Serotonin 1B Receptor Binding Is Associated With Trait Anger and Level of Psychopathy in Violent Offenders

BACKGROUND: The involvement of serotonin in aggression has traditionally been attributed to impaired prefrontal serotonergic inhibitory control of emotional reactions to provocations in antisocial individuals. However, it is unclear which specific serotonergic receptors are involved in the effects. A large body of preclinical research supports a specific role of serotonin 1B receptors (5-HT(1B)Rs) in aggression and impulsivity, but this has never been evaluated in humans. METHODS: Nineteen incarcerated violent offenders and 24 healthy control nonoffenders were included and examined with positron emission tomography, using the radioligand [C-11]AZ10419369 for quantification of cerebral 5-HT1BR binding in three regions of interest: the anterior cingulate cortex, orbitofrontal cortex, and striatum. RESULTS: Group status significantly moderated the association between striatal 5-HT(1B)Rs and trait anger (difference in slopes, p(corrected) = .04). In the violent offender group, striatal 5-HT1BR binding was positively correlated with self-reported trait anger (p = .0004), trait psychopathy (p = .008), and level of psychopathy according to the Psychopathy Checklist-Revised (p = .02). We found no group differences in 5-HT1BR binding. CONCLUSIONS: Our data demonstrate for the first time in humans a specific involvement of 5-HT1BR binding in anger and psychopathy. 5-HT(1B)Rs putatively represent a molecular target for development of pharmacologic antiaggressive treatments.