An Anti-inflammatory Approach to Diagnosis and Treatment of Combines PTSD and Mild TBI

The Specific Aim of this project, as accepted for funding by the Military Clinical Neuroscience Center of Excellence (MCNCoE), is to "Clinically validate the (preclinically) identified epigenetic biomarkers of stress and mTBI on an active duty military population." MCNCoE funding was aimed to augment an ongoing DMRDP-funded study by providing the salary for a I -year FTE clinical research nurse in support of a clinical study at Naval Hospital, Camp Lejeune. This study was designed to recruit active duty personnel returning from deployment, including: 1) Marines with combat experience but no combat-related mild traumatic brain injury (mTBI) or post-traumatic stress disorder (PTSD); 2) Marines with mTBI but no PTSD; 3) Marines with combat-related PTSD but no mTBI; and 4) Marines with combat-related mTBI and PTSD. Blood samples from these subjects were to be used for both the validation of preclinically identified and the de novo identification of epigenetic biomarkers of mTBI, PTSD and their combination. Base rates of neuropsychological impairment on memory, attention/concentration, and other executive functions were to be determined for each group. The clinical record was to include data regarding injuries, including head injury , number of blasts, riding or walking or on post, type of explosive device, grade of the concussion, MRI findings, etc. In addition, for each group of Marines, individuals showing signs of cognitive impairment were to be identified. As part of the clinical study blood was to be collected from each consented participant. DNA samples from blood monocytes were to be used for the evaluation of several candidate epigenetic biomarkers, including those identified in the animal study. An association analysis was planned on the results of genetic analysis vs clinical data, in order to qualify potential candidate biomarkers of mTBI, PTSD, and of mTBI/PTSD association. Inorder to better achieve our objectives a collaborative effort was set up with a New Jersey VA research team led by Dr. Richard Servatius. Our respective study protocols were merged and submitted as ajoint protocol to the IRB overseeing clinical research activity at Naval Hospital , Camp Lejeune.