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

BACKGROUND: Heavy metals are recognized neurotoxicants implicated in depression, yet limited research examines combined metal impacts. This study aimed to investigate the joint effect of heavy metals on depression and identify key contributors within the mixture. 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 8814 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). The mixture analysis revealed both positive and negative exposure-response relationships, which were, respectively, dominated by urinary tungsten (29.3% weight in the WQS index) and blood mercury (44% weight). 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: Our findings link heavy metal mixtures to depression, identifying tungsten and antimony as risk contributors, versus inverse associations for mercury and thallium, with barium as a key interactive factor. Further studies are needed to validate these metal-specific impacts and uncover additional depression-linked metals.