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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 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]
Citations
Cites
(1998) · The Journal of Clinical Psychiatry · Cited by 19,139
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962
The mini international neuropsychiatric interview
Lecrubier, Y., Sheehan, D. V., Hergueta, T., & Weiller, E. (1998) · European Psychiatry · doi:10.1016/s0924-9338(99)80239-9 · Cited by 5,899
Kirkwood, J. M., Strawderman, M. H., Ernstoff, M. S., Smith, T. J., Borden, E. C., & Blum, R. H. (1996) · Journal of Clinical Oncology · doi:10.1200/jco.1996.14.1.7 · Cited by 2,089
Cytokine-Associated Emotional and Cognitive Disturbances in Humans
Reichenberg, A., Yirmiya, R., Schuld, A., Kraus, T., Haack, M., Morag, A., & Pollmächer, T. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.5.445 · Cited by 1,365
Paroxetine for the prevention of depression induced by high-dose interferon alfa.
Musselman, D. L., Lawson, D. H., Gumnick, J. F., Manatunga, A. K., Penna, S., Goodkin, R. S., Greiner, K., Nemeroff, C. B., & Miller, A. H. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103293441303 · Cited by 1,120
Self-citationNégrier, S., Escudier, B. J., Lasset, C., Douillard, J., Savary, J., Chevreau, C., Ravaud, A., Mercatello, A., Pény, J., Mousseau, M., et al. (1998) · New England Journal of Medicine · doi:10.1056/nejm199804303381805 · Cited by 962
Self-citationPsychopharmacology: The Fourth Generation of Progress
Kramlinger, K. G. (1995) · Mayo Clinic Proceedings · doi:10.4065/70.10.1021-a · Cited by 779
Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation?
Mellor, A. L., & Munn, D. H. (1999) · Immunology Today · doi:10.1016/s0167-5699(99)01520-0 · Cited by 653
Maes, M., Meltzer, H. Y., Bosmans, E., Bergmans, R., Vandoolaeghe, E., Ranjan, R., & Desnyder, R. (1995) · Journal of Affective Disorders · doi:10.1016/0165-0327(95)00028-l · Cited by 622
Self-citationThe Neuropsychiatric Effects of Treatment with Interleukin-2 and Lymphokine-Activated Killer Cells
Denicoff, K. D., RUBINOW, D. R., PAPA, M. Z., SIMPSON, C., SEIPP, C. A., LOTZE, M. T., Chang, A. E., ROSENSTEIN, D., & Rosenberg, S. A. (1987) · Annals of Internal Medicine · doi:10.7326/0003-4819-107-2-293 · Cited by 456
Human macrophages convert l -tryptophan into the neurotoxin quinolinic acid
Heyes, M. P., Saito, K., & Markey, S. P. (1992) · Biochemical Journal · doi:10.1042/bj2830633 · Cited by 451
Relapse of depression after rapid depletion of tryptophan
Smith, K., Fairburn, C. G., & Cowen, P. J. (1997) · The Lancet · doi:10.1016/s0140-6736(96)07044-4 · Cited by 428
Turnell, D. C., & Cooper, J. D. (1982) · Clinical Chemistry · doi:10.1093/clinchem/28.3.527 · Cited by 363
THE BIOLOGY OF IMPULSIVITY AND SUICIDALITY
Oquendo, M. A., & Mann, J. J. (2000) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70140-4 · Cited by 325
Effects of Cytokines on Cerebral Neurotransmission: Comparison with the Effects of Stress
Dunn, A. J., Wang, J., & Ando, T. (1999) · Advances in Experimental Medicine and Biology · doi:10.1007/978-0-585-37970-8_8 · Cited by 316
Anisman, H., Ravindran, A. V., Griffiths, J., & Merali, Z. (1999) · Molecular Psychiatry · doi:10.1038/sj.mp.4000436 · Cited by 310
Tryptophan depletion in normal volunteers produces selective impairments in learning and memory
Park, S. B., Coull, J. T., McShane, R. H., Young, A. H., Sahakian, B. J., Robbins, T. W., & Cowen, P. J. (1994) · Neuropharmacology · doi:10.1016/0028-3908(94)90089-2 · Cited by 310
Capuron, L., Ravaud, A., & Dantzer, R. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.10.2143 · Cited by 293
Self-citationDelgado, P. L. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950110025005 · Cited by 289
Cytokines, Stress, and Depression
Dantzer, R., Wollman, E. E., Vitković, L., & Yirmiya, R. (1999) · Advances in experimental medicine and biology · doi:10.1007/978-0-585-37970-8_17 · Cited by 220
Self-citationClinical and Physiological Consequences of Rapid Tryptophan Depletion
Moore, P. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00161-5 · Cited by 210
Fuchs, D., Möller, A. A., Reibnegger, G. J., Stöckle, E., Werner, E. R., & WACHTER, H. (1990) · PubMed · Cited by 203
Kammula, U. S., White, D. E., & Rosenberg, S. A. (1998) · Cancer · doi:10.1002/(sici)1097-0142(19980815)83:4 · Cited by 200
Progress in Tryptophan and Serotonin Research
(1984) · De Gruyter eBooks · doi:10.1515/9783111641546 · Cited by 185
Implications of Interferon-Induced Tryptophan Catabolism in Cancer, Autoimmune Diseases and Aids
Brown, R. R., Ozaki, Y., Datta, S. P., Borden, E. C., Sondel, P. M., & Malone, D. G. (1991) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-5952-4_39 · Cited by 174
Song, C., Merali, Z., & Anisman, H. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00271-1 · Cited by 172
Capuron, L., & Ravaud, A. (1999) · New England Journal of Medicine · doi:10.1056/nejm199904293401716 · Cited by 169
Self-citationSleijfer, D. T., Janssen, R. A., Buter, J., de Vries, E. G. E., Willemse, P. H. B., & Mulder, N. H. (1992) · Journal of Clinical Oncology · doi:10.1200/jco.1992.10.7.1119 · Cited by 169
Carlin, J. M., Borden, E. C., Sondel, P., & Byrne, G. I. (1987) · Journal of Immunology · doi:10.4049/jimmunol.139.7.2414 · Cited by 160
Maes, M. H. J., Meltzer, H. Y., Scharpé, S., Bosmans, E., Suy, E., Meester, I. D., Calabrese, J. R., & Cosyns, P. R. (1993) · Psychiatry Research · doi:10.1016/0165-1781(93)90102-m · Cited by 158
Self-citationFuchs, D., Möller, A. A., Reibnegger, G. J., Werner, E. R., Werner‐Felmayer, G., Dierich, M. P., & WACHTER, H. (1991) · Immunology Letters · doi:10.1016/0165-2478(91)90005-u · Cited by 145
Linthorst, A. C. E., Flachskamm, C., Holsboer, F., & Reul, J. M. H. M. (1994) · Endocrinology · doi:10.1210/endo.135.2.7518383 · Cited by 145
Depression From Interferon Therapy in Patients With Hepatitis C
Miyaoka, H., Otsubo, T., Kamijima, K., Ishii, M., ONUKI, M., & Mitamura, K. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.7.1120 · Cited by 135
Smith, K., Morris, J. S., Friston, K. J., Cowen, P. J., & Dolan, R. J. (1999) · The British Journal of Psychiatry · doi:10.1192/bjp.174.6.525 · Cited by 134
Neumeister, A. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830140043008 · Cited by 134
Däubener, W., & MacKenzie, C. R. (1999) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-4709-9_64 · Cited by 121
Cytokines and brain function: relevance to interferon-alpha-induced mood and cognitive changes.
Licinio, J., Kling, M. A., & Hauser, P. (1998) · PubMed · Cited by 118
Plasma Tryptophan and Five Other Amino Acids in Depressed and Normal Subjects
DeMyer, M. K. (1981) · Archives of General Psychiatry · doi:10.1001/archpsyc.1981.01780310042003 · Cited by 118
Maes, M. H. J., Bonaccorso, S., Marino, V., Puzella, A., Pasquini, M., Biondi, M., Artini, M., Almerighi, C., & Meltzer, H. Y. (2001) · Molecular Psychiatry · doi:10.1038/sj.mp.4000872 · Cited by 108
Self-citationKamata, M. (2000) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(99)00067-x · Cited by 105
Cytokines and anorexia: a brief overview.
Plata‐Saláman, C. R. (1998) · PubMed · Cited by 101
Brown, R. R., Lee, C. M., Kohler, P. C., Hank, J. A., Storer, B. E., & Sondel, P. M. (1989) · PubMed · Cited by 81
Saito, K., Markey, S. P., & Heyes, M. P. (1991) · Brain Research · doi:10.1016/0006-8993(91)91171-v · Cited by 81
Maes, M. H. J. (1996) · Neuropsychopharmacology · doi:10.1016/0893-133x(95)00181-c · Cited by 72
Self-citationUse of neurotransmitter precursors for treatment of depression.
Meyers, S. (2000) · PubMed · Cited by 69
Cytokines, Stress, and Depression
Dantzer, R., Yirmiya, R., & Wollman, E. E. (1999) · Advances in experimental medicine and biology · doi:10.1007/b102345 · Cited by 51
Self-citationLucca, A., Lucini, V., Catalano, M., Alfano, M., & Smeraldi, E. (2008) · Neuropsychobiology · doi:10.1159/000119071 · Cited by 47
Neuropsychiatric symptoms during treatment with interleukin-2 and interferon-α
Fenner, M. H., Hänninen, E. L., Kirchner, H., POLIWODA, H., & Atzpodien, J. (1993) · The Lancet · doi:10.1016/0140-6736(93)90172-d · Cited by 13
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Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
“A role for tryptophan? Immunotherapy alters the clinical biochemistry of patients; the most revealing sign is a pronounced reduction in plasma levels of tryptopha”
BackgroundSelf-citationNewgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., Haqq, A. M., Shah, S. H., Arlotto, M., Slentz, C. A., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.02.002 · Cited by 3,165
“…of tryptophan to its large neutral amino acid competitors (sum of phenylalanine + leucine + isoleucine + valine + tyrosine), the so-called ‘‘tryptophan ratio,’’ have been related to depression (Chevalier et al., 2005; Capuron et al., 2002) and obesity (Ashley et al., 1985; Breum et al., 2003).”
BackgroundCytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009
“mental health clinics) is that IFN-α-induced depression: (i) is responsive to treatment with standard antidepressant therapy [61]; (ii) is associated with alterations in serotonin metabolism, in part related to increased activity of the metabolic enzyme indoleamine 2,3, dioxygenase, which degrades tryptophan to kynure…”
BackgroundSelf-citationThe Bidirectional Relationship of Depression and Inflammation: Double Trouble
Beurel, E., Toups, M., & Nemeroff, C. B. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.002 · Cited by 2,136
Metadata
- 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 (medical) › 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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