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: 8550760
• 负责人: Michelle M Wirth
• 金额: $ 21.55万
• 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 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8550760
• 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; public health relevance; 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.

描述（由申请人提供）：随着时间的推移，对健康和压力的生理测量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得到强调，它产生应激激素皮质醇。然而，现有的研究一般都是在一个单一的时间点调查这个系统，这妨碍了理解哪一个是第一位的：改变HPA轴功能或与之相关的健康结果。需要进行纵向研究，跟踪个人多年，以了解这个生理系统如何影响，并受到影响，情绪，健康和福祉。皮质醇水平通过一个被称为负反馈的过程受到严格调节：皮质醇“关闭”自己的生产，从而在增加后迅速控制皮质醇水平。 个体的负反馈程度不同，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能力。此外，重性抑郁症与低于平均水平的糖皮质激素敏感性和HPA负反馈相关。也有证据表明，负反馈不是一个静态的特征，而是可以随着时间的推移而改变，例如当抑郁症消退时。然而，目前还不知道负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反馈程度的变化。也完全不知道负反馈是如何与情绪、生活压力、健康和幸福的变化联系在一起的，超越了抑郁等心理疾病状态。该项目通过将HPA轴负反馈的测量添加到Notre Dame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。假设一个双向模型，因为一个人的负反馈程度既影响他们的健康和幸福，又受他们的健康和幸福的影响。该项目有两个与此双向模型相关的目标。目的1是了解个人差异变量和背景因素在过去5年的NDHWB数据之前或预测差异的负反馈。目的2是调查现在和未来的健康和幸福的措施与负反馈或预测。为了测试这些目标，将从NDHWB研究中选择150名年龄从18岁到90岁的参与者来评估HPA轴负反馈。这是通过注射低剂量皮质醇引起的上游激素ACTH的抑制程度来测量的（与没有注射皮质醇的对照日相比）。负面反馈数据将与NDHWB研究多年来关于个体差异、生活压力、日常压力源、情绪和健康结果的数据相结合。这将提供一个前所未有的机会来发现压力，情绪和HPA轴失调之间的时间过程关系。这一知识对于了解整个生命周期的福祉和抵御疾病的能力的发展至关重要。