Fatigue, Anhedonia and Cardiac Prognostic Markers in Depressed Patients with Coronary Heart Disease

抑郁症与冠心病心脏病发病率和死亡率的风险增加有关 （CHD）。虽然存在安全且适度有效的治疗重度抑郁症的方法，但只有约30%的患者 完全康复患有抑郁症状的冠心病患者对治疗无反应， 与那些抑郁症状对抑郁症有反应的人相比， 治疗快感缺乏和疲劳是最常见的症状，仍然在治疗后， 抑郁的冠心病患者和医学上良好的精神病患者。在最近的一项研究中，我们发现 心血管发病率和死亡率的几个风险标志物，包括甲状腺正常水平高 无激素甲状腺素（FT 4）、夜间心率变异性低、昼夜心率变钝和睡眠不良 质量预测抑郁症治疗反应和治疗后的疲劳和快感缺乏症状。是 尚不清楚为什么这些风险标志物与残余快感缺乏和疲劳有关。皮质醇水平升高， 慢性交感神经系统激活，HR的迷走神经调节减少，高水平的感知 压力，体力活动水平低，睡眠障碍和隐性亚临床甲状腺疾病是其中 最合理的解释这些因素中的任何一个或全部都可以解释风险标志物之间的关系。 以及残余疲劳和快感缺乏，所有这些都是潜在的可改变的，因此可能是未来的目标。 临床试验拟议研究的目的是确定这些风险标志物的可修改相关性 冠心病伴抑郁症患者的疲劳和快感缺乏。研究受试者将从 华盛顿大学医学院的心脏病学实践。潜在合格患者将 安排了一次结构化的临床面试在BDI-II上得分>14且符合DSM-5标准的人 并且没有排除标准。参与者将在行为评估 华盛顿大学医学院医学中心。评价将在 早上禁食12小时后，并将开始抽血，以获得甲状腺面板，血脂谱，血浆 皮质醇、C反应蛋白和其他生物标志物。受试者将配备一台动态心电图监测仪 和一个腕关节活动记录仪，完成一系列自我报告清单，并被告知如何收集 唾液样本来测量皮质醇ECG监测仪和活动记录仪将佩戴48小时 在连续两个工作日测量ECG标记、活动水平和睡眠参数。唾液 将在两天内每天采集三次样本：唤醒时、中午和之前 睡觉了在样品和设备返回后，将对参与者的时间进行补偿。本研究 将确定后续干预的潜在目标，以加强传统的抑郁症治疗， 从而有助于为随机临床试验奠定基础，以确定是否治疗抑郁症， 冠心病患者的抑郁和无事件生存率均得到改善。

Depression is associated with an increased risk of cardiac morbidity and mortality in coronary heart disease (CHD). Although safe and modestly effective treatments for major depression exist, only about 30% of patients ever achieve full remission. CHD patients with depression symptoms that do not respond to treatment are at high risk for cardiac morbidity and mortality compared to those whose depression symptoms respond to treatment. Anhedonia and fatigue are among the most common symptoms to remain following treatment in both depressed CHD patients and in medically well psychiatric patients. In a recent study, we found that several risk markers of cardiovascular morbidity and mortality including a high normal level of the thyroid hormone free thyroxine (FT4), low nocturnal heart rate variability, blunted circadian heart rate, and poor sleep quality predict depression treatment response and post-treatment symptoms of fatigue and anhedonia. It is unclear why these risk markers are associated with residual anhedonia and fatigue. Elevated cortisol levels, chronic sympathetic nervous system activation, reduced vagal modulation of HR, high levels of perceived stress, low level of physical activity, disordered sleep, and occult subclinical thyroid diseases are among the most plausible explanations. Any or all of these factors may explain the relationship between the risk markers and residual fatigue and anhedonia, and all are potentially modifiable and thus possible targets for future clinical trials. The purpose of the proposed research is to identify modifiable correlates of these risk markers and of fatigue and anhedonia in depressed patients with CHD. Study participants will be recruited from cardiology practices at Washington University School of Medicine. Potentially eligible patients will be scheduled for a structured clinical interview. Those who score >14 on the BDI-II and meet the DSM-5 criteria for major depression and no exclusion criteria will be enrolled. Participants will be evaluated at the Behavioral Medicine Center at Washington University School of Medicine. The evaluation will be performed in the morning after a 12-hour fast, and will start with a blood draw to obtain a thyroid panel, lipid profile, plasma cortisol, C-reactive protein, and other biomarkers. Participants will be fitted with an ambulatory ECG monitor and a wrist actigraph, complete a battery of self-report inventories, and be given instructions for collecting saliva samples at home for cortisol measurement. The ECG monitor and actigraph will be worn for 48 hours on two consecutive weekdays to measure the ECG markers, activity levels, and sleep parameters. Saliva samples will be obtained three times per day for two days: upon awakening, mid-afternoon, and before bedtime. Participants will be compensated for their time upon return of the samples and equipment. This study will identify potential targets for adjunctive interventions to augment traditional depression treatments and thereby help to lay the groundwork for a randomized clinical trial to determine whether treating depression in patients with CHD can improve both depression and event-free survival.