Glucocorticoid sensitivity and well-being in aging: bi-directional relationships

糖皮质激素敏感性和衰老过程中的健康：双向关系

• 批准号: 8428497
• 负责人: Michelle M Wirth
• 金额: $ 19万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8428497
• 关键词: Address; Adrenal Glands; Affect; Age; Aging; Area; Back; Biological; Brain; Chronic; Corticotropin; Data; Development; Disease; Dose; Down-Regulation; Emotional; Emotions; Event; Exercise; Feedback; Future; Glucocorticoids; Goals; Growth; Health; Health Status; Hormones; Hydrocortisone; Hypothalamic structure; Individual; Individual Differences; Injection of therapeutic agent; Intravenous infusion procedures; Investigation; Knowledge; Lead; Life; Life Experience; Life Stress; Longevity; Longitudinal Studies; Major Depressive Disorder; Measurement; Measures; Mental Depression; Mental Health; Modeling; Moods; Outcome; Participant; Pathway interactions; Perception; Personal Satisfaction; Persons; Physiological; Physiology; Pituitary Gland; Pituitary Hormones; Placebos; Plastics; Process; Production; Recovery; Research; Resistance; Role; Saline; Shapes; Social support; Stress; Symptoms; System; Systems Analysis; Testing; Time; acute stress; contextual factors; diaries; hypothalamic-pituitary-adrenal axis; innovation; insight; novel; physical conditioning; prevent; psychologic; resilience; response; satisfaction; stress resilience; stressor; trait

DESCRIPTION (provided by applicant): Relationships over time between health and physiological measures of stress are still poorly understood. A role in health has been highlighted for the hypothalamic- pituitary-adrenal (HPA) axis, which produces the stress hormone cortisol. However, existing studies have generally investigated this system at a single time-point, which prevents understanding of which comes first: altered HPA axis function or the health outcomes associated with it. Longitudinal research is needed following individuals over years to understand how this physiological system both affects, and is affected by, mood, health and well-being. Cortisol levels are tightly regulated via a process known as negative feedback: cortisol "turns off" its own production, thus quickly reining in cortisol levels after an increase. Individuals vary in their degree of negative feedback, depending on their glucocorticoid sensitivity: in other words, how well their brains can detect and respond to cortisol. Interestingl, major depression is associated with lower than average glucocorticoid sensitivity and HPA negative feedback. There is also evidence that negative feedback is not a static trait but can change within an individual over time, e.g. when the depression resolves. It is not yet known, though, whether alterations in negative feedback occur first, and lead to development of mood or other health problems, and/or whether mood or health status cause changes in the degree of negative feedback. It is also completely unknown how negative feedback is associated with changes in mood, life stress, health and well- being beyond psychological disease states such as depression. This project addresses these questions by adding measurement of HPA axis negative feedback to the rich longitudinal data on mood, stress, and health in the Notre Dame Study of Health and Well-Being (NDHWB). A bi- directional model is hypothesized, in that a person's degree of negative feedback both impacts and is impacted by their health and well-being. The project has two goals (Aims) related to this bi-directional model. Aim 1 is to understand which individual difference variables and contextual factors in the preceding 5 years of NDHWB data precede or predict differences in negative feedback. Aim 2 is to investigate which present and future health and well-being measures are associated with or predicted by negative feedback. To test these Aims, 150 participants ranging in age from 18 to 90 will be selected from the NDHWB study to assess HPA axis negative feedback. This is measured by degree of suppression of an upstream hormone, ACTH, caused by an injection of a low dose of cortisol (compared to a control day with no cortisol injection.) Negative feedback data will be combined with the NDHWB study's multiple years of data on individual differences, life stress, daily stressors, mood, and health outcomes. This will provide an unprecedented opportunity to discover time-course relationships between stress, mood, and dysregulation in the HPA axis. This knowledge is of vital importance for understanding the development of well-being and resilience against illness across the lifespan. PUBLIC HEALTH RELEVANCE: Findings from this project will increase our understanding of how life experiences and emotions alter stress physiology over time, and in turn, how stress physiology affects future mental and physical health. The goal of this project is to collect nuanced information about the HPA axis (an important physiological stress system) in the context of an ongoing longitudinal study, which examines stressful life experiences, mood, physical health, and other aspects of well-being over several years, in people of different ages. This project thus has the potential to yield important insights about the physiological underpinnings of how stress and mood affect health across the lifespan.

描述(由申请人提供)：随着时间的推移，健康和生理压力指标之间的关系仍然知之甚少。下丘脑-垂体-肾上腺(HPA)轴在健康中的作用已经被强调，它产生应激激素皮质醇。然而，现有的研究一般是在单个时间点研究这一系统，这使得人们无法理解哪一个是最先发生的：HPA轴功能改变或与其相关的健康后果。多年来，需要对个人进行纵向研究，以了解这种生理系统如何影响情绪、健康和幸福感，以及如何受到影响。皮质醇水平通过一个被称为负反馈的过程受到严格控制：皮质醇“关闭”自身的生产，从而在皮质醇水平上升后迅速控制。 每个人的负面反馈程度不同，这取决于他们对糖皮质激素的敏感性：换句话说，他们的大脑对皮质醇的检测和反应有多好。有趣的是，重度抑郁与糖皮质激素敏感性低于平均水平和HPA负反馈有关。也有证据表明，负面反馈不是一种静态的特征，而是会随着时间的推移而在个体内部发生变化，例如当抑郁症状缓解时。然而，目前还不知道负面反馈的变化是否首先发生，并导致情绪或其他健康问题的发展，和/或情绪或健康状况是否会导致负面反馈程度的变化。除了抑郁等心理疾病状态之外，负面反馈如何与情绪、生活压力、健康和幸福感的变化相关也是完全未知的。这个项目通过将HPA轴负反馈的测量添加到圣母大学健康与幸福研究(NDHWB)中关于情绪、压力和健康的丰富纵向数据来解决这些问题。一个双向模型是假设的，因为一个人的负面反馈程度既影响他们的健康和幸福，也受到他们的影响。该项目有两个与此双向模式相关的目标(目标)。目的1是了解在过去5年的NDHWB数据中，哪些个体差异变量和背景因素先于或预测了负反馈的差异。目标2是调查哪些现在和未来的健康和幸福措施与负面反馈有关或由负面反馈预测。为了测试这些目标，将从NDHWB的研究中挑选150名年龄从18岁到90岁的参与者来评估HPA轴的负面反馈。这是通过注射低剂量皮质醇(与没有注射皮质醇的对照组相比)对上游激素ACTH的抑制程度来衡量的。负面反馈数据将与NDHWB研究的多年数据相结合，这些数据涉及个体差异、生活压力、日常压力、情绪和健康结果。这将提供一个前所未有的机会来发现压力、情绪和HPA轴调节失调之间的时程关系。这一知识对于理解人一生中幸福感的发展和抵御疾病的能力至关重要。 与公共健康相关：这个项目的发现将增加我们对生活经历和情绪如何随着时间的推移改变压力生理学的理解，进而了解压力生理学如何影响未来的心理和身体健康。这个项目的目标是在一项正在进行的纵向研究的背景下，收集关于HPA轴(一个重要的生理压力系统)的细微差别信息，该研究检查了几年来不同年龄段的人的应激生活经历、情绪、身体健康和其他方面的幸福感。因此，这个项目有可能对压力和情绪如何影响人的一生的健康的生理基础产生重要的见解。