title: Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders.
abstract: OBJECTIVE
  This review presents a rationale and evidence for contributions of environmental influences and environmentally vulnerable physiology to autism spectrum disorders (ASDs).
  
  
  RESULTS
  Recent studies suggest a substantial increase in ASD prevalence above earlier Centers for Disease Control figures of one in 150, only partly explicable by data artifacts, underscoring the possibility of environmental contributors to increased prevalence. Some gene variants in ASD confer altered vulnerability to environmental stressors and exposures. De-novo mutations and advanced parental age as a risk factor for ASD also suggest a role for environment. Systemic and central nervous system pathophysiology, including oxidative stress, neuroinflammation, and mitochondrial dysfunction can be consistent with a role for environmental influence (e.g. from air pollution, organophosphates, heavy metals) in ASD, and some of the underlying biochemical disturbances (such as abnormalities in glutathione, a critical antioxidant and detoxifier) can be reversed by targeted nutritional interventions. Dietary factors and food contaminants may contribute risk. Improvement and loss of diagnosis in some with ASD suggest brain circuitry amenable to environmental modulation.
  
  
  CONCLUSIONS
  Prevalence, genetic, exposure, and pathophysiological evidence all suggest a role for environmental factors in the inception and lifelong modulation of ASD. This supports the need for seeking targets for early and ongoing medical prevention and treatment of ASD.
authors.affiliation: TRANSCEND Research Program, Pediatric Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, USA. mherbert1@partners.org
authors.forename: Martha R
authors.initials: MR
authors.lastname: Herbert
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology*; D004777:Environment; D020022:Genetic Predisposition to Disease; D006801:Humans; D008959:Models, Neurological