Effect of olanzapine on changes in serum complement factors levels in patients with first-episode schizophrenia

An increasing number of studies have demonstrated that patients with schizophrenia (SCZ) exhibit complement system disorders, and alterations in serum complement factor levels may serve as biomarkers for guiding the diagnosis, prognosis, and treatment of SCZ. Olanzapine is an atypical antipsychotic medication known for its immune-regulatory and anti-inflammatory properties. In this study, we evaluated alterations in serum complement factor levels in patients with first-episode SCZ, explored their diagnostic biomarker potential, and examined the impact of olanzapine treatment on these complement profiles.

A cohort of 35 individuals with first-episode SCZ and 35 healthy controls were included in this study. The severity of psychiatric symptoms in individuals with SCZ was assessed using the Brief Psychiatric Rating Scale-18 Item Version (BPRS) and the Scales for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS). A panel of 5 serum complement-related assays, namely measurements of complement components (C1, C2, C3, C4) and assessment of total complement activity via the 50% hemolytic complement (CH50) test, was performed using commercially available enzyme-linked immunosorbent assay (ELISA) kits. The levels of serum complement factors in healthy controls and individuals with SCZ were compared at baseline. All patients received olanzapine at a dosage range of 10-20 mg/day for a duration of 4 weeks. The BPRS, SANS, SAPS scores, and serum complement factor levels were compared before and after olanzapine treatment.

Serum C2, C3, C4 levels, and CH50 activity were significantly higher in patients with first-episode SCZ compared to healthy controls (P < 0.05). A combined panel of C1, C2, C3, C4, and CH50 demonstrated high accuracy in differentiating patients with SCZ from healthy controls, with a sensitivity of 91.4%, specificity of 77.1%, and AUC = 0.926. Moreover, there was a positive correlation between SANS scores and serum C3 levels (r = 0.357, P = 0.036), while BPRS scores were negatively correlated with serum C4 levels (r = -0.397, P = 0.018) at baseline. Furthermore, significant reductions were observed in SAPS scores (t = 4.795, P < 0.001), SANS scores (t = 3.809, P = 0.001), and BPRS scores (t = 8.538, P < 0.001) after treatment. Additionally, after 4 weeks of treatment, serum levels of C2 (t = 11.812, P < 0.001), C3 (t = 7.649, P < 0.001), and C4 (t = 2.902, P = 0.006) decreased significantly, whereas the CH50 activity increased significantly (t = -9.202, P < 0.001) compared to pre-treatment levels.

These findings demonstrate the potential of olanzapine to reduce serum levels of complement factors C2, C3, and C4 while increasing serum CH50 activity in patients with first-episode SCZ. However, the exact mechanism underlying this regulatory effect remains unclear and warrants further investigation.