Maternal hair cortisol concentrations, prenatal psychopathology and offspring behavioral phenotypes

项目摘要/摘要 背景：下丘脑-垂体-肾上腺(HPA)轴是人体的自然应激反应之一 并在多个生物过程中发挥重要作用。当被应激源触发时，HPA轴 刺激全身皮质醇的分泌。在过去，皮质醇的特性受到以下限制 使用急性皮质醇浓度指标(唾液、尿液、血浆)。最近，对 头发中的皮质醇已经成为检测HPA轴综合活性的一种经济有效的手段。本研究 旨在确定头发皮质醇浓度的特征，并评估哪些因素影响皮质醇浓度 来自秘鲁利马的一个特征良好的大型队列(N=2700)。另一个主要研究目标是评估 HPA轴失调与母体创伤及围产儿经历的关系 精神变态学。我们将估计HPA轴失调与后代相关的程度 行为结果。最后，我们的目标是评估肝细胞癌在多大程度上推动了这种联系 母亲的精神病理和子代的健康结果之间的关系。影响：拟议的研究是 主要有三个方面的创新。首先，我们利用少数几个预期收集到的头发之一 高危人群中的样本。其次，我们使用了一种新的方法来评估长期皮质醇 头发中的分泌物开启了一个新的生物学研究时代，关于压力在无数 健康结果，包括围产期健康结果。第三，我们使用高级分析，包括调解 分析方法评估HPA轴失调在子代行为健康风险中的因果效应。 这一应用与NIMH战略计划战略2.2一致：“识别和了解风险因素， 生物标记物，以及精神疾病的行为指标和整个生命周期的干预反应。这 该项目将提供有关皮质醇的基础知识，皮质醇是心理健康研究的核心分子，并将 让我们了解影响儿童神经发育的风险因素。

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.