Challenge and Potential for Research on Gene-Environment Interactions in Autism Spectrum Disorder

2017 ◽  
pp. 157-176 ◽  
Author(s):  
Carly L. A. Wender ◽  
Jeremy Veenstra-VanderWeele
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Gene Environment

The Effect of Prenatal Valproate Exposure in Serotonin Transporter Knockout Rats On Anxiety and Cognition: A Gene*Environment Interaction Model of Autism Spectrum Disorder

2021 ◽  
Author(s):  
◽  
Caren L. August
Keyword(s):  
Autism Spectrum Disorder ◽  
Cognitive Ability ◽  
Serotonin Transporter ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Starting Point

<p>Autism Spectrum Disorder is a complex neurodevelopmental disorder which is often associated with increased anxiety and deficits in cognitive ability. The present research investigated a potential gene*environment interaction between two factors previously implicated in ASD in a rat model; prenatal exposure to valproate (VPA) and genetic reduction of the serotonin transporter (SERT). Wildtype and heterozygous SERT knockout rats prenatally exposed to VPA or saline on gestational day12.5 (G12.5) were assessed on measures of anxiety: elevated plus-maze and novelty suppressed-feeding and cognitive ability: prepulse inhibition and latent inhibition. A significant main effect was found for VPA exposure in all paradigms, showing increased anxiety-typical behaviour and abnormal cognitive ability. However, no significant effect of genotype or interaction was observed. Results from the present study do not confirm gene*environment interaction between prenatal VPA and heterozygous SERT knockout but this may be due to several factors that are discussed within the thesis. In any case, this study represents a starting point for further studies investigating other combinations of genetic and environmental factors as models of ASD pathogenesis.</p>

The Effect of Prenatal Valproate Exposure in Serotonin Transporter Knockout Rats On Anxiety and Cognition: A Gene*Environment Interaction Model of Autism Spectrum Disorder

2021 ◽  
Author(s):  
◽  
Caren L. August
Keyword(s):  
Autism Spectrum Disorder ◽  
Cognitive Ability ◽  
Serotonin Transporter ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Starting Point

<p>Autism Spectrum Disorder is a complex neurodevelopmental disorder which is often associated with increased anxiety and deficits in cognitive ability. The present research investigated a potential gene*environment interaction between two factors previously implicated in ASD in a rat model; prenatal exposure to valproate (VPA) and genetic reduction of the serotonin transporter (SERT). Wildtype and heterozygous SERT knockout rats prenatally exposed to VPA or saline on gestational day12.5 (G12.5) were assessed on measures of anxiety: elevated plus-maze and novelty suppressed-feeding and cognitive ability: prepulse inhibition and latent inhibition. A significant main effect was found for VPA exposure in all paradigms, showing increased anxiety-typical behaviour and abnormal cognitive ability. However, no significant effect of genotype or interaction was observed. Results from the present study do not confirm gene*environment interaction between prenatal VPA and heterozygous SERT knockout but this may be due to several factors that are discussed within the thesis. In any case, this study represents a starting point for further studies investigating other combinations of genetic and environmental factors as models of ASD pathogenesis.</p>

scholarly journals A role for gene-environment interactions in Autism Spectrum Disorder is suggested by variants in genes regulating exposure to environmental factors

2019 ◽  
Author(s):  
João Xavier Santos ◽  
Célia Rasga ◽  
Ana Rita Marques ◽  
Hugo F. M. C. Martiniano ◽  
Muhammad Asif ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Environmental Factors ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Environment Interaction ◽  
Postnatal Exposure ◽  
Loss Of Function ◽  
Single Nucleotide Variants ◽  
Gene Environment

AbstractIntroductionAutism Spectrum Disorder (ASD) is a clinically heterogeneous neurodevelopmental disorder defined by deficits in social communication and interaction and repetitive and stereotyped interests and behaviors. ASD heritability estimates of 50-83% support a strong role of genetics in its onset, with large sequencing studies reporting a high burden of rare potentially pathogenic copy number variants (CNVs) and single nucleotide variants (SNVs) in affected subjects. Recent data strongly suggests that prenatal to postnatal exposure to ubiquitous environmental factors (e.g. environmental toxins, medications and nutritional factors) contribute to ASD risk. Detoxification processes and physiological permeability barriers (i.e. blood-brain barrier, placenta and respiratory cilia) are crucial in regulating exposure and response to external agents during early development. Thus, the objectives of this study were: 1) to find genes involved in detoxification and regulation of barriers permeability with a high load of relevant CNVs and SNVs in ASD subjects; 2) to explore interactions between the identified genes and environmental factors relevant for the disorder.Material and MethodsThrough literature and databases review we searched for genes involved in detoxification and regulation of barriers permeability processes. Genetic data collected from large datasets of subjects with ASD (Autism Genome Project (AGP), Simmons Simplex Collection (SSC), and Autism Sequencing Consortium (ASC)) was used to identify potentially pathogenic variants targeting detoxification and barrier genes. Data from control subjects without neuropsychiatric disorder history was used for comparison purposes. The Comparative Toxicogenomics Database (CTD) was interrogated to identify putatively relevant gene-environment interactions reported in humans throughout the literature.ResultsWe compiled a list of 519 genes involved in detoxification and regulation of permeability barriers. The analysis of AGP and SSC data resulted in the identification of 7 genes more-frequently targeted by CNVs in ASD-subjects from both datasets, after Bonferroni correction for multiple testing (AGP: P<3.5211×10−4; SSC: P< 4.587×10−4). Moreover, 8 genes were exclusively targeted by CNVs from ASD subjects. Regarding SNVs analyses using the ASC dataset, we found 40 genes targeted by potentially pathogenic loss-of-function and/or missense SNVs exclusive to 6 or more cases. The CTD was interrogated for interactions between 55 identified genes and 54 terms for unique chemicals associated with the disorder. A total of 212 gene-environment interaction pairs, between 51/55 (92.7%) genes and 38/54 (70.4%) chemicals, putatively relevant for ASD, were discovered. ABCB1, ABCG2, CYP2C19, GSTM1, CYP2D6, and SLC3A2 were the genes that interacted with more chemicals, while valproic acid, benzo(a)pyrene (b(a)p), bisphenol A, particulate matter and perfluorooctane sulfonic acid (PFOS) were the top chemicals.DiscussionThe identified genes code for functionally diverse proteins, ranging from enzymes that increase the degradability of xenobiotics (CYP450s, UGTs and GSTs), to transporters (ABCs and SLCs), proteins that regulate the correct function of barriers (claudins and dyneins) and placental hormones. The identified gene-environment interactions may reflect the fact that some genes and chemicals are understudied and that the potential neurotoxicity of many substances is unreported. We suggest that environmental factors can have pathogenic effects when individuals carry variants targeting these genes and discuss the potential mechanisms by which these genes can influence ASD risk.ConclusionWe reinforce the hypothesis that gene-environment interactions are relevant, at least, for a subset of ASD cases. Given that no treatment exists for the pathology, the identification of relevant modifiable exposures can contribute to the development of preventive strategies for health management policies in ASD.

scholarly journals Exposure to Xenobiotics and Gene-Environment Interactions in Autism Spectrum Disorder: A Systematic Review

2021 ◽  
Author(s):  
João Xavier Santos ◽  
Célia Rasga ◽  
Astrid Moura Vicente
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Signaling Pathways ◽  
Treatment Strategies ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Pharmaceutical Drugs ◽  
Gene Environment ◽  
Xenobiotic Exposure ◽  
Data Collections

Heritability estimates indicate that genetic susceptibility does not fully explain Autism Spectrum Disorder (ASD) risk variance, and that environmental factors may play a role in this disease. To explore the impact of the environment in ASD etiology, we performed a systematic review of the literature on xenobiotics implicated in the disease, and their interactions with gene variants. We compiled 72 studies reporting associations between ASD and xenobiotic exposure, including air pollutants, persistent and non-persistent organic pollutants, heavy metals, pesticides, pharmaceutical drugs and nutrients. Additionally, 9 studies reported that interactions between some of these chemicals (eg. NO2, particulate matter, manganese, folic acid and vitamin D) and genetic risk factors (eg. variants in the CYP2R1, GSTM1, GSTP1, MET, MTHFR and VDR genes) modulate ASD risk. The chemicals highlighted in this review induce neuropathological mechanisms previously implicated in ASD, including oxidative stress and hypoxia, dysregulation of signaling pathways and endocrine disruption. Exposure to xenobiotics may be harmful during critical windows of neurodevelopment, particularly for individuals with variants in genes involved in xenobiotic metabolization or in widespread signaling pathways. We emphasize the importance of leveraging multilevel data collections and integrative approaches grounded on artificial intelligence to address gene–environment interactions and understand ASD etiology, towards prevention and treatment strategies.

Development of Neural Structure and Function in Autism Spectrum Disorder: Potential Implications for Learning Language

2020 ◽  
Vol 29 (4) ◽  
pp. 1783-1797
Author(s):  
Kelly L. Coburn ◽  
Diane L. Williams
Keyword(s):  
Autism Spectrum Disorder ◽  
Language Development ◽  
Diffusion Tensor ◽  
Autism Spectrum ◽  
Language Intervention ◽  
Spectrum Disorder ◽  
Autistic Children ◽  
Neural Structure ◽  
Complex Information ◽  
And Function

Purpose Neurodevelopmental processes that begin during gestation and continue throughout childhood typically support language development. Understanding these processes can help us to understand the disruptions to language that occur in neurodevelopmental conditions, such as autism spectrum disorder (ASD). Method For this tutorial, we conducted a focused literature review on typical postnatal brain development and structural and functional magnetic resonance imaging, diffusion tensor imaging, magnetoencephalography, and electroencephalography studies of the neurodevelopmental differences that occur in ASD. We then integrated this knowledge with the literature on evidence-based speech-language intervention practices for autistic children. Results In ASD, structural differences include altered patterns of cortical growth and myelination. Functional differences occur at all brain levels, from lateralization of cortical functions to the rhythmic activations of single neurons. Neuronal oscillations, in particular, could help explain disrupted language development by elucidating the timing differences that contribute to altered functional connectivity, complex information processing, and speech parsing. Findings related to implicit statistical learning, explicit task learning, multisensory integration, and reinforcement in ASD are also discussed. Conclusions Consideration of the neural differences in autistic children provides additional scientific support for current recommended language intervention practices. Recommendations consistent with these neurological findings include the use of short, simple utterances; repetition of syntactic structures using varied vocabulary; pause time; visual supports; and individualized sensory modifications.

Parent Education in Studies With Nonverbal and Minimally Verbal Participants With Autism Spectrum Disorder: A Systematic Review

2020 ◽  
Vol 29 (2) ◽  
pp. 890-902
Author(s):  
Lynn Kern Koegel ◽  
Katherine M. Bryan ◽  
Pumpki Lei Su ◽  
Mohini Vaidya ◽  
Stephen Camarata
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Parent Education ◽  
Autism Spectrum ◽  
Verbal Communication ◽  
Fidelity Of Implementation ◽  
Spectrum Disorder ◽  
Education Programs ◽  
Minimally Verbal ◽  
Parent Education Programs

Purpose The purpose of this systematic review was to identify parent education procedures implemented in intervention studies focused on expressive verbal communication for nonverbal (NV) or minimally verbal (MV) children with autism spectrum disorder (ASD). Parent education has been shown to be an essential component in the habilitation of individuals with ASD. Parents of individuals with ASD who are NV or MV may particularly benefit from parent education in order to provide opportunities for communication and to support their children across the life span. Method ProQuest databases were searched between the years of 1960 and 2018 to identify articles that targeted verbal communication in MV and NV individuals with ASD. A total of 1,231 were evaluated to assess whether parent education was implemented. We found 36 studies that included a parent education component. These were reviewed with regard to (a) the number of participants and participants' ages, (b) the parent education program provided, (c) the format of the parent education, (d) the duration of the parent education, (e) the measurement of parent education, and (f) the parent fidelity of implementation scores. Results The results of this analysis showed that very few studies have included a parent education component, descriptions of the parent education programs are unclear in most studies, and few studies have scored the parents' implementation of the intervention. Conclusions Currently, there is great variability in parent education programs in regard to participant age, hours provided, fidelity of implementation, format of parent education, and type of treatment used. Suggestions are made to provide both a more comprehensive description and consistent measurement of parent education programs.

The Influence of Language Context on Repetitive Speech Use in Children With Autism Spectrum Disorder

2020 ◽  
Vol 29 (1) ◽  
pp. 327-334 ◽  
Author(s):  
Allison Gladfelter ◽  
Cassidy VanZuiden
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Individual Characteristics ◽  
Receptive Vocabulary ◽  
Spectrum Disorder ◽  
School Age Children ◽  
Social Responsiveness ◽  
Contributing Factors ◽  
Children With Asd ◽  
Language Context

Purpose Although repetitive speech is a hallmark characteristic of autism spectrum disorder (ASD), the contributing factors that influence repetitive speech use remain unknown. The purpose of this exploratory study was to determine if the language context impacts the amount and type of repetitive speech produced by children with ASD. Method As part of a broader word-learning study, 11 school-age children with ASD participated in two different language contexts: storytelling and play. Previously collected language samples were transcribed and coded for four types of repetitive speech: immediate echolalia, delayed echolalia, verbal stereotypy, and vocal stereotypy. The rates and proportions of repetitive speech were compared across the two language contexts using Wilcoxon signed-ranks tests. Individual characteristics were further explored using Spearman correlations. Results The children produced lower rates of repetitive speech during the storytelling context than the play-based context. Only immediate echolalia differed between the two contexts based on rate and approached significance based on proportion, with more immediate echolalia produced in the play-based context than in the storytelling context. There were no significant correlations between repetitive speech and measures of social responsiveness, expressive or receptive vocabulary, or nonverbal intelligence. Conclusions The children with ASD produced less immediate echolalia in the storytelling context than in the play-based context. Immediate echolalia use was not related to social skills, vocabulary, or nonverbal IQ scores. These findings offer valuable insights into better understanding repetitive speech use in children with ASD.

Instruction Using Augmentative and Alternative Communication Supports: Description of Current Practices by Speech-Language Pathologists Who Work With Children With Autism Spectrum Disorder

2020 ◽  
Vol 29 (2) ◽  
pp. 586-596 ◽  
Author(s):  
Kaitlyn A. Clarke ◽  
Diane L. Williams
Keyword(s):  
Autism Spectrum Disorder ◽  
Augmentative And Alternative Communication ◽  
Communication Systems ◽  
Diagnostic Category ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Alternative Communication ◽  
Speech Language Pathologists ◽  
Processing Differences

Purpose The aim of this research study was to examine common practices of speech-language pathologists (SLPs) who work with children with autism spectrum disorder (ASD) with respect to whether or not SLPs consider processing differences in ASD or the effects of input during their instruction. Method Following a qualitative research method, how SLPs instruct and present augmentative and alternative communication systems to individuals with ASD, their rationale for method selection, and their perception of the efficacy of selected interventions were probed. Semistructured interviews were conducted as part of an in-depth case report with content analysis. Results Based on completed interviews, 4 primary themes were identified: (a) instructional method , (b) input provided , (c) decision-making process , and (d) perceived efficacy of treatment . Additionally, one secondary theme, training and education received , was identified . Conclusions Clinicians reported making decisions based on the needs of the child; however, they also reported making decisions based on the diagnostic category that characterized the child (i.e., ASD). The use of modeling when teaching augmentative and alternative communication to individuals with ASD emerged as a theme, but variations in the method of modeling were noted. SLPs did not report regularly considering processing differences in ASD, nor did they consider the effects of input during instruction.

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