ERPs Cognitive Dysfunction and Treatment Response of Geriatric Depression

描述（由申请人提供）：本研究的重点是老年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（额叶功能障碍的临床表现）是：1。常见于老年抑郁症；2. 伴有抑郁症的临床表现，与额叶功能障碍和前扣带皮层（ACC）外侧白质微结构（WM）异常相一致；和3。导致残疾。我们还观察到，包括ACC功能障碍在内的额叶功能障碍指标可以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不良反应相关的额叶处理异常。为此，我们在激活背侧和吻侧ACC分支的任务后进行了ERP研究，这导致了提出的假设。本研究的主要假设是，在色字Stroop反应抑制任务和悲伤词和中性词的“情绪Go/Nogo”辨别任务后，较大的错误相关负性（ERN）和较小的错误正性（Pe）振幅可预测艾司西酞普兰治疗后抑郁老年人抑郁症状、缓解和反应率的变化以及功能的改变。我们将探讨ERN和Pe的振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的变化和抑郁的严重程度有关。这些假设将在120名根据年龄（65-74岁和75-84岁）和执行功能障碍（Stroop）进行分层的重度抑郁症患者中进行检验，这些患者将接受为期12周的对照开放艾司西酞普兰试验，在2周的药物洗脱期后，每日目标剂量为20mg，安慰剂引入。受试者将在基线、第4周和第8周进行脑电图记录，并对影响抑郁症病程的精神病理学和临床参数（基线、8周和12周）进行全面系统的评估。每周对抑郁症状、功能状态和副作用进行评估。在启发式水平上，我们期望我们的发现将为转化研究提供动力，从而导致新的治疗开发和临床试验方法的改变。在临床层面上，识别与抗抑郁药反应差和持续性残疾相关的ERP异常可能为治疗计划提供信息，特别是如果涉及的ERP参数与简单易用的神经心理学测试分数相关。这样的患者可以有针对性地进行警惕的临床随访和综合治疗计划，包括后续药理试验的计划。

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.