Cited by 473Tryptophan and brain disordersTreatment of Major DepressionCancer survivorship and care

The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.

Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy

Capuron, L, Ravaud, A, Neveu, P J, Miller, A H, Maes, M, Dantzer, R·2002·Molecular Psychiatry

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1038/sj.mp.4000995

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Untitled work
(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
Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684.
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-citation
Recombinant Human Interleukin-2, Recombinant Human Interferon Alfa-2a, or Both in Metastatic Renal-Cell Carcinoma
Négrier, 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-citation
Psychopharmacology: 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
Increased Plasma Concentrations of Interleukin-6, Soluble Interleukin-6, Soluble Interleukin-2 and Transferrin Receptor in Major Depression
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-citation

Flagged first, then by citations

Show all 49 references

Sorted by citations

Items 301–400 of 471

p38 MAP kinase activation does not stimulate serotonin transport in rat brain: Implications for sickness behaviour mechanisms
Andreetta, F., Barnes, N. M., Wren, P. B., & Carboni, L. (2013) · Life Sciences · doi:10.1016/j.lfs.2013.05.014 · Cited by 14
“In agreement, an association between reduced TRP blood concentration and the development and intensity of mood impairment symptoms was also highlighted in malignant melanoma patients treated with IFNα and IL-2 (Capuron et al., 2002).”
Background
Cancer fatigue: a review for psychiatrists
Levy, M. R. (2008) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2008.01.004 · Cited by 15
“This may occur via changes in the metabolic enzyme indoleamine2,3-dioxygenase, which is responsible for the breakdown of tryptophan to kynurenine [51–53].”
Background
Psychiatric Disorders - Worldwide Advances
Uehara, T. (2011) · InTech eBooks · doi:10.5772/1289 · Cited by 16
Pilot investigation into the sickness response to influenza vaccination in adults: Effect of depression and anxiety
Harper, J. A., South, C. C., Trivedi, M. H., & Toups, M. S. P. (2017) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2017.07.005 · Cited by 16
“Numerous authors have noted the similarity between sickness behaviors and Major Depressive Disorder (MDD) as well as a strong epidemiological association of inflammatory disorders with MDD and presence of increased inflammatory markers in MDD patients even in the absence of diagnosed inflammatory disorders (9-12).”
Hepatitis C in patients with psychiatric disease and substance abuse: Screening strategies and comanagement models of care
Loftis, J. M., & Hauser, P. (2003) · Current Hepatology Reports · doi:10.1007/s11901-003-0002-5 · Cited by 15
“Increased depression following IFN therapy is related to the depletion of serum serotonin [26], decreases in serum tryptophan [ 27 ], and increases in the catabolism of tryptophan [26,28].”
Background
Comparison between sub-chronic and chronic sleep deprivation-induced behavioral and neuroimmunological abnormalities in mice: Focusing on glial cell phenotype polarization
Niazi, N. U. K., Huang, C.-Y., Yang, Z., Zhang, Y., & Song, C. (2024) · Behavioural Brain Research · doi:10.1016/j.bbr.2024.115067 · Cited by 17
Pegylated interferon-α2b treatment in melanoma patients: influence on amino acids, 5-hydroxyindolacetic acid and pteridine plasma concentrations
Gool, A. R. V., van Ojik, H. H., Kruit, W. H. J., Bannink, M., Mulder, P. G. H., Eggermont, A. M. M., Stoter, G., & Fekkes, D. (2004) · Anti-Cancer Drugs · doi:10.1097/01.cad.0000132230.51759.8d · Cited by 14
Inflammation and Depression: the Neuroimmune Connection
Toups, M. S. P. (2018) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-018-0157-x · Cited by 13
Antidepressant-like effects of the xanthine oxidase enzyme inhibitor allopurinol in rats. A comparison with fluoxetine
Özgür, B. G., Aksu, H., Birincioğlu, M., & Dost, T. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.09.016 · Cited by 14
“Indole amine 2,3-dioxygenase activity is increased by the activation of the immune system (Capuron et al., 2002).”
Background
Immunomodulatory properties of cacao extracts – potential consequences for medical applications
Becker, K., Geisler, S., Ueberall, F., Fuchs, D., & Gostner, J. M. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00154 · Cited by 14
“Reasons can be either the poor or impaired future perspectives, but also the metabolic changes that are associated with diseases (Capuron et al., 2002; Widner et al., 2002).”
Background
Decreased immobility in swimming test by homologous interferon-α in mice accompanied with increased cerebral tryptophan level and serotonin turnover
Wang, J., Dunn, A. J., Roberts, A. J., & Zhang, H. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.01.050 · Cited by 14
Systemic immune changes associated with adjuvant interferon-α2b-therapy in stage III melanoma patients
Chevolet, I., Schreuer, M. S., Speeckaert, R., Neyns, B., Hoorens, I., van Geel, N., Krüse, V., Hennart, B., Allorge, D., Gele, M. V., et al. (2015) · Melanoma Research · doi:10.1097/cmr.0000000000000171 · Cited by 14
Striatal microinjections of interleukin-2 and rat behaviour in the elevated plus-maze
Pawlak, C. R., & Schwarting, R. K. W. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.10.011 · Cited by 14
Time-dependent effects of striatal interleukin-2 on open field behaviour in rats
Karrenbauer, B. D., Ho, Y., Ludwig, V., Löhn, J., Spanagel, R., Schwarting, R. K. W., & Pawlak, C. R. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.12.003 · Cited by 14
“Even more, IL-2 which is known through its application in cancer therapy (Waldmann, 2006), evokes various negative side-effects of emotional and motivational affect during treatment, for example, increasing depressive-like symptoms (Anisman et al., 2005; Capuron et al., 2002).”
Background
Cancer Fatigue: A Neurobiological Review for Psychiatrists
Levy, M. R. (2008) · Psychosomatics · doi:10.1176/appi.psy.49.4.283 · Cited by 13
The Pharmacokinetic-Pharmacodynamic Model of Azithromycin for Lipopolysaccharide-Induced Depressive-Like Behavior in Mice
Hao, K., Qu, Q., Hao, H., Wang, G., Chen, Y., Liang, Y. L., & Xie, L. Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054981 · Cited by 13
“In recent investigation, it has been suggested that inflammation-induced IDO activation resulted in an accumulation of tryptophan metabolite, KYN, ultimately leading to the development of depression [38].”
Background
Cytokines and Sickness Behavior
Dantzer, R. (2003) · Neurobiological foundation of aberrant behaviors · doi:10.1007/978-1-4615-0323-1_7 · Cited by 13
Self-citation
Inflammation, sickness behaviour and depression
Dantzer, R., Castanon, N., Lestage, J., Moreau, M. M., & Capuron, L. (2006) · Cambridge University Press eBooks · doi:10.1017/cbo9780511544293.013 · Cited by 12
Self-citation
Techniques for Measurement of Serotonin: Implications in Neuropsychiatric Disorders and Advances in Absolute Value Recording Methods
Cabrera, J. M. R., Oesterle, T., Rusheen, A. E., Goyal, A., Scheitler, K. M., Mandybur, I., Blaha, C. D., Bennet, K. E., Heien, M. L., Jang, D. P., et al. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00618 · Cited by 14
Exploring environmental exposomes and the gut-brain nexus: Unveiling the impact of pesticide exposure
Khoo, S. C., Zhang, N., Luang‐In, V., Goh, M. S., Sonne, C., & Ling, N. (2024) · Environmental Research · doi:10.1016/j.envres.2024.118441 · Cited by 13
Chronic Unpredictable Stress Alters Brain Tryptophan Metabolism and Impairs Working Memory in Mice without Causing Depression-Like Behaviour
O’Connor, J. C., Porter, G. A., & O’Connor, J. C. (2021) · Neurology and Neurobiology · doi:10.31487/j.nnb.2021.03.03 · Cited by 11
“03 Volume 4(3): 8-10 It has been hypothesized that inflammation-induced depression is driven by a reduction of tryptophan in the brain due to increased kynurenine metabolism, thus limiting the tryptophan supply available for serotonin synthesis [43-46].”
Background
Depression trajectories and cytokines in schizophrenia spectrum disorders - A longitudinal observational study
Hoprekstad, G. E., Kjelby, E., Gjestad, R., Fathian, F., Larsen, T. K., Reitan, S. K., Rettenbacher, M. A., Torsvik, A., Skrede, S., Johnsen, E., et al. (2023) · Schizophrenia Research · doi:10.1016/j.schres.2022.12.049 · Cited by 13
“Accordingly, administration of the pro-inflammatory IL-2 and IFN-α cytokines as part of a medical treatment for hepatitis or cancer has been associated with a rapid development of depressive symptoms (Bonaccorso et al., 2002; Capuron et al., 2002).”
Background
Kynurenine pathway metabolites selectively associate with impaired associative memory function in depression
Chirico, M., Custer, J., Shoyombo, I., Cooper, C. M., Meldrum, S., Dantzer, R., Trivedi, M. H., Rathouz, P. J., & Toups, M. S. P. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100126 · Cited by 12
“Activation of KP is predictive of the development of depression in patients undergoing inflammatory cytokine therapies (Capuron et al., 2002; Dantzer et al., 2008) and increased ratios of KYN/TRP and QUIN/KYNA are associated with depression (Reus et al.”
BackgroundSelf-citation
Metabolic Pathways Associated With Psychoneurological Symptoms in Children With Cancer Receiving Chemotherapy
Bai, J., Withycombe, J. S., & Eldridge, R. C. (2022) · Biological Research For Nursing · doi:10.1177/10998004211069619 · Cited by 12
“A reduced tryptophan and increased kynurenine/tryptophan ratio were associated with an increased burden of pain, fatigue, anxiety, depression (Capuron et al., 2002; Lanser et al., 2020), as well as a lower quality of life (Huang et al., 2002; Schroecksnadel et al., 2007).”
Background
High sensitivity C reactive protein, fibrinogen levels and the onset of major depressive disorder in post-acute coronary syndrome
Lafitte, M., Tastet, S., Perez, P., Serisé, M.-A., Grandoulier, A. A., Aouizerate, B., Sibon, I., Capuron, L., & Couffinhal, T. (2015) · BMC Cardiovascular Disorders · doi:10.1186/s12872-015-0015-3 · Cited by 11
“MDD is associated with an increased level of markers of inflammation and can be induced by pro-inflammatory treatment or cytokine therapy in medically ill patients [12-18].”
BackgroundSelf-citation
Possible changes of New-Generation inflammation markers with occupational lead exposure
Si̇pahi̇, H., Girgin, G., Palabıyık, Ş. S., Tutkun, E., Yilmaz, O. H., & Baydar, T. (2017) · Journal of Occupational Health · doi:10.1539/joh.16-0273-oa · Cited by 12
An Overview and Proposed Research Framework for Studying Co-Occurring Mental- and Physical-Health Dysfunction
Hagerty, S. L., Ellingson, J. M., Helmuth, T. B., Bidwell, L. C., Hutchison, K. E., & Bryan, A. D. (2019) · Perspectives on Psychological Science · doi:10.1177/1745691619827010 · Cited by 12
“, interferon a and interleukin 2) and cognitive dysfunction following immunotherapies (Capuron et al., 2002).”
Background
Association between peripheral plasma cytokine levels and suicidal ideation in first-episode, drug-naïve major depressive disorder
Tian, X. S., Dong, Y., Yuan, J.-Y., Gao, Y. H., Zhang, C., Li, M., & Li, J. (2024) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2024.107042 · Cited by 11
Depression, stress, and tryptophan metabolism through the kynurenine pathway: treatment strategies from the perspective of Chinese herbal medicine
Li, W., Yang, L., Chen, H., Miao, J., Wang, Y., Zhou, C., Chen, Y., Kong, Z., Shen, C., Wu, J., et al. (2024) · Metabolic Brain Disease · doi:10.1007/s11011-024-01461-1 · Cited by 13
“This enzyme is induced by pro - inflammatory cytokines, and when IDO is activated under chronic inflammatory conditions, its activity level is corre - lated with the intensity of depressive symptoms (Capuron et al. 2002).”
Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies
Kositsyn, Y. M., de Abreu, M. S., Kolesnikova, T. O., Lagunin, A. A., Poroikov, V., Harutyunyan, H. S., Yenkoyan, K. B., & Kalueff, A. V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119482 · Cited by 11
Animal Models for Depression Associated with HIV-1 Infection
Barreto, I. C. G., Viegas, P. D. B., Ziff, E. B., & Konkiewitz, E. C. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9518-9 · Cited by 11
“Capuron and colleagues reported that depression elicited by IFN-α therapy was associated with activation of the KYN pathway (Capuron et al. 2002).”
Background
Stress, Negative Emotions, and Inflammation
Gouin, J., Hantsoo, L. V., & Kiecolt‐Glaser, J. K. (2011) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780195342161.013.0054 · Cited by 14
Changes in the tryptophan-kynurenine axis in association to therapeutic response in clinically depressed patients undergoing psychiatric rehabilitation
Reininghaus, B., Riedrich, K., Dalkner, N., Bengesser, S., Birner, A., Platzer, M., Hamm, C., Gostner, J. M., Fuchs, D., & Reininghaus, E. Z. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.04.029 · Cited by 11
Sertoli cell therapy: A novel possible treatment strategy for treatment-resistant major depressive disorder
Loftis, J. M. (2011) · Medical Hypotheses · doi:10.1016/j.mehy.2011.03.017 · Cited by 11
Interferon-alpha-induced psychiatric side effects in patients with chronic viral hepatitis: a prospective, observational, controlled study
Orrù, M. G., Baita, A., Sitzia, R., Costa, A., Muntoni, E., Landau, S., Chessa, L., Farci, M. G., Carpiniello, B., & Pariante, C. M. (2005) · Epidemiologia e Psichiatria Sociale · doi:10.1017/s1121189x00006394 · Cited by 11
Escitalopram or novel herbal treatments differentially alter cytokine and behavioral responses to immune challenge
Avitsur, R., Paley, S., Franko, M., Wolff, N., Eyal, N., & Doron, R. (2017) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2017.05.020 · Cited by 13
“In patients treated chronically with cytokines, behavioral symptoms of sickness appear prior to symptoms of depression (Capuron et al., 2002).”
Interferon, tryptophan and depression
Fekkes, D., & Gool, A. R. V. (2003) · Acta Neuropsychiatrica · doi:10.1034/j.1601-5215.2003.00007.x · Cited by 11
Macromolecules and Antibody-Based Drugs
Su, X., & Yao, S. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-3266-5_20 · Cited by 11
The Gut Microbiota and Major Depressive Disorder: Current Understanding and Novel Therapeutic Strategies
Bahmani, M., Mehrtabar, S., Jafarizadeh, A., Zoghi, S., Heravi, F. S., Abbasi, A., Sanaie, S., Rahnemayan, S., & Leylabadlo, H. E. (2024) · Current Pharmaceutical Biotechnology · doi:10.2174/0113892010281892240116081031 · Cited by 10
Anhedonia and increased evoked immune response
Kudinova, A. Y., Gano, A., James, K. M., Lawlor, C., Terrence Deak, B., & Gibb, B. E. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100090 · Cited by 10
“In addition, individuals suffering from chronic and acute inflammatory conditions demonstrate increased levels of inflammatory markers and depressive symptoms (Capuron et al., 2002; Musselman et al., 2001; Owen et al., 2001).”
Background
Serum Activity of Prolyl Endopeptidase, but Not of Dipeptidyl Peptidase IV, Is Decreased by Immunotherapy with IFN- α in High-Risk Melanoma Patients
Gool, A. R. V., van Ojik, H. H., Kruit, W. H. J., Mulder, P. G. H., Fekkes, D., Bannink, M., Scharpé, S., Stoter, G., Eggermont, A. M. M., Maes, M. H. J., et al. (2004) · Journal of Interferon & Cytokine Research · doi:10.1089/1079990041535629 · Cited by 10
Self-citation
Role of Inflammation in Psychiatric Disease
Raison, C. L., Rook, G. A. W., Miller, A. H., & Begay, T. K. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-398270-4.00026-4 · Cited by 10
Self-citation
The Production and Effects of Cytokines Depend on Brain Lateralization
Neveu, P. J. (2008) · Neuroimmune biology · doi:10.1016/s1567-7443(07)10026-0 · Cited by 10
Self-citation
Psychiatric Side Effects and Fluctuations in Serotonergic Parameters in the Treatment of Chronic Hepatitis C Infection
Bezemer, G., Gool, A. R. V., Fekkes, D., Vrolijk, J., Hansen, B. E., Janssen, H. L. A., & de Knegt, R. J. (2012) · Neuropsychobiology · doi:10.1159/000330585 · Cited by 9
Circadian arrhythmia dysregulates emotional behaviors in aged Siberian hamsters
Prendergast, B. J., Onishi, K. G., Patel, P. N., & Stevenson, T. J. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.12.010 · Cited by 9
Role of metabolic dysfunction in treatment resistance of major depressive disorder
Toups, M. S., & Trivedi, M. H. (2011) · Neuropsychiatry · doi:10.2217/npy.11.49 · Cited by 9
Serum Serotonin Levels are Associated with Antiviral Therapy Outcomes in Patients with Chronic Hepatitis C
Loftis, J. M., Morasco, B. J., Menasco, D., Fuchs, D., Strater, M., & Hauser, P. (2013) · The Open Infectious Diseases Journal · doi:10.2174/1874279301004010132 · Cited by 9
“Peripheral levels of serotonin and changes in tryptophan have been studied and were hypothesized to play a role in the etiology of IFN- -induced depression [26, 27], but serotonin has not been investigated in regards to viral clearance or liver function in patients with chronic HCV infection.”
Depression bei körperlichen Erkrankungen
Arolt, V., & Rothermundt, M. (2004) · Steinkopff eBooks · doi:10.1007/978-3-662-12845-9_19 · Cited by 9
Optimum operational conditions for chiral separation of tryptophan enatiomers using ligand exchange liquid chromatography
Yan, H., & Row, K. H. (2007) · Biotechnology and Bioprocess Engineering · doi:10.1007/bf02931098 · Cited by 9
Cognitive and Affective Symptoms Experienced by Cancer Patients Receiving High-Dose Intravenous Interleukin 2 Therapy
Mann, T. K., Dail, R. B., & Bailey, D. E. (2015) · Cancer Nursing · doi:10.1097/ncc.0000000000000317 · Cited by 7
“Only 2 studies evaluated affective symptoms, and sample sizes for these studies were small, ranging from 16 to 20 participants.(23,26) There was a lack of standardization when assessing and screening for cognitive and affective symptoms in the high-dose IL-2 population.”
BackgroundMethodResultInfluential
Co-infection with HIV associated with reduced vulnerability to symptoms of depression during antiviral treatment for hepatitis C
Fialho, R., Pereira, M., Harrison, N. A., Rusted, J. M., & Whale, R. (2017) · Psychiatry Research · doi:10.1016/j.psychres.2017.03.049 · Cited by 8
“In this context, and considering this biphasic model of depression, it was found that neurovegetative symptoms tend to develop early and depressive-cognitive symptoms tend to occur later (Capuron et al., 2002a, 2002b).”
Novel Therapeutic Targets for Major Depressive Disorder
Lazar, M. A., & McIntyre, R. S. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813333-0.00034-2 · Cited by 9
Effects of stress on endophenotypes of suicide across species: A role for ketamine in risk mitigation
Lamontagne, S. J., Ballard, E. D., & Zarate, C. A. (2022) · Neurobiology of Stress · doi:10.1016/j.ynstr.2022.100450 · Cited by 10
“In these studies, SERT knockout rodents showed increased depressive phenotypes following ELS compared to their wildtype counterparts (e.g., Carola et al., 2008), but the literature is very mixed (for a comprehensive review, see Houwing et al., 2017).”
Background
Indoleamine 2, 3-dioxygenase is responsible for low stress tolerance after intracerebral hemorrhage
Ohnishi, M., Akagi, M., Kotsuki, M., Yonemura, S., Aokawa, H., Yamashita-Ibara, M., Yokofujita, O., Maehara, S., Hata, T., & Inoue, A. (2023) · PLoS ONE · doi:10.1371/journal.pone.0273037 · Cited by 9
“For example, one potential role of IDO that has been suggested for a long time is the involvement in neuropsychiatric symptoms during interferon (IFN) therapy [4, 5].”
Background
The Cytokines and Depression Hypothesis: An Evaluation
Dunn, A. J. (2008) · Neuroimmune biology · doi:10.1016/s1567-7443(07)10023-5 · Cited by 8
Inflammation in Suicidality: Implications for Novel Treatment Options
Janelidze, S., & Brundin, L. (2013) · Modern trends in psychiatry · doi:10.1159/000346085 · Cited by 8
Values of Cytokines and Tryptophan Metabolites over a 12 Weeks Time Course in Patients with Depression and Somatoform Disorder
Krause, D., Kirnich, V. B., Stapf, T. M., Hennings, A., Riemer, S., Riedel, M. J., Schmidmaier, R., Gil, F. P., Rief, W., & Schwarz, M. (2019) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2019.17.1.34 · Cited by 7
Bipolar Disorder and Substance Abuse
Swann, A. C. (2005) · Journal of Dual Diagnosis · doi:10.1300/j374v01n03_03 · Cited by 8
Kynurenine pathway dysregulation in major depressive disorder: the convergence of excitotoxicity, neuroinflammation, and oxidative stress
O’Regan, G., Plummer, Z., Christie, B. R., Shultz, S. R., & Allen, J. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03717-2 · Cited by 11
“Similarly, TRP levels, which were decreased in cancer patients receiving treatment with IL-2 and IFN-α, significantly correlated with the emergence of depressive symptoms [96].”
HTR1A, TPH2, and 5-HTTLPR Polymorphisms and Their Impact on the Severity of Depressive Symptoms and on the Concentration of Tryptophan Catabolites during Hepatitis C Treatment with Pegylated Interferon-α2a and Oral Ribavirin (PEG-IFN-α2a/RBV)
Pawłowski, T., Małyszczak, K., Pawlak, D., Inglot, M., Zalewska, M., Grzywacz, A., Radkowski, M., Laskus, T., Janocha‐Litwin, J., & Frydecka, D. (2023) · Cells · doi:10.3390/cells12060970 · Cited by 7
“(cancer patients undergoing cytokine therapy) [55] and Pawlowski et al.”
Background
Evaluation of the effect of soybean diet on interferon-α-induced depression in male mice.
Fashi, Y. A., Mesripour, A., & Hajhashemi, V. (2017) · Europe PMC (PubMed Central) · doi:10.22038/ajp.2017.20914.1793 · Cited by 7
“In patients undergoing cytokine therapy, a reduction in tryptophan availability, the precursor of serotonin, maybe the underlying cause for the development of depressive symptoms (Capuron et al., 2002b).”
Background
Low plasma tryptophan in carcinoid patients is associated with increased urinary cortisol excretion
Tanke, M. A. C., Kema, I. P., Dijck-Brouwer, J., Doornbos, B., de Vries, E. G. E., & Korf, J. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.07.005 · Cited by 7
“Chronic depletion of tryptophan as observed in somatic diseases coincides with an increased risk of depression, irritability and aggression (Capuron et al., 2002; Russo et al., 2004, 2005).”
Acute administration of ibuprofen increases serum concentration of the neuroprotective kynurenine pathway metabolite, kynurenic acid: a pilot randomized, placebo-controlled, crossover study
Savitz, J. B., Ford, B. N., Kuplicki, R., Khalsa, S. S., Teague, T. K., & Paulus, M. P. (2022) · Psychopharmacology · doi:10.1007/s00213-022-06263-w · Cited by 7
“down of TRP into kynurenine at the expense of serotonin (Capuron et al. 2002; Lapin and Oxenkrug 1969; Widner et al. 2002).”
Background
Rôles des facteurs antiviraux cellulaires et de l’interleukine-6 dans les propriétés anti-VIH de l’IFN-tau dans des macrophages humains
Manéglier, B., Rogez‐Kreuz, C., Dereuddre‐Bosquet, N., Martal, J., Devillier, P., Dormont, D., & Clayette, P. (2008) · Pathologie Biologie · doi:10.1016/j.patbio.2008.06.002 · Cited by 6
Efficacy of Yoga for COVID-19 Stress Prophylaxis
Mitra, S., Mitra, M., Nandi, P., Pandey, M., Chakrabarty, M., Saha, M., & Nandi, D. K. (2023) · Journal of Physical Activity and Health · doi:10.1123/jpah.2023-0035 · Cited by 6
C-reactive protein in midlife is associated with depressive symptoms two decades later among men with coronary heart disease
Ravona‐Springer, R., Lutski, M., Beeri, M. S., Goldbourt, U., & Tanné, D. (2019) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2019.1695284 · Cited by 6
“Potential underlying mechanisms for the association of CRP levels in midlife with late life depressive symptoms include the effect of cytokines on monoamine levels [43], the hypothalamo-pituitaly-adrenal axis [44] as well as brain vasculature [45], all of which are consistently implicated in old age depression [46].”
Background
Inflammation and treatment strategies for suicidal behavior
Behera, C., Gupta, S., Shelton, R. C., & Dwivedi, Y. (2026) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2026.2659772 · Cited by 5
“Clinical studies demonstrate that immune activation also alters tryptophan metabolism: treatment of cancer patients with IL-2 or IFN-α lowers serum tryptophan levels, and the degree of tryptophan reduction correlates with depressive symptoms (Capuron et al. 2002).”
Psychiatric Manifestations of COVID-19: A Literature Review
Khatun, A., Tamilanban, T., & Chitra, V. (2022) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527321666220701152821 · Cited by 5
Nutritional Psychiatry
Staudacher, H. M., Teasdale, S., Cowan, C., Opie, R., Rocks, T., & Jacka, F. N. (2023) · Cambridge University Press eBooks · doi:10.1017/9781009299862 · Cited by 5
Neuroimaging Approaches to the Understanding of Depression and the Identification of Novel Antidepressants
Kumar, P., Harmer, C. J., & Dourish, C. T. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-386945-6.00012-3 · Cited by 6
P2X7 in Bipolar and Depressive Disorders
Barron, M. L., Werry, E. L., McGregor, I. S., & Kassiou, M. (2013) · Springer eBooks · doi:10.1007/978-3-642-40282-1_31 · Cited by 5
Cognitive assessment in patients with Hepatitis C submitted to treatment with Sofosbuvir and Simeprevir or Daclatasvir
Gascón, M. R. P., Benute, G. R. G., de Macedo, E. C., Capitão, C. G., Vidal, J. E., Smid, J., Marcusso, R. M. N., de Lúcia, M. C. S., de Oliveira, A. C. P., & Diament, D. (2020) · Arquivos de Neuro-Psiquiatria · doi:10.1590/0004-282x20200022 · Cited by 5
Consequences of Gut Dysbiosis on the Human Brain
Hickman, R. A., Hussein, M. A., & Pei, Z. (2016) · InTech eBooks · doi:10.5772/64690 · Cited by 5
The effect of stress on the immune system in the course of tumor from the biomedical perspective
Rolińska, A., Furmaga, J., & Czyżewski, W. (2017) · Psychoonkologia · doi:10.5114/pson.2017.71381 · Cited by 4
“Prze łomowe w tym względzie okazały się obserwacje pacjentów z nowotworami poddanych terapii cytokinami, w wyniku której dochodziło do roz woju depresji [51, 52].”
Neurodevelopmental and Neuropsychiatric Disorders
Traetta, M. E., Filho, A. M. C., Akinluyi, E. T., & Tremblay, M. (2024) · Advances in neurobiology · doi:10.1007/978-3-031-55529-9_26 · Cited by 4
Psychiatric Disorders and Inflammation
Dantzer, R. (2017) · Wiley-VCH eBooks · doi:10.1002/9783527692156.ch29 · Cited by 4
Self-citation
Psychiatric, behavioral, and cognitive disorders in patients with extracranial cancers
Pravettoni, G., Dell’Osso, B. M., Bocci, T., Cortese, F., Ferrucci, R., Lampis, V., Rosci, C. E., & Priori, A. (2018) · CNS Spectrums · doi:10.1017/s1092852918000883 · Cited by 4
“An interesting finding was that immune system activation resulting from the systemic administration of IL-2 and IFN-α to cancer patients decreased plasma tryptophan levels, and this reduction correlated with the depressive symptoms.(7) Decreased tryptophan could be due to the activation (mediated by pro inflammatory c…”
Background
Diet Interventions for Anxiety and Depression
Staudacher, H. M., Teasdale, S. B., Cowan, C. S. M., Opie, R., Rocks, T., & Jacka, F. N. (2023) · Cambridge University Press eBooks · doi:10.1017/9781009299862.006 · Cited by 4
Kynurenine pathway: the link between depressive disorders and inflammation
Kubacka, J., Stefańska, A., & Sypniewska, G. (2020) · Postępy Higieny i Medycyny Doświadczalnej · doi:10.5604/01.3001.0014.3454 · Cited by 5
Serotonin Transporters: Implications for Antidepressant Drug Development
White, K. J., Walline, C. C., & Barker, E. L. (2008) · Springer eBooks · doi:10.1007/978-0-387-76678-2_13 · Cited by 4
Viruses and Psychiatric Disorders
Pearce, B. D. (2008) · Springer eBooks · doi:10.1007/978-0-387-84851-8_18 · Cited by 4
Shifts in the balance of brain tryptophan metabolism due to age and systemic administration of lipopolysaccharide
Miura, H., Shirokawa, T., Ozaki, N., & Isobe, K. (2010) · Health · doi:10.4236/health.2010.23032 · Cited by 4
“Studies of depression induced by cytokine therapy have indicated that the severity of depressive symptoms is correlated with decreases in serum TRP and/or increases in KYN [2-4].”
Background
Role of Inflammation in Neuropsychiatric Comorbidity of Obesity: Experimental and Clinical Evidence
Fourrier, C., Capuron, L., & Castanon, N. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811073-7.00020-9 · Cited by 4
Self-citation
Biology of Depression and Cytokines in Cancer
Musselman, D. L., Miller, A. H., Royster, E. B., & McNutt, M. D. (2010) · Wiley eBooks · doi:10.1002/9780470972533.ch3 · Cited by 4
Self-citation
Los efectos conductuales modulados por las citocinas
Becerril‐Villanueva, E., Gutiérrez, M. E. H., Granados-Camacho, I., Alvarez, L., Pérez‐Tapia, S. M., & Romero, L. P. (2012) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · Cited by 3
Vaccines, depression, and neurodegeneration after age 50 years: another reason to avoid the recommended vaccines
Blaylock, R. L. (2008) · Cited by 3
Antiviral activity of interferon-γ involved in impaired immune function in infectious diseases
Sucher, R., Kurz, K., Margreiter, R., Fuchs, D., & Brandacher, G. (2013) · Pteridines · doi:10.1515/pterid-2013-0038 · Cited by 3
“Moreover, during treatment with IFN-α, a relationship between lower tryptophan levels and increased susceptibility of depression was reported recently in malignant melanoma patients [80].”
Background
RETRACTED: The Impact of Chronic Mild Stress and Agomelatine Treatment on the Expression Level and Methylation Status of Genes Involved in Tryptophan Catabolic Pathway in PBMCs and Brain Structures
Wigner, P., Synowiec, E., Jóźwiak, P., Czarny, P. L., Białek, K. I., Bijak, M., Szemraj, J., Gruca, P., Papp, M., & Śliwiński, T. (2020) · Genes · doi:10.3390/genes11091093 · Cited by 3
“A reduced plasma level of tryptophan was observed in the course of depression [3,4].”
Background
Retracted
Bipolar Disorders
Haarman, B. C. M., der Lek, R. F. R., Ruhé, H. G., de Groot, J. C., Nolen, W. A., & Doorduin, J. (2014) · Springer eBooks · doi:10.1007/978-3-642-40384-2_9 · Cited by 3
Inflamed but not impulsive: Acute inflammatory cytokine response does not impact prepotent response inhibition
Madison, A. A., Andridge, R., Renna, M. E., Sheridan, J. F., Lustberg, M. B., Ramaswamy, B., Wesolowski, R., Williams, N. O., Sardesai, S. D., Noonan, A. M., et al. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.09.008 · Cited by 4
Depression in Medical Patients
Arolt, V., & Rothermundt, M. (2004) · KARGER eBooks · doi:10.1159/000079763 · Cited by 3
Serotonin and Cancer Anorexia: Myths or Facts?
Laviano, A., Fanelli, F. R., & Meguid, M. M. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.05.240 · Cited by 3
Prospective study of psychiatric side effects during antiviral therapy of chronic hepatitis C in an Egyptian sample
Elsayed, H., Elsayed, M., Arafa, M., & El‐Bendary, M. (2012) · Middle East Current Psychiatry · doi:10.1097/01.xme.0000407891.12614.d0 · Cited by 2
Interaction Between Inflammatory State and Neurochemical Changes in Major Psychiatric Disorders
Mu, A., & Markus, J. (2011) · InTech eBooks · doi:10.5772/25532 · Cited by 1
Emotion, Interventions, and Immunity
Koh, K. B. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7119-6_22 · Cited by 2
“Activations of both IDO and kynurenine have in turn been associated with the development of depression [ 59 , 61 , 62 ].”
Background
Interferon-α, Molecular Signaling Pathways and Behavior
Wang, J. (2008) · Springer eBooks · doi:10.1007/978-0-387-84851-8_5 · Cited by 2
Depression and Immunity: the HCV model.
Apicella, E. (2014) · PubMed · Cited by 2
Peripheral kynurenines as biomarkers and targets for prevention and treatment of psychiatric conditions associated with SARS-CoV-2 infection
Oxenkrug, G. F., & D, P. S. M. (2021) · Personalized Medicine in Psychiatry · doi:10.1016/j.pmip.2021.100088 · Cited by 2
“Depression is the most frequent (up to 50%) psychiatric complication of interferon-alpha treatment of hepatitis C virus (HCV) [34] and melanoma patients [35], although anxiety and psychoses have observed as Fig.”
Psychoneuroimmunology
Dantzer, R. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-817558-3.00023-8 · Cited by 2
Self-citation
Neuroinflammation in Neurological Dysfunction and Degeneration
Chen, S., Oyarzabal, E. A., Santos, J. H., Wang, Q., Jiang, L., & Hong, J. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800228-5.00018-2 · Cited by 2

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
ORCID: Capuron, L
Ravaud, A
Miller, A H
Maes, M
Dantzer, R
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2002-06-01
Volume: 7
Issue: 5
Pages: 468-473
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/sj.mp.4000995
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks