Central serotonin modulates neural responses to virtual violent actions in emotion regulation networks
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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.
KeywordsSSRI Serotonin Virtual violence Medial prefrontal cortex Pharmaco-fMRI
The authors would like to thank Cordula Kemper for assistance with measurements, the study participants for their participation, and the Brain Imaging Facility of the Interdisciplinary Centre for Clinical Research (ICCR) Aachen for technical support.
This study was funded by the German Research Foundation [DFG IRTG 2150, MA 2631/6-1]; the German Ministry for Education and Research [BMBF; APIC: 01EE1405A, 01EE1405B, 02EE1405C] and the Interdisciplinary Centre for Clinical Research (ICCR) Aachen (N4-2). This project has received funding from the European Union’s Horizon 2020 Framework Programme for Research and Innovation under Grant Agreement No 720270 (Human Brain Project SGA1).
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
The experiment was designed and conducted according to the Code of Ethics of the World Medical Association (Declaration of Helsinki) and the study protocol was approved by the local Ethics Committee.
Informed consent was obtained from all individual participants included in the study.
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