Association between metal exposure and depressive symptoms: The mediating role of fatty acids

Previous studies have shown that metal exposure has been linked to depressive symptoms, with fatty acids potentially playing a role in this connection. Moreover, evidence on broader metal mixtures remains limited. This cross-sectional study aimed to investigate the associations of metal exposures with depressive outcomes, and the mediation role of fatty acids.

Using data from the National Health and Nutrition Examination Survey 2011-2014 cycles, we quantified urinary metal and serum fatty acid levels. Depressive outcomes were assessed using the nine-item Patient Health Questionnaire (PHQ-9). The associations between individual metal exposure and depressive outcomes were examined by both linear and logistic regression models, and the combined effects were evaluated using Bayesian kernel machine regression models. Furthermore, the mediating role of fatty acids was assessed by mediation analyses.

Among the 1125 participants, 89 (7.91%) were identified as having depressive symptoms (PHQ-9 ≥10). Our results revealed that metal mixtures were associated with both elevated PHQ-9 scores and depressive symptoms. Tin, lead, cadmium, and antimony were identified as the main factors contributing to increased PHQ-9 scores, and lead was the most significant species linked to depressive symptoms. Notably, two unsaturated fatty acids, C20:3 n-9 and C24:1 n-9, accounted for a significant proportion (5.45-10.18%) of the positive associations between lead or cadmium and depressive scores.

This study suggests that lead and cadmium exposures are associated with depressive symptoms, with two unsaturated fatty acids, C20:3 n-9 and C24:1 n-9, potentially mediating these relationships.