The high number of OEF/OIF/OND veterans with comorbid PTSD and mTBI seeking care at VA has brought to light a gap in the evidence base of treatment strategies for these conditions. Treating veterans with these two disorders is challenging because the symptoms overlap (e.g., insomnia, irritability, trouble concentrating). Additionally, veterans may present for treatment in Mental Health Clinics or in Polytrauma Clinics where they may undergo different diagnostic procedures and receive treatments that may address only one disorder. Even worse, a treatment designed for one disorder may worsen the symptoms of the other. Coordinated care of mTBI and PTSD is essential in order to ensure `the compatibility of medications and other treatments for both disorders. This can best be done by determining similarities and differences between biological profiles in PTSD and mTBI separately and when they co-occur. To date, very little is known about the underlying pathophysiologies for each disorder separately and for their co-occurrence. Interestingly, however, hormonal dysfunction has been independently identified in both conditions. The project described in this application will examine glucocorticoid (GC) functioning in PTSD and mTBI in order to determine whether people with both conditions show a neuroendocrine profile (i.e., GC sensitivity) that resembles that observed in people with PTSD. One hundred and forty OEF/OIF/OND veterans will participate in the project and will include veterans with no history of mTBI and no current PTSD (mTBI-/PTSD-); veterans with a history of mTBI but no PTSD (mTBI+/PTSD-); veterans with no history of mTBI but a current PTSD diagnosis (mTBI-/PTSD+); veterans with a history of mTBI and a current PTSD diagnosis (mTBI+/PTSD+). The primary study outcomes will include an assessment of hypothalamic-pituitary-adrenal (HPA) axis functioning (i.e.,24 hour urinary cortisol, cortisol (CORT) and adrenocorticotrophin (ACTH) response to dexamethasone (DEX), lysozyme IC50-DEX) and the CORT and ACTH response to glucocorticoid ingestion [i.e., glucocorticoid challenge test (GCT)]. Secondary measures include cognitive testing following the GCT; Exploratory analyses will be conducted to examine group differences in baseline neuropsychological tests and self-report measures (e.g., symptoms) and anterior pituitary hormones associated with post-traumatic hypopituitarism (PTHP). The results of this study will contribute to our understanding of the unique biological signal associated with comorbid mTBI and PTSD, which will enhance coordination of diagnosis and treatment of combat veterans who receive care at VA.
Dysregulated glucocorticoid (GC) activity has been observed in both PTSD and mTBI and although there may be phenotypic similarities across the two disorders, the underlying etiology may differ. Given the overlap in symptoms (e.g., sleep and cognitive problems) and the role that GCs play in regulating these functions, it is of interest to examine GC functioning in these two disorders separately, and when they co-occur. It is imperative to provide coordinated care at VA for OEF/OIF/OND veterans with mTBI and PTSD to ensure that treatments are compatible. Some medications used for the treatment of cognitive problems associated with the mTBI diagnosis may exacerbate PTSD symptoms. Additionally, novel treatments for PTSD that target glucocorticoid functioning have not been tested in people with mTBI. The project described in this application will examine GC functioning in PTSD and mTBI in order to determine whether people with both conditions show a neuroendocrine profile that resembles that observed in people with PTSD alone.
|Flory, Janine D; Yehuda, Rachel (2015) Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations. Dialogues Clin Neurosci 17:141-50|
|Flory, Janine D; Henn-Haase, Clare; Bierer, Linda M et al. (2015) Glucocorticoid functioning in male combat veterans with posttraumatic stress disorder and mild traumatic brain injury. Biol Psychiatry 78:e5-6|