Neurobiological pathways linking stress and emotion to atherosclerosis

将压力和情绪与动脉粥样硬化联系起来的神经生物学途径

• 批准号: 8617857
• 负责人: Peter J Gianaros
• 金额: $ 47.52万
• 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: 2008-04-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8617857
• 关键词: Accounting; Acute; Address; Adult; Affect; Amygdaloid structure; Anterior; Area; Atherosclerosis; Behavioral; Biological; Blood Pressure; Brain; Caliber; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Carotid Atherosclerotic Disease; Cessation of life; Chronic; Clinical; Cognitive; Color; Communities; Coronary heart disease; Coupling; Cross-Sectional Studies; Data Collection; Disease; Emotional; Emotions; Event; Functional Magnetic Resonance Imaging; Future; Grant; Human; Image; Individual Differences; Insula of Reil; Life; Link; Longevity; Measures; Mediating; Morbidity - disease rate; Myocardial Infarction; Neurobiology; Participant; Pathway interactions; Peripheral; Persons; Physiologic Monitoring; Preclinical Testing; Process; Protocols documentation; Psychological Stress; Public Health; Reaction; Regulation; Risk; Risk Factors; Sampling; Severities; Signal Transduction; Site-Directed Mutagenesis; Source; Stress; Symptoms; System; Testing; Thick; Time; To specify; Ultrasonography; Variant; Woman; Work; aged; cardiovascular risk factor; cingulate cortex; disability; emotion regulation; emotional experience; emotional stimulus; follow-up; heart disease risk; in vivo; intima media; men; pre-clinical; premature; prospective; psychologic; psychological stressor; psychosocial; relating to nervous system; stressor; trait

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.

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中临床前动脉粥样硬化的风险增加有关，这是冠心病（CHD）导致过早残疾和死亡的已知预测因素。先前的工作支持这个R 01（HL 089850）的特点是一个网络的大脑系统，调节应激诱发的血压反应，包括扣带皮层，杏仁核和杏仁核的细分。另外的横断面研究表明，这些脑系统中应激诱发的功能活动与临床前颈动脉粥样硬化相关。该延续项目通过检验组织假说扩展了HL 089850，即扣带皮层、杏仁核和杏仁核中应激诱发的功能活动可预测临床前动脉粥样硬化的3年纵向进展。它还通过检验新的假设扩展了HL 089850，即扣带皮层、杏仁核和杏仁核活动在负面情绪体验调节过程中的个体差异也解释了临床前动脉粥样硬化的横截面和纵向变化。为了检验从这些假设中得出的具体预测，将在无临床心血管疾病症状且已知人口统计学、人体测量学、生物学和心理社会心血管风险因素特征良好的男性和女性（年龄30-50岁）的社区样本中追求三个具体目标。参与者将在功能性磁共振成像（fMRI）会议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年后的随访时间点（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：在考虑已知的心血管危险因素后，测试前扣带皮层、前额叶和杏仁核之间的应激诱发功能连接是否可以预测临床前动脉粥样硬化的进展（通过颈动脉内膜中层厚度和外膜直径测量）。目的2：检测应激诱发的血压反应性是否部分介导了应激诱发的功能连接与临床前动脉粥样硬化进展之间的关系。目的3测试在负性情绪刺激的认知重新评价期间，前扣带皮层、前额叶和杏仁核之间的功能连接是否与时间1和进展至时间2的临床前动脉粥样硬化相关。