Association between heavy metals’exposure and depression: Findings of the NHANES from 2003 to 2020

Background Heavy metal exposure is established as depression-related, yet limited research examines combined metal impacts. This study assessed multi-metal exposure's collective risk and identified key contributors. Methods Analyzing National Health and Nutrition Examination Survey data, adults with complete data on nine urinary metals (antimony, barium, cadmium, cobalt, cesium, molybdenum, lead, thallium and tungsten), three blood metals (cadmium, mercury and lead), depression status, and key covariates were assessed via four methods (multivariate logistic regression, restricted cubic spline (RCS) regression, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) to evaluate metal-depression associations. Results Among 8,814 participants (731 with depression), those with depression showed higher urine and blood cadmium levels, but lower blood mercury and urine thallium levels compared to controls. Adjusted analyses linked elevated urine antimony (OR = 1.34, p  = 0.029) and tungsten (OR = 1.42, p  = 0.008) to increased depression risk, while higher urine thallium (OR = 0.52, p < 0.001) and blood mercury (OR = 0.7, p  = 0.005) reduced risk. RCS analysis revealed nonlinear relationships between depression and urine cadmium ( p  = 0.004), cobalt ( p  = 0.005), lead ( p  = 0.024), antimony ( p  < 0.001), tungsten( p  < 0.001), as well as blood cadmium ( p  < 0.001) and mercury ( p  < 0.001). However, the WQS index was postive associated with depression (OR:1.17, 95% CI: 1.02–1.35, p  = 0.026) but a negative correlation (OR:0.81, 95% CI: 0.7–0.94, p  = 0.006). BKMR analysis confirmed multi-metal co-exposure elevates depression risk, and urinary barium showed the highest BKMR-derived posterior inclusion probability (PIP = 0.448). Conclusion Heavy metal mixture exposure elevates depressive disorder risk, with tungsten and antimony as key risk drivers, mercury and thallium showing protective effects, and barium emerging as a potential contributor. Further studies needed to validate these metal-specific impacts and uncover additional depression-linked metals.