Association of Plasma Pro-Brain-Derived Neurotrophic Factor (proBDNF)/Mature Brain-Derived Neurotrophic Factor (mBDNF) Levels with BDNF Gene Val66Met Polymorphism in Alcohol Dependence.

BACKGROUND In a previous study, we reported that pro-brain-derived neurotrophic factor (proBDNF) was involved in the pathology of alcohol dependence, and the single-nucleotide polymorphism (SNP) Val66Met was located at the prodomain of the brain-derived neurotrophic factor gene (BDNF). This polymorphism has been reported to affect intracellular trafficking and activity-dependent secretion of BDNF. Our present research investigated the relationships between the BDNF Val66Met polymorphism and the plasma levels of proBDNF and mature brain-derived neurotrophic factor (mBDNF) in patients with alcohol dependence. MATERIAL AND METHODS The BDNF gene Val66Met polymorphism was genotyped in 59 alcohol-dependent patients and 37 age- and sex-matched controls, and the plasma levels of proBDNF and mBDNF were assessed by enzyme-linked immunosorbent assay in all participants. RESULTS No association was found between the BDNF gene Val66Met polymorphism and alcohol dependence (P>0.05). In comparison with the control group, the level of plasma proBDNF in the alcohol-dependence group was notably increased (Z=-2.228, P=0.026), while the level of mBDNF was remarkedly decreased (Z=-2.014, P=0.044). In the alcohol-dependence group, significant associations were not found between the Val66Met polymorphisms and proBDNF and mBDNF plasma levels (P>0.05). The plasma level of proBDNF was positively correlated with the average daily alcohol consumption in the last month (r=0.344, P=0.008) and drinking history (r=0.317, P=0.014), while the plasma level of mBDNF had negative effects (r=-0.361, P=0.005, with the average daily alcohol consumption; r=-0.427, P=0.001, with drinking history). CONCLUSIONS The BDNF gene Val66Met polymorphism does not appear to affect the secretion of proBDNF and mBDNF in Chinese patients with alcohol dependence. Furthermore, this study reconfirmed that the plasma levels of proBDNF and mBDNF were correlated with the average daily alcohol consumption in the last month and with drinking history.

Analysis of blood mature BDNF and proBDNF in mood disorders with specific ELISA assays.

Previous studies showed that blood BDNF levels in mood disorders were reduced. However, little is known about the changes of BDNF and its precursor proBDNF in lymphocytes. In addition, earlier studies using commercial ELISA kits cannot distinguish mature BDNF from proBDNF. We aimed to investigate the change of mBDNF and proBDNF levels in the peripheral blood and their diagnostic value in the mood disorders using a specific Enzyme-Linked Immunosorbent Assay (ELISA). Serum mBDNF levels were significantly decreased in major depressive disorder (MDD) (n = 90) and bipolar disorder (BD) (n = 15) groups (P < 0.0001), whereas there was no significant change in suicidal group (n = 14) compared to the control group (n = 96). In the subgroups of MDD, the serum mBDNF level in MDD patients with severe symptoms was significantly lower than that with moderate symptoms (P < 0.05). The serum mBDNF levels in antidepressant-free patients were significantly lower than in antidepressant-treated patients (P < 0.01). Serum mBDNF yielded good diagnostic effectiveness for MDD and BD with sensitivity and specificity around 80-83%. The levels of mBDNF, proBDNF and its receptor sortilin were upregulated in lymphocytes of MDD patients relative to control subjects. Specific ELISA assays for mature BDNF confirmed the reduction of serum mBDNF level in MDD and BD. The measurement of mBDNF level could be a potential diagnostic marker with a cut-off point at 12.4 ng/ml. Upregulations of proBDNF and mBDNF in lymphocytes of MDD patients might be considered as novel pathological biomarkers for MDD.