Metabolic hormone and adipokine alterations in major depressive disorder in relation to the acute-phase inflammatory response and early-life adversity

Commun Med (Lond). 2026 May 26. doi: 10.1038/s43856-026-01686-4. Online ahead of print.

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) involves dysregulated neuroimmune, metabolic, and inflammatory pathways. This study characterized metabolic hormone and adipokine profiles in Chinese MDD patients stratified for metabolic syndrome (MetS), and examined associations with depression severity (OSOD), suicidal ideation (SI), illness recurrence (ROI), and physiosomatic symptoms.

METHODS: We enrolled 125 MDD inpatients (age 18-70 years) and 40 healthy controls (age 20-65 years). Fasting serum insulin, glucose, glucagon, GIP, GLP‑1, leptin, secretin, PAI‑1, resistin, ghrelin, and adiponectin were measured. The acute‑phase inflammatory (API) response was assessed using albumin, transferrin, and monomeric CRP. Group comparisons used ANOVA or general linear models (adjusted for age, BMI, MetS) with false discovery rate correction. Associations were tested with Pearson correlations, stepwise multiple regression, and binary logistic regression. Discriminatory performance was evaluated by ROC‑AUC.

RESULTS: MDD showed significantly lower insulin, glucagon, and PAI‑1, along with a higher API index (all adjusted). A composite GAP index (ghrelin, adiponectin, PAI‑1) correlated negatively with OSOD, SI, ROI, physiosomatic symptoms, and adverse childhood experiences (ACEs). A model combining GAP index, API index, and ACEs discriminated MDD from controls with AUC = 0.864 and 80% accuracy.

CONCLUSION: Severe MDD in this Chinese inpatient sample is characterized by suppressed anabolic hormones and lower adipokines coupled with mild chronic inflammation, independent of MetS. This hormonal‑immune‑metabolic signature is integral to MDD pathophysiology.

PMID:42191930 | DOI:10.1038/s43856-026-01686-4