COGFLEX: Pilot Translational Intervention for Pediatric Bipolar Disorder

COGFLEX：小儿双相情感障碍的试点转化干预

基本信息

批准号：
8743421
负责人：
DANIEL P DICKSTEIN
金额：
$ 24.1万
依托单位：
EMMA PENDLETON BRADLEY HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-03-08 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8743421
关键词：
Accounting Adolescent Adult Affect Animals Antipsychotic Agents Applications Grants Area Attention deficit hyperactivity disorder Base of the Brain Behavior Behavioral Biology Biometry Bipolar Disorder Brain Child Clinical Cognitive Cognitive Therapy Cognitive deficits Cognitive remediation Collaborations Computer Assisted Computers Corpus striatum structure Data Development Diagnostic Distal Family Feedback Functional Magnetic Resonance Imaging Functional disorder Goals Health Hospitalization Human Incidence Intervention Interview Learning Lesion Lithium Measures Mediating Mental Depression Mental disorders Morbidity - disease rate Names National Institute of Mental Health Outcome Outcome Measure Participant Performance Pharmaceutical Preparations Phase Prefrontal Cortex Process Psychiatric Hospitals Psychiatric therapeutic procedure Psychotherapy Public Health Randomized Randomized Controlled Trials Research Research Domain Criteria Research Methodology Reversal Learning Rewards Sampling Schizophrenia Staging Stimulus Strategic Planning Symptoms Task Performances Testing Thinking Training Translating Translational Research Translations Unipolar Depression Video Games Work Youth base behavior measurement brain behavior childhood bipolar disorder cognitive training design effective intervention effective therapy efficacy testing flexibility innovation learned behavior neuroimaging nonhuman primate novel relating to nervous system remediation research and development response skills suicide rate therapy development treatment response treatment strategy

项目摘要

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.

描述（由申请人提供）：小儿双相情感障碍（BD）是一个日益严重的健康问题，其发病率在过去十年中增加了 40 倍，目前占精神病院出院儿童总数的 20%。目前针对这一新兴公共卫生问题的治疗方法几乎没有一种是基于我们对儿科双相情感障碍生物学的理解。越来越多的研究表明，儿科双相情感障碍涉及调节认知灵活性的行为和大脑改变，即适应不断变化的奖励的思维和行为的能力。这包括我自己的工作，该工作表明双相障碍青少年在逆转学习中存在行为和功能性 MRI 神经改变。 R21/R33 转化型新颖干预拨款申请的主要目标是加速将我们的数据转化为一种新颖的、基于机制的非药物干预措施，这些数据涉及儿科双相情感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。使用计算机辅助认知矫正进行逆转学习（简称COGFLEX）。我们的中心假设是，COGFLEX 对于儿科 BD 来说是可行且可接受的，因为其他人已经表明，针对相关认知过程的类似干预对于患有 BD、单相抑郁、ADHD 和精神分裂症的成人来说是可行、可接受和有效的治疗成分，并且患有多动症的儿童。我们的研究方法：R21 阶段：与我们在视频游戏开发、治疗开发、儿童认知补救、儿科 BD 和生物统计学方面的跨学科专家团队合作，我们将完善我们的 COGFLEX 干预措施，收集用于技能建设的规范数据并在 50 名正常发育儿童中进行了 1a 期开放试验，研究 COGFLEX 对 15 名 BD 儿童的行为、大脑和症状影响。 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 阶段随机对照试验，其中一半随机接受具有 10 个技能培养级别的完整 COGFLEX 干预，另一半接受对照任务（仅限 COGFLEX 1 级）。我们将完善我们的干预措施，并提交专门设计和支持的 R01 申请，以测试其对儿科 BD 的功效。意义：我们的方法与 PAR 11-177 的目标和 NIMH 的战略 3.1 开发新颖的干预措施和 1.4 RDoC 项目一致，因为我们寻求为儿科 BD 开发一种新颖的、基于机制的非药物干预措施，应用从可观察到的研究中吸取的经验教训行为和神经影像——即逆转学习。因此，该项目有可能通过对基于新型机制的干预进行关键改进，从而改变 NIMH 高优先领域儿科 BD 的治疗方法。