title: Brain-derived neurotrophic factor ( BDNF) gene: no major impact on antidepressant treatment response.
abstract: The brain-derived neurotrophic factor (BDNF) has been suggested to play a pivotal role in the aetiology of affective disorders. In order to further clarify the impact of BDNF gene variation on major depression as well as antidepressant treatment response, association of three BDNF polymorphisms [rs7103411, Val66Met (rs6265) and rs7124442] with major depression and antidepressant treatment response was investigated in an overall sample of 268 German patients with major depression and 424 healthy controls. False discovery rate (FDR) was applied to control for multiple testing. Additionally, ten markers in BDNF were tested for association with citalopram outcome in the STAR*D sample. While BDNF was not associated with major depression as a categorical diagnosis, the BDNF rs7124442 TT genotype was significantly related to worse treatment outcome over 6 wk in major depression (p = 0.01) particularly in anxious depression (p = 0.003) in the German sample. However, BDNF rs7103411 and rs6265 similarly predicted worse treatment response over 6 wk in clinical subtypes of depression such as melancholic depression only (rs7103411: TT < CC, p = 0.003; rs6265: GG < AA, p = 0.001). All SNPs had main effects on antidepressant treatment response in ANOVA models when the remaining SNPs were considered as covariates. The STAR*D analyses did not yield significant results at any of the ten BDNF markers. Our results do not support an association between genetic variation in BDNF and antidepressant treatment response or remission. Post-hoc analyses provide some preliminary support for a potential minor role of genetic variation in BDNF and antidepressant treatment outcome in the context of melancholic depression.
authors.affiliation: Department of Psychiatry, University of Muenster, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
authors.forename: Bruce
authors.initials: B
authors.lastname: Lawford
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Laje
authors.forename: Klaus
authors.initials: K
authors.lastname: Berger
authors.forename: Ross
authors.initials: R
authors.lastname: Young
authors.forename: Phillip
authors.initials: P
authors.lastname: Morris
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Francis J
authors.initials: FJ
authors.lastname: McMahon
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor