BDNF and NTRK2 polymorphisms and antidepressant treatment outcome

Background: Data from clinical studies and results from animal models suggest a major involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment. Methods: We performed a pharmacogenetic study in 398 at least moderately severe depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) study. We tested for single marker association of 82 SNPs tagging the BDNF and NTRK2 gene regions with antidepressant treatment response. In an attempt for replicating the results, we genotyped all nominally significant associated SNPs of the discovery analysis in additional 249 patients of the MARS study and 247 depressed inpatients from an independent sample recruited in Münster, Germany. Results: We identified several SNPs of the BDNF and NTRK2 gene that were significantly associated with antidepressant treatment response. We could partly replicate these associations in a meta-analysis of all samples (total of 894 patients), withstanding correction for multiple testing and adjustment for confounding variables. Conclusions: These findings provide further substantiation for a possible involvement of genetic variations in the BDNF and NTRK2 gene in the antidepressant treatment response.