Moderation of antidepressant response by the serotonin transporter gene by 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 in The British journal of psychiatry : the journal of mental science (2009). PubMed

Abstract

BACKGROUND: 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. AIMS: To test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor). METHOD: 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. RESULTS: 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. CONCLUSIONS: 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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