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Early life stress, telomere attrition, and child prefrontal cortex functioning


? DESCRIPTION (provided by applicant): Early life stress (ELS) increases risk for maladaptive socioemotional, cognitive, and behavioral functioning and mental and physical health problems through adulthood. Methods for identifying children most vulnerable to poor outcomes and for applying effective prevention strategies are lacking. There is a considerable public health need to develop efficient tools for identifying at-risk individuals and to elucidate mechanisms responsible for adverse ELS effects so that appropriate prevention and treatment strategies may be designed. Recent data suggest that telomere length (TL) may be a promising biomarker for identifying individuals at risk for ELS- induced maladaptive outcomes. More rapid TL attrition, an indicator of cellular aging, has been linked to both stress exposures and to poor health outcomes. To date, associations between TL and health outcomes have been tested almost exclusively in animal studies and among adult humans in retrospective, cross-sectional designs. Longitudinal, prospective research is needed to determine the utility of TL in predicting developmental outcomes in childhood. Moreover, related mechanisms may be responsible for links between ELS and TL and between ELS and poor health outcomes. Identifying these mechanisms may lead to novel intervention strategies. The goal of the proposed study is to test associations among repeated measures of ELS, TL, stress reactivity (hypothalamic-pituitary-adrenal axis and autonomic nervous system functioning), oxidative stress, and prefrontal cortex (PFC) functioning, which is involved in a range of socioemotional, cognitive, behavioral, and mental health outcomes throughout life. The study aims will be accomplished by following an established racially/ethnically-mixed urban pregnancy cohort (N=250), the Programming of Intergenerational Stress Mechanisms (PRISM) project (R01HL095606). The proposed study will build on PRISM's extensive database, which includes comprehensive, repeated assessments of stress exposures, stress reactivity, and neurobehavioral functioning from pregnancy through two years of age and an extensive biorepository of repeated collections of blood, saliva, hair, and urine. This new initiative will extend collection of these measures through age 5 years to examine links among (a) prenatal stress and TL at birth; (b) ELS and TL attrition through age 5 years; (c) prenatal stress reactivity, oxidative stress, and TL at birth; (d) stress reactivity, oxidative stress, and TL attrition through age 5 years; (e) TL at birth, TL attrition, and PFC functioning through age 5 years. This study is novel in its (a) comprehensive assessment of stress exposures measured prenatally and in infancy through the preschool period in relation to telomere biology; (b) testing of links between TL and neurobehavioral functioning in childhood; (c) comprehensive, state-of-the-art methods for assessing stress reactivity; (d) prospective longitudinal design, which may increase understanding of direction of effects among exposures, stress reactivity, and cellular aging and PFC functioning. The findings may be translated into strategies to identify and treat at-risk children to prevent a range of maladaptive outcomes across the lifespan.

Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.