Annual Research Review: The role of the environment in the developmental psychopathology of autism spectrum condition

Abstract

Background Although autism spectrum condition (ASC) is strongly genetic in origin, accumulating evidence points to the critical roles of various environmental influences on its emergence and subsequent developmental course. Methods A developmental psychopathology framework was used to synthesise literature on environmental factors associated with the onset and course of ASC (based on a systematic search of the literature using PubMed, PsychInfo and Google Scholar databases). Particular emphasis was placed on gene-environment interplay, including gene-environment interaction (G × E) and gene-environment correlation (rGE). Results Before conception, advanced paternal and maternal ages may independently enhance offspring risk for ASC. Exogenous prenatal risks are evident (e.g. valproate and toxic chemicals) or possible (e.g. selective serotonin reuptake inhibitors), and processes endogenous to the materno-foeto-placental unit (e.g. maternal diabetes, enhanced steroidogenic activities and maternal immune activation) likely heighten offspring vulnerability to ASC. Folate intake is a prenatal protective factor, with a particular window of action around 4 weeks preconception and during the first trimester. These prenatal risks and protective mechanisms appear to involve G × E and potentially rGE. A variety of perinatal risks are related to offspring ASC risk, possibly reflecting rGE. Postnatal social factors (e.g. caregiver-infant interaction, severe early deprivation) during the first years of life may operate through rGE to influence the likelihood of manifesting a full ASC phenotype from a 'prodromal' phase (a proposal distinct to the discredited and harmful 'refrigerator mother hypothesis'); and later postnatal risks, after the full manifestation of ASC, shape life span development through transactions mediated by rGE. There is no evidence that vaccination is a postnatal risk for ASC. Conclusions Future investigations should consider the specificity of risks for ASC versus other atypical neurodevelopmental trajectories, timing of risk and protective mechanisms, animal model systems to study mechanisms underlying gene-environment interplay, large-sample genome-envirome designs to address G × E and longitudinal studies to elucidate how rGE plays out over time. Clinical and public health implications are discussed. Although autism spectrum condition (ASC) is highly genetic, environmental factors play a role in its emergence and development across the life span. Susceptibility to some environmental risks for ASC (e.g. traffic-related air pollution), may be moderated by genotype. Other environmental risks, (e.g. perinatal complications associated with hypoxia) may be part of gene-environment correlations, whereby genetic risk increases the probability of environmental exposure, which in turn shapes the emergence of the ASC phenotype. Based on a developmental psychopathology synthesis of the research literature, this review shows that although genes are highly influential on the aetiology and development of ASC, environmental interventions have the potential to reduce susceptibility to the condition, alleviate symptoms and modify the developmental course. The clinical and public health implications of the findings are discussed, but one clear finding is that there is no evidence that vaccination is a postnatal risk for ASC. Further work on the study of environmental risk and protection will help elucidate aetiological and phenotypic heterogeneity, and will promote the discovery of mechanisms underpinning the emergence and development of ASC, and the recommendations for various study designs are outlined. Read the Commentary on this article at doi: 10.1111/jcpp.12527