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（TRD）是MDD致残的主要原因。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。MBCT是一种新技术，先前已发现可有效预防完全缓解的个体复发，并已显示出对TRD有效的新证据。MBCT是一种以小组为基础、为期8周的干预，以正念冥想为核心治疗成分。它教会人们与抑郁的想法和感受建立不同的关系。本研究将使用一个积极的比较条件，健康促进计划（HEP）。我们计划确定174例TRD患者。然后我们将随机将患者分为两组：MBCT+TAU（常规药物治疗）或HEP+TAU。我们预计150名患者将完成治疗，并在6、9和12个月时进行随访评估。第一阶段研究的具体目的是确定MBCT在减少成人TRD患者抑郁方面的急性疗效。我们还将进行一系列的二次假设和分析，以评估MBCT在减少残疾和提高生活质量方面的功效。研究的第二阶段将评估88名参与者在完成各自干预组之前和之后的功能磁共振成像结果。这一阶段的研究将专门研究MBCT对大脑背侧执行控制和腹侧情感处理系统的影响。在抑郁症的功能磁共振成像研究中，通常发现背侧执行控制系统的激活减少，而腹侧情感系统的激活增加。前一个系统将用一个工作记忆任务来研究，而后一个系统将用一个影响标记任务来研究。我们还将获得干预前后的静息状态分析来评估变化。我们的假设是MBCT在任务执行中特异性地加强背外侧和腹外侧前额叶皮层，作为神经机制介导其在治疗抑郁症中的情绪调节。这些脑区和其他脑区将被研究，以比较MBCT和HEP完成者抑郁严重程度的变化。在研究的第三阶段，TRD患者的基线功能磁共振成像将与健康对照进行比较。这将允许表征TRD中存在的功能异常，特别是在背侧执行控制和情感处理脑区域。这项研究的这一部分还将提供信息，说明成功降低抑郁症严重程度的治疗是否也能逆转功能性大脑异常。最后，这一阶段还将提供关于神经特征的功能磁共振成像数据

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. This grant is a randomized, controlled trial of Mindfulness- Based Cognitive Therapy (MBCT) for the TRD population. MBCT is a new technique that has previously been found effective for prevention of relapse in individuals in complete remission and has shown emerging evidence of efficacy in TRD. 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 t depressive thoughts and feelings. This study will use an active comparator condition, the Health-Enhancement Program (HEP). We plan to identify 174 patients with TRD. We will then randomly assign patients to two groups: MBCT+TAU (treatment as usual medications) or HEP+TAU. We anticipate 150 patients will complete treatment and undergo follow-up assessments at 6, 9 and 12 months The specific aim of the first phase of study is to determine the acute efficacy of MBCT in reducing depression in adults with TRD. We will also conduct a series of secondary hypotheses and analyses to evaluate MBCT's efficacy in reducing disability and improving quality of life. A second phase of the study will evaluate fMRI findings in 88 participants before and after completing their respective intervention groups. This phase of the study will specifically investigate MBCT effects on the brain's dorsal executive control and ventral affective processing systems. The dorsal executive control system has typically been found to have decreased activations in fMRI studies of depression, while the ventral affective system has been associated with increased activations. The former system will be probed with a working memory task while the latter is investigated with an affect labeling task. We will also obtain resting state analyses pre and post intervention to evaluate change. Our hypothesis is that MBCT specifically strengthens the dorsolateral and ventrolateral prefrontal cortices in task execution as neural mechanisms mediating its emotion regulation in treating depression. These and other brain regions will be investigated in comparison to change in depression severity of MBCT and HEP completers. In the third phase of the study, baseline fMRIs of individuals with TRD will be compared to healthy controls. This will allow for a characterization of functional abnormalities present in TRD, particularly in the dorsal executive control and affective processing brain regions. This component of the study will also yield information on whether treatment that is successful in reducing depression severity is also able to reverse functional brain abnormalities. Finally, this phase will also provide fMRI data about the neural signatures of TRD to help predict who the best candidates for MBCT are. PUBLIC HEALTH RELEVANCE: Major depressive disorder is the most prevalent mental health problem in the world. Strikingly, 70% of individuals with major depressive disorder will fail to remit with adequate initial treatment, thus suffering Treatment Resistant Depression (TRD). This supplement builds on a parent study that is a randomized controlled trial of a new treatment for TRD, Mindfulness-Based Cognitive Therapy (MBCT). This supplement would compare individuals with TRD to healthy controls at baseline, to better characterize functional brain abnormalities in TRD. It would also allow an understanding of whether MBCT reverses these abnormalities. The study may also allow for identification of better predictors of who responds best to MBCT. Since TRD is such a widespread disorder and is responsible for much of the morbidity and mortality of major depressive disorder, this study promises to increase our understanding of both the disorder and a new treatment for it. As such, the study would have a major public health impact.