat and mouse models have been used as the most predominant tools to study mechanisms underlying autism spectrum disorder (ASD). However, the apparent evolutionary differences between rodents and humans limit the translational value of rodent models for studying ASD. Recently, several non-human primate models for ASD have been established and characterized. Here, we review current progress, discuss the challenges, and highlight the key issues in the development of non-human primate models for ASD research and drug development.
