The 5‐HTTLPR s/s genotype at the serotonin transporter gene (SLC6A4) increases the risk for depression in a large cohort of primary care attendees: The PREDICT‐gene study

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Abstract
Previous reports and meta‐analyses have yielded inconclusive results as to whether the s/s genotype at the 5‐HTTLPR serotonin transporter polymorphism confers increased risk for depression. We tested the association between s/s genotype and depression in a large cohort (n = 737) of Spanish primary care consecutive attendees participating in a European study on predictors for depression in primary care (PREDICT study). Participants were administered the Composite International Diagnostic Interview (CIDI) depression subscale allowing diagnoses using ICD‐10 criteria for depressive episodes. Participants were genotyped to establish 5HTTLPR genotype. Both univariable and multivariable associations between the s/s genotype and depression were tested twice using two different depressive outcomes (ICD‐10 depressive episode and ICD‐10 severe depressive episode). We found an association between the s/s genotype and both depressive outcomes that was independent of age, sex, family history of psychological problems among first degree relatives and presence of comorbid generalized anxiety disorder. When comparing s/s homozygous versus the rest, the adjusted odds ratio for any ICD‐10 depressive episode and for severe ICD‐10 depressive episode were 1.50 (95% CI: 1.0–2.2; P = 0.045) and 1.79 (95% CI: 1.1–2.8; P = 0.016), respectively. The association was significantly stronger with increasing severity of depression (χ2 for linear association=6.1; P = 0.013) suggesting a dose‐dependent relationship. Our results are consistent with previous reports suggesting a small but independent effect by the s/s 5‐HTTLPR genotype increasing the risk for depression.