Prefrontal Cortical Deficits are a Putative Susceptibility Factor for PTSD

A subset of people who experience a traumatic event develop Post-Traumatic Stress Disorder (PTSD) suggesting that there are susceptibility factors influencing PTSD pathophysiology. While post trauma sequelae factors are extensively studied, susceptibility factors are difficult to study and therefore poorly understood. To address this gap, we previously developed an animal model - Revealing Individual Susceptibility to PTSD-like phenotype (RISP). RISP allows studying susceptibility factors by identifying, before trauma, rats that are likely to develop a PTSD-like phenotype after trauma. Hypofunctioning prefrontal cortex has been reported in people with PTSD, however, it is unclear if it is a susceptibility factor, sequalae factor, or both. Using RISP, we tested the hypothesis that altered medial prefrontal cortical (mPFC) function is a putative susceptibility factor. Susceptible male rats showed altered expression of plasticity-related immediate early genes ( Arc and Homer1a ) in the Prelimbic and Infralimbic subregions of the mPFC following spatial learning. Susceptible rats also showed deficits in attentional set shifting task when task demands increased. These findings suggest that Susceptible rats have mPFC deficits both at the cellular and functional level before trauma. Consistent with the findings in rats, military personnel who showed pre-trauma deficits in cognitive tasks involving mPFC developed PTSD post-trauma. Combined, these findings suggest that mPFC deficits are a putative susceptibility factor for PTSD and enhancing mPFC function in susceptible individuals before trauma may confer resilience to developing PTSD.