title: Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project.
abstract: 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.
authors.affiliation: MRC SGDP, Institute of Psychiatry, King's College London, London, UK. Robert.Keers@kcl.ac.uk
authors.forename: R
authors.initials: R
authors.lastname: Keers
authors.forename: R
authors.initials: R
authors.lastname: Uher
authors.forename: P
authors.initials: P
authors.lastname: Huezo-Diaz
authors.forename: R
authors.initials: R
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Jaffee
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.forename: N
authors.initials: N
authors.lastname: Henigsberg
authors.forename: D
authors.initials: D
authors.lastname: Kozel
authors.forename: O
authors.initials: O
authors.lastname: Mors
authors.forename: W
authors.initials: W
authors.lastname: Maier
authors.forename: A
authors.initials: A
authors.lastname: Zobel
authors.forename: J
authors.initials: J
authors.lastname: Hauser
authors.forename: D
authors.initials: D
authors.lastname: Souery
authors.forename: A
authors.initials: A
authors.lastname: Placentino
authors.forename: E R
authors.initials: ER
authors.lastname: Larsen
authors.forename: M
authors.initials: M
authors.lastname: Dmitrzak-Weglarz
authors.forename: B
authors.initials: B
authors.lastname: Gupta
authors.forename: F
authors.initials: F
authors.lastname: Hoda
authors.forename: I
authors.initials: I
authors.lastname: Craig
authors.forename: P
authors.initials: P
authors.lastname: McGuffin
authors.forename: A E
authors.initials: AE
authors.lastname: Farmer
authors.forename: K J
authors.initials: KJ
authors.lastname: Aitchison
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage*; D015283:Citalopram / Q000008:administration & dosage; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009661:Nortriptyline / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D016032:Randomized Controlled Trials as Topic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D009661:Nortriptyline; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human