Exposure to multiple ambient air pollutants changes white matter microstructure during early adolescence with sex-specific differences

Background: Air pollution is ubiquitous, yet questions remain regarding its impact on the developing brain. Large changes occur in white matter microstructure across adolescence, with notable differences by sex. Methods: We investigate sex-stratified effects of annual exposure to fine particulate matter (PM_2.5), nitrogen dioxide (NO₂), and ozone (O₃) at ages 9–10 years on longitudinal patterns of white matter microstructure over a 2-year period. Diffusion-weighted imaging was collected on 3T MRI scanners for 8182 participants (1–2 scans per subject; 45% with two scans) from the Adolescent Brain Cognitive Development (ABCD) Study. Restriction spectrum imaging was performed to quantify intracellular isotropic (RNI) and directional (RND) diffusion. Ensemble-based air pollution concentrations were assigned to each child’s primary residential address. Multi-pollutant, sex-stratified linear mixed-effect models assessed associations between pollutants and RNI/RND with age over time, adjusting for sociodemographic factors. Results: Here we show higher PM_2.5 exposure is associated with higher RND at age 9 in both sexes, with no significant effects of PM_2.5 on RNI/RND change over time. Higher NO₂ exposure is associated with higher RNI at age 9 in both sexes, as well as attenuating RNI over time in females. Higher O₃ exposure is associated with differences in RND and RNI at age 9, as well as changes in RND and RNI over time in both sexes. Conclusions: Criteria air pollutants influence patterns of white matter maturation between 9–13 years old, with some sex-specific differences in the magnitude and anatomical locations of affected tracts. This occurs at concentrations that are below current U.S. standards, suggesting exposure to low-level pollution during adolescence may have long-term consequences.

Devyn L. Cotter, Hedyeh Ahmadi, Carlos Cardenas-Iniguez, Katherine L. Bottenhorn, W. James Gauderman, Rob McConnell, Kiros Berhane, Joel Schwartz, Daniel A. Hackman, Jiu-Chiuan Chen, Megan M. Herting