Tryptophan depletion and depressive vulnerability

Francisco A. Moreno, Alan J. Gelenberg, George R. Heninger, Rebecca L. Potter, Katherine M. McKnight, John Allen, Aleksandra P. Phillips, Pedro L. Delgado

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


Background: Rapid and transient depletion of tryptophan (TRP) causes a brief depressive relapse in most patients successfully treated with and taking selective serotonin reuptake inhibitors, but little change in drug-free, symptomatic depressed patients. This study investigates the effects of TRP depletion in drug-free subjects in clinical remission from a prior major depressive episode (MDE). Methods: Twelve subjects with a prior MDE, currently in clinical remission and drug-free for at least 3 months (patients), and 12 healthy subjects without personal or family history of Axis I disorder (controls), received TRP depletion. The study was conducted in a double-blind, controlled [full (102-g) and quarter-strength (25 g) 15-amino acid drinks], crossover fashion. Behavioral ratings and plasma TRP levels were obtained prior to, during, and after testing. Results: All subjects experienced significant depletion of plasma TRP on both test-drinks, showing a significant dose-response relation. Healthy control subjects had minimal mood changes, but patients had a depressive response of greater magnitude. Conclusions: In the context of prior TRP depletion studies with antidepressant-treated, and drug-free symptomatic depressed patients, these results suggest that depression may be caused not by an abnormality of 5-HT function, but by dysfunction of other systems or brain regions modulated by 5-HT. Copyright (C) 1999 Society of Biological Psychiatry.

Original languageEnglish (US)
Pages (from-to)498-505
Number of pages8
JournalBiological Psychiatry
Issue number4
StatePublished - Aug 15 1999


  • Depletion
  • Depression
  • Prediction
  • Serotonin
  • Tryptophan
  • Vulnerability

ASJC Scopus subject areas

  • Biological Psychiatry


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