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

摘要：老年家庭痴呆症照料者(DCGS)中抑郁症的高发病率既是公共健康的问题 优先，也是一个机会，研究这一组表达的常见抑郁机制。初步 DCGS(K01MH112683)的目标识别研究评估了睡眠-觉醒行为，这些行为可能是 可修改的目标，与抑郁症状有关。晨间活动缺陷(MAD)是唯一的因素 与持续六个月以上的抑郁症状有关。初步的7T磁共振数据表明，MADS 通过杏仁核和后扣带回静息状态连接增强与抑郁症状相关 皮质(PCC)区域。在现有文献的上下文中，这意味着边缘和默认模式网络 系统，并表明可能涉及反省过程(即，消极的情绪自我关注)。但 在心理和神经生物学因素方面，对这一机制的理解仍然存在差距， 和可修改性。关键的是，靶向MADS是否会“破坏”与抑郁相关的机制和症状？这 建议对60岁DCGS的MADS进行观测和实验相结合的探头研究。参与者将 包括120名患有抑郁症相关MADS水平的DCG(C.1.4)。目标1将这一群体与MADS进行比较 对抗光谱另一端的60个DCG，相对不受抑郁的保护，凭借 “早起的类型。”计划中的神经成像分析将验证先前确定的静息状态生物标记物 这一途径，并支持额外的推断，通过评估组的大脑反应的差异 沉思的暗示。将使用生态瞬时评估(EMA)和行动图来表征 活动、情绪和沉思的模式。我们还将衡量其他看似相关的因素，例如夜间 心理状态和奖励预期。在AIMS 2/3中，120名患有MADS的DCG将被随机分配到现役 探测或控制条件。主动探测器改变了现有行为激活的简单组件的用途 针对MADS的治疗：安排活动和监测早晨(SAMM)。非受控导频数据(n=10) 支持SAMM每周六次会议参与目标(MADS)并影响情绪的可行性。这个 拟议的随机对照探针研究将证实对主观和客观晨间活动的影响 (目标2)并描述假定机制的变化(反省过程；目标3)。完成 这些目的加在一起将增加关于MAD对抑郁症的潜在积极影响的知识 机械装置。建议的研究使用NIMH策略来研究具有多模式的机制 方法(战略2.2)；重新调整现有治疗的用途，以探索目标参与和个性化 关键群体的治疗(战略3.2)。对多模式数据的分析将支持新的 方法检测MADS的潜在过程。实验结果将支持或驳斥定向MADS 将SAMM作为一种以赤字为基础的方法来影响相关机制。这里的发现将支持未来 用MADS对许多受抑郁症影响的人群进行机制/探头普适性测试。

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.