Child Maltreatment and Cardiovascular Disease Risk: Examining Psychosocial and Immunological Pathways in a Prospective, Longitudinal Cohort PI: Hannah M. C. Schreier PROJECT SUMMARY / ABSTRACT Over one third of U.S. youth are investigated for child maltreatment (CM) before the age of 18. CM represents an especially potent early life stressor with a profound impact on youth’s psychological and physical well-being. Among other things, CM increases the risk for cardiovascular disease (CVD), which is responsible for 32% of all deaths in the U.S. and the roots of which can already be found during childhood. Thus, a better understanding of the physiological mechanisms through which CM is associated with increased CVD risk is needed to improve the lifelong health trajectories of youth with a CM history, a high-risk yet understudied group, as well as to better understand biological mechanisms connecting early life adversity to later life health more generally. The proposed project will build on the currently ongoing Child Health Study (CHS; HD089922, PI: Noll, Co-I: Schreier), as part of which 675 youth aged 8-13 years who were recently investigated for CM as well as 225 comparison youth without a history of CM are being recruited and followed prospectively. Taking advantage of this unique and exceptionally well-characterized cohort, we will augment the biopsychosocial data already being collected to examine in-depth immune function outcomes. To this end, this project will assess stimulated pro- and anti-inflammatory cytokine production following in vitro microbial challenge, sensitivity to glucocorticoid signaling among white blood cells, and, finally, latent virus regulation, all across multiple timepoints. This will allow us to investigate prospectively and in detail the associations between exposure to CM and immune function outcomes and will be the first study to do so in a sample of recently maltreated youth. Additionally, we will be able to link the resulting immune function outcomes to early indicators of CVD risk among these youth, both by linking to existing measures of cardiometabolic risk in the cohort and further by linking to youth’s administrative records, specifically Medicaid claims data. This will be the first study to examine connections between immune function outcomes and CVD-relevant health care use among youth. Finally, we will be investigating the extent to which malleable protective factors, including youth lifestyle, family and peer environments, may protect youth from the adverse effects of CM on altered immune function outcomes and the extent to which key demographic moderators (age, pubertal stage, gender, race/ethnicity, CM severity) play a role. The interdisciplinary research team includes expertise in the assessment of immune function outcomes and CVD risk among vulnerable youth; the recruitment and retention of prospective cohorts of CM survivors; and the use of administrative records to answer questions pertaining to the well-being of youth with a history of CM. Resulting data will make important contributions to the CM and early life adversity literatures. It will also inform future prevention and intervention efforts with the ultimate goal of reducing the risk of adverse long-term health consequences among some of the most vulnerable individuals in the population as well as reducing the healthcare costs resulting from CM.

Project Narrative Early life adversity increases the risk of future morbidity and mortality due to cardiovascular disease. This project takes advantage of a large, well-characterized, prospective cohort of youth who were recently investigated for child maltreatment and comparison youth without a maltreatment history to better understand the physiological mechanisms between early adversity and cardiovascular disease risk. By taking advantage of detailed assessments of immune function coupled with administrative health care records and thorough behavioral and psychosocial assessments, we will prospectively examine links between child maltreatment and cardiovascular disease risk, with the hopes of informing future prevention and intervention efforts.