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

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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.