Ratio of mBDNF to proBDNF for Differential Diagnosis of Major Depressive Disorder and Bipolar Depression

There is a high rate of misdiagnosis between major depressive disorder (MDD) and bipolar disorder (BD) in clinical practice. Our previous work provided suggestive evidence for brain-derived neurotrophic factor (BDNF) in differentiating BD from MDD. In this study, we aimed to investigate the role of mature BDNF (mBDNF) and its precursor (proBDNF) in distinguishing bipolar depression (BP) from MDD during acute depressive episode. A total of 105 participants, including 44 healthy controls, 37 MDD patients and 24 BP patients, were recruited. Enzyme-linked immunosorbent assay kits were applied to measure plasma mBDNF levels and proBDNF levels of all participants. Plasma mBDNF levels were significantly decreased in BP group than those in MDD group (P = 0.001) and healthy controls (P = 0.002). Significantly higher ratio of mBDNF to proBDNF (M/P) at baseline was showed in MDD group than those in BP group as well as in healthy controls (P = 0.000 and P = 0.000, respectively). The optimal model for discriminating BP was the M/P ratio (area under the ROC curve = 0.858, 95 % CI 0.753-0.963). Furthermore, the M/P ratio was restored to normal levels after antidepressants treatment in MDD group. In summary, our data demonstrated that both plasma mBDNF levels and M/P ratio were lower in BP compared with MDD. These findings further support M/P ratio as a potential differential diagnostic biomarker for BP among patients in depressive episodes.