Effects of tryptophan depletion on brain potential correlates of episodic memory retrieval

Psychopharmacology (Berl). 2002 Apr;160(4):434-42. doi: 10.1007/s00213-001-0996-8. Epub 2002 Feb 7.


Rationale: Neuropsychological impairments in depressive illness may be secondary to proposed serotonergic abnormalities. Acute tryptophan depletion (ATD) in healthy subjects impairs episodic memory, but the mechanism of this is unclear.

Objectives: To examine the effects of ATD on the neural correlates of episodic memory retrieval in healthy subjects.

Methods: Fourteen healthy men were given an amino acid cocktail drink with or without tryptophan, in a double blind, crossover design. Event related potentials (ERPs) were recorded during a well-validated episodic memory task performed 5 h after drink ingestion. Subjects listened to words spoken in a male or female voice. At test, old and new words were presented visually; subjects judged whether words were old or new, and if old, the gender of the voice at study.

Results: ATD led to an 84+/-5% reduction in plasma free tryptophan concentrations, and significantly impaired episodic memory recall. ERP recordings demonstrated previously reported left parietal and right frontal "old/new" differences for ERPs to items associated with accurate episodic memory retrieval versus correctly rejected new items. ATD increased ERP voltage between 500 and 1400 ms post-stimulus particularly over posterior regions of the scalp, but there was no interaction with item type. Topographical analysis of the old/new difference revealed no significant treatment by site interaction.

Conclusions: ATD impairs episodic memory recall with no effect on the magnitude or topography of the neural correlates of retrieval in healthy subjects. This suggests that the effects of ATD on recall may reflect an impairment of memory encoding and/or consolidation.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Affect / drug effects
  • Affect / physiology
  • Analysis of Variance
  • Brain / drug effects
  • Brain / metabolism*
  • Cross-Over Studies
  • Double-Blind Method
  • Electroencephalography / drug effects
  • Evoked Potentials / drug effects
  • Evoked Potentials / physiology*
  • Female
  • Humans
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Tryptophan / administration & dosage
  • Tryptophan / blood
  • Tryptophan / metabolism*
  • Tryptophan / physiology


  • Tryptophan