3/3-Recurrence markers, cognitive burden and neurobiological homeostasis in late-life depression

3/3-晚年抑郁症的复发标记、认知负担和神经生物学稳态

• 批准号: 10304162
• 负责人: Olusola A. Ajilore
• 金额: $ 64.59万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304162
• 关键词: Affect; Affective; Antidepressive Agents; Behavioral; Clinical; Cognitive; Data; Depressed mood; Development; 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 network; neuroimaging; predictive marker; prospective; relating to nervous system; rumination; single episode major depressive disorder; stress reactivity; young adult

PROJECT ABSTRACT 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.

项目摘要 反复发作的重大抑郁发作对老年人来说尤其成问题，因为他们的 比年轻的成年人更容易恢复。我们的数据显示，尽管接受了抗抑郁药物治疗，近60%的患者病情缓解 老年人会在四年内复发。超越简单地依赖过去的历史和报道 目前，尚不清楚哪些神经生物学因素可能与复发风险有关， 这些因素何时引发复发，以及它们如何导致认知障碍的高比率 在晚年抑郁症(LLD)中观察到。利用网络动态平衡模型，我们假设抑郁 发作的特点是参与情感调节和神经网络的关键神经网络的动态平衡被破坏 认知功能。我们的初步数据表明，接受治疗的非汇款患者有剩余的功能网络 变化和网络高度不稳定(时间信噪比波动较大)。我们假设 具有残留功能网络改变和更大不稳定的汇款仍处于高风险 随着随后的压力暴露而复发。这种失衡导致了亚综合征症状。 然后是完全复发。这些过程也可能导致较高的认知障碍和 在LLD中观察到下降。我们的研究小组报告了缓解期LLD和AN患者认知功能减退的比率升高 复发与大脑加速老化的关系。我们假设对压力有更强的神经反应 可能会加速大脑衰老和认知衰退，以及任务表现的缺陷/可变性 依赖ECN可能作为网络改变的标志，并预示复发风险增加。这个 这项研究的目标是A)确定预测复发风险的神经生物学因素，以及B)检查 认知能力的改变既受同样的神经生物学因素的影响，也能预测 复发风险。我们的方法是对缓解的LLD和LLD进行为期两年的三点纵向研究 从不沮丧的长辈。每8个月我们将进行实验室评估，包括临床、认知 以及神经成像评估和扫描仪内应激范例，以及突发生态瞬间 情绪变异性、压力暴露、认知表现和被动活动的评估(EMA)。AS 作为一个探索性的目标，我们将检查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。一个小组将由EMA和Actigraph持续监测 症状严重程度的状态变化(持续恶化)或变化变化(变异性增加)。当换班时 情绪症状被识别后，他们将进行特别的临床和神经成像测试。由此产生的结果 这项研究可能会通过未来开发易于使用的平台(例如APP)来转化为临床实践 这向临床医生发出的信号增加了即将复发的风险，从而允许迅速进行治疗干预。