Association between the ZJU index and depression in US adults: A cross-sectional NHANES analysis

Depression, affecting over 350 million people globally, demonstrates strong links with metabolic dysfunction including obesity and insulin resistance. The ZJU index - a composite metabolic marker integrating BMI, triglycerides, fasting glucose, and liver enzymes (AST/ALT) - has shown excellent predictive value for NAFLD and other metabolic disorders, but its association with depression remains unexplored.

Utilizing data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) comprising 12,174 U.S. adults, we investigated the association between the ZJU index and depression through multiple analytical approaches. Multivariable logistic regression with progressive adjustment for demographic, lifestyle and clinical covariates. Restricted cubic splines (RCS) with three knots to examine potential nonlinear relationships and threshold effects. And comprehensive subgroup analyses and interaction testing across key stratifying variables. Sensitivity analyses employing inverse probability weighting (IPW) to verify the robustness of our findings against potential confounding.

Our analysis revealed that participants in the highest ZJU index quartile (Q4) exhibited a 32 % significantly increased odds of depression compared to the lowest quartile (Q1) (fully adjusted OR = 1.32, 95 % CI:1.04-1.68, p-trend < 0.001), with a J-shaped nonlinear association identified through restricted cubic spline analysis (p-nonlinearity = 0.011) showing an inflection point at ZJU = 31.39, and these findings remained robust across all subgroup analyses and sensitivity tests using inverse probability weighting (IPW OR = 1.42, 95 % CI:1.14-1.76 for Q4 vs Q1), supporting the ZJU index's components (liver enzymes, lipids, and glycemic markers) through established depression pathways involving neuroinflammation, HPA axis dysregulation, and insulin resistance.

Elevated ZJU index levels demonstrated a statistically significant association with increased depression risk, suggesting its potential utility as a clinically meaningful screening indicator for depression in general populations.