Frontolimbic Morphometric Abnormalities in Intermittent Explosive Disorder and Aggression

Converging evidence from neuroimaging studies suggests that impulsive aggression, the core behavior in the DSM-5 diagnosis intermittent explosive disorder (IED), is regulated by frontolimbic brain structures, particularly orbitofrontal cortex, ventral medial prefrontal cortex, anterior cingulate cortex, amygdala, insula, and uncus. Despite this evidence, no brain volumetric studies of IED have been reported as yet. This study was conducted to test the hypothesis that gray matter volume in frontolimbic brain structures of subjects with IED is lower than in healthy subjects and subjects with other psychiatric conditions.

High-resolution magnetic resonance imaging scans using a three-dimensional magnetization-prepared rapid acquisition gradient-echo sequence were performed in 168 subjects (n = 53 healthy control subjects, n = 58 psychiatric controls, n = 57 subjects with IED). Imaging data were analyzed by voxel-based morphometry methods employing Statistical Parametric Mapping (SPM8) software.

Gray matter volume was found to be significantly lower in subjects with IED compared with healthy control subjects and psychiatric controls in orbitofrontal cortex, ventral medial prefrontal cortex, anterior cingulate cortex, amygdala, insula, and uncus. These differences were not due to various confounding factors or to comorbidity with other disorders previously reported to have reduced gray matter volume. Gray matter volume in these areas was significantly and inversely correlated with measures of aggression.

Reductions in the gray matter volume of frontolimbic structures may be a neuronal characteristic of impulsively aggressive individuals with DSM-5 IED. These data suggest an anatomic correlate accounting for functional deficits in social-emotional information processing in these individuals.