Moderation of antidepressant response by the serotonin transporter gene

• Published in: British journal of psychiatry Vol. 195; no. 1; pp. 30 - 38
• Main Authors: Huezo-Diaz, Patricia, Uher, Rudolf, Smith, Rebecca, Rietschel, Marcella, Henigsberg, Neven, Marušiˇ, 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
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.07.2009; RCP
• Subjects: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Alleles; Antidepressant drugs; Antidepressive Agents, Tricyclic - therapeutic use; Citalopram - therapeutic use; Depression; Depressive Disorder - drug therapy; Depressive Disorder - genetics; extra; Female; Gender; Genes; Genotype; Humans; Male; Middle Aged; Nortriptyline - therapeutic use; Polymorphism, Single Nucleotide - genetics; Serotonin; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin reuptake inhibitors; Serotonin Uptake Inhibitors - therapeutic use; Sex Factors; Young Adult
• ISSN: 0007-1250; 1472-1465
• DOI: 10.1192/bjp.bp.108.062521

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.