Neural Reactivity to Stress

描述(由申请人提供)：一个人对急性心理压力表现出夸大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，颈动脉粥样硬化是冠心病导致过早残疾和死亡的已知预测因素。然而，在人类中，将心理压力与夸大的血压反应性和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说，即血压对心理应激的反应过度和临床前颈动脉粥样硬化的加重通常与应激诱导的大脑系统网络中的过度活动有关，该网络既处理心理应激源，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回皮质、脑岛和杏仁核的功能细分。为了测试这一中心假设的具体预测，将在一个具有代表性的社区样本中对三个具体目标进行评估，这些样本包括75名男性和75名女性(年龄30-50岁)，他们没有临床心血管疾病的症状，并且具有已知和新兴的人口统计学、人体测量学、生物学和心理社会心血管风险因素的特征。参与者将完成一系列心理应激任务，以在功能磁共振成像(FMRI)会话中引发血压反应；他们还将完成无创颈动脉超声方案，以评估临床前动脉粥样硬化。目的1验证这样一种预测，即血压对应激源电池的过度反应将与更大的激活(如更大的fMRI血氧水平依赖[BOLD]反应所揭示的那样)在丘脑周围、背侧和后扣带皮质、前脑岛和杏仁核。目的2验证这样的预测：在考虑了其他心血管危险因素后，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激活，将与更多的临床前动脉粥样硬化相关(如更大的颈动脉内膜-中层厚度所示)。目的通过对30名受试者应激源诱导的fMRI BOLD反应的重测可靠性，验证应激源诱导的脑系统激活是个体稳定反应趋势的预测，这些参与者将在间隔8周的两次重复fMRI会议中进行测试。与健康相关的意义：这项拟议的研究旨在明确可能将心理应激与过度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来针对有症状前期冠心病高危人群的早期调整。公共卫生相关性：提交以回应PA-07-046：关于身心互动和健康的研究。该项目的广泛目标是描绘人类大脑系统，这些系统将心血管反应的个体差异与应激和冠心病(CHD)的风险集中联系起来。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，从而可能增加CHD风险，以及(2)识别可以客观识别的应激相关神经活动的标志物，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.