Neural Reactivity to Stress

神经对压力的反应

• 批准号: 7685704
• 负责人: Peter J Gianaros
• 金额: $ 6.21万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-18 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7685704
• 关键词: Accounting; Acute; Amygdaloid structure; Anterior; Area; Atherosclerosis; Base of the Brain; Behavior; Behavioral; Behavioral Genetics; Behavioral Medicine; Biological; Blood; Blood Pressure; Brain; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Carotid Atherosclerotic Disease; Cessation of life; Clinical; Communities; Coronary heart disease; Coupling; Dorsal; Early Intervention; Etiology; Event; Exhibits; Functional Magnetic Resonance Imaging; Future; Health; Human; Hyperactive behavior; Individual; Individual Differences; Insula of Reil; Invasive; Lead; Life; Link; Longevity; Midbrain structure; Modification; Morbidity - disease rate; Myocardial Infarction; National Institute of Mental Health; Neural Pathways; Neurosecretory Systems; Participant; Pattern; Peripheral; Persons; Phenotype; Platelet Factor 4; Play; Prevention intervention; Process; Protocols documentation; Psychological Stress; Public Health; Reaction; Regulation; Research; Risk; Risk Factors; Role; Sampling; Signal Transduction; Specific qualifier value; Stress; Symptoms; System; Testing; Thick; Time; To specify; Ultrasonography; Week; Woman; aged; blood oxygen level dependent; blood oxygenation level dependent response; cardiovascular risk factor; cingulate cortex; depressive symptoms; design; disability; heart disease risk; indexing; intima media; men; mind body interaction; neuroimaging; novel; pre-clinical; psychologic; psychological stressor; psychosocial; relating to nervous system; response; stressor

DESCRIPTION (provided by applicant): A person's tendency to show exaggerated blood pressure reactions to acute psychological stressors is associated with an increased risk for preclinical atherosclerosis in the carotid arteries, which is a known predictor of premature disability and death by coronary heart disease. However, the neural pathways that link psychological stress to exaggerated blood pressure reactivity and risk for carotid atherosclerosis in humans are unknown. Supported by preliminary results, this project tests the central hypothesis that exaggerated blood pressure reactivity to psychological stress and greater preclinical carotid atherosclerosis are commonly associated with stress-induced hyperactivity in a network of brain systems that both process psychological stressors and regulate autonomic, neuroendocrine, and cardiovascular activity. These brain systems include functional subdivisions of the cingulate cortex, insula, and amygdala. To test specific predictions of this central hypothesis, three specific aims will be evaluated in a representative community sample of 75 men and 75 women (aged 30-50 years) who are asymptomatic for clinical cardiovascular disease and who are well characterized for known and emerging demographic, anthropometric, biological, and psychosocial cardiovascular risk factors. Participants will complete a battery of psychological stress tasks to elicit blood pressure reactivity in a functional magnetic resonance imaging (fMRI) session; they will also complete a non-invasive carotid ultrasound protocol to assess preclinical atherosclerosis. Aim 1 tests the prediction that exaggerated blood pressure reactivity to the stressor battery will be associated with a greater activation (as revealed by greater fMRI blood oxygen level-dependent [BOLD] responses) in the perigenual, dorsal, and posterior cingulate cortex, the anterior insula, and the amygdala. Aim 2 tests the prediction that greater activation in these brain systems to the stressor battery, but not to a non-stressor control task, will be associated with more preclinical atherosclerosis (as indicated by greater carotid intima-media thickness) after accounting for other cardiovascular risk factors. Aim 3 tests the prediction that stressor-induced activation in these brain systems is a stable response tendency of individuals, as determined by the test-retest reliability of stressor-induced fMRI BOLD responses in 30 participants who will be tested in 2 repeat fMRI sessions separated by 8 weeks. Health-related significance: The proposed study is designed to specify the neural pathways that may link psychological stress to exaggerated cardiovascular reactivity and preclinical atherosclerosis. The information provided by this study may reveal a novel stress-related neural phenotype that could be targeted by brain-based interventions for early modification in pre-symptomatic people at high risk for coronary heart disease. PUBLIC HEALTH RELEVANCE: Submitted in response to PA-07-046: Research on Mind-Body Interactions and Health. The broad objective of this project is to delineate the human brain systems that centrally link individual differences in cardiovascular reactions to stress and risk for coronary heart disease (CHD). From a public health perspective, it is important to delineate these brain systems to (1) understand the neural pathways by which psychological stress leads to cardiovascular reactions that may increase CHD risk and (2) identify markers of stress-related neural activity that could be objectively identified and possibly targeted for early modification in people at risk for future CHD.

描述（由申请人提供）：一个人对急性心理压力源表现出夸张的血压反应的倾向与颈动脉临床前动脉粥样硬化的风险增加有关，这是已知的冠心病过早残疾和死亡的预测因素。然而，将心理压力与血压反应过度和人类颈动脉粥样硬化风险联系起来的神经通路尚不清楚。在初步结果的支持下，该项目测试了一个中心假设，即夸大血压对心理压力的反应和更大的临床前颈动脉粥样硬化通常与大脑系统网络中压力引起的过度活跃有关，该网络既处理心理压力源，又调节自主神经、神经内分泌和神经系统。心血管活动。这些大脑系统包括扣带皮层、岛叶和杏仁核的功能细分。为了测试这一中心假设的具体预测，将在 75 名男性和 75 名女性（年龄 30-50 岁）的代表性社区样本中评估三个具体目标，这些样本无临床心血管疾病症状，并且具有已知和新兴人口特征、人体测量、生物和心理社会心血管危险因素。参与者将完成一系列心理压力任务，以在功能磁共振成像 (fMRI) 过程中引发血压反应；他们还将完成一项非侵入性颈动脉超声方案来评估临床前动脉粥样硬化。目标 1 测试预测，血压对应激源电池的过度反应将与膝周、背侧和后扣带皮层、前扣带皮层的更大激活（如更大的 fMRI 血氧水平依赖性 [BOLD] 反应所揭示）相关。岛叶和杏仁核。目标 2 测试了这样的预测：在考虑了其他心血管因素后，这些大脑系统对压力源电池的更大激活，而不是对非压力源控制任务的激活，将与更多的临床前动脉粥样硬化（如颈动脉内膜中层厚度更大所表明的）相关。风险因素。目标 3 测试了这一预测，即这些大脑系统中压力源诱发的激活是个体的稳定反应趋势，这一预测是由 30 名参与者中压力源诱发的 fMRI BOLD 反应的重测可靠性确定的，这些参与者将在 2 个重复的 fMRI 会话中分别进行测试8周后。健康相关意义：拟议的研究旨在明确可能将心理压力与夸大的心血管反应性和临床前动脉粥样硬化联系起来的神经通路。这项研究提供的信息可能揭示了一种新的与压力相关的神经表型，可以通过基于大脑的干预措施来针对冠心病高危人群进行早期修正。公共卫生相关性：针对 PA-07-046 提交：身心相互作用与健康研究。该项目的总体目标是描绘人类大脑系统，该系统将心血管反应的个体差异与压力和冠心病（CHD）风险联系起来。从公共卫生的角度来看，描述这些大脑系统非常重要，以便（1）了解心理压力导致心血管反应的神经通路，而心血管反应可能会增加冠心病的风险；（2）识别与压力相关的神经活动的标志物，这些标志物可能会增加冠心病的风险。客观地识别并可能针对有未来冠心病风险的人群进行早期修改。