Augmentation of serotonin enhances pleasant and suppresses unpleasant cortical electrophysiological responses to visual emotional stimuli in humans

Neuroimage. 2004 Jul;22(3):1084-96. doi: 10.1016/j.neuroimage.2004.03.022.


The serotonergic system is one of the major systems targeted in the pharmacological treatment of a wide range of mood disorders including depression; however, little is known about the neurophysiological mechanisms underlying the effects of serotonin (5-HT) on affective phenomena including emotional behaviours, mood and emotional processing. The aim of the current study was to investigate how 5-HT acutely modulates steady-state visually evoked potentials (SSVEP), heart rate (HR) and verbal ratings associated with the viewing of differently valent emotional images. In a randomised double-blind, placebo-controlled design, 17 healthy subjects were tested under two acute treatment conditions: placebo and citalopram (20 mg) (a selective serotonin re-uptake inhibitor, or SSRI). Participants were tested 2 h post treatment whilst viewing 75 images (categorised as pleasant, neutral or unpleasant). Results indicate that under placebo treatment, processing of unpleasant valence [unpleasant (-) neutral images] was associated with decreases in SSVEP amplitude and latency in frontal and occipital cortices, whereas processing of pleasant valence [pleasant (-) neutral images] was associated with amplitude decreases and latency increases within frontal and left temporoparietal cortices. Decreases in both amplitude and latency are both interpreted as surrogate measures of cortical activation or excitation. Citalopram relative to placebo attenuated the electrophysiological activation to unpleasant valence within frontal and occipital cortices, but potentiated electrophysiological activation (amplitude only) to pleasant valence within parietooccipital cortices. Citalopram relative to placebo also suppressed differences in heart rate associated with the viewing of pleasant and unpleasant images, but did not alter subject's subjective responses to emotional images. Results suggest that responsiveness to pleasant and unpleasant stimuli following neurochemical modulation may vary across different response systems (i.e. self-report, HR and SSVEP). Electrophysiological findings suggest that acute serotonergic augmentation with citalopram modulates cortical processing of emotionally valent stimuli such that response to pleasant valence is potentiated and response to unpleasant valence is suppressed. The findings suggest a possible neurophysiological mechanism underlying antidepressant drug action on emotion.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analysis of Variance
  • Behavior / drug effects
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Citalopram / pharmacology
  • Double-Blind Method
  • Electroencephalography
  • Electrophysiology
  • Emotions / drug effects
  • Emotions / physiology*
  • Evoked Potentials, Visual / drug effects
  • Female
  • Heart Rate / drug effects
  • Homeostasis
  • Humans
  • Male
  • Photic Stimulation*
  • Pleasure-Pain Principle*
  • Reaction Time / drug effects
  • Serotonin / physiology*
  • Serotonin Uptake Inhibitors / pharmacology


  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin