The Relationship between Air Pollution Exposure, Genetic Liability for Schizophrenia, and Brain Outcomes in the ABCD Study

Abstract

Abstract Background and Hypothesis Air pollution exposure has been associated with altered neurodevelopment and increased risk of schizophrenia. Individuals at high genetic risk may be more vulnerable to these effects. Here, we examined how air pollution relates to brain structure and functional connectivity in adolescents, and we tested for the first time whether genetic risk for schizophrenia exacerbates these effects. Study Design We included n = 1580 individuals with information on genetic risk for schizophrenia, air pollution at 9-10 years, and structural and resting-state functional magnetic resonance imaging at 13-14 years from the Adolescent Brain Cognitive Development Study. We used linear mixed-effects models to examine the association between air pollution (ambient particulate matter (PM₂.5), nitrogen dioxide (NO₂), and ozone (O₃)) and brain measures, and test whether genetic risk for schizophrenia moderated these effects. Study Results Higher PM₂.5 was associated with smaller right frontal pole surface area (p-FDR = 0.039). Individuals with low polygenic risk scores for schizophrenia (PRS-SCZ) and medium PM₂.5 had smaller left caudate volumes compared with those with medium PRS-SCZ and medium PM₂.5 (p-FDR = 0.019). In individuals with low PRS-SCZ, higher PM₂.5 was associated with larger left (p-FDR = 0.019) and right (p-FDR = 0.018) caudate volumes. Higher NO₂ was associated with stronger negative functional connectivity between default mode and dorsal attention networks (p-FDR = 0.034) and weaker positive functional connectivity between dorsal attention and frontoparietal networks (p-FDR = 0.034). Conclusions Air pollution and its interplay with genetic risk for schizophrenia are associated with structural and functional changes in areas implicated in schizophrenia pathophysiology. This underscores the potential of lowering air pollution during critical periods of neurodevelopment and informing proactive environmental policies.