Maternal hair cortisol concentrations, prenatal psychopathology and offspring behavioral phenotypes

项目总结/摘要 研究背景：下丘脑-垂体-肾上腺轴（HPA轴）是机体自然应激反应的一种 系统，并在多个生物过程中发挥重要作用。当受到压力刺激时，HPA轴 刺激全身皮质醇的分泌。在过去，皮质醇的表征受到以下因素的限制： 使用急性皮质醇浓度指标（唾液、尿液、血浆）。最近，测量 头发中的皮质醇已经成为测定HPA轴综合活性的成本有效的手段。本研究 旨在描述头发皮质醇浓度（HCC），并评估哪些因素影响皮质醇浓度 在来自秘鲁利马的大型且特征明确的队列中（N= 2，700）。另一个主要研究目的是评估 下丘脑-垂体-肾上腺轴失调与母亲创伤经历及围生儿的关系 精神病理学我们将估计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HCC在多大程度上是这种关联的驱动因素 母亲的精神病理学和后代的健康状况之间的联系影响：拟议的研究是 三大创新方式。首先，我们利用少数几个前瞻性收集头发的群体之一 在高风险人群中的样本。其次，我们使用一种新的方法来评估长期皮质醇 头发中的分泌物，打开了一个新时代的大门，生物学上健全的研究压力的作用，在无数 包括围产期健康结果。第三，我们使用包括调解在内的高级分析 分析方法来评估HPA轴失调在后代行为健康风险中的因果作用。 该应用程序与NIMH战略计划战略2.2一致：“识别和理解风险因素， 生物标志物，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， 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.