No Influence of Brain-derived Neurotrophic Factor (BDNF) Polymorphisms on Treatment Response in a Naturalistic Sample of Patients with Major Depression

Overview

Journal Eur Arch Psychiatry Clin Neurosci

Specialties Neurology
Psychiatry

Date 2012 Sep 12

PMID 22965830

Citations 7

Authors

Richard Musil

Peter Zill

Florian Seemuller

Brigitta Bondy

Michael Obermeier

Ilja Spellmann

Wolfram Bender

Mazda Adli

Isabella Heuser

Joachim Zeiler

Wolfgang Gaebel

Wolfgang Maier

Marcella Rietschel

Dan Rujescu

Rebecca Schennach

Hans-Jurgen Moller

Michael Riedel

Affiliations

Soon will be listed here.

Abstract

The role of the brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depressive disorder (MDD) remains to be elucidated. Recent post hoc analyses indicated a potential association of three polymorphisms in the BDNF gene with worse treatment outcome in patients with the subtype of melancholic depression. We aimed at replicating these findings in a German naturalistic multicenter follow-up. Three polymorphisms in the BDNF gene (rs7103411, rs6265 (Val66Met) and rs7124442) were genotyped in 324 patients with MDD and 470 healthy controls. We applied univariate tests and logistic regression models stratifying for depression subtype and gender. The three polymorphisms were not associated with MDD as diagnosis. Further, no associations were found in univariate tests. With logistic regression, we only found a tendency towards an association of the rs6265 (Val66Met) polymorphism with overall response to treatment (response rates: GG (val/val) < GA (val/met) < AA (met/met); p = 0.0129) and some gender differences for the rs6265 (Val66Met) and rs7103411 polymorphisms. Treatment outcome stratified for subtypes of depression did not differ significantly between the investigated polymorphisms or using haplotype analyses. However, results showed a tendency towards significance. At this stage, we cannot support an influence of these three polymorphisms. Further studies in larger patient samples to increase sample sizes of subgroups are warranted.

Citing Articles

Associations of BDNF/BDNF-AS SNPs with Depression, Schizophrenia, and Bipolar Disorder.

Shkundin A, Halaris A J Pers Med. 2023; 13(9).

PMID: 37763162 PMC: 10533016. DOI: 10.3390/jpm13091395.

The Impact of , , , , , , , , , and Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes.

Santos M, Lima L, Carvalho S, Mota-Pereira J, Pimentel P, Maia D Int J Mol Sci. 2023; 24(7).

PMID: 37047730 PMC: 10095078. DOI: 10.3390/ijms24076758.

Targeted sequencing of the BDNF gene in young Chinese Han people with major depressive disorder.

Zhang C, Ran L, Ai M, Wang W, Chen J, Wu T Mol Genet Genomic Med. 2020; 8(10):e1484.

PMID: 32869548 PMC: 7549566. DOI: 10.1002/mgg3.1484.

Polymorphism of the brain-derived neurotrophic factor and dynamics of the seizure threshold of electroconvulsive therapy.

Stephani C, Shoukier M, Ahmed R, Wolff-Menzler C Eur Arch Psychiatry Clin Neurosci. 2016; 267(8):787-794.

PMID: 27787610 DOI: 10.1007/s00406-016-0744-z.

Pharmacogenetics and Imaging-Pharmacogenetics of Antidepressant Response: Towards Translational Strategies.

Lett T, Walter H, Brandl E CNS Drugs. 2016; 30(12):1169-1189.

PMID: 27752945 DOI: 10.1007/s40263-016-0385-9.

References

Fava M, Rush A, Alpert J, Balasubramani G, Wisniewski S, Carmin C . Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry. 2008; 165(3):342-51. DOI: 10.1176/appi.ajp.2007.06111868. View

Zou Y, Ye D, Feng X, Su H, Pan F, Liao F . Meta-analysis of BDNF Val66Met polymorphism association with treatment response in patients with major depressive disorder. Eur Neuropsychopharmacol. 2010; 20(8):535-44. DOI: 10.1016/j.euroneuro.2009.12.005. View

Verhagen M, van der Meij A, van Deurzen P, Janzing J, Arias-Vasquez A, Buitelaar J . Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity. Mol Psychiatry. 2008; 15(3):260-71. DOI: 10.1038/mp.2008.109. View

DSa C, Duman R . Antidepressants and neuroplasticity. Bipolar Disord. 2002; 4(3):183-94. DOI: 10.1034/j.1399-5618.2002.01203.x. View

Campbell S, MacQueen G . The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci. 2005; 29(6):417-26. PMC: 524959. View

Choi M, Kang R, Lim S, Oh K, Lee M . Brain-derived neurotrophic factor gene polymorphism (Val66Met) and citalopram response in major depressive disorder. Brain Res. 2006; 1118(1):176-82. DOI: 10.1016/j.brainres.2006.08.012. View

Chiba S, Numakawa T, Ninomiya M, Richards M, Wakabayashi C, Kunugi H . Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry. 2012; 39(1):112-9. DOI: 10.1016/j.pnpbp.2012.05.018. View

Domschke K, Lawford B, Laje G, Berger K, Young R, Morris P . Brain-derived neurotrophic factor ( BDNF) gene: no major impact on antidepressant treatment response. Int J Neuropsychopharmacol. 2009; 13(1):93-101. DOI: 10.1017/S1461145709000030. View

Gatt J, Nemeroff C, Schofield P, Paul R, Clark C, Gordon E . Early life stress combined with serotonin 3A receptor and brain-derived neurotrophic factor valine 66 to methionine genotypes impacts emotional brain and arousal correlates of risk for depression. Biol Psychiatry. 2010; 68(9):818-24. DOI: 10.1016/j.biopsych.2010.06.025. View

10.

Chen L, Lawlor D, Lewis S, Yuan W, Abdollahi M, Timpson N . Genetic association study of BDNF in depression: finding from two cohort studies and a meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 2008; 147B(6):814-21. DOI: 10.1002/ajmg.b.30686. View

11.

Bocchio-Chiavetto L, Miniussi C, Zanardini R, Gazzoli A, Bignotti S, Specchia C . 5-HTTLPR and BDNF Val66Met polymorphisms and response to rTMS treatment in drug resistant depression. Neurosci Lett. 2008; 437(2):130-4. DOI: 10.1016/j.neulet.2008.04.005. View

12.

Blugeot A, Rivat C, Bouvier E, Molet J, Mouchard A, Zeau B . Vulnerability to depression: from brain neuroplasticity to identification of biomarkers. J Neurosci. 2011; 31(36):12889-99. PMC: 6623387. DOI: 10.1523/JNEUROSCI.1309-11.2011. View

13.

Kato M, Serretti A . Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Mol Psychiatry. 2008; 15(5):473-500. DOI: 10.1038/mp.2008.116. View

14.

Kurita M, Nishino S, Kato M, Numata Y, Sato T . Plasma brain-derived neurotrophic factor levels predict the clinical outcome of depression treatment in a naturalistic study. PLoS One. 2012; 7(6):e39212. PMC: 3384668. DOI: 10.1371/journal.pone.0039212. View

15.

Licinio J, Dong C, Wong M . Novel sequence variations in the brain-derived neurotrophic factor gene and association with major depression and antidepressant treatment response. Arch Gen Psychiatry. 2009; 66(5):488-97. PMC: 4272010. DOI: 10.1001/archgenpsychiatry.2009.38. View

16.

Hamilton M . Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol. 1967; 6(4):278-96. DOI: 10.1111/j.2044-8260.1967.tb00530.x. View

17.

Papakostas G, Shelton R, Kinrys G, Henry M, Bakow B, Lipkin S . Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: a pilot and replication study. Mol Psychiatry. 2011; 18(3):332-9. DOI: 10.1038/mp.2011.166. View

18.

Kocabas N, Antonijevic I, Faghel C, Forray C, Kasper S, Lecrubier Y . Brain-derived neurotrophic factor gene polymorphisms: influence on treatment response phenotypes of major depressive disorder. Int Clin Psychopharmacol. 2010; 26(1):1-10. DOI: 10.1097/yic.0b013e32833d18f8. View

19.

Gatt J, Nemeroff C, Dobson-Stone C, Paul R, Bryant R, Schofield P . Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Mol Psychiatry. 2009; 14(7):681-95. DOI: 10.1038/mp.2008.143. View

20.

Fuchikami M, Morinobu S, Segawa M, Okamoto Y, Yamawaki S, Ozaki N . DNA methylation profiles of the brain-derived neurotrophic factor (BDNF) gene as a potent diagnostic biomarker in major depression. PLoS One. 2011; 6(8):e23881. PMC: 3166055. DOI: 10.1371/journal.pone.0023881. View