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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]
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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
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Items 401–471 of 471
The Impact of Inflammation on Brain Function and Behavior in Rodent Models of Affective Disorders
Farzana, F., Renoir, T., & Hannan, A. J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811073-7.00005-2 · Cited by 3
Treatment of Depression in Medical Illness
Raison, C. L., Purselle, D. C., Capuron, L., & Miller, A. H. (2005) · Wiley eBooks · doi:10.1002/9783527619672.ch9 · Cited by 2
Self-citationBarnier, P. O. (2011) · Biblos-e Archivo (Universidad Autónoma de Madrid) · Cited by 2
Inflamed brains can trigger the blues, studies suggest
Sinha, G. (2004) · Nature Medicine · doi:10.1038/nm1004-1007b · Cited by 2
Kynurenine-An Old Pathway Retraced
Shader, R. I. (2006) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000231606.45402.fd · Cited by 2
“Decrease tryptophan concentrations have been noted in association with depressive symptomatology in patients with cancer treated with cytokine therapies.(3) Patients undergoing therapy with IFN-alpha for malignant melanoma had more episodes (45%) of secondary MDD than would be expected in any age and sex-matched contr…”
BackgroundBasic Concepts in Immunobiology
Turner, L., & Harrison, N. A. (2021) · Cambridge University Press eBooks · doi:10.1017/9781108539623.002 · Cited by 2
Li, L., Li, C., & Jia, L. (2021) · Journal of Chromatography A · doi:10.1016/j.chroma.2021.462638 · Cited by 1
Chronic C Hepatitis, Interferon and Psychiatric Disorders
Valerio, G., Apicella, E., DAlterio, E., Cecere, A. C., & Bellomo, A. (2013) · InTech eBooks · doi:10.5772/54748
“In fact, it has been demonstrated that, patients treated with IFN α, who develop depression, have lower blood concentra‐ tions of tryptophan [25,26].”
BackgroundPsychopharmacologic Treatment of Depression in Patients With Cancer: A 2013 Update
Strouse, T. B. (2013) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.11.4.450 · Cited by 1
Neuroscience, Molecular Medicine, and New Approaches to the Treatment of Depression and Anxiety
Heninger, G. R. (2005) · Elsevier eBooks · doi:10.1016/b978-012738903-5/50013-8 · Cited by 1
Walker, A. K., Dantzer, R., & Kelley, K. W. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4729-0_6 · Cited by 1
Self-citationYirmiya, D., Rimmerman, N., & Reshef, R. (2015) · Cited by 1
Murakami, Y., & Imamura, Y. (2018) · InTech eBooks · doi:10.5772/intechopen.71013 · Cited by 1
“Another clinical study with cancer patients has shown that immunotherapy with IFN-α significantly increases the severity of depressive symptoms, which is related to a depletion of serum 5-HT and induction of the catabolism of TRP to KYN [27].”
BackgroundCurrent Concepts of Chronic Pelvic Pain Syndrome
Горпинченко, І. І., & Нуріманов, К. Р. (2019) · Health of Man · doi:10.30841/2307-5090.4.2019.195158 · Cited by 1
depresión mayor en la diabetes
Hernández, H. C. (2019) · Entretextos (en línea, León, Gto.)/Entretextos · doi:10.59057/iberoleon.20075316.201932132 · Cited by 1
Molecular Pathogenesis for Schizophrenia and Major Depression
Müller, N., & Schwarz, M. (2008) · Springer eBooks · doi:10.1007/978-0-387-72573-4_36 · Cited by 1
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Pesserl, M. (2015) · ScholarWorks (Walden University) · Cited by 1
Brand, S. J. (2011) · Cited by 1
A clinical study exploring hip and knee osteoarthritis pain transmission using cerebrospinal fluid
Swift, A. (2012) · University of Birmingham Institutional Research Archive (University of Birmingham) · Cited by 1
Biological mechanisms of environmental stressors in psychiatry : the role of the immune system
Guloksuz, I. S. (2015) · Research Publications (Maastricht University) · doi:10.26481/dis.20151202ig · Cited by 1
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Lebedeva, K. A. (2017) · University Library - University of Saskatchewan (University of Saskatchewan) · Cited by 1
Suicide: An Immunological Disorder?Preprint
O'Connor, K. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3783063 · Cited by 1
Giraud, V., Rascle, N., & Ravaud, A. (2005) · Psycho-Oncologie · doi:10.1007/s10332-005-0085-z
Self-citationGuan, S. A. (2015) · eScholarship (California Digital Library)
Bezemer, G. (2012) · RePub (Erasmus University Rotterdam)
Schlegel, H.-M. (2008) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-7473
Pilmore, L. (2014)
Bertazzo, A., Comai, S., Cavalletto, L., Chemello, L., Luise, S., & Costa, C. V. L. (2007) · International Congress Series · doi:10.1016/j.ics.2007.07.008
Loftis, J. M., & Hauser, P. (2005) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.680
“Also, the putative IFN- -induced depletion of tryptophan and serotonin makes SSRIs a logical choice (Bonaccorso et al., 2002; Capuron et al., 2002).”
BackgroundNeumark, E. (2011) · Spectrum Research Repository (Concordia University)
From inflammation to sickness and depression: the cytokine connection
Dantzer, R., & Kelley, K. W. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511780868.014
Self-citationMetabolic-Inflammation Aspects of Depression and Cardiovascular Disease
Rosenblat, J. D., Kakar, R., & McIntyre, R. S. (2016) · Springer eBooks · doi:10.1007/978-3-319-32480-7_14
“Specifi cally, IL-2 and IFN directly increase the enzymatic activity of indolamine 2,3-dioxygenase (IDO) that in turn catalyzes the breakdown of tryptophan-to-tryptophan catabolites (TRYCATs), namely, kynurenine, kynurenic acid, and quinolinic acid (Dunn et al. 2005 ; Rosenblat et al. 2014 ).”
BackgroundInfluentialPhysical health and metabolic dysfunction in bipolar disorder
Rosenblat, J. D., Cha, D. S., Mansur, R. B., & McIntyre, R. S. (2016) · Cambridge University Press eBooks · doi:10.1017/cbo9781107477278.021
Aging and Microglial Activation in Neurodegenerative Diseases
Oyarzabal, E. A., Shih, Y. I., & Hong, J. (2016) · Oxidative stress in applied basic research and clinical practice · doi:10.1007/978-3-319-33486-8_7
Wu, Y., & Han, S. (2016) · Analytical chemistry, an Indian journal
Henry, C. J. (2011) · OhioLink ETD Center (Ohio Library and Information Network)
Immune response effect on dopamine production during Toxoplasma gondii infection
Alsaady, I. (2016) · White Rose eTheses Online (University of Leeds, The University of Sheffield, University of York)
Wong, A. P. (2010) · TSpace (University of Toronto)
The Inflammatory and Neuroanatomical Factors Involved in Post-stroke Depression
Bensimon, K. (2013) · TSpace (University of Toronto)
Bai, Y. (2006) · doi:10.31390/gradschool_theses.2840
“Altered monoamine metabolism (decreased norepinephrine, dopamine, and serotonin levels and activities) (29, 30), altered immune function (increased cytokine secretion) (31-34), an imbalance of cortisol, heredity, and external stressors and significant life changes (28) all contribute to the development of depression.”
BackgroundInfluentialCancer Immunotherapy: Friend or Foe of Mental Health?
Saghazadeh, A., & Rezaei, N. (2017) · Springer eBooks · doi:10.1007/978-3-319-64550-6_16
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Brooks, A. K. (2017) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
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Lodin, K. (2018) · Figshare
Kudinova, A. Y. (2018) · The Open Repository - Binghamton (Binghamton University)
Żylicz, Z. (2019) · Palliative Medicine in Practice · doi:10.5603/pmpi.2019.0010
“Depression induced by IFN-a treatment is associated with a change in serotonin metabolism caused by an increased activity of the indoleamine 2,3-dioxygenase enzyme, which metabolises tryptophan to kynurenine, and is subsequently metabolised to quinolinic acid [37], which reduces the availability of serotonin typical o…”
BackgroundMood Disorders in Patients with CNS Metastases
Chilcote, K. (2020) · Springer eBooks · doi:10.1007/978-3-030-42958-4_11
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Mota, C. M. D. (2020) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2020.tde-13042020-153828
Molecular basis of tryptophan metabolism disorders associated with depression
Wigner, P., Gałecki, P., & Śliwiński, T. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-817935-2.00019-2 · Cited by 1
Neurological Toxicities of Immunotherapy
Pandey, M. R., & Ernstoff, M. S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-67241-2.00020-3
Re: Personality and the Risk of Cancer
Murr, C. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djg092
Inflammatory Bases of Neuropsychiatric Symptom Domains: Mechanisms and Specificity
Aouizerate, B., Vancassel, S., Castanon, N., & Capuron, L. (2021) · Springer eBooks · doi:10.1007/978-3-030-71229-7_20
Self-citationThe Biological Mechanisms Underlying Major Depressive Disorder
Zonca, V. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819641-0.00114-6
Pierucci‐Lagha, A., Covault, J., Bonkovsky, H. L., Feinn, R., Abreu, C., Sterling, R. K., Fontana, R. J., & Kranzler, H. R. (2010) · Psychosomatics · doi:10.1016/s0033-3182(10)70674-5
Stressor and cytokine interactions : implications in depressive-like pathology
Gibb, J. (2011) · Carleton University's Institutional Repository (MacOdrum Library, Carleton University) · doi:10.22215/etd/2011-09658
Davis, M. P., Walsh, D., & Lagman, R. L. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.05.299
Roncalho, A. L. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2022.tde-12072022-152441
Hypothesis of neuroinflammation in depression
Dolfi, A., & Talasman, A.-A. (2017) · Romanian Journal of Psychiatry & Psychotherapy · doi:10.37897/rjpp.2017.4.5
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Trajano, I. P. (2024) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2024.tde-10062024-092642
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Askari, A., & Parmar, C. D. (2025) · Springer eBooks · doi:10.1007/978-981-96-5099-6_1
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Schmid, G. B. (2025) · Springer eBooks · doi:10.2991/978-3-662-70243-7_4
Liu, Y., Shen, J., Zhang, X., Ping, F., Qyu, K., & Shen, X. (2025) · Chinese Journal of Integrative Medicine · doi:10.1007/s11655-025-4211-4 · Cited by 1
Serotonergic system and its interaction with neuroinflammation
Andreetta, F. (2012) · University of Birmingham Institutional Research Archive (University of Birmingham)
Potential muscular doping effects of anti-depressants
Tutakhail, A. (2019) · theses.fr (ABES) · doi:10.70675/f3cbba2dza035z4ef0zaebbz68fe16432b48
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Huet, L. (2019) · theses.fr (ABES) · doi:10.70675/ff26d7c8z4c5fz4c86z9e6ezd8d843268447
Omari-mellal, G., Nacera, H., Aiouez, K., & Raache, R. (2026) · Biologica Nyssana · doi:10.46793/biolnyss.17.1.7m
Salibe, M. (2010) · Repositorio Digital Institucional de la Universidad de Buenos Aires (Universidad de Buenos Aires)
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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