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）的高抑郁率均表现出公共卫生 优先级，也是研究该组中表达的常见抑郁机制的机会。初步的 DCG中的目标识别研究（K01MH112683）评估了睡眠效果行为，这可能是 与抑郁症状有关的可修改目标。早晨激活定义（MAD）是唯一的因素 与六个月以上的抑郁症状持久性有关。初步7T MRI数据表明MADS 与抑郁症状有关，通过杏仁核和后扣带回的静息状态连通性提高 皮质（PCC）区域。在先前文献的背景下，这实现了边缘和默认模式网络 系统，并建议可能涉及反刍过程（即负面情绪自我聚焦）。但 关于心理学和神经生物学因素，差距仍在理解这种机制， 和可修改性。至关重要的是，针对疯狂的“出轨”相关的抑郁机制和症状会吗？这 提案是针对DCGS 60岁以上MAD的合并观察性实验探测研究。参与者会 包括120个与抑郁症相关的疯狂水平的DCG（C.1.4）。 AIM 1将将这个小组与MADS进行比较 在频谱的另一端与60 dCG相对，相对保护，免受抑郁的保护 “早上类型。”计划的神经影像学分析将验证先前鉴定的静息状态生物标志物 在这一途径上，通过评估群体对大脑对的群体差异的差异来支持其他推论 反省提示。生态瞬时评估（EMA）和行摄影将用于表征 活动，情绪和反思的模式。我们还将测量其他可能相关的因素，例如夜间 提及和奖励期待。在目标2/3中，有120个带有疯狂的DCG将被随机分为活动 探针或控制条件。主动探针重新启动了现有行为激活的简单组成部分 针对MAD的疗法：调度活动和监测早晨（SAMM）。不受控制的飞行员数据（n = 10） 支持六次每周SAMM会议与目标（MAD）的可行性并影响情绪。这 拟议的随机对照探针研究将确认对主观和客观早晨激活的影响 （AIM 2）并表征了推定机制的变化（反刍过程；目标3）。完成 这些目标将增加，以了解疯狂对抑郁症的潜在积极影响 机制。拟议的研究员工NIMH使用多模式调查机制的策略 方法（策略2.2）;并重新定位现有治疗方法以探测目标参与和个性化 关键组的治疗（策略3.2）。多模式数据的分析将支持开发新的 检测MAD基础过程的方法。实验结果将支持或反驳目标疯狂 以SAMM作为影响相关机制的基于赤字的方法。这里的发现将支持未来 在许多受疯狂抑郁症影响的许多群体中的机制/探针概括性测试。