title: The serum protein levels of the tPA-BDNF pathway are implicated in depression and antidepressant treatment.
abstract: Evidence demonstrates that brain-derived neurotrophic factor (BDNF) has a pivotal role in the pathogenesis of major depressive disorder (MDD). Precursor-BDNF (proBDNF) and mature BDNF (mBDNF) have opposing biological effects in neuroplasticity, and the tissue-type plasminogen activator (tPA)/plasmin system is crucial in the cleavage processing of proBDNF to mBDNF. However, very little is known about the role of the tPA-BDNF pathway in MDD. We examined serum protein concentrations in the tPA-BDNF pathway, including tPA, BDNF, tropomyosin receptor kinase B (TrkB), proBDNF and p75NTR, obtained from 35 drug-free depressed patients before and after 8 weeks of escitalopram (mean 12.5 mg per day) or duloxetine (mean 64 mg per day) treatment and 35 healthy controls using sandwich ELISA (enzyme-linked immunosorbent assay) methods. Serum tPA and BDNF and the ratio of BDNF/proBDNF were significantly lower in the MDD patients than in controls, whereas TrkB, proBDNF and its receptor p75NTR were higher. After 8 weeks of treatment, tPA, BDNF and proBDNF and the BDNF/proBDNF ratio were reversed, but p75NTR was higher than baseline, and TrkB was not significantly changed. tPA, BDNF, TrkB, proBDNF and p75NTR all yielded fairly good or excellent diagnostic performance (area under the receiver operating characteristic curve (AUC) >0.8 or 0.9). Combination of these five proteins demonstrated much better diagnostic effectiveness (AUC: 0.977) and adequate sensitivity and specificity of 88.1% and 92.7%, respectively. Our results suggest that the tPA-BDNF lysis pathway may be implicated in the pathogenesis of MDD and the mechanisms underlying antidepressant therapeutic action. The combination of tPA, BDNF, TrkB, proBDNF and p75NTR may provide a diagnostic biomarker panel for MDD.
authors.affiliation: Department of Psychosomatics and Psychiatry, ZhongDa Hospital, Medical School of Southeast University, Nanjing, China.|Institute of Psychosomatics, Medical School of Southeast University, Nanjing, China.
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Psychosomatics and Psychiatry, ZhongDa Hospital, Medical School of Southeast University, Nanjing, China.|Institute of Psychosomatics, Medical School of Southeast University, Nanjing, China.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.affiliation: Institute of Pattern Recognition and Intelligent Computing, College of Computer Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, China.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Psychosomatics and Psychiatry, ZhongDa Hospital, Medical School of Southeast University, Nanjing, China.|Institute of Psychosomatics, Medical School of Southeast University, Nanjing, China.
authors.forename: N
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Psychosomatics and Psychiatry, ZhongDa Hospital, Medical School of Southeast University, Nanjing, China.|Institute of Psychosomatics, Medical School of Southeast University, Nanjing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Department of Psychosomatics and Psychiatry, ZhongDa Hospital, Medical School of Southeast University, Nanjing, China.|Institute of Psychosomatics, Medical School of Southeast University, Nanjing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Psychosomatics and Psychiatry, ZhongDa Hospital, Medical School of Southeast University, Nanjing, China.|Institute of Psychosomatics, Medical School of Southeast University, Nanjing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Psychosomatics and Psychiatry, ZhongDa Hospital, Medical School of Southeast University, Nanjing, China.|Institute of Psychosomatics, Medical School of Southeast University, Nanjing, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhi
authors.affiliation: Institute of Pattern Recognition and Intelligent Computing, College of Computer Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, China.
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Psychosomatics and Psychiatry, ZhongDa Hospital, Medical School of Southeast University, Nanjing, China.|Institute of Psychosomatics, Medical School of Southeast University, Nanjing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D003865:Major Depressive Disorder / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011498:Protein Precursors / Q000097:blood; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000097:blood*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D017475:Receptors, Nerve Growth Factor; C426674:brain-derived neurotrophic factor precursor; C579455:BDNF protein, human; D011494:Protein Kinases; C041311:tropomyosin kinase; D010959:Tissue Plasminogen Activator