Acute tryptophan depletion in healthy volunteers enhances punishment prediction but does not affect reward prediction

Neuropsychopharmacology. 2008 Aug;33(9):2291-9. doi: 10.1038/sj.npp.1301598. Epub 2007 Oct 17.


Central serotonin (5-HT) has been implicated in emotional and behavioral control processes for many decades, but its precise contribution is not well understood. We used the acute tryptophan depletion procedure in young healthy volunteers to test the hypothesis that central 5-HT is critical for predicting punishment. An observational reversal-learning task was employed that provided separate measures of punishment and reward prediction. Under baseline, subjects made more prediction errors for punishment-associated stimuli than for reward-associated stimuli. This bias was abolished after central 5-HT depletion, which enhanced the ability to predict punishment while not affecting reward prediction. The selective potentiation of punishment prediction concurs with recent theorizing, suggesting that central 5-HT carries a prediction error for future punishment, but not for future reward (Daw et al, 2002). Furthermore, the finding highlights the importance of central 5-HT in resilience to adversity and may have implications for a variety of neuropsychiatric disorders including depression and anxiety.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Affect
  • Analysis of Variance
  • Conditioning, Operant
  • Discrimination Learning
  • Double-Blind Method
  • Female
  • Food, Formulated
  • Humans
  • Male
  • Neuropsychological Tests
  • Punishment*
  • Reaction Time
  • Reproducibility of Results
  • Reversal Learning / physiology*
  • Self Concept
  • Task Performance and Analysis
  • Tryptophan / deficiency*


  • Tryptophan