Effects of a mixture of ambient air pollution and its metabolites on depression: From epidemiology to molecular mechanisms

This study investigates the relationships between exposures to ambient air pollution-specifically particulate matter 2.5 (PM_2.5) and its metabolites-and the risk of depression_. Nonlinear and linear regression, Bayesian kernel machine regression, and toxicogenomic analysis were key approaches. PM_2.5 exposure was positively associated with the risk of developing depression, whereas phenylglyoxylic acid exposure was negatively associated with depression risk. We found a significant overall relationship between ambient air pollution and depression, particularly at the 55th and 60th percentiles. Although statistical significance was not reached at the 65th percentile, there was a noticeable upward trend, indicating a potential association. Interestingly, no significant connection was found between a combination of metabolites from ambient air pollution and depression. PM_2.5 and phenylglyoxylic acid emerged as the most influential compounds in the models, respectively. PM_2.5 exposure altered the expression of 42 specific targets associated with depression, especially POMC, SCL6A4, IL6, and SOD2. The study identified specific pathways related to insulin secretion, energy metabolism, blood circulation, tube diameter, and maintenance of blood vessel diameter, as well as key molecular mechanisms involving hsa-miR-124-3p, hsa-miR-155-5p, hsa-miR-16-5p, and SP1. These mechanisms were found to underlie the etiology of depression associated with PM_2.5 exposure. In conclusions, PM_2.5 and phenylglyoxylic acid were found to be associated with depression. Further work is needed to gain insight into the molecular mechanisms by which these chemicals affect depression, especially pathways related to insulin secretion and blood circulation.