Brain-derived Neurotrophic Factor and its Precursor proBDNF as Diagnostic Biomarkers for Mood Disorders

Since the discovery of the brain-derived neurotrophic factor (BDNF) in the early 1980s,¹ there has been interest in its involvement in neuronal protection and survival, synaptic transmission and activity-dependent plasticity, as well as in morphogenesis of dendritic spines.

Available data support the notion that BDNF may be involved in the pathophysiology of mood disorders such as major depressive disorder (MDD) and bipolar disorder (BD). Both of these neuropsychiatric conditions are characterized by anomalies in plasma BDNF levels.

According to a new report, it’s possible to differentiate between patients diagnosed with these two conditions by measuring plasma mature BDNF (mBDNF) and its precursor (proBDNF) levels.² These findings were published in Molecular Neurobiology.

In order to examine whether plasma mBDNF levels, proBDNF levels, and mBDNF/proBDNF ratio were different between individuals diagnosed with a mood disorder and healthy individuals, investigators recruited a total of 105 participants, including 37 patients with MDD, 24 patients with BD, and 33 typical, healthy controls. There were no significant differences between the groups with regard to age, gender, or marital status.

The participants were diagnosed according to DSM-IV-TR criteria for MDD and bipolar I disorder. Investigators also used Hamilton Rating Scale for Depression-17 (HAMD), Hamilton Rating Scale for Anxiety (HAMA), and Young Mania Rating Scale (YMRS) at admission, and at every two weeks for 12 weeks total. They measured plasma levels of mBDNF and proBDNF in peripheral venous blood of each participant.

Results indicate that, at baseline, significant difference was observed among individuals in MDD group, BD group, and control group with regard to plasma mBDNF levels. More specifically, BD group had lower plasma levels compared with those of MDD group (269.17±159.23 vs. 397.30±104.82, P=0.000), as well as compared with those of control group (269.17±159.23 vs. 353.80±138.67, P=0.002). No significant differences were reported between patients with MDD and controls. With regard to plasma proBDNF levels, no significant differences were observed among the groups. Researchers did find a significant difference among groups in terms of the baseline mBDNF/proBDNF ratio, with MDD group presenting with higher ratio compared with BD group and control group.

For the participants in the MDD group, the results of correlation analyses indicate negative association between proBDNF and age (r=-0.339, P=0.040) and age of first onset (r=-0.524, P=0.015). For the same group (ie, MDD), a positive association was found between mBDNF/proBDNF ratio and age (r=0.556, P=0.009) and age of first onset (r=0.360, P=0.029).

According to the authors, findings indicate that “mBDNF/proBDNF ratio compared with plasma mBDNF levels and proBDNF levels was more sensitive for discriminating BD from acute depressive episode,” and that mBDNF/proBDNF ratio is a “potential biomarker for discriminating BD among patients in depressive episodes.”

References

1. Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982;1(5):549-553.

2. Zhao G, Zhang C, Chen J, et al. Ratio of mBDNF to proBDNF for differential diagnosis of major depressive disorder and bipolar depression. Mol Neurobiol. 2016. doi: 10.1007/s12035-016-0098-6. [Epub ahead of print]