Val66Met polymorphism association with serum BDNF and inflammatory biomarkers in major depression

Abstract

Objectives: Current evidence supports participation of neurotrophic and inflammatory factors in the pathogenesis of major depressive disorder (MDD). Some studies reported an association between the Val66Met polymorphism (rs6265) of brain-derived neurotrophic factor (BDNF) gene with MDD and peripheral BDNF levels. However, no previous studies have examined the association of this polymorphism with inflammation. The present study assessed the association of the Val66Met polymorphism with serum levels of BDNF and inflammatory markers among depressed outpatients.

Methods: All participants (n = 73) met DSM-IV criteria for a unipolar depressive episode. The serum levels of BDNF and inflammatory biomarkers (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) were compared between individuals presenting with at least one Met allele (Met-carriers) and those homozygous for the Val allele.

Results: In our sample (84.9% female, mean age 52.4 ± 10.3 years), 24.7% (n = 18) were Met-carriers. After Bonferroni correction, the Met allele was significantly associated with higher BDNF and lower TNF-α. These associations persisted after adjusting for potential confounders.

Conclusions: The pattern of low BDNF and high inflammation in MDD may be influenced by the Val66Met polymorphism. The association of a polymorphism in the BDNF gene with inflammatory markers in addition to BDNF levels suggests an interaction between these systems.

Keywords:

• Depression
• brain-derived neurotrophic factor
• genetics
• inflammation
• tumour necrosis factor-alpha

Acknowledgements

M.A.C was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), programme 227 - Pesquisa Pós-doutoral no Exterior (grant 88881.120434/2016-01). F.K. was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico from Brazil (CNPq) and INAGEMP.

Statement of interest

The Authors M.A.C., M.M., S.L.S., E.A.V., F.K., L.S., A.C.B.F. and M.P.F. report no conflicts of interest. Author D.M. has received research support from Nordic Naturals, Methylation Sciences, Inc. (MSI), and PharmoRx Therapeutics. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy. He has received royalties from Lippincott Williams & Wilkins for published book “Natural Medications for Psychiatric Disorders: Considering the Alternatives.”

Additional information

Funding

This work was supported by the Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE-HCPA) [grant number 09-176]; and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant number 473459/2010-8].