Interferon-alpha-induced changes in tryptophan metabolism: Relationship to depression and paroxetine treatment

Lucile Capuron, Gabriele Neurauter, Dominique L. Musselman, David H. Lawson, Charles B. Nemeroff, Dietmar Fuchs, Andrew H. Miller

Research output: Contribution to journalArticlepeer-review

394 Scopus citations


Background: Tryptophan (TRP) degradation into kynurenine (KYN) by the enzyme, indoleamine-2,3-dioxygenase, during immune activation may contribute to development of depressive symptoms during interferon (IFN)-α therapy. Methods: Twenty-six patients with malignant melanoma were randomly assigned in double-blind fashion to receive either placebo or paroxetine, beginning 2 weeks before IFN-α treatment and continuing for the first 12 weeks of IFN-α therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-α treatment, measurements of TRP, KYN, and neopterin (a marker of immune activation), were obtained, along with structured assessments of depression, anxiety, and neurotoxicity. Results: Regardless of antidepressant treatment status, all patients exhibited significant increases in KYN, neopterin, and the KYN/TRP ratio during IFN-α therapy. Among antidepressant-free patients, patients who developed major depression exhibited significantly greater increases in KYN and neopterin concentrations and more prolonged decreases in TRP concentrations than did nondepressed, antidepressant-free patients. Moreover, in antidepressant-free patients, decreases in TRP correlated with depressive, anxious, and cognitive symptoms, but not neurovegetative or somatic symptoms. No correlations were found between clinical and biological variables in antidepressant-treated patients. Conclusions: The results suggest that reduced TRP availability plays a role in IFN-α-induced depressive symptoms, and paroxetine, although not altering the KYN or neopterin response to IFN-α, attenuates the behavioral consequences of IFN-α-mediated TRP depletion.

Original languageEnglish (US)
Pages (from-to)906-914
Number of pages9
JournalBiological Psychiatry
Issue number9
StatePublished - Nov 1 2003
Externally publishedYes


  • Depressive symptoms
  • Indoleamine-2,3- dioxygenase
  • Interferon-alpha
  • Kynurenine
  • Neopterin
  • Tryptophan

ASJC Scopus subject areas

  • Biological Psychiatry


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