Prefrontal cortical deficits are a putative susceptibility factor for PTSD.
Rebecca Nalloor1,2, Khadijah Shanazz1,3, Almira Vazdarjanova1,2
1VA Research Service, Charlie Norwood VA Medical Center, Augusta, GA, United States.
Frontiers in Behavioral Neuroscience
|March 20, 2026
Summary
Pre-trauma medial prefrontal cortex (mPFC) deficits in male rats predict susceptibility to developing Post-Traumatic Stress Disorder (PTSD)-like behaviors. These findings suggest mPFC dysfunction may be a key susceptibility factor for PTSD.
Area of Science:
- Neuroscience
- Psychiatry
- Behavioral Science
Background:
- Post-Traumatic Stress Disorder (PTSD) develops in only a subset of individuals exposed to trauma, indicating underlying susceptibility factors.
- Medial prefrontal cortex (mPFC) hypofunction is observed in PTSD, but its role as a susceptibility factor versus a consequence remains unclear.
Purpose of the Study:
- To investigate whether medial prefrontal cortical (mPFC) function is altered in male rats identified as susceptible to developing PTSD-like phenotypes prior to trauma exposure.
- To explore the potential of mPFC deficits as a susceptibility factor for PTSD.
Main Methods:
- Utilized the Revealing Individual Susceptibility to PTSD-like phenotype (RISP) model to classify male rats as susceptible or resilient before trauma.
- Assessed neuronal expression of plasticity-related genes (Arc, Homer1a) in the mPFC after spatial exploration.
- Evaluated cognitive performance on an attentional set shifting task.
- Analyzed pre-trauma cognitive data from male military personnel who later developed PTSD.
Main Results:
- Susceptible rats exhibited altered immediate early gene expression in mPFC subregions (Prelimbic, Infralimbic) before trauma.
- Susceptible rats demonstrated attentional set shifting deficits, particularly under increased task demands.
- Military personnel who developed PTSD showed pre-trauma cognitive deficits linked to PFC function.
Conclusions:
- Pre-trauma deficits at both cellular and behavioral levels in the mPFC of susceptible rats support its role as a potential susceptibility factor for PTSD.
- Findings in rats, combined with human data, suggest that mPFC alterations may precede trauma in males susceptible to PTSD.
- Future research will focus on whether enhancing mPFC function pre-trauma can confer resilience to PTSD development.
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