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The British Journal of Psychiatry

Year: 2009  |  Volume: 195  |  Issue: 1  |  Page No.: 30 - 38

Moderation of antidepressant response by the serotonin transporter gene

P Huezo Diaz, R Uher, R Smith, M Rietschel, N Henigsberg, A Marusic, O Mors, W Maier, J Hauser, D Souery, A Placentino, A Zobel, E. R Larsen, P. M Czerski, B Gupta, F Hoda, N Perroud, A Farmer, I Craig, K. J Aitchison and P. McGuffin

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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