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Phenotype Predictors of Cognitive Outcomes in Geriatric Depression

老年抑郁症认知结果的表型预测因子

基本信息

批准号：
10606593
负责人：
DAVID C. STEFFENS
金额：
$ 66.4万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-13 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10606593
关键词：
Adult Alzheimer&apos s Disease Antidepressive Agents Anxiety Behavioral Brain Brain imaging Brain region Buffers COVID-19 pandemic Clinical Clinical Trials Cognition Cognitive Complex Data Dementia Depressed mood Desire for food Development Diagnosis Disease remission Economics Elderly Enrollment Epidemiology Exercise Feeling Frustration Functional Magnetic Resonance Imaging Future Health Hippocampus Homeostasis Image Impaired cognition Individual Lead Life Major Depressive Disorder Measures Medial Mediating Medical Mental Depression Modeling Moods Neurobiology Neurotic Disorders Outcome Pattern Personality Personality Traits Pharmaceutical Preparations Phenotype Predisposition Prevention strategy Psychotherapy Recording of previous events Recurrence Relapse Risk Scanning Security Severities Sleep disturbances Social support Statistical Models Stress Structure Vascular Dementia Withdrawal cognitive testing coping depression model executive function experience functional MRI scan functional disability geriatric depression high risk imaging study interpersonal conflict neural neural network novel previous pandemic recruit recurrent depression resilience response serial imaging social stressor suicidal risk

项目摘要

In this competing renewal of R01MH108578, we are seeking to extend findings from the initial study to focus on effects of stress in longitudinal mood and cognitive outcomes of late-life depression (LLD) and to examine stress effects on brain structure and function in LLD. Severe or persistent stressors can result in a number of behavioral and mood changes, including anxiety, dysphoric mood, sleep disruption, altered appetite, and withdrawal from social and pleasurable activities. These stress-related consequences are particularly salient when considering longitudinal outcomes of treated LLD. They may be compounded by an individual's longstanding maladaptive patterns of response to stress, embodied in the construct of neuroticism, which we have shown to be related to poor mood and cognitive LLD outcomes. Moreover, Andreescu et al. (2019) introduced a model of depression recurrence that incorporates the homeostatic disequilibrium hypothesis, which proposes that in geriatric remitted depression, neural networks are in fragile homeostasis that is threatened by stress exposure. Networks of particular importance in stress of LLD outcome are the Default Mode Network (DMN), Salience Network (SN) and Executive Control Network (ECN). The Neurobiology of Late Life Depression (NBOLD) study began enrolling older depressed and never- depressed controls in 2013, enrolling 132 depressed and 44 controls, and currently follows 77 depressed and 22 controls. Subjects are well characterized in terms of mood, cognition, personality and stress (including specific measures obtained during the present COVID pandemic). It is well suited to examine stress effects on longitudinal mood and cognitive outcomes. For the renewal, we will follow current subjects and recruit 75 new subjects, who will be followed for up to 5 years with annual cognitive testing, stress measures and baseline and two-year brain fMRI scan. In preliminary data presented in this application, we show that: 1) In depressed elders, compared with those who developed cognitive decline/dementia in 4 years, those who remained cognitively normal had greater 2-year decrease in neuroticism and increase in Conscientiousness. 2) Worsening in stress over two years is associated with two-year decrease in hippocampal volume and is associated with changes in functional connectivity of key brain regions.. 3) In complex statistical modeling, interactions of changes in neuroticism and changes in the number of stressors recently experienced are associated with cognitive outcome. In this competing renewal, we will examine the following specific aims: 1. To study effects of stressors (obtained on a variety of measures) and neuroticism on longitudinal mood and cognitive outcomes in older adults with history of major depressive disorder (MDD). 2. To study effects of stress and neuroticism on brain structure and function in older adults with MDD history. 3. To explore relationships among variables in Aims 1 and 2 with longitudinal multivariable statistical models.

在这次R 01 MH 108578的竞争性更新中，我们正在寻求将最初研究的发现扩展到关注压力对晚年抑郁症（LLD）的纵向情绪和认知结果的影响，研究应激对LLD患者大脑结构和功能的影响。严重或持续的压力源可能会导致行为和情绪变化的数量，包括焦虑、烦躁情绪、睡眠中断、食欲改变，以及从社交和娱乐活动中退缩这些与压力有关的后果尤其当考虑治疗的LLD的纵向结果时，这一点很突出。它们可能会因个人的长期以来对压力的适应不良模式，体现在神经质的结构中，我们已被证明与不良情绪和认知LLD结果有关。此外，Andreescu等人（2019）引入了一个抑郁复发模型，该模型结合了稳态不平衡假说，该研究提出，在老年缓解型抑郁症中，神经网络处于脆弱的稳态，受到压力的威胁在LLD结果的压力中特别重要的网络是默认的模式网络（DMN）、显着性网络（SN）和执行控制网络（ECN）。晚年抑郁症神经生物学（NBOLD）研究开始招募老年抑郁症和从未... 2013年的抑郁症对照，招募了132名抑郁症患者和44名对照，目前随访了77名抑郁症患者和 22个对照。受试者在情绪、认知、个性和压力方面都有很好的特征（包括于当前COVID疫情期间采取的具体措施）。它非常适合于检查压力对纵向情绪和认知结果。为了更新，我们将遵循当前的主题，并招募75名新的受试者将接受长达5年的随访，每年进行一次认知测试、压力测量和基线测量。和两年的脑功能磁共振成像扫描在本申请中提供的初步数据中，我们表明： 1)在抑郁的老年人中，与4年内发生认知下降/痴呆的老年人相比，认知功能正常的儿童在2年内的神经质下降幅度更大，而在责任心方面的下降幅度更大。 2)两年以上的压力加重与海马体积两年的减少有关，与大脑关键区域功能连接的变化有关。 3)在复杂的统计模型中，神经质变化和神经质数量变化的相互作用，最近经历的压力与认知结果有关。在这一相互竞争的更新中，我们将审查以下具体目标： 1.研究压力源（通过各种测量方法获得）和神经质对纵向情绪和有重度抑郁症（MDD）病史的老年人的认知结果。 2.目的：研究应激和神经质对老年期抑郁症患者脑结构和功能的影响。 3.采用纵向多变量统计模型探索目标1和2中变量之间的关系。