ActiveCBT for depression: Transforming treatment through exercise priming

项目总结/摘要 重度抑郁症（MDD）的一线治疗，包括认知行为疗法（CBT）， 有效性有限，约一半的患者对CBT没有反应，并且在2年内复发。战略 可以增加MDD治疗的效力。我们之前已经展示了大量的心理和 运动后75分钟，MDD成人的神经可塑性得到改善。这在神经学上创造了一个 肥沃的运动后窗口，有可能最大限度地发挥CBT的效果后立即进行 锻炼的我们已经开发了一种新的治疗策略，使用有氧运动来启动随后的CBT session（'ActiveCBT'）。假设运动启动导致CBT机制的更大参与， 通过共同的（例如，工作联盟）和特定（例如，行为激活）因素与 抑郁症的结果;这种CBT增强方法还有待实证检验。我们的出版和 初步研究表明锻炼可以明显改善心理（例如，快感缺乏）和神经可塑性（例如， BDNF）标志物，我们的n = 10试点可行性试验表明，高的可能性后勤 运动启动对靶向机制的成功和合理影响。R61将包括一个为期8周的 一项在40名成年MDD患者中进行30分钟中度运动或安静休息的随机对照试验 （ActiveCBT vs. CalmCBT）在每周CBT会议之前。使用时间和注意力匹配的控制，所有 参与者将在这30分钟的治疗前观看标准化的系列纪录片， 不同群体之间的差异。该项目还将采用尖端的机器学习和 通过Lyssn平台进行自然语言处理，以客观地评估治疗。R61的总体目标是 目的：1）证明运动启动对目标CBT机制（工作联盟和行为）的影响 激活），2）将心理和神经可塑性运动启动与CBT机制联系起来，以及3）探索 基于客观机器学习的标志物从Lyssn到ActiveCBT诱导的治疗差异的敏感性。 在确定工作联盟和/或行为激活的适度组间差异后， 支持ActiveCBT，R33将继续进行2：1随机对照试验（n = 100），比较ActiveCBT 冷静CBT R33的总体目标是：1）确认运动启动对目标CBT机制的影响， 2）确定运动启动的初步功效信号，并确定功效强度 与CBT机制的联系。我们的工作假设是，我们将确认更高的工作联盟和/或 ActiveCBT中的行为激活，在8周和12周后具有更大的抑郁效应， 更大的工作联盟和/或行为激活。这些试验将建立一个潜在的后续 验证性疗效试验，以严格测试运动启动的潜力，以加强治疗。如果这 创新的、生物学上知情的方法成功地"启动"了随后的治疗，这可以用于 增加其他治疗和其他疾病，显着改善心理健康治疗。

PROJECT SUMMARY/ABSTRACT Frontline treatments for major depressive disorder (MDD), including cognitive behavioral therapy (CBT), have limited effectiveness, with ~½ of patients not responding to CBT and ½ relapsing within 2 years. Strategies that could increase the potency of MDD treatments are needed. We have previously shown large psychological and neuroplasticity improvements for 75 minutes post-exercise in adults with MDD. This creates a neurologically fertile post-exercise window with the potential to maximize the effects of CBT performed immediately after exercise. We have developed a novel treatment strategy using aerobic exercise to prime a subsequent CBT session (‘ActiveCBT’). Exercise priming is hypothesized to lead to greater engagement of CBT mechanisms of action through both common (e.g., working alliance) and specific (e.g., behavioral activation) factors linked to depression outcomes; this CBT augmentation approach has yet to be empirically tested. Our published and preliminary work show exercise acutely improves psychological (eg, state anhedonia) and neuroplastic (eg, BDNF) markers in MDD, and our n=10 pilot feasibility trial of this project indicates high likelihood for logistical success and plausible effects of exercise priming on target mechanisms. The R61 will consist of an 8-week randomized controlled trial in 40 adults with MDD performing 30-minutes of moderate exercise or quiet rest (ActiveCBT vs. CalmCBT) prior to weekly CBT sessions. Using a time- and attention-matched control, all participants will view a standardized documentary series for these 30 pre-therapy minutes with the only difference between groups being exercise. This project will also employ cutting-edge, machine learning and natural language processing via the Lyssn platform to objectively evaluate therapy. The overall R61 goals are to: 1) demonstrate exercise priming effects on target CBT mechanisms (working alliance and behavioral activation), 2) link psychological and neuroplastic exercise priming to CBT mechanisms, and 3) explore sensitivity of objective machine learning-based markers from Lyssn to ActiveCBT-induced therapy differences. Upon identification of a moderate between-group difference in working alliance and/or behavioral activation favoring ActiveCBT, the R33 will proceed with a 2:1 randomized, controlled trial (n=100), comparing ActiveCBT to CalmCBT. The overall R33 goals are to: 1) confirm effects of exercise priming on target CBT mechanisms, and 2) determine the preliminary efficacy signal of exercise priming, and determine the strength of the efficacy link with CBT mechanisms. Our working hypotheses are that we will confirm higher working alliance and/or behavioral activation in ActiveCBT, with greater depression effects at 8 weeks and 12 weeks later linked to greater working alliance and/or behavioral activation. These trials will establish the potential for a subsequent confirmatory efficacy trial to rigorously test the potential of exercise priming to enhance treatment. If this innovative, biologically-informed approach successfully ‘primes’ subsequent therapy, this could be used to augment other treatments and in other disorders, significantly improving mental health treatment.