The brain at war: effects of stress on brain structure in soldiers deployed to a war zone

In search of the neural basis of severe trauma exposure and post-traumatic stress disorder (PTSD), a multitude of cross-sectional studies have been conducted, most of them pointing at structural deficits in the hippocampus and medial prefrontal cortex including the anterior cingulate cortex (ACC) and ventromedial prefrontal cortex (vmPFC). Since cross-sectional studies are silent to causality, the core question remains: which brain structural alterations constitute a risk factor for disease and therewith precede the stressor, and which brain regions may undergo alterations as a consequence of exposure to the stressor. We assessed 121 soldiers before and after deployment to regions of war and 40 soldiers as controls, who were not deployed. Analysis using voxel-based morphometry revealed volumetric reductions in the ACC, vmPFC (region of interest analysis, effect does not survive conservative multiple test correction) and in bilateral thalamus (whole-brain analysis) in the deployment group. Remarkably, the ACC and vmPFC volume decrease was not limited to the period of deployment, but continued over the following 6 months after deployment. Volumetric reductions did not correlate with increases in PTSD symptoms. The volume decreases in medial prefrontal cortex and thalamus seem to be driven by trauma exposure rather than a vulnerability factor for PTSD. However, data indicate that the volume decrease in medial prefrontal cortex surpasses the time period of deployment. This may hint at an innate pathological process below a symptom threshold, potentially related to the way the future mental health changes were conducted, most of them pointing at brain structural deficits in hippocampus (HC) and medial prefrontal cortex including anterior cingulate cortex (ACC) and ventromedial prefrontal cortex (vmPFC) in patients in comparison to trauma-exposed controls. Moreover, cross-sectional studies as well as prospective studies that can provide any information about causation or its direction. A still unanswered question is how to best determine whether brain structural alterations are a risk factor for disease and thereby precede trauma and/or onset of the disorder, or whether the alterations are a consequence of exposure to trauma and/or the disease. In order to solve this question, monozygotic (MZ) twin studies have been conducted in which twins were identified of whom one received a diagnosis of PTSD (discordant for PTSD) and other twin pairs who were discordant also for trauma exposure. Since MZ twin pairs share the same genes and most of the environment during upbringing, this study design