Neural Reactivity to Stress

描述（由申请人提供）：一个人对急性心理压力源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，颈动脉粥样硬化是已知的冠心病导致过早残疾和死亡的预测因子。然而，在人类中，将心理压力与血压反应性升高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，该项目验证了一个中心假设，即对心理压力的过度血压反应和更大的临床前颈动脉粥样硬化通常与处理心理压力源和调节自主神经、神经内分泌和心血管活动的大脑系统网络中应激诱导的过度活跃有关。这些脑系统包括扣带皮层、脑岛和杏仁核的功能细分。为了验证这一中心假设的具体预测，将在75名男性和75名女性（年龄在30-50岁）的代表性社区样本中评估三个具体目标，这些人没有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、生物学和社会心理心血管危险因素的特征。参与者将在功能磁共振成像（fMRI）过程中完成一系列心理压力任务，以引发血压反应；他们还将完成一项非侵入性颈动脉超声协议，以评估临床前动脉粥样硬化。目的1验证了这样一种预测，即对应激源电池的过度血压反应将与更大的激活相关（正如更大的fMRI血氧水平依赖性[BOLD]反应所揭示的那样），这些激活发生在扣带皮层、背扣带皮层和后扣带皮层、前脑岛和杏仁核。Aim 2验证了这样一种预测，即在考虑其他心血管危险因素后，这些大脑系统对应激源电池的激活程度越高，而对非应激源控制任务的激活程度越低，将与更多的临床前动脉粥样硬化（如颈动脉内膜-中膜厚度越大所示）相关。目的3通过30名参与者的应激源诱导的fMRI BOLD反应的重测可靠性来验证应激源诱导的这些脑系统激活是个体稳定的反应倾向的预测，这些参与者将在间隔8周的两次重复fMRI测试中进行测试。与健康相关的意义：该研究旨在明确可能将心理应激与心血管反应性夸大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来针对冠心病高危症状前人群进行早期改造。公共卫生相关性：根据PA-07-046：身心相互作用与健康的研究提交。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，描绘这些脑系统对于(1)了解心理压力导致心血管反应的神经通路，从而增加冠心病风险(2)识别与压力相关的神经活动标记物，这些标记物可以客观地识别并可能针对未来冠心病风险人群进行早期修改。

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.