title: The role of BDNF, NTRK2 gene and their interaction in development of treatment-resistant depression: data from multicenter, prospective, longitudinal clinic practice.
abstract: BACKGROUND
  Although genetic variants may play a key role in development of treatment-resistant depression (TRD), relevant research is scarce.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zezhi
authors.initials: Z
authors.lastname: Li
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zuowei
authors.initials: Z
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Jinbo
authors.initials: J
authors.lastname: Fan
authors.forename: Yangtai
authors.initials: Y
authors.lastname: Guan
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Chengmei
authors.initials: C
authors.lastname: Yuan
authors.forename: Wu
authors.initials: W
authors.lastname: Hong
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Wu
authors.forename: Jia
authors.initials: J
authors.lastname: Huang
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Hu
authors.forename: Lan
authors.initials: L
authors.lastname: Cao
authors.forename: Zhenghui
authors.initials: Z
authors.lastname: Yi
authors.forename: Donghong
authors.initials: D
authors.lastname: Cui
authors.forename: Shunying
authors.initials: S
authors.lastname: Yu
authors.forename: Yiru
authors.initials: Y
authors.lastname: Fang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002681:China / Q000208:ethnology; D061218:Depressive Disorder, Treatment-Resistant / Q000191:economics / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D020813:Receptor, trkB / Q000235:genetics* / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB