Central Obesity as a Key Driver of Cardiometabolic Risk in Schizophrenia: Insights from Antipsychotic Therapy

Background: Schizophrenia is associated with a markedly reduced life expectancy, predominantly due to cardiovascular disease (CVD). Metabolic syndrome (MetS) is a central mediator of this excess mortality. Both intrinsic pathophysiological mechanisms and antipsychotic treatment contribute to cardiometabolic risk. Subjects and Methods: A retrospective-prospective cohort study with a hybrid design included 60 patients diagnosed with schizophrenia (ICD-10), treated ≥ 6 months with either typical (n = 30) or atypical (n = 30) antipsychotic monotherapy. The retrospective component included chart review, while metabolic parameters were collected prospectively during January 2004-January 2006. Typical antipsychotic group included both monotherapy and combination regimens, while the atypical group was predominantly monotherapy, mainly clozapine. Anthropometric parameters, fasting plasma glucose, triglycerides, HDL cholesterol, and blood pressure were assessed. MetS was defined according to modified WHO criteria. Statistical analyses included Student’s t-test, χ²-test, odds ratios (OR) with 95% confidence intervals (CI), and multivariate logistic regression adjusting for age, sex, and treatment class. Results: This analysis should be interpreted as exploratory due to the low number of metabolic syndrome cases (n = 3), and reduced HDL cholesterol was used as the primary analytical outcome. Central obesity was present in 70% of patients receiving typical and 83.3% receiving atypical antipsychotics (OR = 2.14; 95% CI 0.63 - 7.29). MetS prevalence was 10% in the typical group and 0% in the atypical group. Multivariate analysis identified waist circumference as an independent predictor of reduced HDL levels (β = ?0.61, p = 0.02). Treatment class was not an independent predictor of MetS after adjustment. Key confounders such as smoking status, illness duration, treatment duration, and living setting were not consistently available and were therefore not included in adjusted analyses. Conclusion: Metabolic abnormalities are highly prevalent among patients with schizophrenia irrespective of antipsychotic class. Interpretation of atypical antipsychotic effects is limited due to the predominance of clozapine in this group. Central obesity appears to be the primary driver of cardiometabolic risk. Integrated somatic-psychiatric care and systematic metabolic monitoring are essential to reduce cardiovascular morbidity.