The changes of tPA/PAI-1 system are associated with the ratio of BDNF/proBDNF in major depressive disorder and SSRIs antidepressant treatment

Increasing evidence demonstrates that brain-derived neurotrophic factor (BDNF) can be regarded as a biomarker for major depression. Our previous work found that the ratio of mature BDNF (mBDNF) to precursor-BDNF (proBDNF) was a pivotal factor in the pathogenesis of major depressive disorder (MDD). But the mechanism behind the ratio is still obscure. Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) both play essential roles in depression by regulating the ratio of BDNF/proBDNF. In present study, we analyzed BDNF, proBDNF, tPA and PAI-1 in the peripheral blood in 57 MDD patients pre- and post-treatment and in 57 healthy controls. We verified that BDNF and tPA levels were significantly decreased, whereas proBDNF and PAI-1 levels elevated obviously in MDD group pre-treatment. And after 4 weeks SSRIs treatment, the BDNF and tPA levels increased while the proBDNF and PAI-1 levels reduced. The MDD pre-treatment group had the lowest ratio of BDNF to proBDNF compared to MDD post-treatment group and control group. Though the ratio of tPA/PAI-1 in MDD pre-treatment had not reached the significance, it was still the lowest one among the three groups. The combination of tPA + PAI + BDNF showed the best diagnostic value for MDD. In summary, our data suggested that the interaction between tPA and PAI-1 implicated to the MDD and the antidepressant treatment which might through regulating the BDNF/proBDNF ratio. The combination of tPA, PAI-1 and BDNF might offer a helpful way for MDD diagnosis.