Pathobiology of Hopelessness, Depression, SES and CVD

描述(摘自研究人员摘要)：高度抑郁和绝望会增加心血管疾病(CVD)的风险、发病率和死亡率。同样，心血管疾病的患病率和发病率与社会经济地位(SES)呈负相关。抑郁、绝望和低SES增加心血管疾病风险的机制尚不清楚；然而，研究表明，传统的冠状动脉危险因素不能解释已观察到的大部分关联。一些研究表明，抑郁和绝望与5-羟色胺(5-羟色胺)功能异常和下丘脑-垂体-肾上腺轴调节失调有关，导致皮质醇分泌过量，皮质醇是一种重要的应激激素。长期的压力暴露和与生活条件恶劣相关的较高水平的心理压力也被认为会对5HT和皮质醇水平产生不利影响。5-羟色胺和皮质醇都有心血管作用，并参与了心血管疾病的发病。然而，据我们所知，先前还没有基于人群的流行病学研究检验5-羟色胺能和糖皮质激素机制是否调节抑郁、绝望、低SES和动脉粥样硬化之间已有文献记载的联系。这项拟议的研究利用了一个独特的机会，在库奥皮奥缺血性心脏病(KIHD)风险因素研究的背景下检验这些假设，这是有史以来对动脉粥样硬化的生物、心理和社会风险因素以及相关的发病率和死亡率进行的最全面的研究。KIHD研究在芬兰库奥皮奥进行，一直处于心血管疾病心理社会决定因素研究的前沿。这项拟议的研究将利用现有的数据来检查血浆皮质醇浓度和全血5-羟色胺和血小板5-羟色胺受体和转运体结合与抑郁、绝望、自发性硬化症和动脉粥样硬化的关系。参与者包括年龄在53-71岁的800名男性和800名女性，这是一个以人口为基础的队列。研究人员认为，抑郁、绝望和低SES将与5HT水平下降和血浆皮质醇升高有关；5HT和皮质醇都将在抑郁、绝望和低SES对颈动脉粥样硬化的影响中起中介作用；在考虑到传统的危险因素后，这些中介效应将显而易见(尽管皮质醇的影响也可能通过其中一些危险因素起作用)；5HT的功能在女性中将低于男性。抑郁症和心血管疾病预计将是未来20-25年内导致残疾的两大原因。此外，广泛的经济差距和相关的健康后果在世界各地都很明显。因此，了解心理状态和SES与心血管疾病的发生和发展有关的机制是一项重要的任务，这将有助于阐明动脉粥样硬化性血管疾病患者和患有抑郁或绝望的患者的治疗和预防策略。重要的是，描绘心理社会属性影响动脉粥样硬化的机制也将促进对心脏疾病过程中重要的心身相互作用的理解。

DESCRIPTION (adapted from investigator's abstract): High levels of depression and hopelessness increase risk of cardiovascular disease (CVD) morbidity and mortality. Likewise, CVD prevalence and incidence are inversely related to socioeconomic status (SES). Mechanisms by which depression, hopelessness, and low SES increase risk for CVD are not well understood; however, research shows that traditional coronary risk factors cannot account for much of the observed associations. Several studies indicate that depression and hopelessness are associated with abnormalities in serotonin (5HT) function and dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in excess secretion of cortisol, an important stress hormone. Chronic stress exposure and higher levels of psychological stress associated with living in poor conditions also are thought to adversely influence 5HT and cortisol levels. Both 5HT and cortisol have cardiovascular effects and are involved in pathogenesis of CVD. However, to our knowledge, no prior population-based epidemiologic studies have examined whether serotonergic and glucocorticoid mechanisms mediate the well-documented associations between depression, hopelessness, low SES and atherosclerosis. The proposed study takes advantage of a unique opportunity to test these hypotheses within the context of the Kuopio Ischemic Heart Disease (KIHD) Risk Factor Study, the most comprehensive study of biopsychosocial risk factors for atherosclerosis and related morbidity and mortality ever to be conducted. The KIHD study is conducted in Kuopio, Finland, and has been at the forefront of research into psychosocial determinants of CVD. The proposed study will utilize existing data to examine plasma cortisol concentrations and whole blood 5HT and platelet 5HT receptor and transporter binding in relation to depression, hopelessness, SES and athersclerosis. Participants include a population-based cohort of 800 men and 800 women aged 53-71. The investigators argue that depression, hopelessness, and low SES will be related to decreased levels of 5HT and elevated plasma cortisol; that both 5HT and cortisol will mediate the effects of depression, hopelessness, and low SES on carotid atherosclerosis; that these mediating effects will be evident after taking into account traditional risk factors (although the effects of cortisol also may operate through some of these risk factors); and that 5HT function will be lower in women compared to men. Depression and CVD are expected to be the two leading causes of disability in the next 20-25 years. Moreover, widespread economic disparities and associated health consequences are evident throughout the world. Thus, understanding mechanisms by which psychological states and SES are related to the development and progression of CVD is a critical task and one that will shed light on treatment and prevention strategies for patients with atherosclerotic vascular disease and for patients suffering from depression or hopelessness. Importantly, delineating the mechanisms by which psychosocial attributes influence atherosclerosis also will advance understanding of important mind-body interactions in cardiac disease processes.