Possible Associations of <i>NTRK2</i> Polymorphisms with Antidepressant Treatment Outcome: Findings from an Extended Tag SNP Approach

<div><p>Background</p><p>Data from clinical studies and results from animal models suggest an 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 (<i>BDNF</i>) and its key receptor Trkb (<i>NTRK2</i>) may therefore influence the response to antidepressant treatment.</p><p>Methods</p><p>We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (<i>N</i> = 249 and <i>N</i> = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the <i>BDNF</i> gene region and 64 tagging SNPs in the <i>NTRK2</i> gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples.</p><p>Results</p><p>In the discovery analysis, 7 <i>BDNF</i> SNPs and 9 <i>NTRK2</i> SNPs were nominally associated with treatment response. Three <i>NTRK2</i> SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects (<i>P_corr</i> = .018, <i>P_corr</i> = .015 and <i>P_corr</i> = .004, respectively). We observed an across-gene <i>BDNF</i>-<i>NTRK2</i> SNP interaction for rs4923468 and rs1387926. No robust interaction of associated SNPs was found in an analysis of BDNF serum protein levels as a predictor for treatment outcome in a subset of 93 patients.</p><p>Conclusions/Limitations</p><p>Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the <i>BDNF</i> and <i>NTRK2</i> genes that might be involved in antidepressant treatment outcome and that have not been previously reported in this context. These new variants need further validation in future association studies.</p>