Socioeconomic mediators in the inflammatory pathways of depression: A cross-sectional study from NHANES data

Emerging evidence suggests a link between systemic inflammation and depressive disorder. However, the specific role of alpha-1-acid glycoprotein (AGP), a pivotal inflammatory marker, and the influence of socioeconomic factors on this relationship have not yet been thoroughly investigated. We analyzed data from a nationally representative National Health and Nutrition Examination Survey cohort (2021-2023; n = 1085 adult women). The severity of depressive symptoms was measured using the Patient Health Questionnaire-9 and serum AGP concentrations were measured using an immunodeficiency assay. Covariates included age, race, educational attainment, marital status, and the family income-to-poverty ratio. Associations and mediation effects were examined using logistic regression, generalized additive models, and causal mediation analysis. Consistent with prior studies, the depression group demonstrated significantly higher levels of AGP than did the control group. Logistic regression analysis identified a positive correlation between AGP levels and the risk of depression, with adjusted odds ratios of 2.55 (95% confidence interval [CI]: 1.41-4.61), 2.36 (95% CI: 1.30-4.30), and 1.89 (95% CI: 1.01-3.54) across the 3 progressively adjusted models. Generalized additive models further revealed a nonlinear upward trend in the association between AGP levels and depression. The mediation analysis indicated that the family income-to-poverty ratio partially mediated this relationship, accounting for 24.4% of the total effect (indirect effect coefficient = 0.02429, 95% CI: 0.01222-0.03766). Elevated AGP levels were independently associated with an increased risk of depression in adult women, with household economic status playing a partially mediating role.