BDNF abnormalities may predict bipolar disorder

By Laura Cowen, medwireNews Reporter

Patients with bipolar disorder show abnormalities in the conversion of pro-brain derived neurotrophic factor (BDNF) to the mature form, which may be used to aid diagnosis of the condition.

Swedish researchers show, in two independent cohorts, that medicated patients with bipolar disorder had significantly higher serum levels of mature BDNF and a significantly higher ratio of mature BDNF to proBDNF than healthy controls.

Levels of serum proBDNF were significantly lower in patients than in controls but there were no differences in serum matrix metalloproteinase (MMP)-9, which cleaves proBDNF to mature BDNF, between the groups in either cohort.

Furthermore, multivariate logistic regression analyses, adjusted for gender, age and body mass index, showed that proBDNF and the matureBDNF/proBDNF ratio were significant predictors of bipolar disorder in both cohorts. Mature BDNF was only significant in one cohort (the Sahlgrenska cohort; 48 mood-stabilised patients with bipolar disorder and 43 mentally healthy controls).

A statistical model that included all four serum markers discriminated between patients and controls in the Sahlgrenska cohort with a sensitivity of 89% and a specificity of 77%. In the second cohort (Karolinska; 215 mood-stabilised patients with bipolar disorder and 112 controls), the sensitivity was 74% and the specificity was 64%.

When the researchers added Global Assessment of Function (GAF) scores to the model, sensitivity in the Sahlgrenska cohort increased to 100% while specificity increased to 95%. This “would be strong enough to work as a clinical biomarker predicting the diagnostic dichotomy,” they remark. GAF data were not available for the Karolinska cohort.

Of note, the team found no significant differences in serum proBDNF, mature BDF, the proBDNF/mature BDNF ratio or MMP-9 levels among patients with bipolar I, bipolar II and bipolar not otherwise specified. There was also no correlation between the serum markers and Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale scores.

Writing in the Journal of Affective Disorders, Kristoffer Södersten (University of Gothenburg, Sweden) and co-authors conclude: “Our results indicate that BDNF measurements have a potential for usage as clinical biomarkers by differentiating bipolar patients from healthy control individuals.

“Future studies should explore whether this usefulness extends to differentiating bipolar disorder from [major depressive disorder] and schizophrenia.”

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