Are leptin levels increased among people with schizophrenia versus controls? A systematic review and comparative meta-analysis

Objective: Leptin may play a role in the pathophysiology of schizophrenia and it remains unclear if levels are raised compared to controls. Therefore, we performed a systematic review and meta-analysis comparing leptin levels among people with schizophrenia and controls. Method: Two authors independently searched major electronic databases from inception until June 2015 for studies measuring blood leptin levels among people with schizophrenia and controls. Random effects meta-analysis calculating hedges g and 95% confidence intervals (CI) and meta-regression analyses were conducted. Results: Twenty-seven articles representing 1674 individuals with schizophrenia (34.6 ± 6.8 years, 55% male (0-100%), BMI 25.2 ± 3.1) and 2033 controls (33.9 ± 7.0 years, 51% male (0-100%), BMI = 24.1 ± 2.1) were included. Across all studies, leptin levels may be marginally higher in schizophrenia (g = 0.164, 95% CI -0.014-0.341, p = 0.07, Q = 217, p < 0.01), particularly when one outlier was removed (g = 0.196, 95% CI 0.210-0.370, p = 0.02) and when we included the smallest effect size from studies with multiple comparisons (g = 0.318, 95% CI 0.125-0.510, p = 0.001). Leptin levels were higher in multi-episode schizophrenia (g = 0.245, 95% CI 0.058-0.433, p = 0.01) and females (g = 0.557 95% CI 0.16-0.954, p = 0.006). Subgroup analyses revealed leptin levels may be higher in participants taking second-generation antipsychotics compared to controls. Multivariate meta-regression demonstrated a lower percentage of males (β = -0.0064, 95% CI -0.0129 to -0.0002, p = 0.05), but not BMI, moderated the results. Conclusion: Our results suggest that schizophrenia is associated with increased blood leptin levels compared to controls, which may not be entirely attributable to antipsychotic medication or BMI. Other illness related and lifestyle choices may play a pivotal role.