Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment

Biol Psychiatry. 2010 Mar 1;67(5):439-45. doi: 10.1016/j.biopsych.2009.11.001. Epub 2009 Dec 24.

Abstract

Background: Selective serotonin reuptake inhibitors (SSRIs) are popular medications for anxiety and depression, but their effectiveness, particularly in patients with prominent symptoms of loss of motivation and pleasure, has been questioned. There are few studies of the effect of SSRIs on neural reward mechanisms in humans.

Methods: We studied 45 healthy participants who were randomly allocated to receive the SSRI citalopram, the noradrenaline reuptake inhibitor reboxetine, or placebo for 7 days in a double-blind, parallel group design. We used functional magnetic resonance imaging to measure the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (sight of moldy strawberries and/or an unpleasant strawberry taste) on the final day of drug treatment.

Results: Citalopram reduced activation to the chocolate stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex. In contrast, reboxetine did not suppress ventral striatal activity and in fact increased neural responses within medial orbitofrontal cortex to reward. Citalopram also decreased neural responses to the aversive stimuli conditions in key "punishment" areas such as the lateral orbitofrontal cortex. Reboxetine produced a similar, although weaker effect.

Conclusions: Our findings are the first to show that treatment with SSRIs can diminish the neural processing of both rewarding and aversive stimuli. The ability of SSRIs to decrease neural responses to reward might underlie the questioned efficacy of SSRIs in depressive conditions characterized by decreased motivation and anhedonia and could also account for the experience of emotional blunting described by some patients during SSRI treatment.

Publication types

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

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Adrenergic Uptake Inhibitors / therapeutic use
  • Adult
  • Affect / drug effects*
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / physiopathology*
  • Citalopram / pharmacology*
  • Citalopram / therapeutic use*
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / physiopathology*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Morpholines / pharmacology
  • Morpholines / therapeutic use
  • Nerve Net / drug effects*
  • Nerve Net / physiopathology*
  • Reboxetine
  • Reward*
  • Serotonin Uptake Inhibitors / pharmacology*
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Young Adult

Substances

  • Adrenergic Uptake Inhibitors
  • Morpholines
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Reboxetine