Stress Biomarkers: Biological Meaning of Field-Friendly Salivary Measures

压力生物标志物：现场友好唾液测量的生物学意义

基本信息

批准号：
9094617
负责人：
James L Abelson
金额：
$ 54.34万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2018-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9094617
关键词：
Accounting Adrenal Glands Area Biological Biological Assay Biological Markers Biological Process Biology Brain CRH gene Cardiovascular Diseases Childhood Collection Corticotropin Corticotropin-Releasing Hormone Receptors Data Detection Developmental Process Dexamethasone Distant Documentation Emotions Epidemiologic Studies Epidemiology Explosion Failure Fatigue Feedback Fostering Future Genes Genetic Glucocorticoids Goals Health Human Hydrocortisone Hypothalamic structure Laboratories Laboratory Study Lead Life Stress Light Link Malignant Neoplasms Measurable Measures Mediator of activation protein Mental Depression Mental Health Metabolic Diseases Metyrapone Minority Morbidity - disease rate Neurobiology Occupations Outcome Pituitary Gland Play Price Process Psychosocial Factor Psychosocial Influences Psychosocial Stress Receptor Gene Recovery Regulation Research Research Personnel Resistance Risk Role Saliva Salivary Sampling Shapes Stress System Testing Translating Trauma Variant Work base cost cost effective developmental genetics dexamethasone suppression test experience field study genetic information genetic variant hypothalamic-pituitary-adrenal axis interest mortality novel pediatric trauma physical conditioning prevent psychosocial public health relevance receptor sensitivity relating to nervous system response risk variant socioeconomics stress reactivity trait

项目摘要

DESCRIPTION (provided by applicant): Stress and emotion impact health. To reduce their costly health consequences, mechanisms through which they alter biological processes must be understood. The hypothalamic-pituitary adrenal (HPA) axis plays a key role in transducing psychosocial experience into bodily changes relevant to health, and HPA stress research is exploding. Salivary cortisol measures provide a stress "biomarker" of HPA activity for use in epidemiological studies, revealing that cortisol is associated with job stress, trauma, depression, fatigue, minority status, cardiovascular disease, and cancer mortality. Laboratory work has dissected HPA activity into biologically important regulatory components (e.g., negative feedback, central drive, stress reactivity) and provides laboratory probes of these components, but there has been little effort to link field and laboratory studies. Psychosocial correlates of field-friendly stress biomarkers are being identified, but we know little about their biological meaning. Markers have been chosen based on ease of use, not on empirical links to specific biological processes of known health relevance. This project will link field and laboratory work, enhancing the value of both, and the value derived from the millions of dollars spent yearly on salivary cortisol assay. The cortisol awakening response (CAR), awakening level, and diurnal decline are commonly used field stress biomarkers. Each likely provides different information about HPA axis regulation, but this has not been explicitly examined. CAR is the most extensively used. Its laboratory correlates have been studied, but are rarely acknowledged - it appears more closely linked to adrenal sensitivity than to theoretically more interesting central HPA measures. Giving biological meaning to field-friendly biomarkers will foster more precise hypotheses, and more efficient bio-sampling to test them. The laboratory probes which will attach biological meaning to salivary measures are themselves influenced by interacting genetic and developmental factors. Childhood adversity, for example, significantly reduces HPA feedback sensitivity, but this effect is only seen in subjects with a particular variant of an HPA gene (CRHR1) and can remain undetected if the genetic effect is ignored. If genes impact laboratory probes, and the field markers link to these probes, genes will impact the field markers. Ignoring this impact will undermine efforts to link psychosocial variables to the stress biomarkers. Documentation of this phenomena and preliminary exploration of relevant genes will be critical to prevent false negative results and replication failures in expensive epidemiological studies that we hope will use the more efficient and biologically meaningful biomarkers we identify in this project. In this study, we will use laboratory probes to give biological meaning to field-friendly HPA biomarkers, identify the most efficient and meaningful set of probes to use, and provide preliminary data on genetic factors that can undermine hypothesis testing in epidemiological stress research using stress biomarkers. This work will deepen understanding of the HPA axis and enhance the value of every future dollar spent on field stress studies.

描述（由申请人提供）：压力和情绪影响健康。为了减少其代价高昂的健康后果，必须了解它们改变生物过程的机制。下丘脑-垂体肾上腺 (HPA) 轴在将心理社会体验转化为与健康相关的身体变化方面发挥着关键作用，并且 HPA 压力研究正在呈爆炸式增长。唾液皮质醇测量提供了 HPA 活性的压力“生物标志物”，可用于流行病学研究，揭示皮质醇与工作压力、创伤、抑郁、疲劳、少数民族状况、心血管疾病和癌症死亡率相关。实验室工作已将 HPA 活性分解为生物学上重要的调节成分（例如负反馈、中枢驱动、应激反应性），并提供这些成分的实验室探针，但几乎没有努力将现场研究和实验室研究联系起来。现场友好的压力生物标志物的心理社会相关性正在被识别，但我们对其生物学意义知之甚少。标记物的选择是基于易用性，而不是基于与已知健康相关的特定生物过程的经验联系。该项目将把现场工作和实验室工作联系起来，提高两者的价值，以及每年在唾液皮质醇测定上花费数百万美元的价值。皮质醇觉醒反应 (CAR)、觉醒水平和昼夜下降是常用的现场应激生物标志物。每个可能提供有关 HPA 轴调节的不同信息，但这尚未得到明确检查。 CAR是应用最广泛的。它的实验室相关性已经被研究过，但很少被承认——它似乎与肾上腺敏感性的联系比理论上更有趣的中枢 HPA 测量的联系更密切。赋予现场友好的生物标志物生物学意义将促进更精确的假设，以及更有效的生物采样来测试它们。将生物学意义赋予唾液测量的实验室探针本身受到相互作用的遗传和发育因素的影响。例如，童年逆境会显着降低 HPA 反馈敏感性，但这种效应仅在具有特定 HPA 基因变体 (CRHR1) 的受试者中可见，并且如果忽略遗传效应，则可能无法检测到。如果基因影响实验室探针，并且现场标记链接到这些探针，则基因将影响现场标记。忽视这种影响将破坏将心理社会变量与压力生物标志物联系起来的努力。这种现象的记录和相关基因的初步探索对于防止昂贵的流行病学研究中的假阴性结果和复制失败至关重要，我们希望这些研究将使用我们在本项目中确定的更有效和具有生物学意义的生物标志物。在这项研究中，我们将使用实验室探针为现场友好的 HPA 生物标志物赋予生物学意义，确定最有效和最有意义的探针组，并提供有关可能破坏流行病学应激研究中假设检验的遗传因素的初步数据。生物标志物。这项工作将加深对 HPA 轴的理解，并提高未来用于现场应力研究的每一美元的价值。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Do diurnal salivary cortisol curves carry meaningful information about the regulatory biology of the HPA axis in healthy humans?

每日唾液皮质醇曲线是否携带有关健康人类 HPA 轴调节生物学的有意义的信息？

DOI：
发表时间：
2023-04
期刊：
影响因子：
3.7
作者：
Abelson, James L;Sánchez, Brisa N;Mayer, Stefanie E;Briggs, Hedieh;Liberzon, Israel;Rajaram, Nirmala
通讯作者：
Rajaram, Nirmala

The psychology of HPA axis activation: Examining subjective emotional distress and control in a phobic fear exposure model.

HPA 轴激活的心理学：在恐惧暴露模型中检查主观情绪困扰和控制。

DOI：
发表时间：
2017-08
期刊：
影响因子：
3.7
作者：
Mayer, Stefanie E;Snodgrass, Michael;Liberzon, Israel;Briggs, Hedieh;Curtis, George C;Abelson, James L
通讯作者：
Abelson, James L

The Neurobiology of Post-Traumatic Stress Disorder (PTSD): Perspectives and Trends

创伤后应激障碍 (PTSD) 的神经生物学：观点和趋势