Can air pollution shape adolescent brain development? New study reveals sex-specific effects of PM2.5, NO2, and O3 on white matter microstructure

In a recent study posted to the Research Square* preprint server, researchers investigated the sex-stratified effects of childhood exposure to ambient air pollutants, such as particulate matter with a diameter less than 2.50 µm (PM_2.5), ozone (O₃), and nitrogen dioxide (NO₂), on white matter (WM) microstructure development in early adolescence.

Study: Sex-specific effects in how childhood exposures to multiple ambient air pollutants affect white matter microstructure development across early adolescence. Image Credit: Tridsanu Thopet/Shutterstock.com

*Important notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Air pollutants, such as PM_2.5 and NO₂, cause pulmonary inflammation and neurotoxic effects on the brain, especially in children. Long-term effects on dynamic neural processes and sex differences remain uncertain.

Research could inform policymakers to update risk assessments of the effects of air pollution exposure on health.

Increased PM_2.5 exposure was related to higher RNI, indicating swelling or activation of support cells. However, it is unclear if air pollution affects WM microstructural growth or the impact of gaseous criterion pollutants on specific WM parameters.

About the study

In the present longitudinal study, researchers evaluated the sex-stratified effects of PM_2.5, NO₂, and O₃ exposure on white matter microstructure using restriction spectrum imaging (RSI).

The study included 8,182 individuals who participated in the Adolescent Brain Cognitive Development (ABCD) study, comprising 21 urban regions in the United States (US), who were aged ≤10.0 years at baseline and were proficient in English.

The team excluded individuals with a history of neurological or other medical disorders, traumatic brain injury history, moderate or severe autism spectrum disorders, schizophrenia, intellectual disabilities, alcohol/substance usage disorders, premature births (gestational age below 28.0 weeks), low birth weight (below 1,200.0 g), and magnetic resonance imaging (MRI) imaging contraindications.

The researchers investigated the impact of a year of PM2.5, NO2, and O3 exposure on WM microstructure at nine years and alterations in WM microstructure trajectories from nine to 13 years of age, stratified by gender.

WM microstructural integrity was assessed by quantifying restricted directional (RND) and restricted normalized isotropic (RNI) diffusion to explore the biological mechanisms contributing to WM microstructural development.

The concentrations of the air pollutants investigated (particulate matter=7.7 ug/m3; O₃=19 parts per billion; and NO₂= 42 parts per billion) were significantly lower compared to the current United States Environmental Protection Agency (EPA) standards.

Linear mixed-effects modeling was performed for the analysis, adjusting for ethnicity, race, income, parental educational attainment, handedness, urbanicity, magnetic resonance imaging (MRI) scan season, scanner manufacturers, tract volumes, and head movement. Only high-resolution MRI scans obtained before 1 March 2020 were analyzed.

Results

One year of PM_2.5 and NO2 exposure was related to higher, whereas O3 was related to lower intracellular diffusion at nine years of age.

In addition, all three pollutants affected trajectories of WM maturation from 9.0 to 13.0 years, with a few sex-based differences in the anatomical regions and numbers of tracts showing altered intracellular diffusion trajectories. The RNI and RND values increased with time, from 9.0 to 13.0 years.

For RND, the effects of PM_2.5 were more widespread among females, while ozone impacted both genders similarly, and nitrogen dioxide had non-significant effects in either gender.

For RNI, nitrogen dioxide and PM_2.5 affected more brain tracts in females with negligible effects in males. In contrast, ozone exerted more effects in tracts concerning limbic association in males and involved the corticospinal tracts among females.

In forceps minor regions, RNI in males increased more rapidly than in females with time; restricted directional diffusion increased among males but was unaltered among females.

At nine years of age, among males, lower RND and RNI values were observed in nearly all tracts, and exposure to PM_2.5 did not significantly modify RNI or RND growth between nine and 13.0 years.

Further, nitrogen dioxide exposure had non-significant effects on restricted directional diffusion for males or females at nine years of age or on delayed directional diffusion development with time.

In most WM tracts of females, higher nitrogen dioxide exposure was associated with higher RNI levels at nine years, but smaller RNI increases with age.

However, in frontal superior and inferior cortical and left cingulate regions, RNI values were similar at nine years but with smaller RNI increases with age. Among males, no significant nitrogen dioxide-age relationships were observed.

WM tracts negatively associated with ozone and restricted directional diffusion at nine years of age included the fornix and corticospinal tracts of the left side among males and the left parahippocampal cingulum area and the inferior frontal-occipital fasciculus in females.

Beyond ozone effects at 9.0 years, a significant ozone-by-age interaction was noted for males' frontal superior corticostriatal tract, with higher ozone concentrations associated with larger RND increases over time.

However, no significant age-ozone interactions in females were observed. Ozone concentrations showed direct associations with RNI at 9.0 years in the bilateral parahippocampal cingulum areas and forceps major regions among males, and the corticospinal tracts bilaterally, corpus callosum, and the superior longitudinal fasciculus of the left parietal lobe in females.

A significant age-ozone interaction was observed in the corticospinal tracts on the right in females, with higher ozone exposure associated with increased restricted normalized isotropic diffusion at nine years but smaller RNI increases with age.

Among males, the team observed ozone-age interactions for the bilateral parahippocampal cingulum areas, the right corticospinal tract, and the corpus callosum, with higher ozone exposure associated with smaller RNI increases from nine to 13 years of age.

Conclusion

Based on the study findings, exposure to even low levels of outdoor air pollutants affects young individuals' WM microstructural development, with different patterns observed among males and females.

The study findings underpin the World Health Organization's (WHO) recommendation of lowering air quality standards to protect the brain health of developing youth, as criterion pollutants significantly impact intracellular isotropic and directional diffusion, affecting tracts related to projection and association.

*Important notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.