Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy
Abstract
Cytokine therapy for cancer or viral diseases is accompanied by the development of depressive symptoms in a significant proportion of patients. Despite the increasing number of studies on the neurotoxic effects of cytokines, the mechanisms by which cytokines induce depressive symptoms remain largely unknown. In view of the relationship between neurotransmitter precursors and mood, the present study aimed at assessing the relationship between serum concentrations of the amino acids tryptophan and tyrosine, major precursors of serotonin and norepinephrine respectively, and depressive symptoms in cancer patients undergoing cytokine therapy. Sixteen cancer patients eligible to receive immunotherapy with interleukin-2 and/or interferon-alpha participated in the study. At baseline and after one week and one month of therapy, depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), and blood samples were collected for the determination of the large neutral amino acids (LNAA) (tryptophan, tyrosine, valine, leucine, isoleucine, phenylalanine) which compete for transport across the blood-brain barrier. Serum concentrations of tryptophan as well as the tryptophan/LNAA ratio significantly decreased between baseline, one week and one month of therapy. The development and severity of depressive symptoms, especially anorexia, pessimistic thoughts, suicidal ideation and loss of concentration were positively correlated with the magnitude of the decreases in tryptophan concentrations during treatment. These findings indicate that the development of depressive symptoms in patients undergoing cytokine therapy could be mediated by a reduced availability of the serotonin relevant amino acid precursor, tryptophan.
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Immunotherapy produces a pronounced reduction in plasma levels of tryptophan, which correlates with patients' depression scores 3 weeks into treatment.
“Immunotherapy alters the clinical biochemistry of patients; the most revealing sign is a pronounced reduction in plasma levels of tryptophan56, which correlates with the patients’ depression scores 3 weeks into the treatment.”
From From inflammation to sickness and depression: when the immune system subjugates the brain (2008) · cites this paper as [56]
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Self-citation
- Authors
- Capuron, L., Ravaud, A., Neveu, P. J., Miller, A. H., Maes, M., & Dantzer, R.
- Affiliations
- Inserm (FR)
- Institut Bergonié (FR)
- Emory University (US)
- Maastricht University (NL)
- Corresponding author
- Capuron, L
- Venue
- Molecular Psychiatry
- Published
- 2002-06-01
- Volume
- 7
- Issue
- 5
- Pages
- 468-473
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2137877753
- Cited by
- 473
- References
- 49
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 11 · 2023: 13 · 2022: 15 · 2021: 17 · 2020: 20 · 2019: 19 · 2018: 22 · 2017: 28 · 2016: 26 · 2015: 25 · 2014: 16 · 2013: 32 · 2012: 23
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Association pour la Recherche sur le Cancer
- Ligue Contre le Cancer
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Keywords
- tryptophan, depressive symptoms, cytokine therapy, cancer patients, interleukin-2, interferon-alpha, large neutral amino acids, serotonin precursor, anorexia, suicidal ideation, mood disorders
- MeSH terms
- Adult, Aged, Blood-Brain Barrier, Depressive Disorder, Female, Humans, Interleukin-2, Male, Middle Aged, Neoplasms, Regression Analysis, Time Factors, Tryptophan, Biomarkers, Cytokines, Interferon-alpha
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