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

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

Abstract

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.

Keywords: Medial prefrontal cortex; Pharmaco-fMRI; SSRI; Serotonin; Virtual violence.

MeSH terms

  • Adult
  • Brain Mapping / methods
  • Citalopram / administration & dosage
  • Cognition* / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Emotions* / drug effects
  • Exposure to Violence / psychology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neural Pathways / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Random Allocation
  • Serotonin / metabolism*
  • Serotonin Uptake Inhibitors / administration & dosage
  • Video Games / psychology*
  • Young Adult

Substances

  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin