title: Risk factors in autism: Thinking outside the brain.
abstract: Autism spectrum disorders (ASD) are complex neurodevelopmental conditions that have been rising markedly in prevalence for the past 30 years, now thought to affect 1 in 68 in the United States. This has prompted the search for possible explanations, and has even resulted in some controversy regarding the "true" prevalence of autism. ASD are influenced by a variety of genetic, environmental, and possibly immunological factors that act during critical periods to alter key developmental processes. This can affect multiple systems and manifests as the social and behavioral deficits that define these disorders. The interaction of environmental exposures in the context of an individual's genetic susceptibilities manifests differently in each case, leading to heterogeneous phenotypes and varied comorbid symptoms within the disorder. This has also made it very difficult to elucidate underlying genes and exposure profiles, but progress is being made in this area. Some pharmaceutical drugs, toxicants, and metabolic and nutritional factors have been identified in epidemiological studies as increasing autism risk, especially during the prenatal period. Immunologic risk factors, including maternal infection during pregnancy, autoantibodies to fetal brain proteins, and familial autoimmune disease, have consistently been observed across multiple studies, as have immune abnormalities in individuals with ASD. Mechanistic research using animal models and patient-derived stem cells will help researchers to understand the complex etiology of these neurodevelopmental disorders, which will lead to more effective therapies and preventative strategies. Proposed therapies that need more investigation include special diets, probiotics, immune modulation, oxytocin, and personalized pharmacogenomic targets. The ongoing search for biomarkers and better treatments will result in earlier identification of ASD and provide much needed help and relief for afflicted families.
authors.affiliation: Division of Rheumatology, Allergy, and Clinical Immunology, Department of Internal Medicine, University of California, Davis, 451 E Health Sciences Drive, Suite 6510 GBSF, Davis, CA 95616, USA; NIEHS Center for Children's Environmental Health, University of California, Davis, USA; The M.I.N.D. Institute, University of California, Davis, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Matelski
authors.affiliation: Division of Rheumatology, Allergy, and Clinical Immunology, Department of Internal Medicine, University of California, Davis, 451 E Health Sciences Drive, Suite 6510 GBSF, Davis, CA 95616, USA; NIEHS Center for Children's Environmental Health, University of California, Davis, USA; The M.I.N.D. Institute, University of California, Davis, USA. Electronic address: javandewater@ucdavis.edu.
authors.forename: Judy
authors.initials: J
authors.lastname: Van de Water
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000453:epidemiology / Q000209:etiology*; D015551:Autoimmunity; D001921:Brain / Q000378:metabolism*; D004198:Disease Susceptibility / Q000276:immunology; D004777:Environment; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D015995:Prevalence; D012307:Risk Factors
keywords: Autism; Gene-environment; Immune dysfunction; Maternal factors; Risk