Neuropsychiatry of Traumatic Brian Injury

描述(由申请人提供)：这份修订后的临床研究学术生涯发展奖申请(K23)概述了一项培训和研究计划，重点是评估和治疗继发于创伤性脑损伤(TBI)的神经精神障碍。这项研究的重点是前额叶功能障碍，因为额叶是脑外伤中最常见的病变部位。这可能会导致执行认知功能受损，情绪障碍，如抑郁，以及行为变化，如冷漠，冲动和攻击性。在美国，每年发生的脑损伤病例超过200万例，导致严重的长期残疾。这些患者经常出现在精神科，但对于这些神经行为障碍的治疗没有明确的指导方针。额叶功能障碍已被证明在其他精神疾病中也发挥了作用，因此研究改善额叶功能的有效治疗方法可能会广泛受益。在这一领域，对精神病学临床研究人员的培训是非常必要的。目前的磁共振成像技术，包括功能磁共振成像和评估白质的技术，如DTI(扩散张量成像)，有可能进一步了解这种脑部疾病。拟议的职业发展计划有两个主要目标。首先，PI将学习利用最先进的MRI结构和功能成像方法，以及神经生理学(动眼运动研究)和神经心理学程序，来评估额叶损伤的影响。这将允许对脑外伤的解剖和神经行为后遗症进行彻底的描述。其次，PI将在这一特殊人群中发展药理临床试验方面的专业知识。缺乏有效的治疗来提高生活质量，突显出需要培训具有填补这一空白的必要技能的精神病学研究人员。此外，在未来几年，对接受培训以评估新药物疗法的认知增强特性的神经精神病学研究人员的需求将非常大。在拟议的职业发展计划中，PI将在一项对照临床试验中使用金刚烷胺对脑外伤后额叶功能障碍患者进行核磁共振成像和神经行为评估。PI将学习将成像结果整合到临床试验中，为选择治疗干预措施制定指南。此应用程序旨在使应聘者能够转变为具有研究神经病理学、结果和干预措施所需的必要研究技能的独立临床调查员。

DESCRIPTION (provided by applicant): This revised application for an academic career development award for clinical research (K23) outlines a program for training and research focusing on the evaluation and treatment of neuropsychiatric disorders secondary to traumatic brain injury (TBI). The particular focus of the research is on prefrontal dysfunction, as the frontal lobes are the most common site of lesion in TBI. This can result in impaired executive cognitive function, mood disorders such as depression, and behavioral changes such as apathy, impulsivity and aggression. Over 2,000,000 cases of TBI occur per year in the US, resulting in significant long term disability. These patients often present to psychiatry, but there are no clear guidelines on treatment of these neurobehavioral disorders. Frontal dysfunction has been shown to play a role in other psychiatric illnesses as well, such that research into effective treatments to improve frontal function could be broadly beneficial. There is a significant need to train psychiatric clinical researchers in this area. Current technologies in MRI, including functional MRI and techniques to assess white matter such as DTI (diffusion tensor imaging) have the potential to further understanding of this brain disorder. There are two primary aims of the proposed career development plan. First, the PI will learn to utilize state of the art structural and functional imaging methods of MRI, along with neurophysiological (oculomotor studies) and neuropsychological procedures, for assessing effects of frontal lobe injury. This will allow for a thorough delineation of the anatomic and neurobehavioral sequelae of TBI. Second, the PI will develop expertise in pharmacologic clinical trials in this special population. The lack of effective treatments to improve quality of life underscores the need to train psychiatric researchers with the necessary skills to fill this void. Further, the need for neuropsychiatric investigators trained to evaluate the cognition-enhancing properties of new pharmacotherapies will be very great in coming years. During the proposed career development program, the PI will utilize MRI and neurobehavioral assessments in a controlled clinical trial with amantadine in patients with frontal lobe dysfunction following TBI. The PI will learn to integrate imaging findings into clinical trials, developing guidelines for selection of therapeutic interventions. This application is designed to enable the candidate to transition into an independent clinical investigator with the necessary research skills needed to study neuropathology, outcomes, and interventions.