Complement C1q in psychiatric disorder : elucidating correlations to synaptic pathology

Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric illnesses. The pathophysiology underlying these disorders is largely unknown, however, previous studies point towards altered immune function as a possible contributor to disorder development. The complement system, a major player in the immune system, has been shown to play a vital role in normal brain development and homeostasis, including contributions to the regulation of neurogenesis, synaptic pruning, and plasticity. C1q is the initiating protein of complement’s classical pathway and has been implicated in tagging vulnerable synaptic elements for engulfment by the brain’s resident immune cells – the microglia. The complement system has been implicated in the pathophysiology of SCZ and BD leading to the hypothesis that levels of complement opsonins, including C1q, are increased in the disorders, contributing to synaptic dysfunction. However, it is not clear whether C1q protein and mRNA expression is altered in the brain in SCZ and BD. Furthermore, recent studies have revealed an important role for triggering receptor expressed on myeloid cells 2 (TREM2) in the regulation of C1q-mediated microglial engulfment. However, it has not yet been studied in psychiatric disorders. To this end, we quantified mRNA and protein expression of C1q and TREM2 in post-mortem brain tissue from individuals with SCZ, BD, and matched controls. C1q was also quantified in blood from the same individuals. We detected a significant increase in C1q protein levels in brain tissue in SCZ relative to controls, suggesting complement system function may be altered in this disorder. Correlations were observed between C1q, TREM2, and pre-synaptic protein levels.