1. Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project
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Bhagwati P. Gupta, Joanna Hauser, Anna Placentino, P Huezo-Diaz, Marcella Rietschel, Daniel Souery, Erik Roj Larsen, Katherine J. Aitchison, F. Hoda, Astrid Zobel, Rudolf Uher, Peter McGuffin, Ian W. Craig, Wolfgang Maier, Dejan Kozel, Anne Farmer, Ole Mors, Sara R. Jaffee, Monika Dmitrzak-Weglarz, Neven Henigsberg, Robert Keers, and Rebecca G. Smith
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Adult ,Male ,Adolescent ,Genotype ,medicine.drug_class ,Drug Resistance ,Tricyclic antidepressant ,Nortriptyline ,Citalopram ,Pharmacology ,Bioinformatics ,Life Change Events ,Young Adult ,depression ,antidepressive agents ,pharmacogenetics ,serotonin transporter ,gene–environment interaction ,stressful life events ,mental disorders ,Genetics ,medicine ,Humans ,Multicenter Studies as Topic ,Escitalopram ,Serotonin Uptake Inhibitors ,Serotonin transporter ,Aged ,Randomized Controlled Trials as Topic ,Serotonin Plasma Membrane Transport Proteins ,Depressive Disorder, Major ,Polymorphism, Genetic ,biology ,business.industry ,Middle Aged ,Antidepressive Agents ,Pharmacogenomics ,biology.protein ,Molecular Medicine ,Female ,business ,Selective Serotonin Reuptake Inhibitors ,medicine.drug - Abstract
Udgivelsesdato: 2010-Mar-9 There is substantial inter-individual variation in response to antidepressants, and genetic variation may, in part, explain these differences. For example, there is evidence to suggest that variation in the serotonin transporter gene (SLC6A4) predicts response to selective serotonin reuptake inhibitors (SSRIs). Environmental factors such as the occurrence of stressful life events before treatment may also be important. One prior report suggests that both factors interact in predicting response to antidepressants. GENDEP, a prospective part-randomized pharmacogenomics trial, collected longitudinal data on the outcome of 811 patients with major depression undergoing treatment with either an SSRI (escitalopram) or a tricyclic antidepressant (nortriptyline). Life events experienced over 6 months preceding treatment were measured using a List of Threatening Experiences Questionnaire, and several polymorphisms in the serotonin transporter gene (SLC6A4) have been genotyped including the serotonin transporter-linked polymorphic region (5-HTTLPR). Stressful life events were shown to predict a significantly better response to escitalopram but had no effect on response to nortriptyline. Variation in the 5-HTTLPR and another polymorphism in the gene, STin4, significantly modified these effects. Gene-environment interactions including life events may therefore be important not only in the aetiology of depression, but also in predicting response to antidepressant medication.The Pharmacogenomics Journal advance online publication, 9 March 2010; doi:10.1038/tpj.2010.14.
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- 2010
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