Thursday, November 21, 2024
11/21/2024
Project Summary Hispanic youth are nearly three times more likely to be at high risk for developmental, behavioral, or social delays compared to white non-Hispanic children. Contributing to this risk disparity is disproportionate rates of Hispanic children living in poverty and heightened risk for exposure to early-life environmental adversity, all of which confers substantial risk for the development of psychopathology and a lifelong risk for chronic diseases. A critical process by which disproportionate experiences of early adversity might influence risk for the development of later psychopathology is through the biological embedding of adversity exposure via epigenetic changes in genes involved in neuroendocrine and inflammatory responses to stress response. Despite promise and progress of social epigenomic research on risk processes, a significant limitation of the extant literature is that a basic understanding of how biological embedding of adversity can be prevented or reversed has yet to be achieved, with little knowledge of the role of protective factors that impact these developmental trajectories. In fact, prior work in humans has been almost exclusively cross-sectional and focused on detrimental environmental impacts, greatly constraining our understanding of epigenomic processes over time and its positive malleability to interventions. The proposed research will leverage an on-going NIH-funded R01 (#HD084497) to evaluate, via a randomized controlled trial of a home-based behavioral parent training intervention, how changing social context (i.e., dysfunctional parenting) alters the epigenome among at-risk Hispanic preschoolers and potentially establishes a biological foundation that promotes resiliency and potentially ameliorates the biological embedding of adversity. In the current proposal, we propose to use a balanced analytical approach that includes (1) a hypothesis-driven pathway analyses for genes involved in neuroendocrine and inflammatory responses to stress, (2) a targeted design that pulls sites previously identified in well-powered EWAS studies to create poly-epigenetic risk scores, and (3) a hypothesis-free epigenome-wide association study. In addition to examining trajectories of change in child DNA methylation, we will determine if exposure to a protective factor (positive parenting) buffers the impact of adversity on biomarkers of accelerated aging during a sensitive developmental stage. Lastly, we will explore epigenomic biosignatures of response to early intervention based on both child and parent DNA methylation. For all aims, we will use a multi-informant, multi-method design that includes observations of parenting, task-based measures of child self-regulation, standardized assessments of child developmental and clinical outcomes, independent clinical evaluators, and both child and parent DNA methylation. This research will facilitate the application of precision medicine and prevention approaches by identifying epigenomic biomarkers of early intervention response patterns that will allow for innovative strategies in risk identification and personalized prevention, together resulting in a new understanding of effective approaches to reducing health disparities.
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