Antidepressant response and the serotonin transporter gene-linked polymorphic region.
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.
Taylor
Matthew J
MJ
Department of Psychiatry, University of Oxford, United Kingdom. matthew.taylor@psych.ox.ac.uk
Sen
Srijan
S
Bhagwagar
Zubin
Z
D000483:Alleles; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012074:Remission Induction; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D000928:Antidepressive Agents; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins