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障碍（HD）的临床结果，这是一种常见的、潜在的使人衰弱的疾病，构成了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），尽管有明显的改进空间，但它似乎还算有效。在目前的研究中，我们建议将这一研究与PI最近美国国立卫生研究院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兴趣区域（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、治疗中和治疗后，患者将在获得和丢弃决策任务期间进行功能磁共振成像（fMRI），该任务已在我们之前的工作中成功使用。此外，患者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）也将完成这些措施作为规范对照组。本研究的主要目的是确定认知行为治疗后HD患者观察到的神经活动模式改变的程度。在此目的下，我们预测HD患者（与hcc相比）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性。我们进一步预测，接受CBT治疗的HD患者（与普通HD患者相比）在这些roi中的活性会下降，并且与接受CBT治疗的hc患者不再存在差异。该研究的第二个目的是确定感兴趣的大脑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的血流动力学活动将与HD症状和决策任务的表现相关；在治疗过程中，大脑活动的变化将与症状和机制的变化相对应。最后，一个探索性的目标是探索，使用数据驱动和模型约束的方法，预测对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，治疗前目标roi的活性将与治疗前到治疗后HD症状的变化显著相关。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），通过关注该人群对社会心理干预反应的生物学和行为调节因子（策略3.1），以及利用疾病的生物学原因研究来了解和开发针对疾病核心特征的社会心理干预措施（策略3.1），促进了NIMH战略计划。该研究的结果有望阐明囤积症患者对CBT治疗成功反应的神经机制，并为进一步的治疗发展和可能的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.