1. Moderation of antidepressant response by the serotonin transporter gene
- Author
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Neven Henigsberg, Bhanu Gupta, Robert Peter Smith, Andrej Marusic, F. Hoda, Marcella Rietschel, Anne Farmer, Ole Mors, Joanna Hauser, Rudolf Uher, Piotr M. Czerski, Astrid Zobel, Ian W. Craig, Daniel Souery, Anna Placentino, Wolfgang Maier, Nader Perroud, Peter McGuffin, Erik Roj Larsen, P Huezo-Diaz, and Katherine J. Aitchison
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Genotype ,Nortriptyline ,Antidepressive Agents, Tricyclic ,Citalopram ,Pharmacology ,Polymorphism, Single Nucleotide ,Young Adult ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,mental disorders ,antidepressant response ,serotonin transport gene ,medicine ,Humans ,Escitalopram ,030212 general & internal medicine ,Serotonin Uptake Inhibitors ,Psychiatry ,Alleles ,Serotonin transporter ,Aged ,Aged, 80 and over ,Serotonin Plasma Membrane Transport Proteins ,Depressive Disorder ,biology ,Age Factors ,Middle Aged ,030227 psychiatry ,Psychiatry and Mental health ,biology.protein ,behavior and behavior mechanisms ,Antidepressant ,Female ,Psychology ,Reuptake inhibitor ,Selective Serotonin Reuptake Inhibitors ,psychological phenomena and processes ,medicine.drug - Abstract
BackgroundThere have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR is modulated by gender, age and other variants in the serotonin transporter gene.AimsTo test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor).MethodThe 5-HTTLPR and 13 additional markers across the serotonin transporter gene were genotyped in 795 adults with moderate-to-severe depression treated with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for Depression (GENDEP) project.ResultsThe 5-HTTLPR moderated the response to escitalopram, with long-allele carriers improving more than short-allele homozygotes. A significant three-way interaction between 5-HTTLPR, drug and gender indicated that the effect was concentrated in males treated with escitalopram. The single-nucleotide polymorphism rs2020933 also influenced outcome.ConclusionsThe effect of 5-HTTLPR on antidepressant response is SSRI specific conditional on gender and modulated by another polymorphism at the 5' end of the serotonin transporter gene.
- Published
- 2009
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