Prefrontal Cortical Deficits are a Putative Susceptibility Factor for PTSD

Almira Vazdarjanova^*Rebecca Ipe NalloorKhadijah Shanazz

• Medical College of Georgia, Augusta University, Augusta, GA, United States

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, male 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. Here we tested the hypothesis that male rats classified as Susceptible with RISP will have altered medial prefrontal cortical (mPFC) function isprior to a putative susceptibility factorPTSD-inducing trauma. Susceptible and Resilient male rats classified with RISP performed spatial exploration and set shifting before trauma. Susceptible rats showed altered expression of plasticity-related immediate early genes (Arc and Homer1a) in the Prelimbic and Infralimbic subregions of the mPFC following spatial exploration. 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 PTSD-inducing trauma. Consistent with the findings in rats, male military personnel who showed pre-trauma deficits in cognitive tasks involving mPFC developed PTSD post-trauma. Combined, these findings suggest that mPFC deficits exist before trauma and thus are a putative susceptibility factor for PTSD and. Whether these deficits are a bona fide susceptibility factor will be determined in future studies by testing if enhancing mPFC function in susceptible individuals before trauma maywill confer resilience to developing PTSD. Building resilience is crucial for minimizing the number of people suffering from PTSD, given that it is difficult to treat and treatments are resource-intensive and benefit only a subpopulation of people suffering from PTSD.