Tryptophan modulation and cognition

Adv Exp Med Biol. 2003;527:207-13. doi: 10.1007/978-1-4615-0135-0_24.


The interest in the function of the serotonergic system in relation to cognition stems from three sources: (1) the association of depression, cognitive dysfunction and 5-HT dysregulation; (2) the association of drug-induced 5-HT dysregulation and cognitive dysfunction; and (3) the association of cognitive performance and serotonergic function per se. We performed several experiments in subjects at risk for cognitive impairment and in healthy volunteers, in which 5-HT was manipulated by means of either tryptophan depletion or tryptophan loading. The results show that tryptophan and cognitive performance are associated in a complex non-linear fashion. Dissociations are observed between cognitive functions: tryptophan depletion impairs memory consolidation but improves focussed attention; as well as between subject groups: tryptophan depletion impairs problem solving in healthy 1st degree relatives of bipolar depressed patients but improves it in healthy volunteers without such a family history. It was demonstrated that the mood- and memory effects of tryptophan-depletion were specifically mediated by the depletion of tryptophan and also that the observed memory and cognitive deficits were emotionally biased in a manner consistent with depressive symptoms. We conclude that experimental manipulations of tryptophan mediate temporal and frontal cognitive functions such as memory consolidation and working memory respectively, in an opposite manner.

Publication types

  • Review

MeSH terms

  • Cognition / physiology*
  • Cognition Disorders / etiology
  • Cognition Disorders / physiopathology
  • Depression / complications
  • Depression / physiopathology
  • Humans
  • Models, Psychological
  • Serotonin / deficiency
  • Serotonin / physiology
  • Tryptophan / deficiency
  • Tryptophan / physiology*


  • Serotonin
  • Tryptophan