AUTHOR=Tordjman Sylvie , Somogyi Eszter , Coulon Nathalie , Kermarrec Solenn , Cohen David , Bronsard Guillaume , Bonnot Olivier , Weismann-Arcache Catherine , Botbol Michel , Lauth Bertrand , Ginchat Vincent , Roubertoux Pierre , Barburoth Marianne , Kovess Viviane , Geoffray Marie-Maude , Xavier Jean TITLE=Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms JOURNAL=Frontiers in Psychiatry VOLUME=5 YEAR=2014 URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2014.00053 DOI=10.3389/fpsyt.2014.00053 ISSN=1664-0640 ABSTRACT=

Several studies support currently the hypothesis that autism etiology is based on a polygenic and epistatic model. However, despite advances in epidemiological, molecular and clinical genetics, the genetic risk factors remain difficult to identify, with the exception of a few chromosomal disorders and several single gene disorders associated with an increased risk for autism. Furthermore, several studies suggest a role of environmental factors in autism spectrum disorders (ASD). First, arguments for a genetic contribution to autism, based on updated family and twin studies, are examined. Second, a review of possible prenatal, perinatal, and postnatal environmental risk factors for ASD are presented. Then, the hypotheses are discussed concerning the underlying mechanisms related to a role of environmental factors in the development of ASD in association with genetic factors. In particular, epigenetics as a candidate biological mechanism for gene × environment interactions is considered and the possible role of epigenetic mechanisms reported in genetic disorders associated with ASD is discussed. Furthermore, the example of in utero exposure to valproate provides a good illustration of epigenetic mechanisms involved in ASD and innovative therapeutic strategies. Epigenetic remodeling by environmental factors opens new perspectives for a better understanding, prevention, and early therapeutic intervention of ASD.