Association between abnormal complement activation and clinical symptoms in schizophrenia

ObjectiveThis study aimed to explore the relationships between serum complement protein levels and psychotic symptoms as well as cognitive function in drug-naïve, first-episode schizophrenia (SCZ) patients.MethodsDrug-naïve first-episode SCZ patients and healthy controls (HC) were included. Serum levels of complement component 1q (C1q), C3, C4, C3a, C3b, C4a, and C-reactive protein (CRP) were measured using enzyme-linked immunosorbent assay (ELISA). Psychotic symptoms were assessed using the positive and negative syndrome scale (PANSS). Cognitive function was evaluated with the MATRICS consensus cognitive battery (MCCB). Serum complement factor levels were compared between the two groups, and their associations with clinical symptoms were examined in the SCZ group.ResultsA total of 76 drug-naïve, first-episode SCZ and 63 HC were enrolled. Compared to HC, SCZ patients exhibited significantly elevated serum levels of C1q [(63.17±21.44) μg/mL vs. (55.04±19.34) μg/mL, P=0.006, PFDR=0.036] and C4a [(6.07±3.84) μg/mL vs. (4.54±3.43) μg/mL, P=0.013, PFDR=0.039]. Among SCZ patients, C3a was positively associated with positive symptoms (r=0.293, P=0.013,PFDR=0.039).ConclusionThese findings suggest that abnormal activation of the peripheral classical complement pathway may be involved in the clinical symptoms of first-episode schizophrenia.