1/3-Recurrence Markers, Cognitive Burden and Neurobiological Homeostasis in Late-life Depression (Rembrandt)

晚年抑郁症的 1/3 复发标记、认知负担和神经生物学稳态（伦勃朗）

• 批准号: 10523127
• 负责人: Warren D Taylor
• 金额: $ 97.04万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10523127
• 关键词: Acceleration; Affect; Affective; Antidepressive Agents; Behavioral; Clinical; Cognitive; Data; Depressed mood; Development; Disease remission; Early Diagnosis; Ecological momentary assessment; Elderly; Environmental Monitoring; Equilibrium; Exhibits; Functional Magnetic Resonance Imaging; Future; Goals; Homeostasis; Impaired cognition; Individual; Laboratories; Longitudinal Studies; Measures; Mental Depression; Monitor; Moods; Neurobiology; Noise; Participant; Performance; Predictive Factor; Prevention; Process; Recording of previous events; Recovery; Recurrence; Regulation; Reporting; Residual state; Risk; Risk Marker; Severities; Signal Transduction; Site; Sleep; Stress; Subgroup; Symptoms; Testing; Therapeutic Intervention; Time; Translating; actigraphy; aging brain; clinical practice; cognitive function; cognitive load; cognitive performance; depressive symptoms; executive function; experience; geriatric depression; high risk; mood symptom; negative affect; network models; neural; neural network; neuroimaging; predictive marker; prospective; recurrent depression; rumination; single episode major depressive disorder; stress reactivity; young adult

PROJECT SUMMARY Repeated major depressive episodes are particularly problematic for older adults who have a more brittle recovery than younger adults. Our data show that, despite antidepressant treatment, almost 60% of remitted older adults experience recurrence within four years. Beyond simply relying on past history and reported current stress, it is unclear what neurobiological factors are prospectively associated with recurrence risk, when these factors trigger recurrence, and how they contribute to the high rates of cognitive impairment observed in late-life depression (LLD). Using a model of network homeostasis, we posit that depressive episodes are characterized by disrupted homeostasis in key neural networks involved in affect regulation and cognitive function. Our preliminary data indicate that treatment non-remitters have residual functional network alterations and high network instability (higher fluctuations in temporal signal-to-noise ratio). We hypothesize that remitters with residual functional network alterations and greater instability remain at high risk of recurrence with subsequent stress exposure. This disequilibrium contributes to subsyndromal symptoms followed by full recurrence. These processes may also contribute to the higher rate of cognitive impairment and decline observed in LLD. Our groups have reported elevated rates of cognitive decline in remitted LLD and an association of recurrence with accelerated brain aging. We hypothesize that greater neural reactivity to stress may accelerate brain aging and cognitive decline and that deficits/variability in performance on tasks dependent on ECN may serve as markers of network alterations and signal increased recurrence risk. The goals of this study are to A) identify neurobiological factors that predict recurrence risk, and B) examine how cognitive performance changes are both influenced by these same neurobiological factors and also predict recurrence risk. Our approach is to conduct a three-site, two-year longitudinal study of remitted LLD and never-depressed elders. Every 8 months we will conduct laboratory assessments, including clinical, cognitive and neuroimaging assessments and an in-scanner stress paradigm, along with burst ecological momentary assessments (EMA) of mood variability, stress exposure, cognitive performance, and passive actigraphy. As an exploratory goal, we will examine whether continuous ecological monitoring of mood and activity can provide early detection of recurrence. A subgroup will be continuously monitored by EMA and actigraphy for state shifts (persistent worsening) or variance shifts (increased variability) in symptom severity. When shifts in mood symptoms are identified, they will engage in ad-hoc clinical and neuroimaging testing. Results from this study may be translated in clinical practice through the future development of easy-to-use platforms (e.g. apps) that signal to clinicians increased risk of impending recurrence, thus allowing for swift therapeutic intervention.

项目概要 对于精神比较脆弱的老年人来说，反复发作的重度抑郁症尤其成问题。 康复程度高于年轻人。我们的数据显示，尽管接受了抗抑郁治疗，但近 60% 的患者病情得到缓解 老年人在四年内会复发。不仅仅是依赖过去的历史和报道 目前的压力，尚不清楚哪些神经生物学因素与复发风险前瞻性相关， 这些因素何时引发复发，以及它们如何导致认知障碍的高发生率 在晚年抑郁症（LLD）中观察到。使用网络稳态模型，我们假设抑郁 发作的特点是参与情绪调节和控制的关键神经网络的稳态被破坏。 认知功能。我们的初步数据表明，治疗非缓解者具有残余功能网络 变化和高网络不稳定性（时间信噪比的较高波动）。我们假设 具有残余功能网络改变和更大不稳定的汇款人仍然面临很高的风险 随后的压力暴露会复发。这种不平衡会导致亚综合征症状 随后完全复发。这些过程也可能导致更高的认知障碍率和 LLD 中观察到下降。我们的研究小组报告称，LLD 缓解后认知能力下降的比例升高，并且 复发与大脑加速老化的关联。我们假设神经对压力的反应更强 可能会加速大脑老化和认知能力下降以及任务表现的缺陷/变化 依赖 ECN 可能作为网络改变的标志并发出复发风险增加的信号。这 本研究的目标是 A) 确定预测复发风险的神经生物学因素，以及 B) 检查如何 认知表现的变化既受到这些相同的神经生物学因素的影响，也预测 复发风险。我们的方法是对已转正的 LLD 和 从不沮丧的长辈。每 8 个月我们将进行一次实验室评估，包括临床、认知 和神经影像评估和扫描仪内压力范式，以及突发生态瞬时 情绪变异、压力暴露、认知表现和被动体动记录仪的评估（EMA）。作为 作为一个探索性目标，我们将研究对情绪和活动的持续生态监测是否可以 提供复发的早期检测。 EMA 和体动记录仪将持续监测一个小组的情况 症状严重程度的状态转变（持续恶化）或方差转变（变异性增加）。当换班时 一旦发现情绪症状，他们将进行临时临床和神经影像学测试。结果由此 通过未来开发易于使用的平台（例如应用程序），研究可以转化为临床实践 这一向临床医生发出的信号增加了即将复发的风险，从而可以迅速进行治疗干预。