Peripheral complement C3 and C4 are associated with clinical features of schizophrenia

Schizophrenia is a severe psychiatric disorder with heterogeneous outcomes; factors such as anxiety, childhood trauma, and duration of untreated psychosis (DUP) may influence symptom severity and disease progression. Growing evidence highlights immune dysregulation-particularly alterations in complement components C3 and C4-in the pathophysiology of schizophrenia; however, findings regarding peripheral complement levels and their clinical associations remain inconsistent.

Thirty-nine patients with schizophrenia underwent clinical assessment using the Childhood Trauma Questionnaire (CTQ), the Positive and Negative Syndrome Scale (PANSS), the State-Trait Anxiety Inventory (STAI), and the Montreal Cognitive Assessment (MoCA). Serum concentrations of C3 and C4 were measured at admission.

In exploratory analyses (nominal p-values), baseline C3 correlated with DUP (r=0.407, p=0.010) and length of hospitalization (r=0.353, p=0.028). Higher C3 was associated with greater symptom severity on PANSS-P₁ (r=0.325, p=0.043) and PANSS-G₁ (r=0.330, p=0.040), while C4 correlated with PANSS-G₁ (r=0.322, p=0.045) and multiple PANSS domains after 12 weeks. C3 was associated with anxiety at baseline and after 3 months (STAI-T₁: r=0.376, p=0.018; STAI-S₁: r=0.372, p=0.020; STAI-T₂: r=0.376, p=0.018; STAI-S₂: r=0.419, p=0.009), whereas C4 correlated with STAI-T₁ (r=0.361, p=0.024), STAI-S₁ (r=0.342, p=0.033), and STAI-S₂ (r=0.338, p=0.038). Higher C3 and C4 levels were associated with CTQ subscales. C3 correlated negatively with cognitive performance (MoCA₁: r=-0.339, p=0.034). However, none of the associations survived Benjamini-Hochberg false discovery rate (BH-FDR) correction (all q>0.05).

These exploratory, within-cohort findings suggest that peripheral complement markers relate to variation in clinical severity and illness-course indicators in schizophrenia. Replication in larger, controlled longitudinal studies is warranted.