Decreased serum levels of mature brain-derived neurotrophic factor (BDNF), but not its precursor proBDNF, in patients with major depressive disorder

Abstract

Background: Meta-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 findings: Sixty-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/significance: These 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.

Figure 1. Scatter plot of proBDNF and mature BDNF serum levels in patients with MDD and healthy controls.

(A): Serum levels of proBDNF in 20 patients with MDD and 29 healthy subjects were below the minimum detectable concentration (0.5 ng/mL) of the proBDNF ELISA kits. Serum levels of proBDNF in patients with MDD did not differ from those of normal controls. (B): In contrast, serum levels (21.09±5.60 ng/mL) of mature BDNF in patients with MDD, were significantly lower than those (23.11±5.90 ng/mL) of normal controls.

Figure 2. Scatter plot of MMP-9 serum levels in patients with MDD and healthy controls.

Serum levels of MMP-9 in patients with MDD did not differ from those of normal controls.

Figure 3. Relationships between MMP-9 serum levels and clinical variables in patients with MDD.

(A): There was a significant negative correlation (ρ = −0.366, p = 0.002) between MMP-9 serum levels and WHOQOL-BREF scores. (B): There was a significant negative correlation (ρ = −0.355, p = 0.003) between MMP-9 serum levels and SASS scores. (C): There was a significant positive correlation (ρ = 0.397, p = 0.001) between MMP-9 serum levels and the SIGH-D score.

Figure 4. Relationships between clinical variables in patients with MDD.

(A): There was a significant negative correlation (r = −0.705, p<0.001) between the SIGH-D score and WHOQOL-BREF score in patients. (B): There was a significant negative correlation (r = −0.579, p<0.001) between the SIGH-D and SASS scores in patients. (C): There was a positive correlation (r = 0.404, p = 0.001) between the CogState composite score and QOL score in patients. (D): There was a positive correlation (r = 0.371, p = 0.002) between the CogState composite score and SASS score in patients.