Mediation roles of oxidative stress, inflammation, and insulin resistance biomarkers in the sitting time-depression association among U.S. adults

Wan, Zihao and Cai, Shanshan and Mo, Hongfei (2026) Mediation roles of oxidative stress, inflammation, and insulin resistance biomarkers in the sitting time-depression association among U.S. adults. Journal of affective disorders, 401: 121326. p. 121326. ISSN 0165-0327

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Abstract

OBJECTIVE: This study aimed to investigate the mediating roles of biomarkers of oxidative stress, inflammation, and insulin resistance in the association between sitting time and depression, and to determine the threshold value of sitting time linked to elevated depression rate. METHODS: Nationally representative data from the United States were analyzed, including 22,410 adults. Sitting time was self-reported using a Global Physical Activity Questionnaire (GPAQ) based interview item. Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9), with a score of ≥10 indicating depression. Mediators included biomarkers of oxidative stress (GGT, UA, HDL, UHR), inflammation (NLR, MLR, NMLR, HRR, RAR, SIRI, SII), and insulin resistance (TYG, TYG_BMI, TYG_WHTR, HOMA_IR, METS_IR). Associations and mediation effects were examined using logistic regression, linear regression, restricted cubic spline (RCS) analyzes, and Bayesian mediation models, adjusted for demographic and comorbidity confounders. RESULTS: Sitting time ≥ 8 h per day was significantly associated with increased rate of depression (OR = 1.39, 95% CI: 1.17-1.66). RCS analysis revealed a nonlinear J-shaped relationship between sitting time and depression (P for nonlinear =0.010), with the curve nadir located around 3.3 h (P = 0.004). Insulin resistance biomarkers showed the strongest mediation effects, with TYG_WHTR accounting for the largest proportion (11.45%), followed by METS_IR (9.25%), TYG_BMI (9.17%), and HOMA_IR (1.53%). Among inflammatory markers, RAR (5.03%) had the highest mediating effect, followed by SIRI (2.36%), NLR (1.26%), NMLR (1.22%), and SII (1.08%). For oxidative stress, HDL and UHR mediated 3.45% and 2.22% of the sitting time-depression association, respectively. CONCLUSION: Sitting time is associated with depression rate partly mediated by biomarkers of oxidative stress, inflammation, and, most notably, insulin resistance. These findings suggest that reducing sitting time is associated with a lower depression risk, and this association may be accompanied by improvements in related biological pathways such as insulin resistance.