Acute pharmacologically induced shifts in serotonin availability abolish emotion-selective responses to negative face emotions in distinct brain networks

Eur Neuropsychopharmacol. 2013 May;23(5):368-78. doi: 10.1016/j.euroneuro.2012.06.003. Epub 2012 Jun 26.


Pharmacological manipulation of serotonin availability can alter the processing of facial expressions of emotion. Using a within-subject design, we measured the effect of serotonin on the brain's response to aversive face emotions with functional MRI while 20 participants judged the gender of neutral, fearful and angry faces. In three separate and counterbalanced sessions, participants received citalopram (CIT) to raise serotonin levels, underwent acute tryptophan depletion (ATD) to lower serotonin, or were studied without pharmacological challenge (Control). An analysis designed to identify distributed brain responses identified two brain networks with modulations of activity related to face emotion and serotonin level. The first network included the left amygdala, bilateral striatum, and fusiform gyri. During the Control session this network responded only to fearful faces; increasing serotonin decreased this response to fear, whereas reducing serotonin enhanced the response of this network to angry faces. The second network involved bilateral amygdala and ventrolateral prefrontal cortex, and these regions also showed increased activity to fear during the Control session. Both drug challenges enhanced the neural response of this set of regions to angry faces, relative to Control, and CIT also enhanced activity for neutral faces. The net effect of these changes in both networks was to abolish the selective response to fearful expressions. These results suggest that a normal level of serotonin is critical for maintaining a differentiated brain response to threatening face emotions. Lower serotonin leads to a broadening of a normally fear-specific response to anger, and higher levels reduce the differentiated brain response to aversive face emotions.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / drug effects
  • Brain / metabolism*
  • Citalopram / pharmacology
  • Emotions / drug effects
  • Emotions / physiology*
  • Facial Expression*
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Nerve Net / drug effects
  • Nerve Net / metabolism
  • Photic Stimulation / methods
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin / metabolism*
  • Tryptophan / antagonists & inhibitors
  • Tryptophan / deficiency*
  • Young Adult


  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin
  • Tryptophan