Wednesday, January 15, 2025
1/15/2025
ABSTRACT Suicide is the second leading cause of death in US youth. Suicidal behavior is complex and is influenced by a combination of multi-level distal and proximal environmental risk factors and lifestyle factors (i.e., exposome), and biological susceptibility. Adverse exposome is key to youth suicide risk, and yet there is variability and most youth who experience adversity do not attempt suicide. To better understand this variability, we need to develop reproducible tools to quantify adverse exposome, to understand how exposome contributes to disparities in risk among minority populations, and to better understand mechanisms of resilience in high-risk youth. Additionally, we need to integrate risk models of environment with biological measures that can improve our understanding of how environmental stress “gets under the skin” and increases suicide attempt risk. Allostatic load, the physiologic “wear and tear” of the body over time in response to environmental stress is a proposed framework to study mechanisms of exposome's effects on mental health and on suicide risk. While exposome and allostatic load were previously linked to suicide risk, no prior studies have integrated both in a common framework. Our proposal will provide the foundation to test how exposomic risk contributes to psychobiological stress burden in youth, improving our understanding of the emergence of suicidal behavior in adolescence. We will quantify aggregate environmental risk burden in a reproducible manner in five different youth cohorts that include >65,000 youth, of whom 25,000 youth have longitudinal data. We will use an exposome-wide-association-study (ExWAS) approach, which applies a data driven method to systematically study associations with an outcome (such as suicide attempt in this case) using large scale data of exposures and applying statistical methods to derive effect sizes of risk associations, accounting for multiple testing and collinearity among exposures. Thereafter, we will compute exposomic risk scores that represent the aggregated burden of risk exposures and apply these scores to address our aims. In Aim 1, we will test generalizability of exposomic risk scores in five different cohorts from different settings, including a clinical sample; test disparities in exposomic risk to suicide attempt and identify resilience factors that are clinically relevant for future interventions. In Aim 2, we will map exposomic risk to allostatic load measures and test their combined contribution to mental health and suicide attempt risk among youth. Last, in Aim 3, we will explore causal mechanisms of environmental exposures, resilience factors and allostatic load to youth suicide attempt risk by applying causal inference methods on longitudinal data. The expected findings will advance suicide research through developing methods that are critical for reproducibility in using environmental exposures' data; will inform suicide prevention efforts through identification of factors that contribute to disparities in risk and to resilience in high-risk youth; and will advance understanding of the biological processes that are associated with risk and resilience to youth suicide attempts in diverse samples.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).