title: Gene × Environment interactions in autism spectrum disorders: role of epigenetic mechanisms.
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.
authors.affiliation: Laboratoire Psychologie de la Perception, Université Paris Descartes, CNRS UMR 8158 , Paris , France ; Pôle Hospitalo-Universitaire de Psychiatrie de l'Enfant et de l'Adolescent, Université de Rennes 1, Centre Hospitalier Guillaume Régnier , Rennes , France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tordjman
authors.affiliation: Laboratoire Psychologie de la Perception, Université Paris Descartes, CNRS UMR 8158 , Paris , France.
authors.forename: Eszter
authors.initials: E
authors.lastname: Somogyi
authors.affiliation: Laboratoire Psychologie de la Perception, Université Paris Descartes, CNRS UMR 8158 , Paris , France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Coulon
authors.affiliation: Laboratoire Psychologie de la Perception, Université Paris Descartes, CNRS UMR 8158 , Paris , France ; Pôle Hospitalo-Universitaire de Psychiatrie de l'Enfant et de l'Adolescent, Université de Rennes 1, Centre Hospitalier Guillaume Régnier , Rennes , France.
authors.forename: Solenn
authors.initials: S
authors.lastname: Kermarrec
authors.affiliation: Department of Child and Adolescent Psychiatry, AP-HP, GH Pitié-Salpétrière, CNRS FRE 2987, University Pierre and Marie Curie , Paris , France.
authors.forename: David
authors.initials: D
authors.lastname: Cohen
authors.affiliation: Laboratoire de Santé Publique (EA3279), School of Medicine of La Timone , Marseille , France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bronsard
authors.affiliation: Laboratoire Psychologie de la Perception, Université Paris Descartes, CNRS UMR 8158 , Paris , France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bonnot
authors.affiliation: Laboratoire Psychologie et Neurosciences de la Cognition et de l'Affectivité, Université de Rouen , Mont Saint Aignan , France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Weismann-Arcache
authors.affiliation: Laboratoire Psychologie de la Perception, Université Paris Descartes, CNRS UMR 8158 , Paris , France ; Service Hospitalo-Universitaire de Psychiatrie de l'Enfant et de l'Adolescent, Université de Bretagne Occidentale, CHU de Brest , Brest , France.
authors.forename: Michel
authors.initials: M
authors.lastname: Botbol
authors.affiliation: Department of Child and Adolescent Psychiatry, Landspitali University Hospital, University of Iceland , Reykjavik , Iceland.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lauth
authors.affiliation: Department of Child and Adolescent Psychiatry, AP-HP, GH Pitié-Salpétrière, CNRS FRE 2987, University Pierre and Marie Curie , Paris , France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ginchat
authors.affiliation: Laboratoire de Génétique Médicale, Génomique Fonctionnelle, INSERM U 910, Université d'Aix-Marseille 2 , Marseille , France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Roubertoux
authors.affiliation: Laboratoire Psychologie de la Perception, Université Paris Descartes, CNRS UMR 8158 , Paris , France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Barburoth
authors.affiliation: Department of Epidemiology and Biostatistics, EHESP School for Public Health, EA 4057 University Paris Descartes , Paris , France.
authors.forename: Viviane
authors.initials: V
authors.lastname: Kovess
authors.affiliation: Service Universitaire de Psychiatrie de l'Enfant et de l'Adolescent Hospitalier Le Vinatier , Bron , France.
authors.forename: Marie-Maude
authors.initials: MM
authors.lastname: Geoffray
authors.affiliation: Department of Child and Adolescent Psychiatry, AP-HP, GH Pitié-Salpétrière, CNRS FRE 2987, University Pierre and Marie Curie , Paris , France.
authors.forename: Jean
authors.initials: J
authors.lastname: Xavier
keywords: autistic spectrum disorders; environment; epigenetics; gene × environment interactions; multidisciplinary; multifactorial