Phenotype Predictors of Cognitive Outcomes in Geriatric Depression

老年抑郁症认知结果的表型预测因子

• 批准号: 10413985
• 负责人: DAVID C. STEFFENS
• 金额: $ 71.38万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 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/10413985
• 关键词: Accounting; Adult; Alzheimer' 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; Economics; Elderly; Enrollment; Epidemiology; Exercise; Feeling; Frustration; Functional Magnetic Resonance Imaging; Future; Health; Hippocampus (Brain); 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; Play; Predisposition; Prevention strategy; Psychotherapy; Recording of previous events; Recurrence; Relapse; Risk; Role; 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 network; novel; pandemic disease; pleasure; recruit; relating to nervous system; resilience; response; serial imaging; social; stressor; suicidal risk

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R01MH108578的竞争续约中，我们正在寻求将发现从初始研究扩展到 关注压力在纵向情绪和后期抑郁症（LLD）的认知结果中的影响 检查应力对LLD中大脑结构和功能的影响。严重或持续的压力源可能导致 行为和情绪变化的数量，包括焦虑，烦躁不安，睡眠中断，食欲改变， 并退出社会和愉悦的活动。这些与压力有关的后果尤其是 考虑处理过的LLD的纵向结果时，很有意义。他们可能被一个人的 长期以来对压力反应的不良适应性模式，体现在神经质的构造中，我们 已证明与情绪低落和认知结局有关。此外，Andreescu等。 （2019） 引入了一种抑郁复发模型，该模型结合了稳态不平衡假设， 这表明在老年降低抑郁症中，神经网络处于脆弱的稳态，那就是 受压力暴露的威胁。在LLD结局压力中特别重要的网络是默认的 模式网络（DMN），显着网络（SN）和执行控制网络（ECN）。 后期生活抑郁症的神经生物学（NBOLD）研究开始注册较老的抑郁症，从未 - 2013年的抑郁控​​制措施，注册132次抑郁症和44个控制，目前遵循77次抑郁症和 22个控件。受试者在情绪，认知，个性和压力方面都具有很好的特征（包括 在目前的同性恋大流行期间获得的特定措施。它非常适合检查对压力的影响 纵向情绪和认知结果。对于续订，我们将遵循当前的主题并招募75个新主题 受试者，通过年度认知测试，压力度量和基线，最多可追踪5年 和两年的大脑fMRI扫描。在本应用程序中介绍的初步数据中，我们表明： 1）在沮丧的长辈中，与4年内发展认知能力下降/痴呆的人相比 保持正常状态的神经质和良心性增加的2年降低。 2）在两年内压力恶化与海马体积减少两年有关，IS 与关键大脑区域功能连通性的变化有关。 3）在复杂的统计建模中，神经质变化的相互作用和数量的变化 最近经历的压力源与认知结果有关。 在这种竞争的续约中，我们将研究以下具体目标： 1。研究压力源（根据各种措施获得的影响）和神经质对纵向情绪和 患有重度抑郁症病史（MDD）的老年人的认知结果。 2。研究压力和神经质对具有MDD病史的老年人的大脑结构和功能的影响。 3。与纵向多变量统计模型中的目标1和2中的变量之间的关系。