This application is submitted jointly but separately by Dr. Rachel Yehuda of Mount Sinai Medical School and Dr. Edna Foa of the University of Pennsylvania in response to Program Announcement PA-98-017 inviting collaborative research efforts on Collaborative R0-1 for Clinical Studies in Mental Health. Previously this grant was submitted as an R0-1 with Dr. Foa and PI and Dr. Yehuda as subcontractor. Following review, in consultation with the Chief of the Adult Psychopathology and Prevention Research Branch, we have changed the funding mechanism. Thus, this grant represents the first submission for Dr. Yehuda and a resubmission of R01 MH62003 for Dr. Foa. The grant proposes to employ a longitudinal design to examine alterations in the biology of PTSD in individuals whose symptoms are expected to improve following prolonged exposure therapy (PE). Because a great majority of trauma victims who receive PE show significant improvement in clinical symptoms, examining biological parameters before, during, and after this manipulation provides an opportunity to explore the relationships among biological alterations, changes in PTSD symptom severity, and cognitions related to the disorder. Thus, this study is interested in the relationship between biological alterations and psychological factors (including dysfunctional cognitions about the danger of the world and self-incompetence) that have been implicated in chronic PTSD, particularly as they may change with reduction in PTSD symptoms. Furthermore, the study will assess whether biological alterations associated with chronic PTSD predict, or are altered in relation to, therapeutic outcome. The longitudinal design with multiple measurements will allow us to obtain data that address the temporal relationship between changes in symptom severity with biological and cognitive variables. If biological alterations are principally related to symptom severity and/or cognitive factors that maintain PTSD, then successfully treating the symptoms should alter biological findings in the direction of normality. However, it is possible that changes in symptom severity may occur in the absence of significant shifts in neuroendocrine profile, suggesting a pattern related to underlying risk rather than to symptomatic expression in this disorder. The resolution of these questions has important implications for understanding the pathophysiology of PTSD, and may provide insight into the mechanisms associated with successful psychological treatment for this disorder.
