Applying Mindfulness-Based Cognitive Therapy to Treatment-Resistant Depression

描述（由申请人提供）：重度抑郁症（MDD）是世界上导致残疾的主要原因。难治性抑郁症（Treatment-Resistant Depression，TRD）是导致大多数MDD残疾的原因。值得注意的是，50%的MDD患者在两次充分的抗抑郁药物试验后都无法缓解，从而遭受TRD。在目前资助的R 01项目中，我们正在对TRD人群进行一项基于正念的认知疗法（MBCT）的随机对照试验。MBCT是一种以小组为基础的为期8周的干预，使用正念冥想作为其核心治疗成分。它教导人们对抑郁的想法和感受有不同的关系。这项研究使用健康促进计划（HEP）作为比较。HEP的特点是身体功能，营养和音乐治疗。该研究设计包括招募124名MDD患者，这些患者使用抗抑郁药治疗历史表软件记录了两项或更多充分的抗抑郁药试验失败。然后将患者随机分配到两组之一：MBCT+TAU或HEP+TAU。本研究的总体目的是使用汉密尔顿抑郁量表在8周的时间内测试MBCT+TAU在减少抑郁症状和提高缓解率和应答率方面比HEP+TAU更有效的假设。在目前提出的对R 01研究的修订中，我们正在响应NIH关于增加对治疗干预的生物学理解的呼吁。我们建议从R 01中招募80名参与者，在8周MBCT+TAU或HEP+TAU干预前后立即接受fMRI评估。我们建议在执行控制（情绪工作记忆）任务期间，在功能磁共振成像扫描期间实施情绪调节（情绪标记）和情绪干扰，以探测MBCT或HEP八周前后的腹侧情感处理和背侧执行控制系统。我们假设，与HEP+TAU参与者相比，MBCT+TAU参与者将在治疗过程中表现出背外侧前额叶皮层的更大增加和腹外侧前额叶皮层和杏仁核的激活的更大减少。因为正念认知疗法专注于注意力训练，我们相信与其他形式的心理治疗相比，它在直接激活这些情绪调节系统方面是独一无二的。有新的证据表明，正念与这些系统中每个系统的组件的增强激活有关。这项研究的结果将在确定TRD的有效治疗方面以及阐明与MBCT相关的神经机制方面具有明显的公共卫生益处。这可以允许治疗的细化和增强的患者选择。 公共卫生相关性：重度抑郁症（MDD）是世界上导致残疾的主要原因，也是北美的头号原因。难治性抑郁症（Treatment-Resistant Depression，TRD）是导致大多数MDD残疾的原因。值得注意的是，50%的MDD患者在两次充分的抗抑郁药物试验后都无法缓解，从而遭受TRD。目前TRD的药物和心理治疗策略的有效性有限，因此需要新的技术。这项资助是一项针对TRD人群的基于正念的认知疗法（MBCT）的随机对照试验。如果MBCT在这项研究中被证明是有效的，它将具有重大的公共卫生意义。它可以减轻残疾，降低发病率，减少医疗并发症，并减少个人痛苦的成本效益的干预。本研究的第二阶段调查了对MBCT反应的fMRI神经模式，这可能有助于改善其疗效，并更好地预测谁可能从治疗中获益最多。

DESCRIPTION (provided by applicant): Major depressive disorder (MDD) is a leading cause of disability in the world. Treatment-Resistant Depression (TRD) causes the majority of MDD's disability. Strikingly, 50% of individuals with MDD will fail to remit with two adequate trials of antidepressant medications, thus suffering TRD. In a currently funded R01 project now in its second year, we are conducting a randomized, controlled trial of Mindfulness-Based Cognitive Therapy (MBCT) for the TRD population. MBCT is a group-based, 8-week intervention that uses mindfulness meditation as its core therapeutic ingredient. It teaches people to have a different relationship to depressive thoughts and feelings. This study uses the Health-Enhancement Program (HEP) as a comparator. HEP features physical functioning, nutrition, and music therapy. The study design involves enrollment of 124 patients with MDD who have failed two or more adequate antidepressant trials documented with the Antidepressant Treatment History Form software. Patients are then randomly assigned to one of two groups: MBCT+TAU or HEP+TAU. The overall aim of this study is to test the hypothesis that MBCT+TAU is more effective than HEP+TAU in reducing depressive symptoms and enhancing remission and response rates using the Hamilton Rating Scale for Depression over a period of 8 weeks. In the currently proposed revision to the parent R01 study, we are responding to NIH calls for increased biological understanding of therapeutic interventions. We propose to enroll 80 participants from the R01 to receive fMRI assessments immediately before and after the 8-week MBCT+TAU or HEP+TAU interventions. We propose to implement both emotion regulation (affect labeling) and emotional interference during executive control (emotional working memory) tasks during fMRI scanning to probe the ventral affective processing and dorsal executive control systems before and after the eight weeks of MBCT or HEP. We hypothesize that MBCT+TAU participants will demonstrate greater increases in the dorsolateral prefrontal cortex and greater decreases in activation in the ventrolateral prefrontal cortex and amygdala over the course of treatment, compared to the HEP+TAU participants. Because MBCT focuses on attentional training, we believe it is unique compared to other forms of psychotherapy in directly activating these emotion regulation systems. There is emerging evidence that mindfulness is associated with enhanced activation of components within each of these systems. The results of this study will have clear public health benefits both in terms of identifying an effective treatment for TRD, but also, in elucidating the neural mechanisms associated with MBCT. This may allow for refinement of treatment and enhanced patient selection. PUBLIC HEALTH RELEVANCE: Major depressive disorder (MDD) is a leading cause of disability in the world and the number one cause in North America. Treatment-Resistant Depression (TRD) causes the majority of MDD's disability. Strikingly, 50% of individuals with MDD will fail to remit with two adequate trials of antidepressant medications, thus suffering TRD. Current pharmacological and psychotherapeutic treatment strategies for TRD are limited in effectiveness so new techniques are needed. This grant is a randomized, controlled trial of Mindfulness-Based Cognitive Therapy (MBCT) for the TRD population. If MBCT is shown to be efficacious in this study, it will be of major public health significance. It may lessen disability, decrease morbidity, decrease medical comorbidity and reduce personal suffering in a cost effective intervention. The second phase of this study investigates the fMRI neural patterns of response to MBCT which may help refine its efficacy and lead to better predictions of who may benefit the most from the treatment.