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Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy

The Pharmacogenomics Journal volume 9, pages 61–70 (2009)Cite this article

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.

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Acknowledgements

We acknowledge financial support from the Medical Research Council (Grant numbers G0000271 and G0000281).

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Authors and Affiliations

  1. Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK

    M J V Wilkie, G Smith & C R Wolf

  2. Department of Psychiatry, Ninewells Hospital and Medical School, Dundee, UK

    R K Day & K Matthews

  3. Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK

    D Smith & D Blackwood

  4. Department of Mental Health, Institute of Medical Sciences, Forresterhill Hospital, Aberdeen, UK

    I C Reid

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  1. M J V Wilkie
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Correspondence to C R Wolf.

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Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj)

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Wilkie, M., Smith, G., Day, R. et al. Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy. Pharmacogenomics J 9, 61–70 (2009). https://doi.org/10.1038/sj.tpj.6500491

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  • DOI: https://doi.org/10.1038/sj.tpj.6500491

Keywords

  • serotonin
  • depression
  • antidepressants
  • treatment response
  • polymorphism
  • pharmacogenetics

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