The influence of 5-HTTLPR and STin2 polymorphisms in the serotonin transporter gene on treatment effect of selective serotonin reuptake inhibitors in depressive patients.
BACKGROUND
Serotonin transporter gene (SLC6A4) variations have been proposed as an explanation for interindividual differences in selective serotonin reuptake inhibitors (SSRIs) effects. Quantitative assessment of genetic influences is necessary to evaluate whether genetic testing before antidepressant prescription would lead to earlier treatment effects. This study evaluates the influence of two polymorphisms (5-HTTLPR and STin2) on SSRI treatment outcome in depression.


METHODS
We included 50 SSRI nonresponders (cases) and 164 referents meeting Diagnostic and Statistical Manual Of Mental Disorder-IV criteria for major depression and using an SSRI for at least 6 weeks. Blood samples or buccal swabs were gathered to determine 5-HTTLPR (N=48 for cases and 161 for referents) and STin2 (N=50 for cases and 162 for referents) genotypes. The association between genotype and SSRI response was assessed by use of logistic regression.


RESULTS
Patients with the 5-HTTLPR s-allele had a nonsignificantly increased risk of SSRI nonresponse; odds ratio (OR) 1.60, 95% confidence interval (CI) 0.66-3.89. 5-HTTLPR effects were strongest in female patients (OR 3.54, 95% CI 1.05-11.92), and for male patients 5-HTTLPR seemed to have no effect (OR 0.29, 95% CI 0.04-2.34). An age-dependent effect of 5-HTTLPR was observed; patients under 44 years of age had an increased nonresponse risk (OR 9.34, 95% CI 1.41-61.98). STin2 genotype had no clear influence on treatment outcome.


CONCLUSIONS
Our findings indicate that women with the 5-HTTLPR s-allele have a less favorable response to SSRI treatment. To our knowledge, this is the first time that a gender-dependent influence of 5-HTTLPR is reported. More research is needed, particularly in subgroups of patients, before implementation of genetic testing can be recommended.
Smits
Kim M
KM
Department of Epidemiology, Maastricht University, Maastricht, The Netherlands. kim.smits@epid.unimaas.nl
Smits
Luc J M
LJ
Peeters
Frenk P M L
FP
Schouten
Jan S A G
JS
Janssen
Rob G J H
RG
Smeets
Hubert J M
HJ
van Os
Jim
J
Prins
Martin H
MH
D000328:Adult; D000483:Alleles; D016001:Confidence Intervals; D003863:Depression / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human