A Multi-Method Investigation to Distinguish Sluggish Cognitive Tempo from ADHD

 描述(由申请者提供)：我的长期职业目标是建立一个研究项目，以了解注意力缺陷/多动障碍(ADHD)共病的病因和发展后果，特别强调迟缓的认知节奏(SCT)。作为开发这个研究项目的第一步，我领导了一系列研究，考察ADHD和SCT是否不仅在统计学上是不同的，而且与青少年的功能也有不同或唯一的联系。我的前期工作表明，尽管SCT与ADHD注意力不集中、抑郁、焦虑和白天嗜睡的发生率较高相关，但SCT在统计上与这些领域截然不同。我还发现，即使在控制了ADHD之后，SCT症状也与学业和社交障碍有关。由于SCT的症状在统计学上与ADHD截然不同，并与一系列损害唯一相关，因此有人认为SCT可能是与ADHD分开的障碍。此外，SCT结构的临床意义被初步数据强调，该数据显示SCT升高的存在可以预测ADHD儿童对精神刺激性药物的较差反应。这表明，频繁使用的循证ADHD治疗对于同时表现为SCT的ADHD儿童来说是不够的。这些发现指出了SCT的重要性，以及对SCT的病因、外部相关因素和发展进程进行系统研究的必要性。我目前是辛辛那提儿童医院医学中心(CCHMC)行为医学和临床心理学部门的研究人员，K23机制将使我能够集中时间和精力发展独立临床研究人员的职业生涯。随着我的研究兴趣的发展，我认识到有必要接受神经心理学和神经生理学的额外培训，以便对ADHD和SCT进行更全面、多模式的检查。我的培训目标是解决我知识上的重大差距，为我的独立研究生涯做好准备。具体地说，我计划(1)获得大脑-行为关系方面的专门知识，重点是神经心理学；(2)获得神经科学和神经成像方法方面的知识，重点是脑磁图(MEG)和脑电图(EEG)；(3)获得与儿科人群神经心理和神经生理学研究相关的统计学和编程方面的培训；(4)提高赠款的编写技能，扩大研究传播。我将通过课程作业、我的导师和顾问的指导，特别是我培训计划中的专业知识，完成我的研究项目，以及参加相关的研讨会、研讨会和会议来实现这些培训目标。培训和职业发展计划的完成将使我能够实现我的长期目标，即在以患者为导向的研究中建立独立的职业生涯，大大促进我们对SCT和ADHD共病的理解。为了分离出SCT的独特相关性，我提出了一个研究项目，这将是第一个直接比较儿童与SCT的研究项目 将SCT(伴有和不伴有ADHD)提升到典型的发育儿童和ADHD儿童-仅使用多种方法的神经成像和行为方法。我的研究将使用最近验证的SCT措施招募184名儿童(8-12岁)，分成四组(每组46人)：仅接受SCT、仅患有ADHD、SCT+ADHD，以及典型的发育对照组。所有儿童都将完成一项全面的评估，其中包括一次诊断面谈，评估SCT、ADHD和精神疾病的共病，智力和学业成就测试，以及一系列神经心理测试。一部分参与者将在进行脑磁图(与结构核磁共振共同注册)的同时执行一项评估不同注意网络的任务，这是一种最佳的成像方法，因为它具有出色的空间和时间分辨率。这个项目将使我能够确定将SCT与ADHD区分开来的潜在功能障碍和损害，进而与理论、病因学和干预有明显的相关性。辛辛那提儿童医院为我的发展提供了一个极好的环境，使我成为一名研究ADHD和SCT中大脑行为关系的独立研究员。我们组建了一支出色的指导团队，为我的培训和职业发展提供支持。在杰弗里·爱泼斯坦博士(主要赞助人)的指导下，ADHD中心是一个世界级的ADHD专科中心。同样在CCHMC，向静博士(MEG中心主任，共同导师)和Dean Beebe博士(神经心理学项目主任，共同导师)将分别提供MEG和神经心理学方面的指导。Leanne Tamm博士和James Peugh博士将分别提供ADHD神经成像和统计学方面的现场专业知识。最后，埃里克博士 科罗拉多大学博尔德分校的Willutt和加州大学洛杉矶分校的Sandra Loo博士将提供外部专业知识，介绍神经心理学和神经生理学方法如何特别地为ADHD共病模型提供信息。我在培训计划中积累的经验将为独立研究计划奠定基础，目标是在K23奖项结束之前获得R01。

 DESCRIPTION (provided by applicant): My long-term career goal is to establish a research program to understand the etiology and developmental consequences of attention-deficit/hyperactivity disorder (ADHD) comorbidities, with a particularly emphasis in sluggish cognitive tempo (SCT). As an initial step in developing this research program, I have led a series of studies examining whether ADHD and SCT are not only distinct statistically but also differentially or uniquely associated with youths' functioning. My pilot work shows that while SCT is associated with higher rates of ADHD inattention, depression, anxiety, and daytime sleepiness, SCT is nonetheless statistically distinct from these domains. I have also found that SCT symptoms are associated with both academic and social impairments, even after controlling for ADHD. Since SCT symptoms are statistically distinct from ADHD and are uniquely associated with a range of impairments, it has been argued that SCT may be disorder separate from ADHD. Moreover, the clinical significance of the SCT construct is underscored by preliminary data showing the presence of elevated SCT to predict a poorer response to psychostimulant medication in children with ADHD. This suggests that frequently-used, evidence-based ADHD treatments are inadequate for children with ADHD who also display SCT. These findings point to the importance of SCT and the need for systematic research investigating the etiology, external correlates, and developmental progression of SCT. I am currently a research faculty member within the Division of Behavioral Medicine and Clinical Psychology at Cincinnati Children's Hospital Medical Center (CCHMC), and the K23 mechanism will enable me to focus my time and effort to develop a career as an independent clinical researcher. As my research interests have evolved, I recognize the need to obtain additional training in neuropsychology and neurophysiology to allow for a more comprehensive, multi-modal examination of ADHD and SCT. My training objectives are intended to address critical gaps in my knowledge to prepare me for an independent research career. Specifically, I plan to (1) obtain expertise in brain-behavior relationships with a specific emphasis in neuropsychology, (2) gain knowledge in neuroscience and neuroimaging methods with a specific emphasis in magnetoencephalography (MEG) and electroencephalography (EEG), (3) obtain training in statistics and programming relevant to neuropsychological and neurophysiological research with pediatric populations, and (4) improve grant-writing skills and extend research dissemination. I will accomplish these training objectives through coursework, guidance from my mentors and consultants with expertise in particular components of my training plan, completion of my research project, and attendance at relevant seminars, workshops, and conferences. Completion of the training and career development plan will enable me to achieve my long-term goal to establish an independent career in patient-oriented research that significantly advances our understanding of SCT and ADHD comorbidity. In order to separate out the unique correlates of SCT, I propose a research project that will be the first study to directly compare children with elevated SCT (with and without ADHD) to typically developing children and children with ADHD-only using a multi-method neuroimaging and behavioral approach. My study will use recently-validated SCT measures to recruit 184 children (ages 8-12 years) into four groups (n = 46 per group): SCT-only, ADHD-only, SCT+ADHD, and typically developing controls. All children will complete a comprehensive assessment that includes a diagnostic interview assessing SCT, ADHD, and psychiatric comorbidities, intelligence and academic achievement testing, and a battery of neuropsychological tests. A subset of participants will perform a task assessing distinct attentional networks while undergoing MEG (co- registered with structural MRI), an optimal imaging methodology given its excellent spatial and temporal resolution. This project will allow me to identify the underlying dysfunctions and impairments that distinguish SCT from ADHD, in turn having clear relevance for theory, nosology, and intervention. Cincinnati Children's Hospital provides an excellent environment to facilitate my development as an independent investigator studying brain-behavior relationships in ADHD and SCT. An exceptional mentoring team has been assembled to support my training and career development. Under the direction of Dr. Jeffery Epstein (primary sponsor), the Center for ADHD is a world-class ADHD specialty center. Also at CCHMC, Dr. Jing Xiang (Director, MEG Center; co-mentor) and Dr. Dean Beebe (Director, Neuropsychology Program; co- mentor) will provide mentorship in MEG and neuropsychology, respectively. Drs. Leanne Tamm and James Peugh will provide on-site expertise in ADHD neuroimaging and statistics, respectively. Finally, Dr. Erik Willcutt (University of Colorado Boulder) and Dr. Sandra Loo (University of California, Los Angeles) will provide external expertise in how neuropsychological and neurophysiological methods can inform models of ADHD comorbidity specifically. The cumulative experiences laid out in my training plan will provide the foundation for an independent research program with the goal of receiving an R01 prior to the end of the K23 award.