Brain Biomarkers of Clinical Response to Cognitive Treatment of PTSD in Youth

描述（由申请人提供）：本申请将联合收割机研究者的神经影像学专业知识与临床试验方法和治疗过程的新知识相结合。我们的目标是产生一个独特的技能集，理想的领先的临床医生和基础科学家的跨学科团队在与治疗儿科创伤相关疾病的大脑变化的研究。拟议的研究将采用这种培训。我们将调查与认知行为治疗有关的脑功能变化，用于患有创伤后应激障碍的受虐待青少年。每位导师将提供项目所需的特定培训部分。Stewart Agras博士是临床试验方法学的公认领导者，他将深入了解进行高质量临床试验的复杂性，以及治疗过程的知识基础。维克托卡里翁博士，在儿科创伤后应激障碍的专家，将提供评估，招募和保留儿科创伤后应激障碍样本的理解。Carrion博士还将直接监督该研究的治疗部门。Judith Cohen博士是我们研究中使用的治疗方法（创伤认知行为治疗）的共同创造者，她将提供对治疗的实际理解：加勒特博士将在Cohen博士每周与治疗师进行的咨询中跟踪每个治疗病例。科恩博士还将就领先的临床研究中的重要问题提供指导，包括与多学科合作伙伴的合作，伦理问题以及治疗保真度的灵活实施。Kiki Chang博士加入了指导团队，以提供一个成功的神经影像学治疗研究模型，并以他正在进行的R 01项目为例。此外，加勒特博士将通过参加张博士制定的KSADS可靠性培训方案和参加他指导的诊断会议来了解临床评估。Allan Reiss博士将确保神经影像学分析和解释的卓越性，Booil Jo博士将提供统计咨询，Greg Siegle博士将根据他在该领域的领导地位，在领先的CBT治疗相关神经影像学研究中提供指导。在这个全面的指导团队的协助下，拟议的研究项目将提供有关PTSD恢复的介质（潜在机制）的新信息，并为儿科PTSD异常脑功能的文献做出贡献。在修订后的申请中，我们将研究地点转移到了斯坦福大学，以允许导师直接提供正在进行的临床研究指导。青少年将在12周治疗前后进行扫描。分析将确定与PTSD有关的大脑区域（杏仁核、海马体和内侧前额叶皮层）中与治疗相关的激活变化，并测试激活变化与症状改善之间的关联。将在相同时间间隔扫描的匹配对照样本中研究fMRI测量的测试/重测信度，并分析功能连接性。鉴于申请人已经建立了相当多的神经成像专业知识，导师对治疗的直接监督以及斯坦福大学临床研究环境提供的支持，本研究是可行的。这项研究将使加勒特博士成为创伤后应激障碍青少年神经影像学治疗研究领域的独立科学家，并导致R 01应用程序，扩展和探索研究结果的临床实用性。

DESCRIPTION (provided by applicant): This application will combine the neuroimaging expertise of the investigator with new knowledge of clinical trials methodology and treatment processes. The goal is to produce a unique skill set, ideal for leading interdisciplinary teams of clinicians and basic scientists in studies of brain changes associated with treatment of pediatric trauma-related disorders. The proposed research study will apply this training. We will investigate changes in brain function associated with cognitive behavioral therapy for abused youth suffering from PTSD. Each mentor will provide a specific training component needed for the project. Dr. Stewart Agras, an established leader in clinical trials methodology, will provide in-depth knowledge of the intricacies of conducting high quality clinical trials, and a knowledge base of treatment processes. Dr. Victor Carrion, an expert in pediatric PTSD, will provide understanding of assessment, recruitment, and retention of pediatric PTSD samples. Dr. Carrion also will directly oversee the treatment arm of the research study. Dr. Judith Cohen, co-creator of the treatment used in our study (trauma-focused cognitive-behavioral therapy) will provide a practical understanding of treatment: Dr. Garrett will follow each treatment case during Dr. Cohen's weekly consultations with therapists. Dr. Cohen also will provide guidance on important issues in leading clinical research, including collaborating with multidisciplinary partners, ethical issues, and flexible implementation of treatment fidelity. Dr. Kiki Chang has joined the mentoring team in order to provide a model of a successful neuroimaging treatment study exemplified by his ongoing R01 project. Also, Dr. Garrett will learn about clinical assessment by undergoing in Dr. Chang's established protocol for KSADS reliability training, and attending his mentored diagnostic meetings. Dr. Allan Reiss will ensure excellence in neuroimaging analysis and interpretation, Dr. Booil Jo will provide statistical consultation, and Dr. Greg Siegle will provide guidance in leading CBT treatment-related neuroimaging studies based on his leadership in this field. With the assistance of this comprehensive mentoring team, the proposed research project will provide novel information about the mediators (potential mechanisms) of recovery from PTSD and contribute to the literature on abnormal brain function in pediatric PTSD. In the revised application, we have moved the site of the study to Stanford University, to allow mentors to provide direct ongoing clinical research guidance. Youths will be scanned before and after the 12 week treatment. Analyses will identify treatment-related changes in activation in brain regions implicated in PTSD: the amygdala, hippocampus, and medial prefrontal cortex- and test the associations between changes in activation and improvements in symptoms. Test/retest reliability of fMRI measures will be investigated in a matched control sample scanned at the same interval, and functional connectivity will be analyzed. This study is feasible given the considerable expertise in neuroimaging already established by the applicant, the direct supervision of treatment by mentors, and the support provided by Stanford's clinical research setting. This study will establish Dr. Garrett as an independent scientist in the field of neuroimaging treatment studies in youths with PTSD, and lead to an R01 application that expands and probes the clinical utility of the findings.