Sofi da Cunha-Bang1, Liv Vadskjaer Hjordt1, Erik Perfalk1, Vincent Beliveau1, Camilla Bock2, Szabolcs Lehel3, Carsten Thomsen4, Dorte Sestoft5, Claus Svarer6, Gitte Moos Knudsen7. 1. Neurobiology Research Unit and Center for Integrated Molecular Imaging, Rigshospitalet; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen. 2. Neurobiology Research Unit and Center for Integrated Molecular Imaging, Rigshospitalet; The Danish Prison and Probation Service, Institution of Herstedvester, Herstedvester. 3. PET and Cyclotron Unit, Rigshospitalet. 4. Department of Radiology, Rigshospitalet. 5. Ministry of Justice, Clinic of Forensic Psychiatry, Copenhagen, Denmark. 6. Neurobiology Research Unit and Center for Integrated Molecular Imaging, Rigshospitalet. 7. Neurobiology Research Unit and Center for Integrated Molecular Imaging, Rigshospitalet; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen. Electronic address: gmk@nru.dk.
Abstract
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-HT1BRs) 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 [11C]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-HT1BRs and trait anger (difference in slopes, pcorrected = .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-HT1BRs putatively represent a molecular target for development of pharmacologic antiaggressive treatments.
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-HT1BRs) 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 [11C]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-HT1BRs and trait anger (difference in slopes, pcorrected = .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-HT1BRs putatively represent a molecular target for development of pharmacologic antiaggressive treatments.
Authors: Hanne D Hansen; Joseph B Mandeville; Christin Y Sander; Jacob M Hooker; Ciprian Catana; Bruce R Rosen; Gitte M Knudsen Journal: J Neurosci Date: 2017-10-02 Impact factor: 6.167
Authors: Louise M Jørgensen; Tove Henriksen; Skirmante Mardosiene; Sune H Keller; Dea S Stenbæk; Hanne D Hansen; Bo Jespersen; Carsten Thomsen; Pia Weikop; Claus Svarer; Gitte M Knudsen Journal: J Cereb Blood Flow Metab Date: 2021-01-18 Impact factor: 6.200
Authors: Sofi da Cunha-Bang; Patrick M Fisher; Liv Vadskjær Hjordt; Erik Perfalk; Anine Persson Skibsted; Camilla Bock; Anders Ohlhues Baandrup; Marie Deen; Carsten Thomsen; Dorte M Sestoft; Gitte M Knudsen Journal: Soc Cogn Affect Neurosci Date: 2017-05-01 Impact factor: 3.436