Tryptophan depletion and depressive vulnerability

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

Research output: Contribution to journalArticle

92 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
Publication statusPublished - Aug 15 1999



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

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Moreno, F., Gelenberg, A. J., Heninger, G. R., Potter, R. L., McKnight, K. M., Allen, J. JB., ... Delgado, P. L. (1999). Tryptophan depletion and depressive vulnerability. Biological Psychiatry, 46(4), 498-505.