title: An integrative review of methylation at the serotonin transporter gene and its dialogue with environmental risk factors, psychopathology and 5-HTTLPR.
abstract: Gene-environment (G×E) interactions have largely been regarded as the root of many complex disorders, including several psychiatric disorders. In this regard, it has been hypothesized that epigenetic mechanisms may be the main mediators of such interactions. Of particular interest is the previously described interaction between psychosocial stress and genetic variability of the serotonin transporter gene (SLC6A4) in its polymorphic region 5-HTTLPR. Here we review the literature concerning SLC6A4 methylation in association with environmental, clinical or genetic variables. While SLC6A4 hypermethylation has typically been described to be independently associated with both early life stress and depressive disorders, only a few papers address whether methylation could mediate the interaction between stress and 5-HTTLPR in predicting psychopathological risk. Nevertheless, research preliminarily indicates a methylation-driven increased vulnerability of carriers of the short allele of 5-HTTLPR to psychiatric disorders when exposed to early stress or soon after exposure to stress.
authors.affiliation: Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain.
authors.forename: H
authors.initials: H
authors.lastname: Palma-Gudiel
authors.affiliation: Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain. Electronic address: lfananas@ub.edu.
authors.forename: L
authors.initials: L
authors.lastname: Fañanás
mesh_terms: D019175:DNA Methylation; D005838:Genotype; D006801:Humans; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013315:Stress, Psychological
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: 5-HTTLPR; DNA methylation; G×E interaction; SLC6A4 gene