Role of environmental factors and epigenetics in autism spectrum disorders

doi:10.1016/bs.pmbts.2020.05.002

Progress in Molecular Biology and Translational Science

Volume 173, 2020, Pages 35-60

https://doi.org/10.1016/bs.pmbts.2020.05.002 Get rights and content

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder thought to be caused by predisposing high-risk genes that may be altered during the early development by environmental factors. The impact of maternal challenges during pregnancy on the prevalence of ASD has been widely studied in clinical and animal studies. Here, we review some clinical and pre-clinical evidence that links environmental factors (i.e., infection, air pollution, pesticides, valproic acid and folic acid) and the risk of ASD. Additionally, certain prenatal environmental challenges such as the valproate and folate prenatal exposures allow us to study mechanisms possibly linked to the etiology of ASD, for instance the epigenetic processes. These mechanistic pathways are also presented and discussed in this chapter.

Section snippets

Context: Genetics yes, but not only

According to the Centers for Disease Control and Prevention (CDC), since 2000, Autism Spectrum Disorders (ASD) incidence has increased from 1/150 births to ~ 1/68.¹ Current (2017) CDC data shows US ASD prevalence at ~ 1.47%, and demonstrates that all ethnic, racial, and socio-economic groups are affected by ASD.¹ If children with ASD are identified early and provided with appropriate intervention, core social symptoms characterized by a phenotype of serious social/communication deficits, and

Maternal stress during pregnancy and ASD

Numerous types of maternal challenges during pregnancy have been linked to increased risk of ASD from a variety of neurotoxins and pollutants such as pesticides and insecticides,⁵⁸ viral and bacterial infections,⁵⁹ exposure to metals such as mercury and lead,⁵⁹ to low level of electromagnetic radiations.⁶⁰ Though these exposures have not directly been linked to specific fetal development time points, exposure to these pollutants and maternal stressors during pregnancy has been linked to ASD

Environmental animal models for ASD

Mammalian development follows a pattern of fertilization, embryonic development, and fetal growth such that researchers have been able to design studies examining subtle neurodevelopmental effects, such as behavioral disorders, by subjecting pregnant animals such as rats and mice to chemicals or other exposures known to induce brain defects. By timing these exposures so that they occur on specific prenatal days, it is possible to measure their developmental effects, and study both immediate and

Epigenetics mechanisms: The examples of valproate and folate

Stress during pregnancy could impact the brain development of the children through several mechanisms. For instance, a functional immune system is crucial for the early brain development and maternal immune activation could be a common pathway to environmental challenges such as infections and social stress in pregnancy. Another pathway which could be common to various stressors such as pesticides prenatal exposure are epigenetic processes. Here we will describe how environmental challenges,

Conclusion

There are several challenges during pregnancy linked to the prevalence of ASD and their study could lead us to better understand the complexities and commonalities of pathways in the etiology of ASD. One common aspect developed in this manuscript is the direct and indirect links to epigenetic alterations, but the maternal and fetal neuroimmune responses to a variety of stressors during pregnancy is another crucial domain of research which remains to be explored further. Finally, the time window

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Chapter Two - Role of environmental factors and epigenetics in autism spectrum disorders

Abstract

Section snippets

Context: Genetics yes, but not only

Maternal stress during pregnancy and ASD

Environmental animal models for ASD

Epigenetics mechanisms: The examples of valproate and folate

Conclusion

Psychiatry (Abingdon)

Curr Opin Genet Dev

Lancet Neurol

Cell

Cell

Neurosci Biobehav Rev

Int J Dev Neurosci

Neuron

Brain Res

Mol Autism

Neuroimage

Psychiatry Res

Neurotoxicology

Reprod Toxicol

Med Hypotheses

J Autoimmun

J Pediatr

Brain Behav Immun

Exp Neurol

Curr Probl Pediatr Adolesc Health Care

Seizure

Neurotoxicol Teratol

Am J Clin Nutr

Gut dysbiosis and neurobehavioral alterations in rats exposed to silver nanoparticles

Sci Rep

The epidemiology of autism spectrum disorders

Annu Rev Public Health

Autism Spectrum Disorder (ASD)

Autism as a strongly genetic disorder: evidence from a British twin study

Psychol Med

Common genetic variants, acting additively, are a major source of risk for autism

Mol Autism

A genome-wide survey of transgenerational genetic effects in autism

PLoS One

Epigenetics of autism spectrum disorder

Adv Exp Med Biol

Etiology in psychiatry: embracing the reality of poly-gene-environmental causation of mental illness

World Psychiatry

Neurodevelopmental disorders and environmental toxicants: epigenetics as an underlying mechanism

Int J Genomics

DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders?

Environ Epigenetics

Environmental toxicants and autism spectrum disorders: a systematic review

Transl Psychiatry

Annual research review: the role of the environment in the developmental psychopathology of autism spectrum condition

J Child Psychol Psychiatry

The use of genetic epidemiology to guide classification in child and adult psychopathology

Int Rev Psychiatry

A twin study of heritable and shared environmental contributions to autism

J Autism Dev Disord

SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs)

Mol Autism

Advancing the understanding of autism disease mechanisms through genetics

Nat Med

From the genetic architecture to synaptic plasticity in autism spectrum disorder

Nat Rev Neurosci

Autism and maternally derived aberrations of chromosome 15q

Am J Med Genet

Association of Genetic and Environmental Factors with autism in a 5-country cohort

JAMA Psychiatry

Medical history of discordant twins and environmental etiologies of autism

Transl Psychiatry

Genetic and environmental factors of schizophrenia and autism spectrum disorder: insights from twin studies

J Neural Transm

Familial confounding on the ability to read minds: a co-twin control study

Autism

Genetic influences and infantile autism

Nature

A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden

J Child Psychol Psychiatry

The genetics of autism spectrum disorders and related neuropsychiatric disorders in childhood

Am J Psychiatry