Improving Therapeutic Learning in Depression: Proof of Concept

项目摘要/摘要 尽管药物治疗和心理治疗在治疗重度抑郁症方面都取得了进展，但无反应和 部分应答仍然是相对常见的结果，促使人们寻找新的治疗方法。这 应用涉及一种这样的新疗法的开发，基于一种特殊的 翻译研究的成功：基于暴露的认知行为疗法(CBT)的加强 D-环丝氨酸(Dcs)。在这一应用中，我们提出了一项关于分布式控制系统对于增强 与抑郁症的治疗相关的治疗性学习(即，在消退学习之外，在哪里 已经被证明是成功的)。具体地说，对于R-21机制(PA-11-261)，我们 研究DCs在增强抑郁个体的陈述性记忆中的作用，通过以下评估 标准化测试和认知治疗课程材料的保留。在寻求延长治疗性治疗 为了增强DC的靶点，我们还建议研究一种活性比较剂。这位特工， 莫达非尼似乎在睡眠剥夺和非睡眠剥夺中都提供了认知增强效果 个体，但似乎也有药物状态(例如，情绪和副作用)的影响，这不是DCS的特征 增强功能。出于这个原因，药物背景效应可能会随着时间的推移影响记忆保持。因此，我们将 评估药物作用期间和一周后的记忆增强效果 有人吸毒了。总体而言，我们建议通过4项研究来检查认知功能和记忆表现 对96名患有严重抑郁症的男性和女性进行治疗，他们将以双盲方式随机 分配给：(1)50毫克DCS50毫克，(2)250毫克DCS250毫克，(3)莫达非尼100毫克，或(4)研究中使用的安慰剂 记忆测试包括给定研究周所特有的两个项目(即，项目分类， HVLT和数字倒退)，以及随时间重复的内存任务(逻辑内存任务 认知疗法内容)，允许在一周内评估记忆和保持效果 (即从第2周到第3周和从第3周到第4周)。我们相信这项研究是合乎逻辑的下一步 朝着扩大CBT对抑郁症的增强效应的目标前进。如果在R21中实现了研究目标 研究，我们将在资助期结束时继续R01申请，努力表明 治疗学习的增强导致抑郁症的更早和/或更有力的治疗反应 接受CBT的患者。

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.