Novel neural circuit biomarkers of depression response to computer-augmented CBT

每年有超过20%(5500万)的美国成年人口患有严重的抑郁症。(MDD)。 虽然有有效的治疗方法可用，但抑郁症仍然没有得到充分的诊断和治疗，部分原因是 费用和治疗的可获得性。在本申请中，针对NIMH NOT-14-007，我们提出了一种 研究抑郁症治疗反应的潜在新生物标志物的临床试验，而不是测试 一种高效、经济高效的计算机增强认知行为治疗(CCBT)形式，已经 已被证明有效。我们提供的试点数据支持CBT在功能连接方面的改进 MDD中的任务诱导激活。我们在以前的工作中也发现，这种CCBT模型，称为 未来好日子(GDA)，对MDD的疗效不逊于传统的个体化CBT疗法 在8周和16周的治疗中，尽管治疗师的平均接触时间从16小时减少到不到5小时 几个小时。我们现在提出，这种新的认知疗法，它取代了密集的计算机- 进行数小时的治疗师联系的技能培训，将与我们拥有的相同的大脑目标进行接触 以前在CBT中见过。我们假设这是一段排练时间，在这段时间里，个人积极投入 在矫正技能训练中，“修复”大脑的连通性，促进康复。我们将招聘总共 60例MDD患者和40例匹配的健康志愿者来自北京的门诊部 宾夕法尼亚大学的医院。考虑到非特定因素的影响，一半的 MDD参与者将在基线评估后立即随机接受CCBT，一半的参与者将 首次接受为期8周的抑郁症护理管理(DCM)(临床上负责任的替代方案 传统的等待名单对照组，包括支持和临床管理)，然后在随后接受 Ccbt. 目标1：比较基础静息状态、功能连接性和任务诱导活动 和控制。目的2：评估CCBT治疗对静息状态、功能连接和任务的影响。 比较CCBT治疗组和DCM治疗组的MDD患者的诱导激活。 探索性目标：1a：预测基线成像措施对治疗结果的影响；1b： 预测基线执行功能对治疗结果的影响。

Every year more than 20% (55 million) of the adult American population suffers from major depression. (MDD). While effective treatments are available, depression remains under-diagnosed and under-treated, in part due to cost and availability of treatment. In the current application in response to NIMH NOT-14-007 we propose a clinical trial to study potential novel biomarkers of depression treatment response rather than to test efficacy of an efficient, cost-effective form of computer-augmented cognitive behavioral therapy (CCBT) which already has proven efficacy. We present pilot data supporting CBT-induced improvements in functional connectivity and task-induced activation in MDD. We also have found in previous work that this model of CCBT, known as Good Days Ahead (GDA), has efficacy for MDD that is not inferior to conventional individual CBT therapy across 8 and 16 weeks of treatment, despite reducing average therapist contact from 16 hours to less than 5 hours. We now propose that this new variation of cognitive therapy, which substitutes intensive, computer- administered skills training for hours of therapist contact, will engage the same brain targets we have previously seen with CBT. We hypothesize that it is rehearsal time during which an individual actively engages in corrective skills training that “mends” the brain connectivity and promotes recovery. We will recruit a total of 60 patients with MDD and 40 matched comparison healthy participants from the outpatient clinics of the Hospitals of the University of Pennsylvania. To take into account the impact of nonspecific factors, half of the MDD participants will be randomized to receive CCBT immediately after baseline assessments and half will first receive 8 weeks of Depression Care Management (DCM) (a clinically responsible alternative to a traditional wait-list control group that includes support and clinical management) before subsequently receiving CCBT. Aim 1: Compare baseline resting state functional connectivity and task-induced activity between MDD and controls. Aim 2: Assess CCBT treatment effects on resting state functional connectivity and task- induced activation in MDD comparing CCBT-treated participants to DCM –treated participants. Exploratory Aim: 1a:Predict the effects of baseline imaging measures on treatment outcomes; 1b: Predict the effects of baseline executive function on treatment outcomes.