Sex-specific Effects of Outdoor Air Pollution on Subcortical Microstructure and Weight Gain: Findings from the ABCD Study

Obesity is associated with structural alterations of brain regions that support eating behavior. Exposure to air pollutants might exacerbate this association through neurotoxic effects on the brain. This study evaluated whether air pollution exposure 9-10 years old children, coupled with brain microstructure development in appetite-regulating regions, is associated with body mass index (BMI) changes over two years, and whether these associations differ by sex. Data were gathered from the Adolescent Brain Cognitive Development Study(R) (nbaseline=4,802, ages=9-10, males=49.9%, nfollow-up=2,439, ages=11-12, males=51.1%). Annual average estimates of ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), ground-level ozone (O3), and redox-weighted oxidative capacity (Oxwt, a joint measure of NO2 and O3) were gathered from youths residential addresses. Brain microstructure in 16 subcortical regions was assessed using diffusion-weighted MRI, focusing on proxies of cellular and neurite density: restricted normalized isotropic (RNI) and directional (RND) diffusion, respectively. Linear mixed-effects models examined whether air pollution and brain microstructure are related to BMI changes over two years, and whether these associations differed by sex. Exposure to PM2.5 coupled with high RND estimates in right caudate nucleus, bilateral putamen, and pallidum were associated with higher BMI over time, with pronounced effects in males (all p<0.05). PM2.5 coupled with greater neurite density in regions involved in reward-processing and decision-making were associated with higher BMI over a 2-year follow-up, especially in males. This research highlights air pollution as a modifiable risk factor for how differences in basal ganglia neurite density map onto obesity risk, with important implications for public health policy. HIGHLIGHTSO_LIHigh PM2.5 exposure and subcortical neurite density is associated with weight gain C_LIO_LIPM2.5 and subcortical development associations with BMI are pronounced in males C_LIO_LISignificant associations with BMI were found in regions involved in food intake C_LI