Pathobiology of Hopelessness, Depression, SES and CVD

描述（改编自研究者摘要）：高水平的抑郁和绝望增加了心血管疾病（CVD）发病率和死亡率的风险。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、绝望和低经济地位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（5HT）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（一种重要的应激激素）分泌过量。长期压力暴露和与恶劣生活条件相关的较高水平的心理压力也被认为对5HT和皮质醇水平产生不利影响。5HT和皮质醇都有心血管作用，并参与CVD的发病机制。然而，据我们所知，之前没有以人群为基础的流行病学研究考察了血清素和糖皮质激素机制是否介导了抑郁症、绝望、低SES和动脉粥样硬化之间的充分记录的关联。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，这是迄今为止对动脉粥样硬化及相关发病率和死亡率的生物心理社会风险因素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。拟议的研究将利用现有数据检测血浆皮质醇浓度、全血5HT和血小板5HT受体和转运体结合与抑郁、绝望、SES和动脉粥样硬化的关系。参与者包括一个以人口为基础的队列，包括800名男性和800名女性，年龄在53-71岁之间。研究人员认为，抑郁、绝望和低SES与5HT水平下降和血浆皮质醇升高有关；5HT和皮质醇均介导抑郁、绝望和低SES对颈动脉粥样硬化的影响；在考虑了传统的风险因素后，这些中介效应将是明显的（尽管皮质醇的影响也可能通过其中一些风险因素起作用）；女性的5HT功能会比男性低。抑郁症和心血管疾病预计将成为未来20-25年致残的两大主要原因。此外，世界各地普遍存在的经济差距和相关的健康后果是显而易见的。因此，了解心理状态和SES与CVD发生和进展相关的机制是一项关键任务，它将为动脉粥样硬化性血管疾病患者以及患有抑郁症或绝望的患者提供治疗和预防策略。重要的是，描述社会心理属性影响动脉粥样硬化的机制也将促进对心脏病过程中重要的身心相互作用的理解。

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.