This study investigated the association between exposure to environmental toxicants and depressive symptoms in a sample of 3427 adults from the National Health and Nutrition Examination Survey (NHANES). The researchers identified 27 environmental toxicants in 6 of 10 categories that were associated with the prevalence of depressive symptoms, including VOC metabolites and total nicotine equivalent-2. Men and younger individuals appeared more vulnerable to environmental toxicants than women and older individuals. Peripheral white blood cell count mediated 5% to 19% of the associations. The study suggests that systemic inflammation may play a mediating role in the relationship between environmental toxicants and depressive symptoms. The findings highlight the importance of addressing environmental toxicant exposure as a potential target for mechanistic research into the causes of depression and for reducing environmental exposures to prevent depression. The study used an exposome-wide association study and a deletion-substitution-addition algorithm to assess the associations between environmental toxicants and depressive symptoms. The results indicate that environmental toxicants may contribute to the development of depressive symptoms, and that systemic inflammation could be a key mediator in this process. The study also found that certain environmental toxicants, such as nicotine metabolites and VOC metabolites, were associated with an increased risk of depressive symptoms. The study's findings suggest that reducing exposure to environmental toxicants could be an important strategy for preventing depression.This study investigated the association between exposure to environmental toxicants and depressive symptoms in a sample of 3427 adults from the National Health and Nutrition Examination Survey (NHANES). The researchers identified 27 environmental toxicants in 6 of 10 categories that were associated with the prevalence of depressive symptoms, including VOC metabolites and total nicotine equivalent-2. Men and younger individuals appeared more vulnerable to environmental toxicants than women and older individuals. Peripheral white blood cell count mediated 5% to 19% of the associations. The study suggests that systemic inflammation may play a mediating role in the relationship between environmental toxicants and depressive symptoms. The findings highlight the importance of addressing environmental toxicant exposure as a potential target for mechanistic research into the causes of depression and for reducing environmental exposures to prevent depression. The study used an exposome-wide association study and a deletion-substitution-addition algorithm to assess the associations between environmental toxicants and depressive symptoms. The results indicate that environmental toxicants may contribute to the development of depressive symptoms, and that systemic inflammation could be a key mediator in this process. The study also found that certain environmental toxicants, such as nicotine metabolites and VOC metabolites, were associated with an increased risk of depressive symptoms. The study's findings suggest that reducing exposure to environmental toxicants could be an important strategy for preventing depression.