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Brain Struct Funct. 2018 Sep;223(7):3327-3345. doi: 10.1007/s00429-018-1693-2. Epub 2018 Jun 8.

Central serotonin modulates neural responses to virtual violent actions in emotion regulation networks.

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Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical Faculty, RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical Faculty, RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
Centre and Discipline of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Division of Psychiatry and Clinical Neurosciences and Division of Paediatrics and Child Health, School of Medicine, The University of Western Australia, Perth, Australia.
Specialised Child and Adolescent Mental Health Services, Department of Health in Western Australia, Perth, Australia.
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
Media Neuroscience Lab, Department of Communication, University of California Santa Barbara, Santa Barbara, CA, USA.
Department of Pharmacy, RWTH Aachen, Aachen, Germany.
Department of Pharmacology and Toxicology, RWTH Aachen, Aachen, Germany.
JARA-Translational Brain Medicine, Aachen, Germany.


Disruptions in the cortico-limbic emotion regulation networks have been linked to depression, anxiety, impulsivity, and aggression. Altered transmission of the central nervous serotonin (5-HT) contributes to dysfunctions in the cognitive control of emotions. To date, studies relating to pharmaco-fMRI challenging of the 5-HT system have focused on emotion processing for facial expressions. We investigated effects of a single-dose selective 5-HT reuptake inhibitor (escitalopram) on emotion regulation during virtual violence. For this purpose, 38 male participants played a violent video game during fMRI scanning. The SSRI reduced neural responses to violent actions in right-hemispheric inferior frontal gyrus and medial prefrontal cortex encompassing the anterior cingulate cortex (ACC), but not to non-violent actions. Within the ACC, the drug effect differentiated areas with high inhibitory 5-HT1A receptor density (subgenual s25) from those with a lower density (pregenual p32, p24). This finding links functional responses during virtual violent actions with 5-HT neurotransmission in emotion regulation networks, underpinning the ecological validity of the 5-HT model in aggressive behavior. Available 5-HT receptor density data suggest that this SSRI effect is only observable when inhibitory and excitatory 5-HT receptors are balanced. The observed early functional changes may impact patient groups receiving SSRI treatment.


Medial prefrontal cortex; Pharmaco-fMRI; SSRI; Serotonin; Virtual violence

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