Post-traumatic stress disorder (PTSD) is a mental disorder that occurs after exposure to severe stress. Voxel-based morphometry (VBM) is a comprehensive gray matter volume analysis by normalizing with a standardized template on brain MRI images. Several VBM studies demonstrated that the insular cortex, anterior cingulate gyrus, amygdala, and hippocampus showed atrophy in PTSD patients. However, it is unclear whether the neurological change is caused by the stress or by the patient's genetic disposition. In order to verify a causal relationship between severe stress and atrophy, VBM analysis in rats upon PTSD-model stress was carried out.

Method: Rats (male, 7 weeks old) in the experimental group were exposed to Single Prolonged Stress (SPS); 1) immobilization for 2 hours, 2) forced swimming for 20 min, 3) ether anesthesia. Rats in the sham group were exposed only to ether anesthesia. The rats were fixed 7days after SPS, and their brains were removed and immersed in Fluorinert (proton free medium, 3M). High quality 3D-T2WI animal brain MRI images were then acquired. Gray matter regions were segmented using the standardized anatomical template that was created by SD 8-week-old male rats (n=9). Then, VBM analysis was performed using Statistical Parametrical Mapping (SPM)8.

Results and Discussion: Significant atrophy was detected in both sides of the ventral thalamus, right amygdala, and right visual cortex (SPS: n=7, Sham: n=9, uncorrected P<0.001). On the other hand, atrophy of the ventral thalamus and visual cortex has not been observed in clinical PTSD studies, whereas atrophy of the amygdala and other regions as above has been observed. This discrepancy may be explained by the pathophysiology of PTSD, in which both stress and genetic background for stress-vulnerability is involved.