Effects of Urban Chemical and Non-Chemical Stressors on Preadolescent Mental Health

PROJECT SUMMARY Anxiety and depression are highly debilitating mental health disorders with origins in early life, making research in children and adolescents a critical public health need. The prevalence of both disorders in this age group has rapidly increased over the past decade, particularly in urban areas. Though the etiologies of child and adolescent mental health disorders remain poorly understood, increasing trends over mere decades point to environmental causes more than genetics. We propose that non-chemical stressors (noise, violence, negative life events, and neighborhood environment) in the urban environment play a major role and interact with environmental factors that show strong urban-rural gradients, such as air pollution. The neurocognitive toxicity of air pollution has been intensely studied in animal and epidemiologic research but its role in anxiety and depression is poorly understood, with only a few studies in adults, and even less in younger populations. Further, the mechanisms by which air pollution impacts the brain are poorly understood, although altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis and its role in regulating cortisol secretion is a prime candidate. This study will determine whether early life PM2.5 and non- chemical stressors impact symptoms of depression and anxiety in preadolescence/ late childhood and whether cortisol mediates and/or modifies these relationships. We will leverage resources from an established longitudinal birth cohort in Mexico City - Programming Research in Obesity, Growth, Environment and Social Stress (PROGRESS). Specifically, we will examine time-specific and cumulative PM2.5 exposure in relation to mental health outcomes in 8-11 year olds (Aim 1), the role of individual and combined urban non-chemical stressors in relation to mental health symptoms (Aim 2), and the role of hair cortisol levels on the biological pathway from PM2.5 to mental health symptoms (Aim 3). In order to more comprehensively characterize urban stressors in environmental epidemiology and assess their impacts on mental health in preadolescents, I will cross-train in child and adolescent psychopathology and enhance my skills in geospatial modeling. I will additionally train in advanced statistical mixtures and causal mediation to better characterize biological pathways from PM2.5 and stress to mental health outcomes. I will develop these skills through didactic training, independent study, and mentorship from experts in developmental psychology, pediatrics, geography, social epidemiology, and biostatistics, specifically - Drs. Rosalind Wright, Robert Wright, Itai Kloog, Daniel Klein, and Brent Coull. At the end of this training period, I will be uniquely positioned to more comprehensively examine the effectsof multiple urban stressors on mental health outcomes in future research. Further, I will use the knowledge gained and the noise model I develop in future grants, setting the stage for my long-term goal of studying the effects of chemical and non-chemical stressors in the urban environment on brain development and mental health outcomes across the life course.