Increased serum levels of leptin and insulin in both schizophrenia and major depressive disorder: A cross-disorder proteomics analysis

•Leptin and insulin levels are elevated in both schizophrenia and depression.•Current episode patients show even more marked elevations of leptin and insulin.•Leptin and insulin resistance may act as cross-disorder mechanisms. We investigated whether there are similar serum alterations in schizophrenia and major depressive disorder (MDD). We investigated serum analytes in two epidemiological studies on schizophrenia (N = 121) and MDD (N = 1172) versus controls. Serum analytes (N = 109) were measured with a multi-analyte profiling platform and analysed using linear regression models, adjusted for site, age, gender, ethnicity, anti-inflammatory agents, smoking, cardiovascular disease and diabetes, and adjusted for multiple comparisons. An increase in leptin and insulin levels was observed for both schizophrenia patients (Cohen's d (d): 0.26 and 0.65, respectively) and MDD patients (d: 0.29 and 0.12, respectively) compared to their respective controls. Lower angiopoietin-2 levels were seen in both schizophrenia (d: -0.22) and MDD (d: -0.13). Four analytes differed in only schizophrenia patients (increased levels of C-peptide and prolactin, and decreased levels of CD5 antigen-like and sex hormone binding globulin) and one analyte differed in only MDD patients (increased angiotensinogen levels) compared to their respective controls. Restricting analyses to patients with a current episode of disease showed even more marked elevations of insulin and leptin. Our results suggest the presence of insulin and leptin resistance as cross-disorder mechanisms that could contribute to the higher somatic comorbidity and decreased life-span seen in both disorders.