State-dependent decrease in levels of brain-derived neurotrophic factor in bipolar disorder: a meta-analytic study.

Evidence has suggested a role of brain-derived neurotrophic factor (BDNF) in the pathogenesis of bipolar disorder (BD). Recent studies have examined BDNF levels in BD patients, but showed inconsistent results. In current study, meta-analyses by random-effects model were performed to compare blood BDNF levels between BD patients and healthy controls, and examine patients based on different affective status (manic, depressed, or euthymic state). Fifteen studies from 10 citations were included into the analysis. Pooling of results from all studies indicated that, overall, patients with BD had a lower level of BDNF than healthy controls (p=1x10(-4)). But when separating these studies based on different affective status, it showed that the significance existed only when comparing patients in manic (p=0.0008) or depressed (p=0.02) state with controls, but not in euthymic state (p=0.25). In addition, BDNF level was significantly increased after pharmacological treatment of manic state (p=0.01). These findings indicate that BDNF levels are abnormally reduced in manic and depressed states of BD, and the reduced level in manic state increases after treatment. They suggest a role of blood BDNF level as a state-dependent biomarker of bipolar disorder.