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)的临床结果，HD是一种常见的、可能使人虚弱的疾病，构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)，该疗法似乎中等有效，尽管仍有明显的改进空间。在目前的研究中，我们建议将这一系列研究与PI最近由NIH支持的神经成像研究合并，该研究指出了与认知和情感决策过程相关的兴趣区(ROI)的特定功能异常。HD患者(n=80)将被随机分配到CBT或等待名单(WL)。在治疗前、治疗中期和治疗后，患者将接受功能磁共振成像(FMRI)，在获取和丢弃决策任务期间，我们已经成功地使用了我们以前的工作。此外，患者还将完成一些旨在评估决策能力和损伤的实验室任务。一组健康对照(HC)参与者(n=40)也将作为正常对照组完成这些措施。这项拟议研究的主要目的是确定在CBT后HD患者观察到的神经活动模式改变的程度。在这一目标下，我们预测HD患者(与HCS患者相比)将在与决策的认知和情感方面相关的ROI中表现出更大的血流动力学活动。我们进一步预测，接受CBT(与WL)的HD患者将在这些ROI中表现出活动减少，并且在CBT后将不再与HCS不同。这项拟议的研究的第二个目的是确定大脑感兴趣区域活动的变化与囤积相关症状和损害之间的关系。我们预计，靶ROI的血流动力学活动将与HD的症状和决策任务的表现相关；脑活动的变化将与治疗过程中的症状和机制变化相对应。最后，一个探索性的目标是使用数据驱动和模型约束的方法来探索预测CBT反应的治疗前神经活动模式。我们预测，在接受治疗的HD患者中，目标ROI中的治疗前活动将与治疗前到治疗后的HD症状变化显著相关。这项研究通过确定和整合与HD相关的生物标记物和行为指标来促进NIMH战略计划(战略1.3)，重点关注这一人群对心理社会干预的反应的生物和行为调节因素(战略3.1)，并利用对障碍的生物原因的研究来提供信息和制定针对疾病核心特征的心理社会干预措施(战略3.1)。这项拟议的研究结果有望阐明囤积症患者对CBT治疗成功反应的神经机制，并为进一步的治疗开发和可能改善这种疾病的结果奠定基础。

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.