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: 7881540
• 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/7881540
• 关键词: Adverse effects; Affect; Aftercare; Age; Aging; Anisotropy; Anterior; Antidepressive Agents; Brain; Caring; Clinical; Clinical Trials; Clinical dementia rating scale; Color; Complement 3a; Complement 3b; Complement 3c; Complement 3d; Complement 4b; Complement component C4a; 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; Recurrence; Relapse; Research Personnel; Residual state; Risk; Sampling; Series; Severities; Specificity; Structure; Symptoms; Testing; Time; Translational Research; age related; base; cingulate cortex; complement C2a; complement C2b; 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 response; 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（由申请人提供）：本研究的重点是老年抑郁症的正面处理异常及其与治疗反应的关系。它的目的是根据我们的研究从经验上演变而来的，表明执行功能障碍（额叶功能障碍的临床表达）为：1。在老年抑郁症中常见； 2。与抑郁症的临床表现相关，与额叶功能障碍一致以及与前扣带回皮层（ACC）的微结构白质（WM）异常相关； 3。有助于残疾。我们还观察到，额叶功能障碍（包括ACC功能障碍）的指标预测晚期抑郁症对抗抑郁药的反应不佳。逻辑下一步是寻找与抗抑郁反应不良有关的额叶处理异常。为此，我们进行了ERP研究，该任务激活了背侧和rostral ACC细分，这导致了拟议的假设。主要假设假设指出，在颜色词障碍响应抑制任务和“情绪go/nogo”歧视任务后，较大的与错误相关的负率（ERN）和较小的误差阳性（PE）幅度（PE）振幅预测了SAD和中性单词的歧视任务，可以预测抑郁症状，缓解症状，缓解率和反应率的变化，并在抑郁症患者的功能中受到ExcitialItalOpram的功能。我们将探讨ERN和PE振幅在治疗过程中是否发生变化，并检查其变化是否与执行功能的变化和抑郁症的严重程度有关。这些假设将在120名受试者中进行测试，该受试者根据年龄（65-74和75-84岁）和执行功能障碍（Stroop）进行了重大抑郁症，他们将在2周的药物冲刷后，将接受一项为期12周的，受控的，开放的苏联抗氧释式试验，目标每日20毫克的目标剂量为20 mg。受试者将在基线和第4周和第8周进行脑电图记录，并对影响抑郁症进程的心理病理学和临床参数进行全面的系统评估（基线，8周和12周）。抑郁症状，功能状态和副作用将每周评级。在启发式层面上，我们希望我们的发现将为翻译研究提供动力，从而导致新的治疗发展和临床试验方法的变化。在临床水平上，确定与抗抑郁药反应和持续性残疾相关的ERP异常可能会导致治疗计划，尤其是在牵涉的ERP参数与数十种简单的ADMINISTER神经心理学测试相关的情况下。这些患者可以针对警惕的临床随访和全面的治疗计划，包括连续的药理学试验计划。