A double dissociation in the roles of serotonin and mood in healthy subjects

Biol Psychiatry. 2009 Jan 1;65(1):89-92. doi: 10.1016/j.biopsych.2008.10.001. Epub 2008 Nov 8.


Background: Affective disorders are associated with altered cognitive performance. However, the precise interaction between affect and cognition is unclear. The manipulation of serotonin (5-HT), a neurotransmitter implicated in affect, influences performance on "hot" cognitive tasks that require the processing of affective stimuli, but manipulation of affect via mood induction influences performance on "cold" cognitive tasks that do not involve affective stimuli. We attempted to disentangle the influence of affect on cognition by examining the effect of manipulating both serotonin (via acute tryptophan depletion [ATD]) and mood on established hot and cold cognitive tasks.

Methods: In a double blind, placebo-controlled crossover design, 33 healthy mood-induced (positive, negative, or neutral) subjects completed the (hot) affective go/no-go (AGNG) and (cold) one touch tower (OTT) following both placebo and ATD.

Results: Mood influenced performance on the OTT but not AGNG; ATD influenced performance on the AGNG but not OTT.

Conclusions: A double dissociation was demonstrated between the influence of ATD and mood on cognition, indicating that serotonin and mood are not closely linked. We hypothesize that this is due to the differences between emotions and moods and that aberrant cognition in affective disorders may be provoked through both bottom-up and top-down mechanisms.

Publication types

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

MeSH terms

  • Adult
  • Affect / physiology*
  • Cognition / physiology*
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Mood Disorders / etiology
  • Placebos
  • Psychomotor Performance
  • Serotonin / metabolism*
  • Serotonin / physiology
  • Tryptophan / blood


  • Placebos
  • Serotonin
  • Tryptophan