Cerebrospinal fluid concentration of complement component 4A is increased in first-episode schizophrenia

Excessive synapse loss is a core feature of schizophrenia and is linked to the complement component 4A gene (C4A). In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in first-episode psychosis patients who develop schizophrenia and correlates with CSF measurements of synapse density. Using patient-derived cellular modeling, we find that disease-associated cytokines increase neuronal C4A expression and that IL-1beta associates with C4A in patient-derived CSF.