title: Quetiapine modulates functional connectivity in brain aggression networks.
abstract: Aggressive behavior is associated with dysfunctions in an affective regulation network encompassing amygdala and prefrontal areas such as orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC). In particular, prefrontal regions have been postulated to control amygdala activity by inhibitory projections, and this process may be disrupted in aggressive individuals. The atypical antipsychotic quetiapine successfully attenuates aggressive behavior in various disorders; the underlying neural processes, however, are unknown. A strengthened functional coupling in the prefrontal-amygdala system may account for these anti-aggressive effects. An inhibition of this network has been reported for virtual aggression in violent video games as well. However, there have been so far no in-vivo observations of pharmacological influences on corticolimbic projections during human aggressive behavior. In a double-blind, placebo-controlled study, quetiapine and placebo were administered for three successive days prior to an fMRI experiment. In this experiment, functional brain connectivity was assessed during virtual aggressive behavior in a violent video game and an aggression-free control task in a non-violent modification. Quetiapine increased the functional connectivity of ACC and DLPFC with the amygdala during virtual aggression, whereas OFC-amygdala coupling was attenuated. These effects were observed neither for placebo nor for the non-violent control. These results demonstrate for the first time a pharmacological modification of aggression-related human brain networks in a naturalistic setting. The violence-specific modulation of prefrontal-amygdala networks appears to control aggressive behavior and provides a neurobiological model for the anti-aggressive effects of quetiapine.
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Germany; JARA-Translational Brain Medicine, RWTH Aachen University, Germany. Electronic address: mklasen@ukaachen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Klasen
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Germany; JARA-Translational Brain Medicine, RWTH Aachen University, Germany.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Zvyagintsev
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Germany; JARA-Translational Brain Medicine, RWTH Aachen University, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schwenzer
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Germany; JARA-Translational Brain Medicine, RWTH Aachen University, Germany; Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Germany.
authors.forename: Krystyna A
authors.initials: KA
authors.lastname: Mathiak
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Germany; JARA-Translational Brain Medicine, RWTH Aachen University, Germany.
authors.forename: Pegah
authors.initials: P
authors.lastname: Sarkheil
authors.affiliation: Department of Communication and Cognitive Science Program, University of California, Santa Barbara, CA, USA.
authors.forename: René
authors.initials: R
authors.lastname: Weber
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School, RWTH Aachen University, Germany; JARA-Translational Brain Medicine, RWTH Aachen University, Germany; INM-1, Forschungszentrum Jülich GmbH, Jülich, Germany; Institute of Psychiatry, King's College London, London, UK.
authors.forename: Klaus
authors.initials: K
authors.lastname: Mathiak
mesh_terms: D000328:Adult; D000374:Aggression / Q000187:drug effects*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000187:drug effects*; D000069348:Quetiapine Fumarate; D018910:Video Games; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate