Behavior, serotonin and cardiovascular risk

行为、血清素和心血管风险

• 批准号: 6564891
• 负责人: Stephen B Manuck
• 金额: $ 15.94万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564891
• 关键词: angiocardioultrasonography; behavioral /social science research tag; behavioral medicine; cardiovascular function; clinical research; disease /disorder proneness /risk; emotions; genetic polymorphism; genetic susceptibility; high risk behavior /lifestyle; human genetic material tag; human subject; nutrition related tag; pathogenic diet; psychological stressor; psychopharmacology; psychophysiology; questionnaires; serotonin; serotonin inhibitor; socioenvironment; vasomotion

The principle objective of this Project is to establish whether psychosocial, socio-environmental and lifestyle-related risk factors for cardiovascular disease are associated, individually and in aggregate, with interindividual variability in central nervous system serotonergic (5-HT) responsivity. Behavioral risk factors of interest include hostility, depression, low socio-economic status, social isolation (low social support), contemporaneous stress, smoking, imprudent diet, physical inactivity, and excessive consumption of alcohol. A second aim is to determine whether individual differences in central serotonergic responsivity also covary with preclinical indicators of vascular disease and cumulative risk factor exposure (viz., endothelium-mediated dilation of the branchial artery, carotid artery intimal-medial thickness and atherosclerotic plaque). A third aim is to determine whether population variability in central serotonergic function may be predicted, in part, by polymorphic variation in candidate genes of the 5-HT system. We propose to recruit a community sample of 600 men and women, 30-50 years of age and without clinical history of atherosclerotic cardiovascular disease. Subjects will be administered a neuropsychopharmacologic challenge to evaluate central serotonergic responsivity (plasma prolactin and ACTH responses to the 5-HT re-uptake inhibitor, citalopram) and data will be collected in each of the foregoing domains of behavioral risk for cardiovascular disease. The latter will include a batter of diagnostic and assessment interviews, as well as standardized questionnaires. Ultrasound evaluations of vascular reactivity and carotid artery disease will be obtained on 300 subjects, derived from the upper and lower tertiles on the distribution of central 5-HT responsivity (as indexed by subjects' citalopram-induced prolactin responses). In addition, blood for DNA analysis will be obtained from all study participants. Project 1 will provide a first systematic test of the hypothesis that diverse sources of behavior risk for cardiovascular disease aggregate, in part, under the influence of a common neurobiologic mechanism involving altered central serotonergic function. Support for this hypothesis will further our understanding of the origins of behavioral influences on heart disease and provide clues to possible commonalities of etiology and pathogenicity.

该项目的主要目标是确定心血管疾病的社会心理、社会环境和生活方式相关危险因素是否与中枢神经系统血清素（5-HT）反应性的个体间差异相关（无论是个体还是总体）。值得关注的行为风险因素包括敌意、抑郁、社会经济地位低、社会孤立（社会支持低）、同时存在的压力、吸烟、不节制的饮食、缺乏身体活动和过量饮酒。第二个目的是确定中枢血清素反应性的个体差异是否也与血管疾病的临床前指标和累积危险因素暴露（即内皮介导的鳃动脉扩张、颈动脉内膜中层厚度和动脉粥样硬化斑块）共变。第三个目标是确定中枢血清素能功能的群体变异是否可以部分地通过 5-HT 系统候选基因的多态性变异来预测。我们建议招募 600 名男性和女性社区样本，年龄在 30-50 岁之间，没有动脉粥样硬化性心血管疾病的临床病史。受试者将接受神经精神药理学挑战，以评估中枢血清素能反应性（血浆催乳素和 ACTH 对 5-HT 再摄取抑制剂西酞普兰的反应），并将收集上述心血管疾病行为风险领域的数据。后者将包括一系列诊断和评估访谈以及标准化问卷。将对 300 名受试者进行血管反应性和颈动脉疾病的超声评估，这些评估来自中央 5-HT 反应性分布的上三分位数和下三分位数（以受试者西酞普兰诱导的催乳素反应为索引）。此外，将从所有研究参与者处获取用于 DNA 分析的血液。项目 1 将对这一假设进行首次系统测试，即心血管疾病的不同行为风险来源在一定程度上是在涉及中枢血清素功能改变的常见神经生物学机制的影响下聚集的。对这一假设的支持将进一步加深我们对行为对心脏病影响的起源的理解，并为病因学和致病性可能的共性提供线索。