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: 10226538
• 负责人: DAVID C. STEFFENS
• 金额: $ 80.13万
• 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/10226538
• 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的竞争更新中，我们正在寻求将最初研究的结果扩展到