Depression and heart failure associated cardiovascular pathology

抑郁症既是一种衰弱的心理障碍，也是一种影响个人身体健康的疾病。抑郁症是公认的心脏病风险因素。研究表明，抑郁症易导致心肌梗死、猝死、动脉粥样硬化、血栓形成和心律失常。虽然抑郁的行为和认知方面已经得到了广泛的研究，但研究情绪障碍的生理后果的机制的研究要少得多。啮齿动物暴露在一系列慢性轻度应激源(CMS)下会产生人类抑郁的关键行为特征，这些特征是可观察和可量化的。实验诱导的抑郁(ID)的CMS模型模拟了对愉悦刺激(快感缺乏)的反应降低，这是抑郁症的关键诊断标准。 在CMSdD模型中，快感缺乏是由持续时间不同的轻微的不可预测的应激源(例如，成对的住房、频闪照明、白噪声)引起的。在大鼠中，快感缺乏症被定义为对先前证明的增强剂(奖励)的反应减少。最近，我们已经开始研究患有CMS-ID的大鼠的心血管功能。我们发现，暴露于CMS 4周的大鼠表现出快感缺失和 心血管疾病。与抑郁症和心力衰竭患者类似，CMSgD大鼠的静息心率较高，心率变异性较低。此外，暴露于CMS的大鼠增加了实验诱导的室性早搏的易感性。在调查心力衰竭的行为后果的其他研究中，我们发现了实验性心肌梗死大鼠出现快感缺乏(即实验性抑郁)的证据。拟议的研究计划将扩展我们对实验诱导的抑郁伴随的心血管变化的表征，并调查脑5-羟色胺能机制的作用，这些机制被假设为在伴随实验抑郁和实验心力衰竭的心血管改变的中介中常见。

Depression is both a debilitating psychological disorder and a condition that affects an individual's physical well-being. Depression is a recognized risk factor for heart disease. Research has demonstrated that depression predisposes an individual to myocardial infarction, sudden death, atherosclerosis, thrombosis and arrhythmias. While the behavioral and cognitive aspects of depression have been studied extensively, there has been much less research investigating the mechanisms responsible for the physiological consequences of mood disorders. Exposure of rodents to a series of chronic mild stressors (CMS) generates key behavioral characteristics of human depression that are observable and quantifiable. The CMS model of experimentally-induced depression (ID) mimics the reduced responsiveness to pleasurable stimuli (anhedonia)which is a pivotal diagnostic criterion seen in depression. In the CMSdD model, anhedonia is induced by presenting mild unpredictable stressors (e.g., paired housing, stroboscopic illumination, white noise) of varying durations. In rats,anhedonia is operationally defined as a decrease in responding for a previously demonstrated reinforcer (reward). Recently, we have begun to characterize cardiovascular function in rats with CMS-ID. We have found that rats exposed to CMS for 4 weeks showed anhedonia along with cardiovascular alterations. Similar to patients with depression and with heart failure,CMSgD rats had elevated resting heart rates and reduced heart rate variability. In addition, rats exposed to CMS have increased susceptibility to experimentally-induced premature ventricular contractions. In other studies investigating the behavioral consequences of heart failure, we have found evidence of anhedonia (i.e., experimental depression) in rats with experimental myocardial infarction. The proposed research program will extend our characterization of the cardiovascular changes that accompany experimentally-induced depression and investigate the role of brain serotonergic mechanisms that are hypothesized to be common in the mediation of cardiovascular alterations that accompany both experimental depression and experimental heart failure.