Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
PLoS One. 2012;7(8):e42676. doi: 10.1371/journal.pone.0042676. Epub 2012 Aug 3.
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.
荟萃分析已经确定脑源性神经营养因子(BDNF)的血清水平是重度抑郁症(MDD)的一个潜在生物标志物。然而,当时,由于 BDNF 抗体特异性有限,商业上可获得的人 ELISA 试剂盒无法区分前脑源性神经营养因子(BDNF 的前体)和成熟 BDNF。在这项研究中,我们研究了 MDD 患者的前脑源性神经营养因子(proBDNF)、成熟 BDNF 和基质金属蛋白酶-9(MMP-9)(将 proBDNF 转化为成熟 BDNF)的血清水平是否发生变化。
方法/主要发现:共纳入 69 名 MDD 患者和 78 名年龄和性别匹配的健康对照者。采用 17 项汉密尔顿抑郁评定量表结构访谈指南对患者进行评估。采用 CogState 电池对认知障碍进行评估。采用 ELISA 试剂盒测定 proBDNF、成熟 BDNF 和 MMP-9 的血清水平。MDD 患者的成熟 BDNF 血清水平明显低于正常对照组。相反,患者和正常对照组之间 proBDNF 和 MMP-9 的血清水平没有差异。虽然 proBDNF 或成熟 BDNF 的血清水平与临床变量无关,但 MMP-9 的血清水平与患者抑郁严重程度、生活质量评分和社会功能评分之间存在显著相关性。
结论/意义:这些发现表明成熟 BDNF 可能是 MDD 的生物标志物,而 MMP-9 可能在 MDD 的病理生理学中发挥作用。需要使用更大的样本量进一步研究这些结果。