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Brain-derived neurotrophic factor gene polymorphisms: influence on treatment response phenotypes of major depressive disorder

Kocabas, Neslihan Ayguna,g; Antonijevic, Irinah; Faghel, Carolea; Forray, Carlosh; Kasper, Siegfriedi; Lecrubier, Yvesj; Linotte, Sylvieb; Massat, Isabellea; Mendlewicz, Juliend; Noro, Magalib; Montgomery, Stuartk; Oswald, Pierref; Snyder, Lenoreh; Zohar, Josephl; Souery, Danielc,e

International Clinical Psychopharmacology: January 2011 - Volume 26 - Issue 1 - p 1–10
doi: 10.1097/YIC.0b013e32833d18f8
Original Articles

Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor family of neurotrophins, has pivotal roles in neuronal survival, proliferation, and synaptic plasticity in the brain. Both clinical and pharmacological studies have implicated the common single nucleotide polymorphism (SNP) at position 196, Val66Met in the pathophysiology of major depressive disorder (MDD), and antidepressant response. However, inconsistent results were found between Val66Met (rs6265) polymorphism and treatment response phenotypes in genetic association studies. The functional Val66Met polymorphism and seven other tagging SNP markers selected to capture the major allelic variations across BDNF locus were analyzed in depressed patients, treated with antidepressants, and 76 control patients. Two hundred and six patients with Diagnostic and Statistical Manual of Mental Disorders-IV MDD were recruited for this study and genotyped for eight BDNF tagging SNPs (rs11030096, rs925946, rs10501087, rs6265, rs12273363, rs908867, rs1491850, and rs1491851) to investigate the functional impact of genotypes/haplotypes in the susceptibility of depression and on treatment response. None of the eight SNPs, including the rs6265, were significantly associated with MDD after permutation correction. However, we found an association for rs10501087, rs6265 with nonresponse to antidepressant treatment (corrected permutation P: 0.03599; 0.0399 and power: 0.1420; 0.1492, respectively). Analysis of each two-marker, three-marker, and four-marker sliding window haplotypes showed significance in haplotype combinations. Especially rs10501087 (C), rs6265 (A), and rs1491850 (C) together or with the other SNP haplotypes showed a similar pattern in all treatment response phenotypes. Despite the limited power of analysis, our results suggest that these three SNPs may play a role in antidepressant treatment response phenotypes in MDD.

aLaboratoire de Neurologie Expérimentale

bFonds de la Recherche Scientifique (FNRS)

cLaboratoire de Psychologie Médicale

dUniversité Libre de Bruxelles

eCentre Européen de Psychologie Médicale, Psy-Pluriel, Bruxelles

fPsychiatric center Le Chêne Aux Haies, Mons, Belgium

gDepartment of Toxicology, Faculty of Pharmacy, University of Gazi, Etiler, Ankara, Turkey

hTranslational Research, Lundbeck Research USA, Paramus, New Jersey, USA

iDepartment of General Psychiatry, Medical University of Vienna, Austria

jINSERM U, Hôpital de la Pitié-Salpêtrière, Paris, France

kImperial College School of Medicine, London, UK

lChaim Sheba Medical Center Tel-Hashomer, Israel

Correspondence to Dr Neslihan Aygun Kocabas, MSc, PhD, Université Libre de Bruxelles, Laboratoire de Neurologie Expérimentale, Campus Hôpital Erasme C2.124, 808 Route de Lennik, 1070 Bruxelles, Belgıum Tel: +322 5556408; fax: +322 5554121; e-mail:

All supplementary data are available directly from the authors.

Received September 28, 2009

Accepted June 10, 2010

© 2011 Lippincott Williams & Wilkins, Inc.