March 3, 2026Journal of Affective Disorders2 citations

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

ZWZihao WanShanghai International Studies University SCShanshan CaiLancaster University HMHongfei MoPreventive Cardiology

Key Points

Depression is linked to longer sitting times, indicating a potential health risk for U.S. adults.
Biomarkers of oxidative stress and inflammation are significant in understanding this association.

Structured PICO

Does prolonged sitting time increase the rate of depression in U.S. adults, and is this mediated by oxidative stress, inflammation, and insulin resistance?

Population

22,410 U.S. adults from nationally representative data

Intervention

Sitting time (self-reported via Global Physical Activity Questionnaire)

Comparator

Lower sitting time (e.g., < 8 hours per day)

Outcome

Depression (assessed with Patient Health Questionnaire-9, score ≥10)patient reported

Prolonged sitting time (≥8 hours/day) is associated with an increased risk of depression, a relationship partially mediated by insulin resistance, inflammation, and oxidative stress.

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, TYGBMI, TYGWHTR, HOMAIR, METSIR). 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 TYGWHTR accounting for the largest proportion (11. 45%), followed by METSIR (9. 25%), TYGBMI (9. 17%), and HOMAIR (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.

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