Morning Activation Deficits and Depression Symptoms: Mechanisms and Modifiability in Dementia Caregivers

早晨激活缺陷和抑郁症状：痴呆症护理人员的机制和可修改性

• 批准号: 10362081
• 负责人: Stephen F Smagula
• 金额: $ 78.02万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10362081
• 关键词: Address; Affect; Age; Amygdaloid structure; Architecture; Attention; Behavior; Behavioral; Biological Assay; Biological Markers; Brain; Caregivers; Clinical; Cues; Data; Dementia caregivers; Development; Disease; Ecological momentary assessment; Emotional; Exhibits; Family; Functional Magnetic Resonance Imaging; Future; Intervention; Knowledge; Light; Link; Literature; Magnetic Resonance Imaging; Measures; Mediating; Mental Depression; Methods; Modeling; Monitor; Moods; National Institute of Mental Health; Neurobiology; Parietal; Participant; Pathway interactions; Patient Self-Report; Pattern; Pilot Projects; Process; Psychology; Randomized; Reporting; Research; Rest; Risk; Schedule; Sleep; Symptoms; System; Testing; Therapeutic; Time; actigraphy; base; cingulate cortex; depressive symptoms; improved; mood symptom; morphogens; multidimensional data; multimodal data; multimodality; neuroimaging; novel strategies; personalized therapeutic; psychologic; public health priorities; resilience; response; reward anticipation

ABSTRACT: High rates of depression in older family dementia caregivers (dCGs) present both a public health priority, and an opportunity, to study the common depression mechanisms expressed in this group. Preliminary target-identification research in dCGs (K01MH112683) evaluated sleep-wake behaviors, which are potentially modifiable targets, in relation to depression symptoms. Morning activation deficits (MADs) were the only factor related to depression symptom persistence over six-months. Preliminary 7T MRI data indicate that MADs related to depression symptoms via heightened resting-state connectivity of amygdala and posterior cingulate cortex (PCC) regions. In the context of prior literature, this implicates limbic and default mode network systems, and suggests that ruminative processes may be involved (i.e., negative emotional self-focus). But gaps remain in understanding of this mechanism, with respect to psychological and neurobiological factors, and modifiability. Critically, will targeting MADs “derail” related depression mechanisms and symptoms? This proposal is for a combined observational-experimental probe study of MADs in dCGs age 60+. Participants will include 120 dCGs with depression-relevant levels of MADs (C.1.4). Aim 1 will compare this group with MADs against 60 dCGs on the other end of the spectrum, relatively protected from depression, by virtue of being “morning types.” Planned neuroimaging analyses will validate the resting-state biomarker previously identified on this pathway, and support additional inference, by evaluating group differences in brain responses to rumination cues. Ecological Momentary Assessment (EMA) and actigraphy will be used to characterize patterns of activity, mood, and rumination. We will also measure other plausibly relevant factors, e.g., nocturnal mentation and reward anticipation. In Aims 2/3, the 120 dCGs with MADs will be randomized to an active probe or control condition. The active probe repurposes a simple component of existing behaviorally activating therapies to target MADs: Scheduling Activity and Monitoring Mornings (SAMM). Uncontrolled pilot data (n=10) support the feasibility that six weekly sessions of SAMM engages the target (MADs) and influences mood. The proposed randomized controlled probe study will confirm effects on subjective and objective morning activation (Aim 2) and characterize changes in the putative mechanism (ruminative processes; Aim 3). Accomplishing these aims together will add to knowledge regarding the potential active effects that MADs have on depression mechanisms. The proposed study employs NIMH strategies of investigating mechanisms with multi-modal methods (Strategy 2.2); and re-purposing existing treatments to probe target engagement and personalize therapeutics for key groups (Strategy 3.2). Analyses of multi-modal data will support the development of new methods to detect the process underlying MADs. Experimental results will support or refute targeting MADs with SAMM as a deficit-based approach for influencing related mechanisms. Findings here will support future tests of mechanism/probe generalizability across the many groups affected by depression with MADs.

摘要：老年家庭痴呆症护理人员 (dCG) 的抑郁症发病率较高，这既影响公共健康，又影响公共健康。 初步研究该群体中表达的常见抑郁机制的优先事项和机会。 DCG 中的目标识别研究 (K01MH112683) 评估了睡眠-觉醒行为，这可能是 与抑郁症状相关的可修改目标是唯一的因素。 初步 7T MRI 数据表明 MAD 与抑郁症状持续存在相关。 通过杏仁核和后扣带回的呼吸静息状态连接与抑郁症状相关 在先前文献的背景下，这涉及边缘和默认模式网络。 系统，并表明可能涉及沉思过程（即消极情绪自我关注）。 在心理和神经生物学因素方面，对这一机制的理解仍然存在差距， 至关重要的是，针对 MAD 是否会“破坏”相关的抑郁机制和症状？ 该提案旨在对 60 岁以上的 dCG 中的 MAD 进行综合观察实验探索研究。 包括 120 个具有抑郁相关 MAD 水平的 dCG（C.1.4）将该组与 MAD 进行比较。 与频谱另一端的 60 个 DCG 相比，由于 “早晨类型。”计划的神经影像分析将验证先前确定的静息态生物标志物 在此途径上，并通过评估大脑反应的群体差异来支持额外的推论 生态瞬时评估（EMA）和活动记录仪将用于表征。 我们还将测量其他可能相关的因素，例如夜间活动。 在目标 2/3 中，具有 MAD 的 120 个 dCG 将被随机分配到活跃组。 主动探针重新利用了现有行为激活的简单组件。 针对 MAD 的治疗：安排活动和监测早晨 (SAMM) 非受控试点数据 (n=10)。 支持 SAMM 每周六次会议吸引目标 (MAD) 并影响情绪的可行性。 拟议的随机探索研究将证实对主观和客观早晨激活的影响 （目标 2）并描述假定机制的变化（反思过程；实现目标 3）。 这些目标共同将增加人们对 MAD 对抑郁症潜在积极影响的认识 拟议的研究采用 NIMH 策略来研究多模式机制。 方法（策略 2.2）；并重新利用现有治疗方法来探索目标参与度并个性化 针对关键人群的治疗方法（策略 3.2）。多模式数据分析将支持新疗法的开发。 检测 MAD 背后过程的方法 实验结果将支持或反驳目标 MAD。 SAMM 作为一种基于赤字的方法来影响相关机制。这里的研究结果将为未来提供支持。 对受 MAD 抑郁症影响的许多群体进行机制/探针普遍性测试。