Phenotypic aging mediates the association between blood cadmium and depression: a population-based study

Depression is a serious public health problem today, especially in middle-aged and older adults. Although the etiology of the disease has not been fully elucidated, environmental factors are increasingly not negligible. Cadmium is widely used in industrial production. The general population may be chronically exposed to low doses of cadmium. This study aimed to investigate the association between blood cadmium and depression and to explore the mediating role of aging indicators in this process. We conducted a cross-sectional study on blood cadmium (N = 7195, age ≥ 20 years) using data from the 2007-2010 National Health and Nutrition Examination Survey (NHANES). Aging indicators (biological and phenotypic age) are calculated by combining multiple biochemical and/or functional indicators. To determine the relationship between blood cadmium concentrations and depressive symptoms, we used weighted multivariate logistic regression and restricted cubic spline functions and employed mediation analysis to explore the possible mediating effects of aging indicators in the process. We found a significant positive association between blood cadmium and depression with an odds ratio (OR) and 95% confidence interval (CI): 1.22 (1.04,1.43). Restricted cubic spline analysis found a linear positive association between blood cadmium and depression. In the fully covariate-adjusted model, we found a positive association between blood cadmium and biological age and phenotypic age with β and 95% CI: 1.02 (0.65, 1.39) and 2.35 (1.70, 3.01), respectively. In the mediation analysis, we found that phenotypic age mediated 21.32% of the association between blood cadmium and depression. These results suggest that even exposure to low doses of cadmium can increase the risk of depression and that this process may be mediated by phenotypic aging.