The joint effects of early life lead exposure, and psychosocial co-exposures, on physiological stress and cardiometabolic health across the life course - SUMMARY Globally one in three children, or around 800 million, have elevated blood lead levels. Though the detrimental neurocognitive, cardiometabolic, and behavioral effects of lead (Pb) exposure appear universal, some individuals are more susceptible to such outcomes than others, suggesting potential risk and protective factors. Differences in health outcomes may be explained in part by the joint effects of toxicants and psychosocial co-exposures on similar physiological stress targets and resulting dysregulation, which, over time, can increase risk for life course cardiometabolic dysfunction. In essence, experiencing toxicant exposure and negative psychosocial exposures in early development may create a “double hit” on stress pathways, making some individuals more susceptible to poor cardiometabolic health later in life. Conversely, experiencing positive psychosocial exposures may protect against detrimental effects. We hypothesize that the joint effects of Pb exposure, other metals, and psychosocial stressors are stronger than that of a single exposure alone. Despite their similar physiological targets and likelihood of co-exposure, no human studies have tested the joint effects of early life toxicant and psychosocial exposures on later cardiometabolic health or examined physiological stress as a potential unifying mechanistic pathway. The overall objective for this application is to a) characterize the risk and protective effects of environmental co-exposures on adolescent (K99) and young adult (R00) cardiometabolic health and, b) provide new insight on the role physiological stress plays in the path between early life environmental co- exposures and cardiometabolic health (R00). In the mentored K99 phase, the Candidate will first utilize data from the ongoing ELEMENT Mexican cohort and begin by examining the joint effects of 1) early life and 2) childhood heavy metals (Pb, As, Cd, Hg, Mn), SEP, and HOME scores on adolescent cardiometabolic health (K99/Aim 1). The independent R00 phase, the Candidate will construct an ancillary study to the upcoming ELEMENT U24 young adult follow-up and examine joint effects of heavy metals, SEP, HOME scores, and adverse childhood experiences (ACEs) on young adult cardiometabolic health and changes from adolescence (R00/Aim 2) and test physiological stress (i.e., chronic and reactive cortisol) as a mechanistic pathway (R00/Aim 3). This work will identify modifiable psychosocial risk and protective factors and physiological mediators that can be targeted to improve life course health of individuals exposed to Pb in early life. Through a training plan that utilizes the interdisciplinary environment and expertise at the University of Michigan School of Public Health, the Candidate will develop and enhance their skills pertaining to concepts and methods essential for studying environmental co-exposures, mechanisms, and life course health, advanced statistical techniques, physiological stress biomarkers, and study management. This training and research will launch the Candidate’s career as a children’s environmental health nurse scientist and a successful transition to research independence.
