Project Summary:
The overall goal of this project is to understand whether exposure to fine particulate air pollution (PM2.5) during
development has long-lasting effects on neuropsychiatric traits in adulthood, including identifying sensitive
periods, the neural bases of these effects, and evaluating if the effects of exposure are moderated by specific
genetic risk factors. Whereas there has been considerable research linking PM2.5 exposure to poor
cardiovascular and respiratory health, PM2.5’s impact on mental health is only beginning to be appreciated. As
such, several fundamental questions pertaining to the long-term neuropsychiatric effect of PM2.5 exposure
remain unaddressed. Of particular importance is determining whether exposure to PM2.5 at distinct
developmental timepoints has differential effects on adult psychiatric and neuroanatomical outcomes. It also
remains unknown the degree to which genetic risk factors may make individuals more susceptible to
neuropsychiatric effects of exposure. By better understanding the relationships between PM2.5 and adult
neuropsychiatric outcomes, as well as the genetic factors driving individual differences in these relationships,
we may gain insight into the specific biological pathways linking PM2.5 exposure to mental illness. In the current
proposal, we will address these issues in a well characterized sample of over 700 participants who have been
followed for the first three decades of life. Integrating across geospatial, neuroimaging, psychiatric, and genetic
methodologies, we will pursue two complementary aims. In Specific Aim #1, we will test for effects of PM2.5
exposure at multiple developmental timepoints on individual differences in psychiatric outcomes in young
adulthood. We hypothesize that PM2.5 exposure is an environmental risk factor associated with higher severity
of transdiagnostic symptom dimensions, but that the specific timing and trajectory of exposure has differential
effects on this risk. Furthermore, we test whether the trajectory of developmental exposure influences the
trajectory of mental illness across the lifespan, providing insight into whether reducing PM2.5 levels across
development may ameliorate effects of perinatal exposure. In Specific Aim #2, we will leverage neuroimaging
and molecular genetic data to investigate the biological bases through which developmental PM2.5 exposure
affects the brain and subsequent mental illness. In neuroimaging analyses, we determine whether PM2.5
exposure at different developmental timepoints leads to neuroanatomical alterations in distinct brain systems.
In molecular genetic analyses, we utilized pathway-specific polygenic risk scores to test for gene-by-
environment interactions which influence the effects of PM2.5 exposure on neuropsychiatric outcomes. We
hypothesize genetic risk for adverse effects of PM2.5 exposure on these outcomes will be isolated to specific
biological pathways related to immune response and oxidative stress. Taken together, these aims provide a
targeted research plan to begin to identify the biological pathways through which environmental toxins may
affect mental health decades into the future.
