Dual Brain Pathology in Patients With Affective Aggressive Episodes

Recently, Raine et al¹ reported significant reduction of prefrontal gray matter and reduced skin-conductance responses to aversive stimuli in patients with antisocial personality disorder (APD) and high rates of violence perpetration (as compared with healthy men or men with other psychiatric disorders).¹ In his commentary to this article, Damasio pointed out that it is important to test the specificity of this finding.² Similar and highly significant reductions of cortical gray matter that could not be detected on visual inspection of the magnetic resonance imaging scan have been reported in patients with intermittent explosive disorder, and epilepsy without any other psychiatric disorder.³ Interestingly, this finding was clearly lateralized to the left dorsolateral prefrontal cortex. Unfortunately, Raine et al¹ did not comment on whether their interesting finding was lateralized or whether it was more pronounced in the dorsolateral, orbiofrontol, or frontomedial prefrontal cortex. Using a voxel-based analysis following the study by Wright et al⁴ as an example, Raine could clarify which prefrontal region contributed most to the observed loss of gray matter. Furthermore, as Damasio points out,² other brain areas, subcortical areas in particular, could contribute to the antisocial and aggressive psychopathological behavior seen in patients with APD. In the patient sample with the intermettent explosive disorder described above, in addition to prefrontal loss of gray matter brain pathological features affecting amygdala, circuitries could be found in almost 50% of patients following quantitative analysis of structural magnetic resonance imaging scans.⁵ Since the amygdala is known to play an important role in fear conditioning,⁶ additional amygdala pathological abnormalities (as in the sample with intermittent explosive disorder) might explain the second observation of reduced skin-conductance in men with APD. Therefore, it might be that a dual brain pathology (with abnormalities of the amygdala resulting in dysfunctional arousal states and abnormalities of the prefrontal brain resulting in dyscontrol states) is responsible for the psychopathology of hyperarousal-dyscontrol states seen in patients with intermittent explosive disorder and APD. Simultaneous quantitative analysis of cortical and subcortical brain regions might help answer questions like this in future research.