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.
Conclusion: 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.