Air pollution interacts with genetic risk to influence cortical networks implicated in depression

Significance Air pollution is ubiquitous and may increase neuropsychiatric risk, including for depression. However, the neural underpinnings and whether this environmental risk acts independently or interactively with genetic risk mechanisms are not well understood. In healthy individuals exposed to significant air pollution, we find that combined high air pollution exposures and relatively high polygenic risk for depression disproportionately augmented stress-related effects on brain circuitry. The coexpression of depression-associated genes across the brain tracked corresponding brain connectivity, driven by individuals with higher polygenic risk and with higher exposures to air pollution. These findings add to the mechanistic understanding of brain processes implicated in how individuals with high genetic risk for depression may be particularly vulnerable to the brain effects of air pollution.