The role of BDNF, NTRK2 gene and their interaction in development of treatment-resistant depression: data from multicenter, prospective, longitudinal clinic practice.

Although genetic variants may play a key role in development of treatment-resistant depression (TRD), relevant research is scarce.,To examine whether the polymorphisms of BDNF (rs6265) and NTRK2 (rs1387923, rs2769605 and rs1565445) genes confer risk for TRD in major depressive disorder (MDD), a total of 948 MDD patients were recruited in a 12-week, multicenter, prospective longitudinal study.,Our study showed a significant allelic association between rs1565445 and TRD with an excess of the T allele in the TRD group, compared to non-TRD group (OR = 1.43, 95%CI: 1.16-1.76, p = 0.0008); while patients with genotype C/C and T/C in rs1565445 were less likely to develop TRD than those carrying T/T (OR = 0.52, 95%CI: 0.33-0.82; OR = 0.72, 95%CI: 0.54-0.97, respectively; p = 0.005). Haplotype T-T (rs1565445 and rs1387923) had 1.41-fold increased risk of TRD (p = 0.0014). Furthermore, significant four-locus (rs1387923-rs1565445-rs2769605-rs6265) gene-gene interactions were detected by the Multifactor-dimensionality reduction (MDR) method.,These results suggest that the interactions of BDNF (rs6265) with NTRK2 (rs1387923, rs2769605 and rs1565445) gene polymorphisms likely play an essential role in the development of TRD in Han Chinese MDD patients.