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Front Psychiatry. 2014 Aug 4;5:53. doi: 10.3389/fpsyt.2014.00053. eCollection 2014.

Gene × Environment interactions in autism spectrum disorders: role of epigenetic mechanisms.

Author information

1
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.
2
Laboratoire Psychologie de la Perception, Université Paris Descartes, CNRS UMR 8158 , Paris , France.
3
Department of Child and Adolescent Psychiatry, AP-HP, GH Pitié-Salpétrière, CNRS FRE 2987, University Pierre and Marie Curie , Paris , France.
4
Laboratoire de Santé Publique (EA3279), School of Medicine of La Timone , Marseille , France.
5
Laboratoire Psychologie et Neurosciences de la Cognition et de l'Affectivité, Université de Rouen , Mont Saint Aignan , France.
6
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.
7
Department of Child and Adolescent Psychiatry, Landspitali University Hospital, University of Iceland , Reykjavik , Iceland.
8
Laboratoire de Génétique Médicale, Génomique Fonctionnelle, INSERM U 910, Université d'Aix-Marseille 2 , Marseille , France.
9
Department of Epidemiology and Biostatistics, EHESP School for Public Health, EA 4057 University Paris Descartes , Paris , France.
10
Service Universitaire de Psychiatrie de l'Enfant et de l'Adolescent Hospitalier Le Vinatier , Bron , France.

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.

KEYWORDS:

autistic spectrum disorders; environment; epigenetics; gene × environment interactions; multidisciplinary; multifactorial

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