Blunted Prefrontal Cortical 18Fluorodeoxyglucose Positron Emission Tomography Response to Meta-Chlorophenylpiperazine in Impulsive Aggression

BACKGROUND Impulsive aggression is a prevalent problem and yet little is known about its neurobiology. Preclinical and human studies suggest that the orbital frontal cortex and anterior cingulate cortex play an inhibitory role in the regulation of aggression. METHODS Using positron emission tomography, regional metabolic activity in response to a serotonergic stimulus, meta-chlorophenylpiperazine (m-CPP), was examined in 13 subjects with impulsive aggression and 13 normal controls. The anterior cingulate and medial orbitofrontal regions were hypothesized to respond differentially to m-CPP in patients and controls. In the frontal cortex, regional metabolic glucose response to m-CPP was entered into a group (impulsive aggressive, control) × slice (dorsal, middle, orbital) × position (medial, lateral) × location (anterior, posterior) × hemisphere (right, left) mixed-factorial analysis of variance design. A separate group (impulsive aggressive, controls) × anteroposterior location (Brodmann areas 25, 24, 31, 29) × hemisphere (right, left) analysis of variance was used to examine regional glucose metabolism in the cingulate gyrus. RESULTS Unlike normal subjects, patients with impulsive aggression did not show activation specifically in the left anteromedial orbital cortex in response to m-CPP. The anterior cingulate, normally activated by m-CPP, was deactivated in patients; in contrast, the posterior cingulate gyrus was activated in patients and deactivated in controls. CONCLUSIONS The decreased activation of inhibitory regions in patients with impulsive aggression in response to a serotonergic stimulus may contribute to their difficulty in modulating aggressive impulses.Arch Gen Psychiatry. 2002;59:621-629-->