Decreased Serum Levels of Mature Brain-Derived Neurotrophic Factor (BDNF), but Not Its Precursor proBDNF, in Patients with Major Depressive Disorder

Taisuke Yoshida,Tomihisa Niitsu,Akihiro Shiina,Kenji Hashimoto,Masaomi Iyo,Tadashi Hasegawa,Masayo Enohara,Atsushi Kimura,Tasuku Hashimoto,Masatomo Ishikawa,Nobuhisa Kanahara,Hiroyuki Watanabe,Tetsuya Shiraishi,Michiko Nakazato,Takeo Yoshikawa

doi:10.1371/journal.pone.0042676

Abstract

BackgroundMeta-analyses have identified serum levels of brain-derived neurotrophic factor (BDNF) as a potential biomarker for major depressive disorder (MDD). However, at the time, commercially available human ELISA kits are unable to distinguish between proBDNF (precursor of BDNF) and mature BDNF because of limited BDNF antibody specificity. In this study, we examined whether serum levels of proBDNF, mature BDNF, and matrix metalloproteinase-9 (MMP-9), which converts proBDNF to mature BDNF, are altered in patients with MDD.Methodology/Principal FindingsSixty-nine patients with MDD and 78 age- and gender-matched healthy subjects were enrolled. Patients were evaluated using 17 items on the Structured Interview Guide for the Hamilton Depression Rating Scale. Cognitive impairment was evaluated using the CogState battery. Serum levels of proBDNF, mature BDNF, and MMP-9 were measured using ELISA kits. Serum levels of mature BDNF in patients with MDD were significantly lower than those of normal controls. In contrast, there was no difference in the serum levels of proBDNF and MMP-9 between patients and normal controls. While neither proBDNF nor mature BDNF serum levels was associated with clinical variables, there were significant correlations between MMP-9 serum levels and the severity of depression, quality of life scores, and social function scores in patients.Conclusions/SignificanceThese findings suggest that mature BDNF may serve as a biomarker for MDD, and that MMP-9 may play a role in the pathophysiology of MDD. Further studies using larger sample sizes will be needed to investigate these results.

Highlights

Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of major depressive disorder (MDD), as well as the therapeutic mechanisms of antidepressants [1,2,3,4,5,6]
BDNF levels in human blood can be measured using commercially available human BDNF ELISA kits, due to the limited specificity of the BDNF antibody, early versions of these kits were unable to distinguish between proBDNF and mature BDNF [18]
Serum levels of proBDNF, mature BDNF, and matrix metalloproteinase-9 (MMP-9) In 20 patients and 29 controls, serum levels of proBDNF were below the minimum detectable concentration (0.5 ng/mL) of the proBDNF ELISA kits

Summary

Introduction

Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of major depressive disorder (MDD), as well as the therapeutic mechanisms of antidepressants [1,2,3,4,5,6]. BDNF levels in human blood can be measured using commercially available human BDNF ELISA kits, due to the limited specificity of the BDNF antibody, early versions of these kits were unable to distinguish between proBDNF and mature BDNF [18]. We reported that serum levels of proBDNF and mature BDNF in healthy subjects were measurable using newly available human proBDNF and BDNF ELISA kits [18]. Meta-analyses have identified serum levels of brain-derived neurotrophic factor (BDNF) as a potential biomarker for major depressive disorder (MDD). At the time, commercially available human ELISA kits are unable to distinguish between proBDNF (precursor of BDNF) and mature BDNF because of limited BDNF antibody specificity. We examined whether serum levels of proBDNF, mature BDNF, and matrix metalloproteinase-9 (MMP-9), which converts proBDNF to mature BDNF, are altered in patients with MDD

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