Neural Mechanisms of CBT Response in Hoarding Disorder

描述（由申请人提供）：拟议研究的长期目标是改善囤积症（HD）的临床结局，这是一种常见的潜在衰弱性疾病，会造成严重的公共卫生负担。PI已经开发并测试了一种认知行为疗法（CBT），该疗法似乎适度有效，但仍有明显的改进空间。在本研究中，我们建议将这一系列研究与PI最近的NIH支持的神经影像学研究相结合，该研究指出了与认知和情感决策过程相关的感兴趣区域（ROI）的特定功能异常。HD患者（n = 80）将被随机分配至CBT或等候名单（WL）。在治疗前、治疗中和治疗后，患者将在我们以前的工作中成功使用的获取和丢弃决策任务期间接受功能性磁共振成像（fMRI）。此外，患者将完成一些旨在评估决策能力和损害的实验室任务。一组健康对照（HC）受试者（n = 40）也将作为规范对照组完成这些测量。拟议研究的主要目的是确定在CBT后HD中观察到的神经活动模式变化的程度。在这一目标下，我们预测HD患者（与HC相比）将在与决策的认知和情感方面相关的ROI中显示出更大的血流动力学活动。我们进一步预测，接受CBT的HD患者（与WL相比）将显示这些ROI的活动减少，并且将不再与CBT后的HC不同。这项研究的第二个目的是确定大脑感兴趣区域的活动变化与囤积相关症状和损伤之间的关系。我们预计，目标ROI中的血流动力学活动将与HD症状和决策任务的表现相关;并且大脑活动的变化将对应于治疗过程中的症状和机制变化。最后，一个探索性的目的是探索，使用数据驱动和模型约束的方法，预测对CBT的反应的治疗前神经活动的模式。我们预测，在接受治疗的HD患者中，目标ROI的治疗前活动将与治疗前至治疗后的HD症状变化显著相关。本研究通过识别和整合与HD相关的生物标志物和行为指标（策略1.3），通过关注该人群对心理社会干预反应的生物学和行为调节剂（策略3.1），并利用对疾病生物学原因的研究来告知和开发针对疾病核心特征的心理社会干预（策略3.1），促进NIMH战略计划。这项研究的结果有望阐明囤积症患者成功应对CBT治疗的神经机制，并为进一步的治疗开发和可能改善这种疾病的结局奠定基础。

DESCRIPTION (provided by applicant): The long-term goal of the proposed research is to improve clinical outcomes for Hoarding Disorder (HD), a common and potentially debilitating condition that poses a severe public health burden. The PI has developed and tested a cognitive-behavioral therapy (CBT) that appears moderately effective, although there is clear room for improvement. In the present study, we propose to merge this line of research with the PI's recent NIH-supported neuroimaging research that points to specific functional abnormalities in regions of interest (ROIs) related to cognitive and affective decision- making processes. Patients with HD (n = 80) will be randomized to CBT or wait list (WL). At pre-treatment, mid-treatment, and post-treatment, patients will undergo functional magnetic resonance imaging (fMRI) during an acquiring and discarding decision-making task that has been used successfully in our previous work. In addition, patients will complete a number of laboratory tasks designed to assess decision-making capacity and impairment. A group of healthy control (HC) participants (n = 40) will also complete these measures as a normative control group. The primary aim of the proposed study is to determine the extent to which the observed patterns of neural activity in HD change following CBT. Under this aim, we predict that HD patients (vs. HCs) will show greater hemodynamic activity in ROIs associated with cognitive and affective aspects of decision-making. We further predict that HD patients receiving CBT (vs. WL) will show decreased activity in those ROIs, and will no longer differ from HCs following CBT. A secondary aim of the proposed study is to determine the relationship between change in activity in brain regions of interest and hoarding-related symptoms and impairments. We expect, that hemodynamic activity in the target ROIs will correlate with symptoms of HD and with performance on decision-making tasks; and that change in brain activity will correspond to both symptom and mechanism changes over the course of treatment. Finally, an exploratory aim is to explore, using both data-driven and model-constrained approaches, patterns of pre-treatment neural activity that predict response to CBT. We predict that among treated HD patients, pre-treatment activity in the target ROIs will correlate significantly with HD symptom change from pre- to post- treatment. This study promotes the NIMH strategic plan by identifying and integrating biomarkers and behavioral indicators associated with HD (Strategy 1.3), by focusing on the biological and behavioral moderators of response to psychosocial intervention in this population (Strategy 3.1), and using research on the biological causes of disorder to inform and develop psychosocial interventions that target core features of disease (Strategy 3.1). Results of the proposed study are expected to elucidate the neural mechanisms of successful response to CBT treatment for hoarding patients, and to set the stage for further treatment development and possible improvements in outcome for this disorder.