title: Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders.
abstract: Age at onset (AAO) of bipolar disorders (BD) could be influenced both by a repeat length polymorphism (5HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) and exposure to childhood trauma. We assessed 308 euthymic patients with BD for the AAO of their first mood episode and childhood trauma. Patients were genotyped for the 5HTTLPR (long/short variant) and the rs25531. Genotypes were classified on functional significance (LL, LS, SS). A sample of 126 Brazilian euthymic patients with BD was used for replication. In the French sample, the correlation between AAO and trauma score was observed only among 'SS' homozygotes (p = 0.002) but not among 'L' allele carriers. A history of at least one trauma decreased the AAO only in 'SS' homozygotes (p = 0.001). These results remained significant after correction using FDR. Regression models suggested an interaction between emotional neglect and 'SS' genotype on the AAO (p = 0.009) and no further interaction with other trauma subtypes. Partial replication was obtained in the Brazilian sample, showing an interaction between emotional abuse and 'LS' genotype on the AAO (p = 0.02). In conclusion, an effect of childhood trauma on AAO of BD was observed only in patients who carry a specific stress responsiveness-related SLC6A4 promoter genotype.
authors.affiliation: Inserm U955, Equipe Psychiatrie Translationelle, Créteil, 94000, France.|AP-HP, Hôpitaux Universitaires Henri Mondor, DHU PePSY, Pôle de Psychiatrie et d'Addictologie, Créteil, 94000, France.|Université Paris Est, Faculté de Médecine, Créteil, 94000, France.|Fondation Fondamental, Fondation de Coopération Scientifique, Créteil, 94000, France.
authors.forename: B
authors.initials: B
authors.lastname: Etain
authors.affiliation: Inserm U955, Equipe Psychiatrie Translationelle, Créteil, 94000, France.|Fondation Fondamental, Fondation de Coopération Scientifique, Créteil, 94000, France.
authors.forename: M
authors.initials: M
authors.lastname: Lajnef
authors.affiliation: Inserm U955, Equipe Psychiatrie Translationelle, Créteil, 94000, France.|Université Paris Est, Faculté de Médecine, Créteil, 94000, France.|Fondation Fondamental, Fondation de Coopération Scientifique, Créteil, 94000, France.
authors.forename: A
authors.initials: A
authors.lastname: Henrion
authors.affiliation: Laboratório de Psiquiatria Molecular, Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre, Programa de Pós-Graduação em Psiquiatria, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: A A
authors.initials: AA
authors.lastname: Dargél
authors.affiliation: UT Center for Molecular Psychiatry, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center, Houston, TX, USA.|Laboratório de Psiquiatria Molecular, Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Stertz
authors.affiliation: UT Center for Molecular Psychiatry, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center, Houston, TX, USA.|Laboratório de Psiquiatria Molecular, Instituto Nacional de Ciência e Tecnologia - Translacional em Medicina (INCT), Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Kapczinski
authors.affiliation: INSERM UMR-S958, Université Paris 7, Faculté de Médecine de Villemin, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Mathieu
authors.affiliation: Inserm U955, Equipe Psychiatrie Translationelle, Créteil, 94000, France.|AP-HP, Hôpitaux Universitaires Henri Mondor, DHU PePSY, Pôle de Psychiatrie et d'Addictologie, Créteil, 94000, France.|Université Paris Est, Faculté de Médecine, Créteil, 94000, France.|Fondation Fondamental, Fondation de Coopération Scientifique, Créteil, 94000, France.
authors.forename: C
authors.initials: C
authors.lastname: Henry
authors.affiliation: Pôle 3-4-7, Service de Psychiatrie Adulte, Centre Expert Trouble Bipolaire, Hôpital Charles Perrens, Bordeaux, France.|Fondation Fondamental, Fondation de Coopération Scientifique, Créteil, 94000, France.
authors.forename: S
authors.initials: S
authors.lastname: Gard
authors.affiliation: Fondation Fondamental, Fondation de Coopération Scientifique, Créteil, 94000, France.|Service de Psychiatrie et Psychologie Clinique, CHU de Nancy, Hôpitaux de Brabois, Vandoeuvre Les Nancy, Nancy, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Kahn
authors.affiliation: Inserm U955, Equipe Psychiatrie Translationelle, Créteil, 94000, France.|AP-HP, Hôpitaux Universitaires Henri Mondor, DHU PePSY, Pôle de Psychiatrie et d'Addictologie, Créteil, 94000, France.|Université Paris Est, Faculté de Médecine, Créteil, 94000, France.|Fondation Fondamental, Fondation de Coopération Scientifique, Créteil, 94000, France.
authors.forename: M
authors.initials: M
authors.lastname: Leboyer
authors.affiliation: Inserm U955, Equipe Psychiatrie Translationelle, Créteil, 94000, France.|Fondation Fondamental, Fondation de Coopération Scientifique, Créteil, 94000, France.
authors.forename: S
authors.initials: S
authors.lastname: Jamain
authors.affiliation: Fondation Fondamental, Fondation de Coopération Scientifique, Créteil, 94000, France.|APHP, Hôpital Fernand Widal, Pôle Addictologie-Toxicologie-Psychiatrie, Paris, France.|Université Paris-7, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Bellivier
mesh_terms: D000328:Adult; D017668:Age of Onset; D001714:Bipolar Disorder / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins