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Abstract

Schizophrenia (SCZ) and bipolar disorder (BD), are severe psychiatric conditions linked to immune system dysfunction. The complement system, crucial for innate immunity and synaptic pruning and plasticity, is tightly regulated to prevent neuronal damage. While the pathophysiology of SCZ and BD is complex, CUB and Sushi Domains 1 (CSMD1), a negative regulator of complement activity, has been identified as a potential risk gene for SCZ through genome-wide association studies. SCZ and BD patients also display altered serum levels of complement regulators such as complement factor I (CFI), CSMD1, seizure-related protein (SEZ6) and decay-accelerating factor (CD55). Previous research suggests that complement dysregulation, particularly of complement regulators, may contribute to synaptic disorganization in these disorders. However, most existing research has focused on peripheral markers, leaving a gap in understanding complement regulation within the central nervous system (CNS). To address this, mRNA and protein expression levels of the target regulators were quantified in postmortem prefrontal cortex tissue from individuals with SCZ, BD and controls, using qPCR and Western blotting. Statistical analyses were performed to identify diagnostic differences and correlations with synaptic density. The results showed no significant differences in brain mRNA or protein expression levels of CFI, CSMD1, or CD55 attributable to diagnosis. However, SEZ6 mRNA was decreased in SCZ compared to controls. Correlations between complement regulators and synaptic density markers were observed, suggesting that disrupted complement-synaptic interactions may be a feature of both SCZ and BD. These findings underscore the complex relationship of complement regulation in the pathophysiology of SCZ and BD.