Increased Serotonin 2A Receptor Availability in the Orbitofrontal Cortex of Physically Aggressive Personality Disordered Patients

Background: Impulsive physical aggression is a common and problematic feature of many personality disorders. The serotonergic system is known to be involved in the pathophysiology of aggression, and multiple lines of evidence have implicated the serotonin 2A receptor (5-HT2AR). We sought to examine the role of the 5-HT2AR in impulsive aggression specifically in the orbitofrontal cortex (OFC), given that our own studies and an extensive literature indicate that serotonergic disturbances in the OFC are linked to aggression. We have previously hypothesized that increased 5-HT2AR function in the OFC is a state phenomenon that promotes impulsive aggression. Methods: Serotonin 2A receptor availability was measured with positron emission tomography and the selective 5-HT2AR antagonist radioligand [C-11]MDL100907 in two groups of impulsively aggressive personality disordered patients-14 with current physical aggression, and 15 without current physical aggression-and 25 healthy control subjects. Clinical ratings of various symptom dimensions were also obtained. Results: Orbitofrontal 5-HT2AR availability was greater in patients with current physical aggression compared with patients without current physical aggression and healthy control subjects; no differences in OFC 5-HT2AR availability were observed between patients without current physical aggression and healthy control subjects. No significant differences in 5-HT2AR availability were observed in other brain regions examined. Among both groups of impulsively aggressive personality disordered patients combined, OFC 5-HT2AR availability was correlated, specifically, with a state measure of impulsive aggression. Conclusions: These findings are consistent with our previously described model in which impulsive aggression is related to dynamic changes in 5-HT2AR function in the OFC.