The International Journal of Neuropsychopharmacology

Thematic Section: New Aspects in the Treatment of Affective Disorders

Brain-derived neurotrophic factor (BDNF) gene: no major impact on antidepressant treatment response

Katharina Domschkea1, Bruce Lawforda2a3, Gonzalo Lajea4, Klaus Bergera5, Ross Younga3, Phillip Morrisa3, Jürgen Deckerta6, Volker Arolta1, Francis J. McMahona4 and Bernhard T. Baunea7 c1

a1 Department of Psychiatry, University of Muenster, Germany

a2 Division of Mental Health, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia

a3 Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia

a4 Genetic Basis of Mood and Anxiety Disorders Unit, NIMH, NIH, USDHHS

a5 Institute of Epidemiology and Social Medicine, University of Muenster, Germany

a6 Department of Psychiatry, University of Wuerzburg, Germany

a7 Department of Psychiatry, James Cook University, Queensland, Australia

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.

(Received July 30 2008)

(Reviewed September 03 2008)

(Revised November 25 2008)

(Accepted January 13 2009)

(Online publication February 23 2009)

Correspondence:

c1 Address for correspondence: Professor B. T. Baune, Ph.D., M.D., M.P.H., Department of Psychiatry and Psychiatric Neuroscience, School of Medicine and Dentistry, James Cook University, Queensland 4811, Australia. Tel.: 0061 7 4781 6731 Fax: 0061 7 4781 6841 Email: bernhard.baune@jcu.edu.au