MRI studies using the manual tracing method have shown a smaller-than-normal hippocampal volume in patients with posttraumatic stress disorder (PTSD). However, these studies have yielded inconsistent results, and brain structures other than the hippocampus have not been well investigated. A recently developed, fully automated method called voxel-based morphometry enables an exploration of structural changes throughout the brain by applying statistical parametric mapping to high-resolution MRI. Here we first used this technology in patients with PTSD. Participants were 9 victims of the Tokyo subway sarin attack with PTSD and 16 matched victims of the same traumatic event without PTSD. The voxel-based morphometry showed a significant gray-matter volume reduction in the left anterior cingulate cortex (ACC) in trauma survivors with PTSD compared with those without PTSD. The severity of the disorder was negatively correlated with the gray-matter volume of the left ACC in PTSD subjects. There were no significant differences in other gray-matter regions or any of the white-matter regions between two groups. The present study demonstrates evidence for structural abnormalities of ACC in patients with PTSD. Together with previous functional neuroimaging studies showing a dysfunction of this region, the present findings provide further support for the important role of ACC, which is pivotally involved in attention, emotional regulation, and conditioned fear, in the pathology of PTSD.F indings from neuroimaging studies of patients with posttraumatic stress disorder (PTSD) have suggested that some brain pathology plays an important role in the disorder (1, 2). Six structural MRI studies have shown that combat-related or childhood physically and͞or sexually abused subjects with PTSD have a smaller-than-normal hippocampal volume (3-8). However, almost the same number of studies failed to show reduced hippocampal volume in chronically maltreated children (9-11), survivors of acute traumatic events (12), nonalcoholic combat veterans (13), and alcoholic patients (14) with PTSD. In contrast, brain structures other than the hippocampus have received less attention, although a few studies have reported whole-brain volume reduction (9), reduced total white-matter volume (7), smaller corpus callosum (9), larger superior temporal gyrus gray-matter volume (15), and attenuation of frontal lobe asymmetry (11). Therefore, it is unclear whether structural abnormality in brain structures other than the hippocampus exists in patients with PTSD.In contrast to the emphasis on the hippocampus in previous structural MRI studies, symptom-provocation and cognitiveactivation studies using functional neuroimaging have revealed greater activation of the amygdala, anterior paralimbic structures, Broca's region, and other neocortical regions and a failure of activation of anterior cingulate cortex (ACC) in response to trauma-related stimuli in individuals with PTSD (1, 2, 16). Furthermore, one study (17) showed a reduced N-acetylaspartate͞creatine ratio...
