Translational Research to Enhance Cognitive Control

增强认知控制的转化研究

• 批准号: 7480927
• 负责人: James McCracken
• 金额: $ 45.12万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7480927
• 关键词: Academic achievement; Acute; Adolescent; Affect; Attention deficit hyperactivity disorder; Behavior; Behavioral; Behavioral Symptoms; Biological; Brain; Characteristics; Child; Chronic; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Combination Drug Therapy; Complex; Data; Data Set; Decision Making; Development; Diagnosis; Disease; Dopamine; Electroencephalography; End Point; Enrollment; Etiology; Failure; Genes; Genetic; Goals; Guanfacine; Intervention; Investments; Learning; Literature; Long-Term Effects; Maintenance; Measures; Methodology; Methylphenidate; Monitor; Neurobehavioral Manifestations; Neurosciences; Norepinephrine; Other Genetics; Outcome; Performance; Pharmaceutical Preparations; Phase; Pilot Projects; Prevalence; Problem Solving; Psychopathology; Randomized; Rate; Research; Research Design; Safety; Short-Term Memory; Standards of Weights and Measures; Surveys; Symptoms; Testing; Translational Research; base; clinically significant; cognitive control; cognitive function; comparative; design; disorder risk; executive function; family genetics; improved; innovation; neurochemistry; neuropsychological; novel; response; treatment effect

Although current medication therapies ameliorate ADHD behavioral symptoms, problems with inadequate response or tolerability are common. Most perplexing, in consideration of ADHD-related cognitive deficits and in spite of several hundred studies demonstrating acute behavioral response to stimulants, is the failure of many decades of research to demonstrate long-term, stimulated-related enhancements in learning. This manifest inadequacy of current therapies highlights the potential importance of developing treatments that specifically remediate executive function deficits as an important path to improve outcome. Neurochemical influences on cognitive functions in ADHD are complex. The over-arching premise of this project is that optimal behavioral and cognitive responses are possible with treatments that robustly enhance both dopamine (DA) and norepinephrine (NE). Our goal is to test the short-term efficacy of a combination pharmacotherapy, derived from translational research and clinical observations, against standard stimulant monotherapy on both symptom and cognitive endpoints. In addition, a novel aspect of the study will be to test prospectively whether a dual benefit on both behavior and cognition predicts clinically significant improvements in learning over longer-term treatment. Lastly, based upon our preliminary data and hypothesized mechanisms of treatment response, the proposed study will examine the potential of electroencephalography (EEC) in predicting optimal long-term benefit. The clinical trial will enroll 180 children and adolescents with ADHD-Combined Type in an active-controlled randomized parallel group study testing the comparative efficacy of guanfacine (GUAN), methylphenidate (MPH), and combination GUAN/MPH on ADHD symptoms and clinical response rates. Improvements in cognition during the acute treatment phase will predict greater academic achievement over the 12 month maintenance period. The project will represent an initial scientific investment in a new phase of translational treatment research on cognition in developmental psychopathologies. The designs and methodology tested in the proposed trial will serve as a platform for testing other interventions.

尽管目前的药物治疗可以缓解多动症行为症状，但不足的问题 响应或耐受性很常见。考虑到与ADHD相关的认知缺陷，最困惑 尽管有数百项研究表明对兴奋剂的急性行为反应，但还是失败的 在数十年的研究中，可以证明学习长期，刺激相关的学习。这 明显的当前疗法不足强调了开发疗法的潜在重要性 特别将执行功能赤字作为改善结果的重要途径。 神经化学对多动症认知功能的影响很复杂。这是整理的前提 项目是，可以通过鲁棒增强的治疗方法可以做出最佳的行为和认知反应 多巴胺（DA）和去甲肾上腺素（NE）。我们的目标是测试组合的短期功效 药物疗法，源自转化研究和临床观察结果，针对标准兴奋剂 症状和认知终点的单一疗法。此外，研究的新方面将是 前瞻性测试行为和认知的双重益处是否预测临床意义 长期治疗的学习改善。最后，根据我们的初步数据和 假设的治疗反应机制，拟议的研究将检查 脑电图（EEC）预测最佳的长期收益。临床试验将注册180 在主动控制的随机平行组研究中，具有多动症混合类型的儿童和青少年 测试鸟法氨酸（鸟甲甲酯（MPH）和组合）的比较疗效 Guan/mph的多动症症状和临床反应率。急性期间认知的改善 治疗阶段将预测在12个月的维护期内的学术成就。 该项目将在转化治疗研究的新阶段代表初始科学投资 关于发展心理病理学的认知。在拟议的试验中测试的设计和方法论 将作为测试其他干预措施的平台。