Sex-specific effects in how childhood exposures to multiple ambient air pollutants affect white matter microstructure development across early adolescence

Abstract

Ambient air pollution is ubiquitous, yet questions remain as to how it might impact the developing brain. Large changes occur in the brain’s white matter (WM) microstructure across adolescence, with noticeable differences in WM integrity in male and female youth. Here we report sex-stratified effects of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) on longitudinal patterns of WM microstructure from 9-13 years-old in 8,182 (49% female) participants using restriction spectrum imaging. After adjusting for key sociodemographic factors, multi-pollutant, sex-stratified models showed that one-year annual exposure to PM2.5 and NO2 was associated with higher, while O3 was associated with lower, intracellular diffusion at age 9. All three pollutants also affected trajectories of WM maturation from 9-13 years-old, with some sex-specific differences in the number and anatomical locations of tracts showing altered trajectories of intracellular diffusion. Concentrations were well-below current U.S. standards, suggesting exposure to these criteria pollutants during adolescence may have long-term consequences on brain development.

Prenatal and childhood air pollution exposure, cellular immune biomarkers, and brain connectivity in early adolescents

“…Previous studies by our research team have identified links between childhood air pollution and brain connectivity in adolescents from the ABCD Study ( Burnor et al, 2021 ; Sukumaran et al, 2023 ; Cotter et al, 2023b ; Cotter et al, 2023a ). The current analyses build upon these initial studies to include prenatal estimates in addition to childhood exposure, and utilizes a multivariate approach that allows for quantification of both joint and independent effects of highly correlated variables, such as co-exposures of different criterion pollutants from two different periods of neurodevelopment.…”

“…In this regard, the developing brain may be especially sensitive to the neurotoxicant effects of ambient air pollution. Air pollution during the prenatal and childhood periods has been shown to impact the brain connectome ( Herting et al, 2019 ; Burnor et al, 2021 ; Sukumaran et al, 2023 ; Cotter et al, 2023b ; Pérez-Crespo et al, 2022 ; Binter et al, 2022 ; Lubczyńska et al, 2021 , 2020 ; Cotter et al, 2023a ; Peterson et al, 2022 ; Guxens et al, 2022 ). Defined as the spatial map of neural connections that give rise to function ( Shi and Toga 2017 ), the brain connectome can be characterized both structurally and functionally using multimodal neuroimaging methods, such as diffusion-weighted imaging (DWI) and resting-state functional magnetic resonance imaging (rs-fMRI) ( Power et al, 2011 ; Smith et al, 2009 ; Yeo et al, 2011 ; Laumann et al, 2017 ).…”

“…Beyond rsFC, both prenatal and early childhood exposure to outdoor air pollution has been linked to differences in structural connectivity as measured by white matter microstructural integrity estimated using diffusion tensor imaging ( Binter et al, 2022 ; Lubczyńska et al, 2020 ; Peterson et al, 2022 ). Building upon this research, our team implemented an advanced multi-compartment DWI modeling technique, known as restriction spectrum imaging (RSI), to cross-sectionally and longitudinally assess how air pollution exposure during childhood influences intracellular compartments of white matter tissue ( Burnor et al, 2021 ; Cotter et al, 2023a ). Our findings suggested unique sex- and pollutant-specific associations between air pollution exposure and white matter microstructural integrity.…”