Abnormality in serum levels of mature brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in mood-stabilized patients with bipolar disorder: A study of two independent cohorts

Background: Early detection and diagnosis of bipolar disorder can be difficult. Tools are needed to help clinicians detect bipolar disorder earlier, which would ameliorate the prognosis. Methods: ELISA kits that distinguish between mature brain derived neurotrophic factor (BDNF) and proBDNF, we compared serum levels of mature BDNF, proBDNF, and matrix metalloproteinase-9 (MMP-9) in two independent cohorts (Sahlgrenska cohort and Karolinska cohort) of mood-stabilized bipolar patients and healthy controls. The total sample size in both cohorts consisted of 263 (48 I 215) bipolar patients and 155 (43 1 112) healthy controls. Results: Levels of mature BDNF and the ratio mature BDNF/proBDNF were significantly higher in patients than in controls. Serum levels of proBDNF were significantly lower in patients compared to controls. Serum levels of MMP-9 did not differ between the groups but MMP-9 correlated positively and significantly with mature BDNF. Mature BDNF, proBDNF, the ratio of mature BDNF/proBDINIF and interactions with MMP-9 explained the diagnostic dichotomy in both cohorts with high significance, using multivariate logistic ANCOVA (gender, age, and BMI were covaried out). The model explained 41% of the diagnostic variance in the Sahlgrenska cohort (p < 0.0001) and 15% in the Karolinska cohort (p < 0.0001). In both cohorts, the equations provided good power for diagnostic classification. The diagnostic sensitivity was 89% in the Sahlgrenska and 74% in the Karolinska cohort, and specificity 77% and 64%, respectively. Limitation: The study is cross-sectional with no longitudinal follow up. The cohorts are relatively small with no medication-free patients. There are no ill patient controls. Conclusion: Abnormalities in the conversion of proBDNF to mature BDNF may be associated with pathogenesis of bipolar disorder. Clinical use of these biomarkers may provide opportunities for earlier detection and correct treatment. (C) 2014 Elsevier B.V. All rights reserved.