Methylphenidate and Atomoxetine in ADHD: fMRI Measures of Mechanisms and Response

哌醋甲酯和托莫西汀治疗 ADHD：机制和反应的功能磁共振成像测量

• 批准号: 7146554
• 负责人: JEFFREY H NEWCORN
• 金额: $ 20.21万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-03 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7146554
• 关键词: Methylphenidate; Atomoxetine; ADHD; fMRI; Measures

DESCRIPTION (provided by applicant): Despite a general convergence of findings implicating impairments of the frontostriatal regions and/or the brainstem catecholamine systems that innervate these networks in the pathophysiology of ADHD, the specific neural basis of the disorder remains elusive. Even less is known about the mechanisms by which medication treatments for ADHD exert their effects. The fact that stimulants are highly efficacious in reducing ADHD symptoms, coupled with their known effects on dopamine (DA) activity in the basal ganglia, provide strong evidence that DA mechanisms are highly relevant to ADHD. However, virtually all medications known to improve ADHD symptoms facilitate noradrenergic neurotransmission, and the efficacy of atomoxetine, a specific noradrenaline (NA) reuptake-inhibitor, demonstrates the importance of NA mechanisms in ADHD. Moreover, recent research in rodents indicating that both stimulants and atomoxetine directly influence DA and NA neurotransmission suggests that there are likely similarities as well as differences in their mechanisms of action. Better delineating how these treatments work is an important first step in matching treatments to patients, and would substantially enhance our understanding of the pathophysiology of ADHD. We are currently in an excellent position to use functional magnetic resonance imaging (fMRI) to better understand the neurobiological mechanisms of pharmacological treatments for ADHD. We were recently funded to study the comparative and differential effects of four to six weeks of methylphenidate and atomoxetine treatment in 160 children and adolescents with ADHD, using a cross-over design in which each subject receives both treatments (R01 MH070935-01). The current application proposes to conduct fMRI scans in 60 children 7-12 years (n=30 for each treatment) pre- and post-treatment, in the first medication arm of the parent cross-over study. The addition of fMRI scanning to this treatment study would provide a unique opportunity to evaluate whether proposed similarities and differences in actions between methylphenidate and atomoxetine derived from animal studies can be documented in children with ADHD, and to examine the degree to which clinical response to the two treatments is accounted for by shared or distinct mechanisms of action. We will also collect pilot data on neurobiological predictors of differential response.

描述（由申请人提供）：尽管发现的一般性融合暗示了额叶区域和/或脑干儿茶酚胺系统的损害，这些系统将这些网络神化为ADHD的病理生理学，但该疾病的特定神经基础仍然难以捉摸。关于ADHD的药物治疗的作用的机制甚至更少。兴奋剂在减少多动症症状以及其对基底神经节中多巴胺（DA）活性的已知影响的情况下高度有效，这一事实提供了有力的证据，表明DA机制与ADHD高度相关。但是，几乎所有已知改善多动症症状的药物都促进了去甲肾上腺素能神经传递，并且特定的去甲肾上腺素（NA）再摄取抑制剂的阿托莫西汀的疗效都证明了NA机制在ADHD中的重要性。此外，最近对啮齿动物的研究表明，刺激剂和原子苷直接影响DA和NA神经传递表明，其作用机理可能存在相似性以及差异。更好地描述这些治疗方法是与患者匹配治疗的重要第一步，并大大增强了我们对ADHD病理生理学的理解。目前，我们处于使用功能磁共振成像（fMRI）来更好地了解ADHD药理治疗的神经生物学机制。我们最近资助了我们使用跨界设计的160名儿童和ADHD儿童和青少年在160名儿童和青少年中研究四到六周的哌醋甲酯和阿托莫西汀治疗的比较和差异作用，每个受试者都接受这两种治疗方法（R01 MH070935-01）。当前的申请建议在父母交叉研究的第一个药物部门中进行7-12岁儿童（每种治疗方法n = 30）进行fMRI扫描（n = 30）。在这项治疗研究中添加fMRI扫描将提供一个独特的机会，以评估提出的相似性和在ADHD儿童中是否可以记录在动物研究的哌醋甲酯和阿托莫西汀之间的作用差异，并研究对两种治疗的临床反应的程度。我们还将收集有关差异反应的神经生物学预测指标的试点数据。