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

摘要：老年痴呆症家庭照顾者（dCG）的抑郁症发病率高， 优先考虑，并有机会研究这一组中表达的常见抑郁机制。初步 dCG中的目标识别研究（K 01 MH 112683）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。早晨激活缺陷（MAD）是唯一的因素， 与抑郁症状持续6个月有关。初步的7 T MRI数据表明， 通过杏仁核和后扣带回的静息态连接增强与抑郁症状相关 皮质（PCC）区域。在以前的文献中，这涉及边缘系统和默认模式网络 系统，并表明可能涉及反刍过程（即，消极的情绪自我关注）。但 在心理和神经生物学因素方面， 和可修改性。关键的是，瞄准MAD是否会“破坏”相关的抑郁机制和症状？这 建议是对60岁以上dCG中的MAD进行观察-实验联合探测研究。参与者将 包括120名抑郁相关MAD水平的dCG（C.1.4）。目标1将比较该组与MAD 相对于光谱另一端的60个dCG，相对地免受抑郁症的影响， “早起型”计划的神经影像学分析将验证先前确定的静息状态生物标志物 在这条途径上，并支持额外的推理，通过评估大脑反应的群体差异， 沉思暗示将使用生态瞬时评估（EMA）和体动记录仪来表征 活动、情绪和沉思的模式。我们还将衡量其他可能相关的因素，例如，夜间 心理状态和奖励预期。在目标2/3中，将120例有MAD的dCG随机分配至活性药物组， 探头或控制条件。主动探测器重新利用现有的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）。非对照试验数据（n=10） 支持SAMM每周六次会议参与目标（MAD）并影响情绪的可行性。的 拟议的随机对照探索研究将证实对主观和客观早晨激活的影响 (Aim 2）并描述假定机制的变化（反刍过程;目标3）。完成 这些目标的结合将增加关于MAD对抑郁症的潜在积极影响的知识 机制等该研究采用NIMH策略，研究多模态的机制， 方法（策略2.2）;以及重新利用现有的治疗方法来探测目标参与和个性化 关键群体的治疗（战略3.2）。对多模态数据的分析将支持开发新的 方法来检测潜在的MAD的过程。实验结果将支持或反驳瞄准MAD SAMM作为影响相关机制的基于赤字的方法。研究结果将支持未来 在许多受抑郁症和MAD影响的群体中进行机制/探针概括性测试。

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.