PMID- 22880079 OWN - NLM STAT- MEDLINE DCOM- 20130110 LR - 20220330 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 7 IP - 8 DP - 2012 TI - Decreased serum levels of mature brain-derived neurotrophic factor (BDNF), but not its precursor proBDNF, in patients with major depressive disorder. PG - e42676 LID - 10.1371/journal.pone.0042676 [doi] LID - e42676 AB - 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. FAU - Yoshida, Taisuke AU - Yoshida T AD - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. FAU - Ishikawa, Masatomo AU - Ishikawa M FAU - Niitsu, Tomihisa AU - Niitsu T FAU - Nakazato, Michiko AU - Nakazato M FAU - Watanabe, Hiroyuki AU - Watanabe H FAU - Shiraishi, Tetsuya AU - Shiraishi T FAU - Shiina, Akihiro AU - Shiina A FAU - Hashimoto, Tasuku AU - Hashimoto T FAU - Kanahara, Nobuhisa AU - Kanahara N FAU - Hasegawa, Tadashi AU - Hasegawa T FAU - Enohara, Masayo AU - Enohara M FAU - Kimura, Atsushi AU - Kimura A FAU - Iyo, Masaomi AU - Iyo M FAU - Hashimoto, Kenji AU - Hashimoto K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120803 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Protein Precursors) RN - 0 (brain-derived neurotrophic factor precursor) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM EIN - PLoS One. 2013;8(2). doi:10.1371/annotation/85a3fa48-980b-4f95-bb43-b33b1c3e0ac6 MH - Adult MH - Brain-Derived Neurotrophic Factor/*blood MH - Case-Control Studies MH - Demography MH - Depressive Disorder, Major/*blood/enzymology MH - Female MH - Humans MH - Male MH - Matrix Metalloproteinase 9/blood MH - Middle Aged MH - Protein Precursors/*blood MH - Young Adult PMC - PMC3411809 COIS- Competing Interests: Kenji Hashimoto is a member of Editorial Board of PLoS ONE. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. The other authors have declared that no competing interests exist. EDAT- 2012/08/11 06:00 MHDA- 2013/01/11 06:00 PMCR- 2012/08/03 CRDT- 2012/08/11 06:00 PHST- 2012/06/12 00:00 [received] PHST- 2012/07/10 00:00 [accepted] PHST- 2012/08/11 06:00 [entrez] PHST- 2012/08/11 06:00 [pubmed] PHST- 2013/01/11 06:00 [medline] PHST- 2012/08/03 00:00 [pmc-release] AID - PONE-D-12-16776 [pii] AID - 10.1371/journal.pone.0042676 [doi] PST - ppublish SO - PLoS One. 2012;7(8):e42676. doi: 10.1371/journal.pone.0042676. Epub 2012 Aug 3.