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.

项目摘要/摘要 尽管在药物治疗和心理治疗方面都取得了进步 部分响应仍然是相对常见的结果，激励人们寻找新的治疗方法。这 应用与一种特定的一种新型治疗有关的一种新型治疗 转化研究的成功：基于暴露的认知行为疗法的增强（CBT） 与d-cycloserine（DCS）。在此应用中，我们提出了DC增强功效的研究 治疗性学习与抑郁症的治疗相关（即，在灭绝学习之外 已显示出成功）。具体而言，适合R-21机制（PA-11-261），我们 通过评估 标准化测试和认知疗法会话材料的保留。寻求扩展治疗性 DC增强的目标，我们还建议研究主动比较剂。这个代理， 莫达非尼，似乎在剥夺睡眠和非睡眠的剥夺的睡眠和非睡眠之间具有认知增强的效果 个体，但似乎也具有DC的特征的药物状态（例如，情绪和侧面）效应 增强。因此，药物含量效应可能会随着时间的流逝而影响记忆的保留。因此，我们会的 在药物作用期间以及一周后，评估记忆增强效果 吸毒了。总体而言，我们建议在4个研究中检查认知功能和记忆表现 96个患有重度抑郁症的男性和女人的会议，以双盲方式将是随机的 分配给：（1）50mg DC，（2）250mg DCS，（3）100mg莫达非尼或（4）安慰剂在研究中给药 第2和第3周。记忆测试包括给定学习周独有的两个项目（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 认知疗法含量），可以评估一个星期的记忆和保留效应 （即，从第2周到第3周，从第3周到​​第4周）。我们认为这项研究是下一个合乎逻辑的步骤 目的是扩大CBT增强效应对抑郁症的影响。如果在此R21中实现了学习目标 研究，我们将在资金期结束时继续进行R01申请，努力表明是否是否 增强治疗性学习会导致抑郁症的早期和/或更强大的治疗反应 接受CBT的患者。