The independent and joint effects of outdoor air pollution exposure and genetic risk on mental health trajectories during adolescence

Air pollution exposure has been associated with increased risk of developing mental health problems. It is possible that individuals at high genetic risk for psychopathology may be more vulnerable to these effects; however, this question remains to be investigated. We leveraged longitudinal data from n=10,620 participants from the Adolescent Brain Cognitive Development Study to first investigate sex-stratified associations of particulate matter (PM2.5) exposure and genetic risk with mental health trajectories across 9-16 years including internalizing symptoms and psychotic like experiences (PLEs). Additionally, we tested whether genetic risk for schizophrenia (PRS-SCZ) and major depressive disorder (PRS-MDD) exacerbate the association with PM2.5 exposure and change in symptoms over time. PM2.5 exposure was associated with lower decreases in PLEs over time in females (p-FDR=0.005), with no effects on internalising symptom trajectories in either sex. Genetic influences were sex-specific, with higher PRS-SCZ and PRS-MDD linked to greater increases in internalising symptoms in females (p-FDR=0.009; p-FDR=0.022) and higher PRS-MDD associated with greater decreases in PLEs in males (p-FDR=0.001). In females we also observed an interaction between PM2.5 and PRS-MDD on PLEs trajectories (p-FDR=0.048) such that those with high genetic risk and high PM2.5 exposure demonstrated increases in PLEs over time. Our results suggest that PM2.5 exposure and polygenic risk for depression jointly shape mental health during adolescence. This underscores the potential of interventions aimed at lowering air pollution during sensitive periods of neurodevelopment in improving adolescent mental health.