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Huezo-Diaz, Patricia; Uher, Rudolf; Smith, Rebecca; Rietschel, Marcella; Henigsberg, Neven; Marusic, Andrej; Mors, Ole; Maier, Wolfgang; Hauser, Joanna; Souery, Daniel; Placentino, Anna; Zobel, Astrid; Larsen, Erik Roj; Czerski, Piotr M; Gupta, Bhanu; Hoda, Farzana; Perroud, Nader; Farmer, Anne; Craig, Ian; Aitchison, Katherine J; McGuffin, Peter
British journal of psychiatry 195, Issue: 1Journal Article
There 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. To test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor). The 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. The 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. The 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.
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