Epigenetics, air pollution, and childhood mental health

Project Summary
Anxiety and depression are among the most debilitating disorders worldwide and increase the
risk for later-life adverse health outcomes including chronic anxiety and depression, substance
abuse and suicide. Anxiety and depression are also the most common psychiatric disorders
among adolescents with symptoms presenting as early as 4-5 years of age. Yet, we still have a
poor understanding of the etiology of anxiety and depression in youth and the mechanisms
involved. Air pollutants are widely recognized for their ability to affect the central nervous system
and adversely impact neurodevelopment during childhood. The epigenome is particularly
sensitive to environmental stimuli and studies targeting inflammatory and oxidative stress
pathways have identified DNA methylation changes resulting with exposure to air pollutants.
Oxidative stress and inflammation, however, are not the only pathways involved in air pollution
neurotoxicity or the pathophysiology of mental health disorders. Thus, utilizing an epigenome-
wide platform may help identify novel biomarkers of exposure and effect which may otherwise
be overlooked with a targeted approach. The goal of this proposal is to determine whether
exposure to fine particulate matter (PM2.5) and traffic-related air pollution (TRAP) during
childhood and adolescence impacts the epigenome and whether changes in DNA methylation
can be used to identify children at increased risk for anxiety and depression. Using the
Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) and Health Outcomes and
Measures of the Environment (HOME) study birth cohort, we will: 1) conduct an unbiased
epigenome-wide search for DNA methylation biomarkers associated with PM2.5 and TRAP
exposure prenatally through age 12 years (n=500) and 2) identify unique and pollution-related
DNA methylation signatures associated with anxiety and depression. In addition, we will
replicate our findings in a third, independent birth cohort, Project Viva (n=652), with similar
sociodemographic characteristics and available air pollution and neurodevelopmental outcome
data. The study design, based on three well-established birth cohorts with nearly two
decades of follow-up, will allow for longitudinal and cross-sectional analyses of air pollution,
DNA methylation, and mental health assessments all of which will increase the rigor and
generalizability of our study.

Grant Number: 5R01ES031054-06
NIH Institute/Center: NIH
Principal Investigator: Kelly Brunst