Autism and the Environment: Challenges and Opportunities for Advancing the Science

In response to the urgent public health significance of autism spectrum disorder (ASD), research efforts in this field have increased markedly over the past five years. Important advances have been made in some areas, including autism surveillance and genetics, yet the role of the environment remains poorly understood.  There is an urgent need for more environmental health scientists to bring their expertise to bear on this problem. Clues emerging from clinical and genetic studies in autism point to perturbation of specific pathways (e.g., immune, synaptic homeostasis), but more work is needed to translate these findings to animal models and model systems. Few exposures have been studied with sufficient rigor and a systematic effort to assess autism risk from the universe of potential exposures is past due. Traditional epidemiologic clues that derive from variation in time and space are elusive in the case of ASD because secular changes in awareness, diagnosis and service provision can obscure real increases in prevalence.  Improved infrastructure is needed to support reliable prevalence estimation in many other countries and enable comparison of prevalence in populations with varying exposures. Most of the available evidence supports prenatal origins of ASD, yet measuring exposures during pregnancy requires costly prospective pregnancy cohorts or careful retrospective assessments in other study designs.  The collection of environmental data, when it occurs, is not standardized in ways that allow pooling across studies. This is in contrast to the autism genetics field, where combining of data sets is accomplished routinely. Rare structural variants (copy number variation) have been identified as playing key roles in autism causation, yet how and whether environmental exposures contribute to CNVs are unknown.  Results from ASD genome wide association studies (GWAS) of normal genetic variation have been inconclusive. This may reflect a failure to consider gene environment interplay. An appreciation of epigenetics as an interface between environment and genes is emerging, yet is only slowly being applied to address questions of autism etiology. In summary, there are many exciting translational challenges in autism research that could benefit from greater involvement of environmental health scientists.