Antidepressant response and the serotonin transporter gene-linked polymorphic region

Biol Psychiatry. 2010 Sep 15;68(6):536-43. doi: 10.1016/j.biopsych.2010.04.034. Epub 2010 Jul 7.


Background: The serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been proposed as a predictor of antidepressant response. Insertion or deletion of a 44-base pair-long region gives rise to short "S" and long "L" forms of the promoter region, the "S" form being associated with reduced serotonin transporter expression.

Methods: A systematic review and meta-analysis was performed to clarify the effect of 5-HTTLPR on antidepressant response and remission rates. Data were obtained from 28 studies with 5408 participants. Three genotype comparisons were tested-SS versus (SL or LL), (SS or SL) versus LL, and SS versus LL.

Results: There was no statistically significant effect on antidepressant response. Compared with L carriers, there was an apparent effect of the SS genotype on remission rate (relative risk: .88; 95% confidence interval: .79-.98; p = .02). However, after trim and fill correction for missing data, the effect disappeared (relative risk: .92; 95% confidence interval: .81-1.05; p = .23), indicating that the initial significant effect was likely the result of publication bias. No significant effect on remission rate was seen for SS versus LL and SS/SL versus LL. Substantial unexplained heterogeneity of effect sizes was observed between studies, pointing to additional interacting factors contributing to an association in some cases.

Conclusions: The 5-HTTLPR biallelic short/long polymorphism by itself does not seem to usefully predict antidepressant response.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Alleles
  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / genetics
  • Genotype
  • Humans
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Remission Induction
  • Serotonin Plasma Membrane Transport Proteins / genetics*


  • Antidepressive Agents
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins