Mobile-Assisted Cognitive Behavior Therapy for Negative Symptoms in Schizophrenia

 描述(申请人提供)：精神分裂症是人类已知的最具破坏性的疾病之一，也是全球十大严重功能残疾的原因之一。精神分裂症的阴性症状是精神分裂症功能不良的主要原因，在很大一部分患者中，这是一种未得到满足的治疗需求。我们建议使用一种实验治疗学的方法来测试一种新型的心理社会干预方法，该方法结合了面对面和基于智能手机的认知行为疗法(CBT)，用于治疗精神分裂症的经验性阴性症状，称为移动辅助CBT治疗阴性症状(MCBTn)。MCBTn是从我们的认知行为社交技能训练(CBSST)团体治疗和我们之前的临床试验研究的移动智能手机干预中针对失败主义态度的CBT组件的新颖提取和集成。该项目的主要目的是测试mCBTn是否可以降低一种新的治疗目标的严重性：失败主义行为态度。在一个前景看好的新模型中，Beck及其同事提出，失败主义态度(例如，“为什么麻烦，我总是失败”，“这不值得努力”)会导致精神分裂症患者出现消极症状，如缺乏动力和孤僻，并最终导致功能低下，因为失败主义态度会导致避免费力的目标导向活动。 我们的方法集中在这样的假设上，即失败主义态度导致经验性负面症状，包括动力和努力减弱，最终导致精神分裂症功能低下。此外，该领域目前依靠症状评定表和主观患者报告来衡量动机和努力；需要更客观的措施。这项拟议的项目将确定瞳孔反应是否可以提供一个客观的心理生理学努力生物标记物，对阴性症状的临床试验中的变化敏感。更大的瞳孔放大意味着更大的任务努力分配。我们建议在患有精神分裂症谱系障碍的消费者中进行两项mCBTn的序贯临床试验，这些患者具有持续的中到重度经验性阴性症状。在R61阶段，我们建议进行一项开放试验，以确定mCBTn是否改变了失败主义态度目标，并将确定与目标交战的最佳剂量。在R33阶段，我们提出了一项随机对照试验，将mCBTn与支持性接触对照进行比较，并将确定mCBTn是否能更大程度地减少失败主义态度，从而促进经验性阴性症状的改善。在这两个试验中，瞳孔反应将被记录为次要结果，以确定其作为动机和努力临床试验终点的潜力。

 DESCRIPTION (provided by applicant): Schizophrenia is one of the most devastating diseases known to humankind and is one of the top 10 causes globally of profound functional disability. Negative symptoms of schizophrenia account for much of the poor functional outcome in schizophrenia and are an unmet treatment need in a large proportion of patients. We propose to use an experimental therapeutics approach to test a novel psychosocial intervention that combines in-person and smartphone-based cognitive behavior therapy (CBT) for experiential negative symptoms in schizophrenia called, Mobile-assisted CBT for Negative symptoms (mCBTn). mCBTn is a novel extraction and integration of the CBT components that target defeatist attitudes from our cognitive behavioral social skills training (CBSST) group therapy and mobile smartphone interventions from our prior clinical trials research. The primary aim of the project is to test whether mCBTn can reduce severity of a novel treatment target: defeatist performance attitudes. In a promising new model, Beck and colleagues proposed that defeatist attitudes (e.g., "Why bother, I always fail," "It's not worth the effort") contribute to experientil negative symptoms like amotivation and asociality, and ultimately poor functioning in schizophrenia, because defeatist attitudes lead to avoidance of effortful goal-directed activities. Our approach centers on the hypothesis that defeatist attitudes contribute to experiential negative symptoms, including diminished motivation and effort, which ultimately leads to poor functioning in schizophrenia. In addition, the field currently relies on symptom rating scales and subjective patient reports to measure motivation and effort; more objective measures are needed. The proposed project will determine whether pupillary responses can provide an objective psychophysiological biomarker of effort that is sensitive to change in a clinical trial fr negative symptoms. Greater pupil dilation indicates greater task effort allocation. We propose two sequential clinical trials of mCBTn in consumers with schizophrenia spectrum disorders with persistent moderate-to-severe experiential negative symptoms. In the R61 phase, we propose an open trial to determine whether mCBTn changes the defeatist attitude target and will identify the optimal dose to engage the target. In the R33 phase, we propose an RCT comparing mCBTn with a supportive contact control and will determine whether mCBTn produces greater reduction in defeatist attitudes that mediates improvement in experiential negative symptoms. Pupillary responses will be recorded as a secondary outcome in both trials to determine its potential as an end point in clinical trials of motivation and effort.