The study aimed to clarify the causal relationship between stress, particularly from war zone deployment, and brain structural alterations, specifically addressing whether such alterations precede trauma or are a consequence of it. Existing cross-sectional studies have linked trauma exposure and PTSD to structural deficits in the hippocampus and medial prefrontal cortex (including ACC and vmPFC), but these studies cannot establish causality. The researchers hypothesized that exposure to extreme stressors during military deployment would lead to observable changes in brain structure, potentially clarifying the temporal relationship between stress and these structural changes. Understanding this relationship is crucial for developing effective prevention and treatment strategies for PTSD and other trauma-related disorders. The study used a longitudinal design, scanning soldiers before and after deployment, to overcome the limitations of cross-sectional studies. The use of a control group further strengthens the study's ability to isolate the effects of deployment.

Numerous cross-sectional studies have reported structural deficits in the hippocampus (HC) and medial prefrontal cortex (including ACC and vmPFC) in individuals with PTSD compared to trauma-exposed controls. However, these studies are unable to determine the direction of causality. To address this limitation, some researchers have utilized monozygotic (MZ) twin studies, comparing PTSD-discordant twins or twins discordant for trauma exposure. Since MZ twins share identical genes and similar upbringing environments, this design helps disentangle genetic predisposition from environmental influences on brain structure.

This study employed a longitudinal design with 121 soldiers scanned before and after deployment to a war zone, and 40 non-deployed control soldiers. Voxel-based morphometry (VBM) using CAT12 software was applied to analyze gray matter volume changes. Several self-report questionnaires (PDS, STAI, ASI, BDI-II, RSQ, AUDIT) were used to assess psychological symptoms. Region of interest (ROI) analyses focused on the ACC, vmPFC, and left hippocampus, based on findings from previous meta-analyses. Whole-brain analyses were also conducted. Statistical analyses included group × time analyses for questionnaires, controlling for age, and group × time interaction analyses for VBM data, with FWE correction applied. Bayesian statistics were used in some instances to assess evidence for the null hypothesis.

The study found volumetric reductions in the ACC, vmPFC (ROI analysis, not surviving conservative multiple test correction), and bilateral thalamus (whole-brain analysis) in the deployed soldiers compared to controls. Importantly, the ACC and vmPFC volume reductions persisted for six months after deployment. These volumetric changes did not correlate with PTSD symptom severity, as measured by the PDS. Depressive symptoms, measured by the BDI-II, showed a significant increase in the deployed group after deployment. The whole-brain analysis revealed a significant cluster in the bilateral thalamus showing a group × time interaction. Post-hoc tests revealed significant volume decreases in the ACC and vmPFC between baseline and follow-up assessments. Notably, the volume reductions continued from the end of deployment to the second follow-up assessment for both the ACC and vmPFC. No significant changes were observed in the control group's ACC or vmPFC.

The findings suggest that the observed volumetric reductions in the ACC, vmPFC, and thalamus are consequences of trauma exposure during deployment, rather than pre-existing risk factors for PTSD. The sustained volumetric decreases in the ACC and vmPFC beyond the deployment period imply a potential ongoing pathological process, possibly related to the trauma experience, which could be below the symptom threshold for PTSD. The lack of correlation between brain structure changes and PTSD symptom severity indicates that these structural alterations may be a broader consequence of severe stress exposure and not specifically linked to the development of PTSD.

This longitudinal study demonstrates that deployment to a war zone is associated with volumetric reductions in several brain regions, including the ACC, vmPFC, and thalamus. These changes appear to be a consequence of trauma exposure and are not strongly correlated with PTSD symptom severity. Future research should investigate the long-term consequences of these structural changes and explore potential interventions to mitigate their impact.

The study's sample size, while substantial, could be further increased to enhance statistical power. The reliance on self-report questionnaires for assessing psychological symptoms may be subject to biases. The combat experience was assessed using retrospective self-report, which is prone to recall bias and subjective interpretation. 26.5% of the soldiers reported less experience after deployment than before which is impossible and points to a potential limitation in the methods used to assess the combat experience.