title: 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.
authors.affiliation: Research Department of Clinical, Educational and Health Psychology, University College London, London, UK.
authors.forename: William
authors.initials: W
authors.lastname: Mandy
authors.affiliation: Child and Youth Mental Health Collaborative at The Centre for Addiction and Mental Health and The Hospital for Sick Children, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.|Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Lai
mesh_terms: D000067877:Autism Spectrum Disorder / Q000139:chemically induced / Q000209:etiology*; D002648:Child; D002657:Child Development; D004777:Environment; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008297:Male; D008423:Maternal Age; D010331:Paternal Age; D012307:Risk Factors
keywords: Asperger's syndrome; Autism spectrum condition; autism; autism spectrum disorder; developmental psychopathology; environment; genetics