ERPs Cognitive Dysfunction and Treatment Response of Geriatric Depression

ERPs 认知功能障碍和老年抑郁症的治疗反应

• 批准号: 7304612
• 负责人: GEORGE S ALEXOPOULOS
• 金额: $ 31.05万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7304612
• 关键词: Adverse effects; Affect; Aftercare; Age; Aging; Anisotropy; Anterior; Antidepressive Agents; Brain; Caring; Classification; Clinical; Clinical Trials; Clinical dementia rating scale; Color; Complement 3a; Complement 3b; Complement 3c; Complement 3d; Complement 4b; Complement component C4a; Daily; Depressed mood; Diffusion Magnetic Resonance Imaging; Discrimination; Disease remission; Dorsal; Dose; EP300 gene; Elderly; Electroencephalography; Emotional; Escitalopram; Evaluation; Event; Evolution; Functional disorder; Goals; Impaired cognition; Impairment; Lateral; Left; Literature; Major Depressive Disorder; Mediating; Memory; Mental Depression; Methodology; Neuropsychological Tests; Outcome; Patients; Peat; Performance; Pharmaceutical Preparations; Placebos; Process; Psychopathology; Quality of life; Rate; Recurrence; Relapse; Research Personnel; Residual state; Risk; Sampling; Score; Series; Severities; Specificity; Structure; Symptoms; Testing; Time; Translational Research; Week; age related; base; cingulate cortex; complement C2a; complement C2b; concept; depressive symptoms; disability; executive function; follow-up; functional disability; functional status; geriatric depression; health care service utilization; heuristics; indexing; instrumental activity of daily living; neuroimaging; novel; response; therapy development; treatment planning; treatment trial; white matter

DESCRIPTION (provided by applicant): This study focuses on frontal processing abnormalities in geriatric depression and their relationship to treatment response. Its aims evolved empirically from our studies suggesting that executive dysfunction (a clinical expression of frontal dysfunction) is: 1. Common in geriatric depression; 2. associated with a clinical presentation of depression consistent with frontal dysfunction and with microstructural white matter (WM) abnormalities lateral to the anterior cingulate cortex (ACC); and 3. contributes to disability. We also observed that indices of frontal dysfunction, including ACC dysfunction, predict poor response of late-life depression to antidepressants. A logical next step was a search for frontal processing abnormalities associated with poor antidepressant response. To this end, we conducted ERP studies following tasks activating the dorsal and the rostral ACC subdivisions, which led to the proposed hypotheses. The primary hypotheses postulate that large error-related negativity (ERN) and small error positivity (Pe) amplitude following the Color-Word Stroop response-inhibition task and an "emotional Go/Nogo" discrimination task of sad and neutral words predict change in depressive symptoms, remission and response rates and change in function in depressed elders treated with escitalopram. We will explore whether ERN and Pe amplitudes change during the treatment course and examine whether their change is associated with change in executive functions and in severity of depression. These hypotheses will be tested in 120 subjects with major depression stratified according to age (65-74 and 75-84 years) and executive dysfunction (Stroop), who will undergo a 12-week, controlled, open escitalopram trial with a target daily dose of 20 mg after a 2 week drug washout, placebo lead-in. The subjects will have EEG recording at baseline and weeks 4 and 8, and a comprehensive systematic evaluation of psychopathology and of clinical parameters that influence the course of depression (baseline, 8 weeks, and 12 weeks). Depressive symptomatology, functional status, and side effects will be rated weekly. On heuristic level, we expect that our findings will provide the impetus for translational research leading to novel treatment development and a change in clinical trials methodology. On a clinical level, identifying ERP abnormalities associated with poor antidepressant response and persistent disability may inform treatment planning, especially if the implicated ERP parameters are correlated with scores of simple-to-administer neuropsychological tests. Such patients could be targeted for a vigilant clinical follow-up and a comprehensive treatment plan including a plan for successive pharmacological trials.

描述(申请人提供)：这项研究的重点是老年性抑郁症的额叶加工异常及其与治疗反应的关系。我们的研究表明，执行功能障碍(额叶功能障碍的一种临床表现)的目的是：1.在老年抑郁症中常见；2.与抑郁症的临床表现相一致，与额叶功能障碍和前扣带回皮质(ACC)外侧的微结构白质(WM)异常相关；以及3.导致残疾。我们还观察到，额叶功能障碍的指数，包括ACC功能障碍，预测晚年抑郁症对抗抑郁药物的不良反应。合乎逻辑的下一步是寻找与抗抑郁药反应差相关的额叶处理异常。为此，我们在激活ACC背侧和吻侧亚区的任务后进行了事件相关电位研究，这导致了提出的假设。本研究的主要假设是，颜色词Stroop反应抑制任务后的大错误相关负性(ERN)和小错误正性(Pe)幅值以及悲伤词和中性词的“情绪去/去”辨别任务预示着艾司匹兰治疗的抑郁症老年人抑郁症状、缓解和反应率的变化以及功能的变化。我们将探索ERN和Pe波幅在治疗过程中是否发生变化，并检查它们的变化是否与执行功能和抑郁症严重程度的变化有关。这些假设将在120名患有严重抑郁症的患者中进行测试，这些患者根据年龄(65-74岁和75-84岁)和执行功能障碍(Stroop)进行分层，他们将接受为期12周的对照开放艾司匹兰试验，目标日剂量为20毫克，在两周的药物洗脱和安慰剂引入后。受试者将在基线以及第4周和第8周进行脑电记录，并对影响抑郁症病程的精神病理学和临床参数进行全面系统的评估(基线、8周和12周)。抑郁症状、功能状态和副作用将每周进行评级。在启发式水平上，我们希望我们的发现将为转化性研究提供动力，导致新的治疗开发和临床试验方法的改变。在临床层面上，识别与抗抑郁药物反应差和持续性残疾相关的ERP异常可能会为治疗计划提供信息，特别是如果所涉及的ERP参数与易于管理的神经心理测试评分相关时。可以针对这些患者进行警惕的临床跟踪和全面的治疗计划，包括后续的药理试验计划。