Association between mixed metal exposure and depressive symptoms in the elderly: The moderating role of magnesium and mediating role of amino acids.

Depressive symptoms in the elderly have emerged as a pressing public health challenge globally. Environmental metal exposure is a well-recognized risk factor for mental health impairment, yet the combined effects of multiple metal co-exposures, the protective role of magnesium (Mg), and the underlying neurotoxic mechanisms remain poorly understood. In this study, 1293 community-dwelling elderly participants were recruited. Whole-blood concentrations of Al, Ba, Cu, Sr, Mo, and Mg were measured by inductively coupled plasma mass spectrometry, and depressive symptoms were assessed using the Geriatric Depression Scale (GDS-30) with a cutoff of ≥11. Key metals were screened by univariate logistic regression (P < 0.1) followed by LASSO penalized regression. Restricted cubic splines (RCS), weighted quantile sum (WQS), quantile g-computation (QGComp), and Bayesian kernel machine regression (BKMR) models were applied to evaluate metal-health associations. Moderation analysis was stratified by the median Mg level, and mediation analysis was conducted with the bootstrap method. Al, Ba, Cu, Sr, and Mo were identified as significant risk factors for depressive symptoms, whereas Mg was a protective factor. Mg concentration significantly moderated the adverse effect of Sr. Mixed metal exposure was positively associated with depressive risk, and this association was stronger in the low-Mg subgroup. Glutamate and glycine exerted significant mediating effects on the associations between Mo/Ba and depressive symptoms. Mixed environmental metal exposure is an important risk factor for late-life depressive symptoms, and Mg may modulate this association. Amino acid metabolism pathways may mediate the neurotoxic effects of metals, highlighting the need for further research to validate these findings and clarify the underlying mechanisms.