COGFLEX: Pilot Translational Intervention for Pediatric Bipolar Disorder

描述（由申请人提供）：儿童双相情感障碍（BD）是一个日益严重的健康问题，其发病率在过去十年中上升了40倍，目前占精神病院所有出院儿童的20%。目前针对这一新兴公共健康问题的治疗方法，几乎没有一个是基于我们对儿童双相障碍生物学的理解。越来越多的研究表明，儿童双相障碍涉及行为和大脑改变，介导认知灵活性。即根据奖励的变化调整自己的思维和行为的能力。这包括我自己的工作，表明双相障碍青少年在逆向学习中有行为和功能MRI神经改变。这项R21/R33转化新干预资助申请的主要目的是加速将我们的数据转化为一种新的、基于机制的、使用计算机辅助认知修复逆转学习的非药物干预（称为COGFLEX），这些数据涉及儿童双相障碍病理生理学中逆转学习和认知灵活性的大脑/行为改变。我们的中心假设是，鉴于其他研究表明，对相关认知过程的类似干预对于成人双相障碍、单极抑郁症、多动症、精神分裂症和多动症儿童是一种可行、可接受和有效的治疗成分，COGFLEX对于儿童双相障碍是可行和可接受的。我们的研究方法：R21阶段：我们将与我们在视频游戏开发、治疗开发、儿童认知修复、儿科双相障碍和生物统计学方面的跨学科专家团队合作，完善我们的COGFLEX干预措施，收集50名典型发育儿童的技能建设水平的规范数据，并对15名双相障碍儿童进行COGFLEX行为、大脑和症状影响的1a期公开试验。R33阶段：我们将在40名儿童BD参与者中进行可行性和可接受性的1b期随机对照试验，其中一半随机接受具有10个技能培养水平的完整COGFLEX干预，另一半接受对照任务（仅COGFLEX 1级）。我们将完善我们的干预措施，并提交一份专门设计和支持的R01申请，以测试其对儿童双相障碍的疗效。意义：我们的方法符合PAR 11-177和NIMH战略3.1开发新型干预措施和1.4 RDoC项目的目标，因为我们寻求开发一种新的、基于机制的儿童双相障碍非药物干预措施，应用可观察行为和神经影像学研究的经验教训。，逆向学习。因此，该项目有可能通过对一种基于新机制的干预进行关键改进，来改变NIMH儿科双相障碍高优先级领域的治疗。

DESCRIPTION (provided by applicant): Pediatric bipolar disorder (BD) is a growing health problem, whose incidence has risen 40-fold in the past decade and now accounts for 20% of all children discharged from psychiatric hospitals. Of the current treatments for this burgeoning public health problem, virtually none are based on our understanding of the biology of pediatric BD. A growing body of research has shown that pediatric BD involves behavioral and brain alterations mediating cognitive flexibility-i.e., the ability to adapt one's thinking and behavior n response to changing rewards. This includes my own work showing that BD youths have behavioral and functional MRI neural alterations in reversal learning. THE PRIMARY OBJECTIVE of this R21/R33 Translational Novel Interventions grant application is to accelerate the translation of our data implicating brain/behavior alterations in reversal learning and cognitive flexibility in the pathophysiology of pediatric BD into a novel, mechanism-based, non-medication intervention using computer-assisted cognitive remediation for reversal learning (referred to as COGFLEX). OUR CENTRAL HYPOTHESIS is that COGFLEX will be feasible and acceptable for pediatric BD, given that others have shown similar interventions for related cognitive processes are a feasible, acceptable, and effective treatment component for adults with BD, unipolar depression, ADHD, and schizophrenia, and in children with ADHD. OUR RESEARCH METHOD: R21 PHASE: In collaboration with our cross-disciplinary team of experts in video game development, treatment development, cognitive remediation in children, pediatric BD, and biostatistics, we will refine our COGFLEX intervention, gather normative data for skill-building levels in 50 typically-developing children, and conduct a stage 1a open trial of the behavior, brain, and symptom effects of COGFLEX on 15 BD children. R33 PHASE: We will conduct a stage 1b randomized controlled trial of feasibility and acceptability in 40 pediatric BD participants, half randomized to receive the full COGFLEX intervention with 10 skill-building levels, and half receiving a control task (COGFLEX level 1 only). We will refine our intervention and submit an R01 application specifically designed and powered to test its efficacy for pediatric BD. SIGNIFICANCE: Our approach aligns with the objectives of PAR 11-177 and NIMH's strategies 3.1 Develop Novel Interventions and 1.4 RDoC project because we seek to develop a novel, mechanism-based non- medication intervention for pediatric BD, applying lessons learned from studies of observable behavior and neuroimaging-i.e., reversal learning. Thus, this project has the potential to transform the treatment for the NIMH high-priority area of pediatric BD by allowing critical refinements for a novel mechanism-based intervention.