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

描述(由申请者提供)：这项申请将结合研究人员的神经成像专业知识与临床试验方法和治疗过程的新知识。其目标是培养一套独特的技能，非常适合领导临床医生和基础科学家组成的跨学科团队，研究与儿科创伤相关疾病治疗相关的大脑变化。拟议的研究性研究将应用这一培训。我们将研究认知行为疗法对患有创伤后应激障碍的受虐青少年脑功能的影响。每位导师将提供项目所需的特定培训部分。斯图尔特·阿格拉斯博士是临床试验方法学领域的知名领导者，他将深入了解进行高质量临床试验的复杂性，并提供治疗过程的知识库。儿童创伤后应激障碍专家Victor Carrion博士将提供对儿科创伤后应激障碍样本的评估、招募和保留的理解。卡里昂博士还将直接监督这项研究的治疗部分。朱迪思·科恩博士是我们研究中使用的治疗方法(以创伤为重点的认知-行为疗法)的共同创造者，他将提供对治疗的实际理解：在科恩博士每周与治疗师进行咨询期间，加勒特博士将跟踪每个治疗案例。科恩博士还将就领先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、伦理问题和灵活实施治疗保真度。Kiki Chang博士加入了指导团队，以提供一个成功的神经成像治疗研究的模型，他正在进行的R01项目就是一个例子。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的有指导的诊断会议来了解临床评估。Allan Reiss博士将确保卓越的神经成像分析和解释，Booil Jo博士将提供统计咨询，Greg Siegle博士将基于他在该领域的领导能力，在领导与CBT治疗相关的神经成像研究方面提供指导。在这个综合指导团队的帮助下，拟议的研究项目将提供有关创伤后应激障碍康复的媒介(潜在机制)的新信息，并为儿童创伤后应激障碍脑功能异常的文献做出贡献。在修改后的申请中，我们将研究地点移至斯坦福大学，以允许导师提供直接的正在进行的临床研究指导。青少年在12周的治疗前后都会接受扫描。分析将确定创伤后应激障碍涉及的大脑区域：杏仁核、海马体和内侧前额叶皮质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系。将在以相同间隔扫描的匹配对照样本中调查功能磁共振测量的测试/重测可靠性，并将分析功能连通性。这项研究是可行的，考虑到申请人在神经成像方面已经建立了相当的专业知识，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。这项研究将使加勒特博士成为青少年创伤后应激障碍神经成像治疗研究领域的独立科学家，并导致R01的应用，扩大和探索这些发现的临床实用价值。

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.