REVEALING SUSCEPTIBILITY FACTORS FOR POST TRAUMATIC STRESS DISORDER

Experiencing an emotionally traumatic event, even without physical injury, results indeveloping a debilitating condition, termed Post-Traumatic Stress Disorder (PTSD) in anestimated 20-30% of people, including the over 2 million US military personnel deployedin guerilla-type warfare (Operations Enduring Freedom and Iraqi Freedom) which ischaracterized with high level of unpredictable and recurring exposure to traumatic events.Thus, it is not surprising that PTSD inflicts rising costs to the Veteran’s Administrationand society, in general, due to loss of productivity and quality of life. The VA costsassociated with paying PTSD-related disability have been steadily rising since 1999,reaching over $2 billion in treatment costs (2004-2009), plus nearly 5 billion in disabilitypayments. Considering that 80% continue to require treatment past 3 years afterdiagnosis, it is clear that decreasing the number of veterans requiring treatment for PTSDwould decrease VA costs associated with this disorder, and, importantly, increase thequality of life for many veterans. A previous history of PTSD or other anxiety disordersrenders some people more susceptible to developing PTSD after subsequent traumaticevents. Thus, veterans treated for PTSD, or with PTSD susceptibility, are more likely todevelop PTSD when they experience non-combat trauma, such as auto accidents, assault,and natural disasters. Therefore, identifying susceptibility and ways to prevent it coulddecrease PTSD-associated VA costs.Understanding the susceptibility factors for developing PTSD can help reduce theprobability of occurrence after experiencing emotional trauma. The goal of this grant isto build upon our recent discovery of susceptibility and sequelae factors of emotionaltrauma. We propose to investigate whether an elevated pro-inflammatory profile is asusceptibility factor and whether it contributes to the disrupted function of the medialprefrontal cortex (mPFC) and hippocampus before emotional trauma (Aim 1) that wehave already identified. In Aim 2, we propose to investigate whether decreasing the pro-inflammatory state in susceptible rats will increase their resilience, measured by theirpost-trauma behavior and functional activation of the mPFC and hippocampus.For the proposed studies, we will combine two indispensable tools: 1) RISP: ourbehavioral rat model for revealing individual susceptibility to a PTSD-like phenotypebefore experiencing emotional trauma (fear conditioning). This phenotype includes:impaired fear extinction, lasting elevated startle response and generalized anxiety-likebehavior. 2) Arc/Homer 1a catFISH method: the sensitive cellular imaging method, co-developed by the PI, which can assess both size and overlap of neuronal ensemblesengaged in plasticity after two distinct behavioral events. The findings from this researchhave the potential to revolutionize the assessment of susceptibility to PTSD-like behaviorsand suggest new ways to build resilience.