title: Possible associations of NTRK2 polymorphisms with antidepressant treatment outcome: findings from an extended tag SNP approach.
abstract: BACKGROUND
  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 (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment.
  
  
  METHODS
  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 (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples.
  
  
  RESULTS
  In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 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 (Pcorr  = .018, Pcorr  = .015 and Pcorr  = .004, respectively). We observed an across-gene BDNF-NTRK2 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.
  
  
  CONCLUSIONS
  Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the BDNF and NTRK2 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.
authors.affiliation: Max-Planck-Institute of Psychiatry, Munich, Germany. hennings@mpipsykl.mpg.de
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Hennings
authors.forename: Martin A
authors.initials: MA
authors.lastname: Kohli
authors.forename: Darina
authors.initials: D
authors.lastname: Czamara
authors.forename: Maria
authors.initials: M
authors.lastname: Giese
authors.forename: Anne
authors.initials: A
authors.lastname: Eckert
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolf
authors.forename: Angela
authors.initials: A
authors.lastname: Heck
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
authors.forename: Sonja
authors.initials: S
authors.lastname: Horstmann
authors.forename: Tanja
authors.initials: T
authors.lastname: Brückl
authors.forename: Torsten
authors.initials: T
authors.lastname: Klengel
authors.forename: Andreas
authors.initials: A
authors.lastname: Menke
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.forename: Susanne
authors.initials: S
authors.lastname: Lucae
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D019295:Computational Biology; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020813:Receptor, trkB / Q000235:genetics*; D015203:Reproducibility of Results; D012727:Sex Characteristics; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; D020813:Receptor, trkB