Glial and neuronal markers in bipolar disorder: A meta-analysis testing S100B and NSE peripheral blood levels

S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) might be peripheral markers reflecting glia and neuronal abnormalities in subjects with bipolar disorder. We carried out a systematic review and meta-analysis, searching for studies indexed in main electronic databases, to clarify whether S100B and NSE blood levels might be increased in bipolar disorder. Eleven studies met eligibility criteria, with data on S100B levels and/or NSE levels in subjects with bipolar disorder and healthy controls, respectively. Random-effects meta-analysis estimated higher levels of S100B in bipolar disorder (standardized mean difference [SMD] = 0.81; p < .001), with some inconsistency across studies (I² = 81.7%). Findings were confirmed by relevant sensitivity analyses. Meta-regression analyses did not estimate any effect for tested covariates. On the other hand, no differences in NSE levels between individuals with bipolar disorder and healthy controls were estimated (SMD = -0.32; p = .374), with high heterogeneity across studies (I² = 89.9%). Meta-regression analyses showed that the effect size was influenced by both mean age (p < .001) and illness duration (p = .001) of subjects with bipolar disorders. Our findings support the hypothesis of a possible role of glial abnormalities in the pathophysiology of bipolar disorder.