1. ¹Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
2. ²Department of Psychiatry, Ninewells Hospital and Medical School, Dundee, UK
3. ³Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK
4. ⁴Department of Mental Health, Institute of Medical Sciences, Forresterhill Hospital, Aberdeen, UK

Correspondence: Professor CR Wolf, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK. E-mail: c.r.wolf@dundee.ac.uk

Received 25 April 2006; Revised 18 January 2007; Accepted 26 November 2007; Published online 5 February 2008.

Abstract

The majority of antidepressant drugs act by increasing synaptic serotonin levels in the brain. Genetic variation in serotonin-related genes may therefore influence antidepressant efficacy. In this study, nine polymorphisms in four serotonin receptor genes (HTR1B, HTR2A, HTR5A and HTR6) and the serotonin transporter gene (SLC6A4) were analysed to investigate their influence on antidepressant response in a well-characterized unipolar depressive population (n=166) following a protocolized treatment regimen. 5-HTTLPR short-allele homozygotes were significantly associated with both remission (odds ratios (OR)=4.00, P=0.04) and response (OR=5.06, P=0.02) following second switch treatment, with a similar trend observed following initial treatment and paroxetine therapy. Following initial treatment, unipolar patients homozygous for the SLC6A4 intron 2 repeat polymorphism were significantly associated with lack of remission (OR=0.38, P=0.02) and lack of response (OR=0.42, P=0.01). Additionally, the HTR2A C₁₃₅₄T polymorphism showed an association with remission (OR=7.50, P=0.002) and response (OR=5.25, P=0.01) following paroxetine therapy. These results suggest that genetically determined variation in serotonin receptor genes makes a significant contribution to the efficacy of commonly prescribed antidepressant drugs.