Neural Reactivity to Stress

描述（由申请人提供）：一个人对急性心理应激源表现出夸大的血压反应的倾向与颈动脉中临床前动脉粥样硬化的风险增加有关，这是冠心病导致过早残疾和死亡的已知预测因素。然而，将心理压力与过度血压反应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，该项目测试了中心假设，即对心理压力的血压反应性夸大和临床前颈动脉粥样硬化通常与大脑系统网络中的压力诱导的过度活跃相关，这些大脑系统既处理心理压力源，又调节自主神经，神经内分泌和心血管活动。这些大脑系统包括扣带皮层、杏仁核和杏仁核的功能分区。为了检验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价三个具体目标，这些样本无临床心血管疾病症状，并且具有已知和新出现的人口统计学、人体测量学、生物学和心理社会心血管风险因素的良好特征。参与者将完成一系列心理压力任务，以在功能性磁共振成像（fMRI）会议中引起血压反应;他们还将完成一项非侵入性颈动脉超声方案，以评估临床前动脉粥样硬化。目的1测试预测，夸大的血压反应性的应激电池将与更大的激活（如更大的功能磁共振成像血氧水平依赖性[BOLD]反应所揭示的）在膝周，背侧，后扣带回皮质，前额叶，杏仁核。目的2测试预测，在考虑其他心血管风险因素后，这些大脑系统对应激源电池的更大激活，而不是对非应激源控制任务的更大激活，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示）相关。目的3测试的预测，在这些大脑系统中的应激诱导的激活是一个稳定的反应倾向的个人，确定的重测信度的应激诱导的fMRI BOLD反应在30名参与者将在2个重复的fMRI会议间隔8周进行测试。与健康相关的重要性：这项拟议的研究旨在详细说明可能将心理压力与夸大的心血管反应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应激相关神经表型，可以通过基于大脑的干预措施对冠心病高风险症状前人群进行早期修饰。公共卫生相关性：提交以回应PA-07-046：身心互动与健康研究。该项目的主要目标是描述人类大脑系统，这些系统将心血管对压力的反应和冠心病（CHD）风险的个体差异集中联系起来。从公共卫生的角度来看，重要的是描绘这些大脑系统，以（1）了解心理应激导致心血管反应的神经通路，这些反应可能增加CHD风险，（2）确定与应激相关的神经活动的标志物，这些标志物可以客观地识别，并可能针对未来CHD风险人群的早期调整。

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.