Bipolar disorder patients display reduced serum complement levels and elevated peripheral blood complement expression levels

Bipolar disorder (BD) patients have recently been shown to exhibit increased proinflammatory cytokine levels indicating the role of inflammation in this disease. As inflammatory responses often include complement level alterations and complement production is influenced by cytokines, we aimed to find out whether complement system is activated in BD in a time-dependent manner and complement factors are involved in BD pathogenesis.Serum C4, factor B, sC5b-9 and neuron-specific enolase levels were measured by enzyme-linked immunosorbent assay, whereas peripheral blood mononuclear cell messenger RNA (mRNA) expression levels of C1q, C4, factor B and CD55 were measured by real-time polymerase chain reaction in chronic BD patients (n=22), first episode BD patients (n=24) and healthy controls (n=19).Serum complement levels were significantly reduced in chronic BD patients as compared with first episode BD patients and healthy controls. Serum levels of complement factors showed significant inverse correlation with disease duration, severity of manic symptoms and serum neuron-specific enolase levels. In chronic BD patients, peripheral blood mononuclear cell mRNA expression levels of C1q, C4 and factor B were significantly elevated, whereas the mRNA expression level of the complement inhibitor CD55 was significantly reduced.Our results suggest that complement factor levels are reduced in BD presumably due to overconsumption of the complement system and complement production is increased at mRNA level possibly as a compensation measure. Complement factors might potentially be used as indicators of disease severity, neuronal loss and cognitive dysfunction.