Neurobiological pathways linking stress and emotion to atherosclerosis

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临床前动脉粥样硬化的风险增加有关，颈动脉粥样硬化是一种已知的预测过早残疾和死于冠心病(CHD)的指标。在此R01(HL089850)的支持下，先前的工作已经表征了调节应激源诱发的血压反应的大脑系统网络，包括扣带皮质、脑岛和杏仁核的细分。另外的横断面研究表明，这些大脑系统中应激源诱发的功能活动与临床前颈动脉粥样硬化有关。这个延续项目扩展了HL089850，通过测试组织假设，即扣带皮质、脑岛和杏仁核中应激源诱发的功能活动预测临床前动脉粥样硬化的3年纵向进展。它还扩展了HL089850，测试了新的假设，即在负面情绪体验调节期间扣带皮质、脑岛和杏仁核活动的个体差异也解释了临床前动脉粥样硬化的横断面和纵向差异。为了测试从这些假设中得出的特定预测，将在社区样本中追求三个特定目标，这些男性和女性(年龄30-50岁)没有临床心血管疾病的症状，并且具有已知的人口统计学、人体测量学、生物学和心理社会心血管危险因素的特征。参与者将在功能磁共振成像(FMRI)会话中完成一系列心理应激反应和情绪调节任务，同时进行外周生理监测。他们还将完成一项无创颈动脉超声方案，以评估临床前动脉粥样硬化，以及在基线时间点(时间1)和3年后的后续时间点(时间2)评估其他已知和新出现的CHD风险因素的方案。目的1检测应激源诱发的前扣带回皮质、前脑岛和杏仁核之间的功能连接在排除已知的心血管危险因素后是否可以预测临床前动脉粥样硬化(以颈动脉内中膜厚度和外膜直径衡量)的进展。目的2测试应激源诱发的血压反应性是否部分中介了应激源诱发的功能连接性与临床前动脉粥样硬化进展之间的关系。目的3检测负性情绪刺激认知再评估过程中，扣带回前皮质、前脑岛和杏仁核之间的功能连接是否与时间1和进展到时间2的临床前动脉粥样硬化有关。

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, a known predictor of premature disability and death by coronary heart disease (CHD). Prior work supported by this R01 (HL089850) has characterized a network of brain systems that regulate stressor-evoked blood pressure reactions, encompassing subdivisions of the cingulate cortex, insula, and amygdala. Additional cross-sectional work showed that stressor-evoked functional activity in these brain systems is associated with preclinical carotid atherosclerosis. This continuation project extends HL089850 by testing the organizing hypothesis that stressor-evoked functional activity in the cingulate cortex, insula, and amygdala predicts the 3-year longitudinal progression of preclinical atherosclerosis. It also extends HL089850 by testing the new hypothesis that individual differences in cingulate cortex, insula, and amygdala activity during the regulation of negative emotional experiences also accounts for cross-sectional and longitudinal variation in preclinical atherosclerosis. To test specific predictions derived from these hypothesis, three specific aims will be pursued in a community sample of men and women (aged 30-50 years) who are asymptomatic for clinical cardiovascular disease and who are well characterized for known demographic, anthropometric, biological, and psychosocial cardiovascular risk factors. Participants will complete a battery of psychological stress reactivity and emotion regulation tasks in a functional magnetic resonance imaging (fMRI) session with concurrent peripheral physiological monitoring. They will also complete a non-invasive carotid artery ultrasound protocol to assess preclinical atherosclerosis, as well as protocols to assess other known and emerging CHD risk factors at a baseline time point (Time 1) and at a follow-up time point 3-years later (Time 2). Aim 1 tests whether stressor-evoked functional connectivity between the anterior cingulate cortex, anterior insula, and amygdala predicts the progression of preclinical atherosclerosis (as measured by carotid intima-media thickness and adventitial diameter) after accounting for known cardiovascular risk factors. Aim 2 tests whether stressor-evoked blood pressure reactivity partially mediates the associations between stressor-evoked functional connectivity and the progression of preclinical atherosclerosis. Aim 3 tests whether the functional connectivity between the anterior cingulate cortex, anterior insula, and amygdala during the cognitive reappraisal of negative emotional stimuli associates with preclinical atherosclerosis at Time 1 and progression to Time 2.