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Cell Mol Life Sci. 2019 Apr;76(7):1275-1297. doi: 10.1007/s00018-018-2988-4. Epub 2018 Dec 20.

The contribution of environmental exposure to the etiology of autism spectrum disorder.

Author information

1
Department of Women's and Children's Health, Karolinska Institutet & Child and Adolescent Psychiatry, Stockholm Health Care Services, Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Stockholm County Council, Stockholm, Sweden. sven.bolte@ki.se.
2
Curtin Autism Research Group, School of Occupational Therapy, Social Work and Speech Pathology, Curtin University, Perth, WA, Australia. sven.bolte@ki.se.
3
Curtin Autism Research Group, School of Occupational Therapy, Social Work and Speech Pathology, Curtin University, Perth, WA, Australia.
4
Department of Women's and Children's Health, Karolinska Institutet & Child and Adolescent Psychiatry, Stockholm Health Care Services, Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Stockholm County Council, Stockholm, Sweden.
5
Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
6
iDN-interdisciplinary Developmental Neuroscience, Department of Phoniatrics, Medical University of Graz, Graz, Austria.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition of heterogeneous etiology. While it is widely recognized that genetic and environmental factors and their interactions contribute to autism phenotypes, their precise causal mechanisms remain poorly understood. This article reviews our current understanding of environmental risk factors of ASD and their presumed adverse physiological mechanisms. It comprehensively maps the significance of parental age, teratogenic compounds, perinatal risks, medication, smoking and alcohol use, nutrition, vaccination, toxic exposures, as well as the role of extreme psychosocial factors. Further, we consider the role of potential protective factors such as folate and fatty acid intake. Evidence indicates an increased offspring vulnerability to ASD through advanced maternal and paternal age, valproate intake, toxic chemical exposure, maternal diabetes, enhanced steroidogenic activity, immune activation, and possibly altered zinc-copper cycles and treatment with selective serotonin reuptake inhibitors. Epidemiological studies demonstrate no evidence for vaccination posing an autism risk. It is concluded that future research needs to consider categorical autism, broader autism phenotypes, as well as autistic traits, and examine more homogenous autism variants by subgroup stratification. Our understanding of autism etiology could be advanced by research aimed at disentangling the causal and non-causal environmental effects, both founding and moderating, and gene-environment interplay using twin studies, longitudinal and experimental designs. The specificity of many environmental risks for ASD remains unknown and control of multiple confounders has been limited. Further understanding of the critical windows of neurodevelopmental vulnerability and investigating the fit of multiple hit and cumulative risk models are likely promising approaches in enhancing the understanding of role of environmental factors in the etiology of ASD.

KEYWORDS:

Autism; Environment; Etiology; Genes; Neurodevelopmental disorders; Twins

PMID:
30570672
PMCID:
PMC6420889
DOI:
10.1007/s00018-018-2988-4
[Indexed for MEDLINE]
Free PMC Article

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