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

N. Çakici, Mariska Bot, F. Lamers, Thomas Janssen, Peter J. van der Spek, Lieuwe de Haan, Sabine Bahn, Brenda W.J.H. Penninx, Nico J.M. van Beveren

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)835-846
Number of pages12
JournalEuropean neuropsychopharmacology
Issue number7
Publication statusPublished - 1 Jul 2019


  • Cross-disorder
  • Depressive disorder
  • Insulin resistance
  • Leptin
  • Proteomics
  • Schizophrenia

Cite this