Serum IL-1ra, a novel biomarker predicting olanzapine-induced hypercholesterolemia and hyperleptinemia in schizophrenia

Abstract

Olanzapine (OLZ) is efficacious whereas leads to adverse metabolic effects thus lead to higher risk of cardiovascular diseases (CVD) on schizophrenia. Cytokines have been found associated with metabolic disorders. Therefore, pretreatment prediction of OLZ-induced adverse metabolic effects is urgently needed. To investigate if baseline cytokine levels could become biomarkers for pathogenesis of schizophrenia or prediction for OLZ-induced adverse metabolic effects, we recruited 75 participants, including 23 schizophrenia inpatients, who were antipsychotic-free over the past 6 months or first episode and drug-naive and 52 matched health controls, in our prospective cohort study and cross-sectional study. We simultaneously examined 7 serum cytokine levels (IFN-γ, IL-1ra, IL-1β, IL-8, TNF-α, MCP-1, VEGF) before OLZ treatment by using liquid suspension array technique and obtained clinical correlates at 4-week intervals in total 8 weeks. The psychopathology was assessed with the Positive and Negative Symptom Scale (PANSS). The metabolic parameters were BMI, TG, total cholesterol, LDL, HDL, ApoA1, ApoB, lipoprotein a, fasting glucose, HbA1c, insulin, and leptin. At baseline, IL-1ra and MCP-1 levels in schizophrenia were significantly higher than health controls (t = 4.55, P = 0.0001, t = 3.08 P = 0.003). BMI, fasting insulin, cholesterol, triglyceride, LDL, ApoB and leptin were significantly increased in patients with schizophrenia after 8 weeks of olanzapine treatment. Correlation analysis showed that the baseline IL-1ra level were significantly correlated with the increased levels of cholesterol (P = 0.004), LDL (P = 0.005), ApoB (P = 0.018) and leptin (P = 0.010), but not with the increased BMI, insulin or triglycerides. Further stepwise multiple linear regression analysis indicated that IL-1ra levels prior to treatment remained significantly associated with increased levels of cholesterol, LDL, ApoB and leptin. Above all, higher IL-1ra and MCP-1 levels may be biomarkers indicating pathogenesis of schizophrenia. Higher serum levels of IL-1ra may predict subsequent higher possibility of hypercholesterolemia and hyperleptinemia following OLZ treatment in schizophrenia patients.

Keywords: Adverse metabolic effect; Biomarker; IL-1ra; Schizophrenia.