Maternal hair cortisol concentrations, prenatal psychopathology and offspring behavioral phenotypes

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PROJECT SUMMARY / ABSTRACT Background: The hypothalamic–pituitary–adrenal (HPA) axis is one of the body’s natural stress-response systems and is critically involved in multiple biological processes. When triggered by stressors, the HPA axis stimulates the secretion of cortisol throughout the body. In the past, characterization of cortisol was limited by the use of acute cortisol concentration indicators (saliva, urine, plasma). More recently, measurement of cortisol in hair has emerged as a cost-effective means of assaying integrated HPA axis activity. This study seeks to characterize hair cortisol concentration (HCC) and evaluate which factors affect cortisol concentration in a large and well-characterized cohort from Lima, Peru (N=2,700). Another primary study aim is to evaluate the effects of HPA axis dysregulation in relation to maternal experiences of trauma and perinatal psychopathology. We will estimate the extent to which HPA axis dysregulation is associated with offspring behavioral outcomes. Finally, we aim to evaluate the extent to which HCC acts as a driver of the association between maternal psychopathology and offspring health outcomes. Implications: The proposed research is innovative in three major ways. First, we leverage one of the few cohorts with prospectively collected hair samples among a high-risk population. Second, we use a novel method of assessing long-term cortisol secretion in hair that opens the door for a new era of biologically sound studies on the role of stress in a myriad of health outcomes including perinatal health outcomes. Third, we use advanced analysis including mediation analytic methods to assess the causal effects of HPA axis dysregulation in offspring behavioral health risk. This application is consistent with the NIMH Strategic Plan Strategy 2.2: “Identify and understand risk factors, biomarkers, and behavioral indicators of mental illness and of intervention response across the lifespan.” This project will provide foundational knowledge about cortisol, a central molecule in mental health research and will inform our understanding of risk factors that affect child neurodevelopment.