Improving Therapeutic Learning in Depression: Proof of Concept

改善抑郁症的治疗学习：概念证明

• 批准号: 8621206
• 负责人: Michael W. Otto
• 金额: $ 24.66万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8621206
• 关键词: Adverse effects; Affect; Agonist; Antidepressive Agents; Anxiety; Anxiety Disorders; Characteristics; Cognitive; Cognitive Therapy; Combined Modality Therapy; Cycloserine; Delayed Memory; Depressed mood; Development; Digit structure; Disease; Dose; Double-Blind Method; Drug effect disorder; Evaluation; Fatigue; Funding; Goals; Guidelines; Immediate Recalls; Individual; Intervention; Investigation; Learning; Major Depressive Disorder; Memory; Mental Depression; Modafinil; Modality; Moods; N-Methyl-D-Aspartate Receptors; Outcome; Participant; Patients; Performance; Pharmaceutical Preparations; Pharmacotherapy; Placebo Control; Placebos; Psychotherapy; Randomized; Relative (related person); Research; Role; Short-Term Memory; Sleep; Sleep Disorders; Testing; Therapeutic; Time; Translational Research; Treatment Efficacy; Visit; Woman; Work; alertness; base; clinical application; cognitive function; design; improved; learning extinction; memory process; memory retention; men; novel; partial response; positive mood; psychosocial; public health relevance; success; therapeutic target; treatment response; treatment strategy

PROJECT SUMMARY/ABSTRACT Despite advances in both pharmacotherapy and psychotherapy for major depression, non-response and partial-response remain relatively common outcomes, motivating the search for new treatments. This application is concerned with the development of one such novel treatment, based on one of the particular successes of translational research: the augmentation of exposure-based cognitive-behavior therapy (CBT) with d-cycloserine (DCS). In this application, we propose a study of the efficacy of DCS for augmenting therapeutic learning relevant for the treatment of depression (i.e., outside the extinction learning where DCS has been shown to have success). Specifically, appropriate to an R-21 mechanism (PA-11-261), we investigate the role of DCS in enhancing declarative memory in depressed individuals, as evaluated by standardized tests and the retention of cognitive therapy session material. In seeking to extend the therapeutic targets for DCS augmentation, we are also proposing to study an active comparison agent. This agent, modafinil, appears to offer cognitive enhancing effects among both sleep deprived and non-sleep deprived individuals, but also appears to have drug-state (e.g., mood and side) effects that are not characteristic of DCS augmentation. For this reason, drug-context effects may affect memory retention over time. Hence, we will evaluate memory enhancement effects both during the period of drug action as well as one week later when no drug is taken. Overall, we propose to examine cognitive function and memory performance over 4 study sessions in 96 men and women with major depression, who, in a double-blind fashion, will be randomly assigned to either: (1) 50mg DCS, (2) 250mg DCS, (3) 100mg modafinil, or (4) placebo administered on Study Weeks 2 and 3. The memory tests include both items unique to a given study week (i.e., item categorization, the HVLT, and digits backward), and memory tasks that are repeated over time (logical memory tasks and the cognitive therapy content), that allow assessment of memory and retention effects across one-week periods (i.e., from Week 2 to Week 3 and from Week 3 to Week 4). We believe this study is the next logical step toward the goal of extending CBT augmentation effects for depression. If study aims are achieved in this R21 study, we will proceed with a R01 application at the conclusion of the funding period, working to show whether augmentation of therapeutic learning leads to an earlier and/or more robust treatment response for depressed patients undergoing CBT.

项目概要/摘要 尽管针对重度抑郁症的药物治疗和心理治疗都取得了进展，但治疗无反应和 部分缓解仍然是相对常见的结果，这促使人们寻找新的治疗方法。这 应用程序涉及基于一种特定的治疗方法的开发 转化研究的成功：基于暴露的认知行为疗法（CBT）的增强 与 d-环丝氨酸（DCS）。在此应用中，我们提出一项 DCS 增强功效的研究 与抑郁症治疗相关的治疗性学习（即，在消退学习之外，DCS 已被证明是成功的）。具体来说，适合 R-21 机制 (PA-11-261)，我们 研究 DCS 在增强抑郁症个体陈述性记忆中的作用，评估如下： 标准化测试和认知治疗课程材料的保留。为了寻求延长治疗时间 DCS 增强的目标，我们还建议研究一种活性比较剂。这位经纪人， 莫达非尼似乎对睡眠剥夺和非睡眠剥夺的人都有认知增强作用 个体，但也似乎具有 DCS 所不具有的药物状态（例如情绪和副作用）效应 增强。因此，药物环境效应可能会随着时间的推移影响记忆保留。因此，我们将 评估药物作用期间以及一周后无症状时的记忆增强效果。 药物被服用。总的来说，我们建议通过 4 项研究来检查认知功能和记忆表现 对 96 名患有重度抑郁症的男性和女性进行了治疗，他们将以双盲方式随机分组 分配给：(1) 50mg DCS，(2) 250mg DCS，(3) 100mg 莫达非尼，或 (4) 研究中施用的安慰剂 第 2 周和第 3 周。记忆测试包括给定学习周特有的两个项目（即项目分类、 HVLT 和数字向后），以及随时间重复的内存任务（逻辑内存任务和 认知治疗内容），可以评估一周内的记忆和保留效果 （即从第 2 周到第 3 周以及从第 3 周到第 4 周）。我们相信这项研究是下一个合乎逻辑的步骤 旨在扩大 CBT 对抑郁症的增强效果。如果本 R21 的研究目标得以实现 研究，我们将在资助期结束时继续进行 R01 申请，努力证明是否 治疗学习的增强可以使抑郁症得到更早和/或更强有力的治疗反应 接受 CBT 的患者。