Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies

Molecular Psychiatry volume 26, pages 4158–4178 (2021)Cite this article

Subjects

Abstract

The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges’ g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: PRISMA flow diagram of the included studies.
Fig. 2: Forest plots with the summary effect size (Hedge’s g) of kynurenine metabolites in people with Major Depressive Disorder, Bipolar Disorder, or Schizophrenia compared to healthy controls.
Fig. 3: Summary representation of the altered metabolites in the kynurenine pathway in Major Depressive Disorder, Bipolar Disorder, or Schizophrenia.

Similar content being viewed by others

References

  1. Myint AM. Kynurenines: from the perspective of major psychiatric disorders. FEBS J. 2012;279:1375–85.

    CAS  PubMed  Google Scholar 

  2. Pu J, Liu Y, Zhang H, Tian L, Gui S, Yu Y, et al. An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder. Mol Psychiatry. 2020. https://doi.org/10.1038/s41380-020-0645-4. [Epub ahead of print].

  3. Höglund E, Øverli Ø, Winberg S. Tryptophan metabolic pathways and brain serotonergic activity: a comparative review. Front Endocrinol. 2019;10:158.

    Google Scholar 

  4. Fernstrom JD. A perspective on the safety of supplemental tryptophan based on its metabolic fates. J Nutr. 2016;146:2601S–2608S.

    CAS  PubMed  Google Scholar 

  5. Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA. Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med. 2006;8:1–27.

    PubMed  Google Scholar 

  6. Schwarcz R, Bruno JP, Muchowski PJ, Wu H-Q. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci. 2012;13:465–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Cervenka I, Agudelo LZ, Ruas JL. Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health. Science. 2017;357:eaaf9794. https://doi.org/10.1126/science.aaf9794.

    Article  CAS  PubMed  Google Scholar 

  8. Stone TW, Forrest CM, Darlington LG. Kynurenine pathway inhibition as a therapeutic strategy for neuroprotection. FEBS J. 2012;279:1386–97.

    CAS  PubMed  Google Scholar 

  9. Stone TW, Darlington LG. Endogenous kynurenines as targets for drug discovery and development. Nat Rev Drug Disco. 2002;1:609–20.

    CAS  Google Scholar 

  10. Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Kynurenine pathway metabolism and the microbiota-gut-brain axis. Neuropharmacology. 2017;112(Pt B):399–412.

    CAS  PubMed  Google Scholar 

  11. Lovelace MD, Varney B, Sundaram G, Lennon MJ, Lim CK, Jacobs K, et al. Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases. Neuropharmacology. 2017;112(Pt B):373–88.

    CAS  PubMed  Google Scholar 

  12. Campbell BM, Charych E, Lee AW, Möller T. Kynurenines in CNS disease: regulation by inflammatory cytokines. Front Neurosci. 2014;8:12.

    PubMed  PubMed Central  Google Scholar 

  13. Espey MG, Chernyshev ON, Reinhard JF Jr, Namboodiri MA, Colton CA. Activated human microglia produce the excitotoxin quinolinic acid. Neuroreport. 1997;8:431–4.

    CAS  PubMed  Google Scholar 

  14. Felger JC, Lotrich FE. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience. 2013;246:199–229.

    CAS  PubMed  Google Scholar 

  15. Tavares RG, Tasca CI, Santos CE, Alves LB, Porciuncula LO, Emanuelli T, et al. Quinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes. Neurochem Int. 2002;40:621–7.

    CAS  PubMed  Google Scholar 

  16. Erhardt S, Schwieler L, Imbeault S, Engberg G. The kynurenine pathway in schizophrenia and bipolar disorder. Neuropharmacology. 2017;112(Pt B):297–306.

    CAS  PubMed  Google Scholar 

  17. Linderholm KR, Skogh E, Olsson SK, Dahl ML, Holtze M, Engberg G, et al. Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia. Schizophr Bull. 2012;38:426–32.

    PubMed  Google Scholar 

  18. Olsson SK, Samuelsson M, Saetre P, Lindstrom L, Jonsson EG, Nordin C, et al. Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder. J Psychiatry Neurosci. 2010;35:195–9.

    PubMed  PubMed Central  Google Scholar 

  19. Olsson SK, Sellgren C, Engberg G, Landen M, Erhardt S. Cerebrospinal fluid kynurenic acid is associated with manic and psychotic features in patients with bipolar I disorder. Bipolar Disord. 2012;14:719–26.

    CAS  PubMed  Google Scholar 

  20. Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA. Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology. 2001;25:455–67.

    CAS  PubMed  Google Scholar 

  21. de Lucena D, Fernandes BS, Kunz M, Fries GR, Stertz L, Aguiar B, et al. Lack of association between serum brain-derived neurotrophic factor levels and improvement of schizophrenia symptoms in a double-blind, randomized, placebo-controlled trial of memantine as adjunctive therapy to clozapine. J Clin psychiatry. 2010;71:91.

    PubMed  Google Scholar 

  22. Plitman E, Iwata Y, Caravaggio F, Nakajima S, Chung JK, Gerretsen P, et al. Kynurenic acid in schizophrenia: a systematic review and meta-analysis. Schizophrenia Bull. 2017;43:764–77.

    Google Scholar 

  23. Arnone D, Saraykar S, Salem H, Teixeira AL, Dantzer R, Selvaraj S. Role of Kynurenine pathway and its metabolites in mood disorders: a systematic review and meta-analysis of clinical studies. Neurosci Biobehav Rev. 2018;92:477–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Ogyu K, Kubo K, Noda Y, Iwata Y, Tsugawa S, Omura Y, et al. Kynurenine pathway in depression: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2018;90:16–25.

    CAS  PubMed  Google Scholar 

  25. Moher D, Liberati A, Tetzlaff J, Altman DG. The PG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

    PubMed  PubMed Central  Google Scholar 

  26. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.

    PubMed  PubMed Central  Google Scholar 

  27. Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat methods Med Res. 2018;27:1785–805.

    PubMed  Google Scholar 

  28. Borenstein MHLV, Higgins JPT, Rothstein HR, Comprehensive meta-analysis version 3. Biostat 104 Englewood, NJ, 2011.

  29. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clin trials. 1986;7:177–88.

    CAS  PubMed  Google Scholar 

  30. Mander A, Clayton D. Assessing the influence of a single study in meta-analysis. Stata Tech Bull Repr. 1999;8:108–10.

    Google Scholar 

  31. Higgins JPT, GSe. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. The Cochrane Collaboration: Available at: http://www.cochrane-handbook.org. Accessed 28 May 2014.

  32. Anderson I, Parry-Billings M, Newsholme E, Poortmans J, Cowen P. Decreased plasma tryptophan concentration in major depression: relationship to melancholia and weight loss. J Affect Disord. 1990;20:185–91.

    CAS  PubMed  Google Scholar 

  33. Baranyi A, Amouzadeh-Ghadikolai O, Von Lewinski D, Breitenecker RJ, Stojakovic T, März W, et al. Beta-trace protein as a new non-invasive immunological marker for quinolinic acid-induced impaired blood-brain barrier integrity. Sci Rep. 2017;7:43642.

    PubMed  PubMed Central  Google Scholar 

  34. Barry S, Clarke G, Scully P, Dinan T. Kynurenine pathway in psychosis: evidence of increased tryptophan degradation. J Psychopharmacol. 2009;23:287–94.

    CAS  PubMed  Google Scholar 

  35. Bhagwagar Z, Hafizi S, Cowen P. Cortisol modulation of 5-HT-mediated growth hormone release in recovered depressed patients. J Affect Disord. 2002;72:249–55.

    CAS  PubMed  Google Scholar 

  36. Brundin L, Sellgren C, Lim C, Grit J, Pålsson E, Landen M, et al. An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation. Transl psychiatry. 2016;6:e865.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Cao B, Wang D, Brietzke E, McIntyre RS, Pan Z, Cha D, et al. Characterizing amino-acid biosignatures amongst individuals with schizophrenia: a case–control study. Amino acids. 2018;50:1013–23.

    CAS  PubMed  Google Scholar 

  38. Castillo MFR, Murata S, Schwarz M, Schütze G, Moll N, Martin B, et al. Celecoxib augmentation of escitalopram in treatment-resistant bipolar depression and the effects on quinolinic acid. Neurol, Psychiatry Brain Res. 2019;32:22–9.

    Google Scholar 

  39. Chiappelli J, Notarangelo FM, Pocivavsek A, Thomas MA, Rowland LM, Schwarcz R, et al. Influence of plasma cytokines on kynurenine and kynurenic acid in schizophrenia. Neuropsychopharmacology. 2018;43:1675–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Chiappelli J, Postolache TT, Kochunov P, Rowland LM, Wijtenburg SA, Shukla DK, et al. Tryptophan metabolism and white matter integrity in schizophrenia. Neuropsychopharmacology. 2016;41:2587–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Chiaroni P, Azorin J-M, Bovier P, Widmer J, Jeanningros R, Barré A, et al. A multivariate analysis of red blood cell membrane transports and plasma levels of L-tyrosine and L-tryptophan in depressed patients before treatment and after clinical improvement. Neuropsychobiology. 1990;23:1–7.

    CAS  PubMed  Google Scholar 

  42. Cho HJ, Savitz J, Dantzer R, Teague TK, Drevets WC, Irwin MR. Sleep disturbance and kynurenine metabolism in depression. J Psychosom Res. 2017;99:1–7.

    PubMed  PubMed Central  Google Scholar 

  43. Coppen A, Eccleston E, Peet M. Total and free tryptophan concentration in the plasma of depressive patients. Lancet. 1973;302:60–63.

    Google Scholar 

  44. Cowen P, Parry-Billings M, Newsholme E. Decreased plasma tryptophan levels in major depression. J Affect Disord. 1989;16:27–31.

    CAS  PubMed  Google Scholar 

  45. Czermak C, Hauger R, Drevets WC, Luckenbaugh DA, Geraci M, Charney DS, et al. Plasma NPY concentrations during tryptophan and sham depletion in medication-free patients with remitted depression. J Affect Disord. 2008;110:277–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Dahl J, Andreassen OA, Verkerk R, Malt UF, Sandvik L, Brundin L, et al. Ongoing episode of major depressive disorder is not associated with elevated plasma levels of kynurenine pathway markers. Psychoneuroendocrinology. 2015;56:12–22.

    CAS  PubMed  Google Scholar 

  47. DeMyer MK, Shea PA, Hendrie HC, Yoshimura NN. Plasma tryptophan and five other amino acids in depressed and normal subjects. Arch Gen psychiatry. 1981;38:642–6.

    CAS  PubMed  Google Scholar 

  48. Domingo EF, Krause RR. Plasma tryptophan tolerance curves in drug free normal controls, schizophrenic patients and prisoner volunteers. J Psychiatr Res. 1974;10:247–61.

    Google Scholar 

  49. Domingues DS, Crevelin EJ, de Moraes LAB, Cecilio Hallak JE, de Souza Crippa JA, Costa Queiroz ME. Simultaneous determination of amino acids and neurotransmitters in plasma samples from schizophrenic patients by hydrophilic interaction liquid chromatography with tandem mass spectrometry. J Sep Sci. 2015;38:780–7.

    CAS  PubMed  Google Scholar 

  50. Doolin K, Allers KA, Pleiner S, Liesener A, Farrell C, Tozzi L, et al. Altered tryptophan catabolite concentrations in major depressive disorder and associated changes in hippocampal subfield volumes. Psychoneuroendocrinology. 2018;95:8–17.

    CAS  PubMed  Google Scholar 

  51. Ebesunun M, Eruvulobi H, Olagunju T, Owoeye O. Elevated plasma homocysteine in association with decreased vitamin B12, folate, serotonin, lipids and lipoproteins in depressed patients. Afr J Psychiatry. 2012;15:25–29.

    CAS  Google Scholar 

  52. Fazio F, Lionetto L, Curto M, Iacovelli L, Cavallari M, Zappulla C, et al. Xanthurenic acid activates mGlu2/3 metabotropic glutamate receptors and is a potential trait marker for schizophrenia. Sci Rep. 2015;5:17799.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Fekkes D, Bode WT, Zijlstra FJ, Pepplinkhuizen L. Eicosanoid and amino acid metabolism in transient acute psychoses with psychedelic symptoms. Prostaglandins, Leukotrienes Essent Fat acids. 1996;54:261–4.

    CAS  Google Scholar 

  54. Freedman DX, Belendiuk K, Belendiuk GW, Crayton JW. Blood tryptophan metabolism in chronic schizophrenics. Arch Gen Psychiatry. 1981;38:655–9.

    CAS  PubMed  Google Scholar 

  55. Fukushima T, Iizuka H, Yokota A, Suzuki T, Ohno C, Kono Y, et al. Quantitative analyses of schizophrenia-associated metabolites in serum: serum D-lactate levels are negatively correlated with gamma-glutamylcysteine in medicated schizophrenia patients. PloS One. 2014;9:e101652. https://doi.org/10.1371/journal.pone.0101652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Guicheney P, Leger D, Barrat J, Trevoux R, LIGNIÈRES BD, Roques P, et al. Platelet serotonin content and plasma tryptophan in peri‐and postmenopausal women: variations with plasma oestrogen levels and depressive symptoms. Eur J Clin Investig. 1988;18:297–304.

    CAS  Google Scholar 

  57. Hayward G, Goodwin GM, Cowen PJ, Harmer CJ. Low-dose tryptophan depletion in recovered depressed patients induces changes in cognitive processing without depressive symptoms. Biol Psychiatry. 2005;57:517–24.

    CAS  PubMed  Google Scholar 

  58. Healy D, Carney P, Leonard B. Monoamine-related markers of depression: changes following treatment. J Psychiatr Res. 1982;17:251–60.

    PubMed  Google Scholar 

  59. Hennings A, Schwarz MJ, Riemer S, Stapf TM, Selberdinger VB, Rief W. Exercise affects symptom severity but not biological measures in depression and somatization–results on IL-6, neopterin, tryptophan, kynurenine and 5-HIAA. Psychiatry Res. 2013;210:925–33.

    CAS  PubMed  Google Scholar 

  60. Hoekstra R, Fekkes D, Loonen A, Pepplinkhuizen L, Tuinier S, Verhoeven W. Bipolar mania and plasma amino acids: increased levels of glycine. Eur Neuropsychopharmacol. 2006;16:71–7.

    CAS  PubMed  Google Scholar 

  61. Hoekstra R, van den Broek WW, Fekkes D, Bruijn JA, Mulder PG, Pepplinkhuizen L. Effect of electroconvulsive therapy on biopterin and large neutral amino acids in severe, medication-resistant depression. Psychiatry Res. 2001;103:115–23.

    CAS  PubMed  Google Scholar 

  62. Hu L-J, Li X-F, Hu J-Q, Ni X-J, Lu H-Y, Wang J-J, et al. A simple HPLC–MS/MS method for determination of tryptophan, kynurenine and kynurenic acid in human serum and its potential for monitoring antidepressant therapy. J Anal Toxicol. 2017;41:37–44.

    CAS  PubMed  Google Scholar 

  63. Joaquim HP, Costa AC, Gattaz WF, Talib LL. Kynurenine is correlated with IL-1β in plasma of schizophrenia patients. J Neural Transm. 2018;125:869–73.

    CAS  PubMed  Google Scholar 

  64. Joseph MS, Brewerton TD, Reus VI, Stebbins GT. Plasma-tryptophan/neutral amino acid ratio and dexamethasone suppression in depression. Psychiatry Res. 1984;11:185–92.

    CAS  PubMed  Google Scholar 

  65. Karege F, Widmer J, Bovier P, Gaillard J-M. Platelet serotonin and plasma tryptophan in depressed patients: effect of drug treatment and clinical outcome. Neuropsychopharmacology. 1994;10:207–14.

    CAS  PubMed  Google Scholar 

  66. Kim Y-K, Myint A-M, Verkerk R, Scharpe S, Steinbusch H, Leonard B. Cytokine changes and tryptophan metabolites in medication-naive and medication-free schizophrenic patients. Neuropsychobiology. 2009;59:123–9.

    CAS  PubMed  Google Scholar 

  67. Krause D, Kirnich VB, Stapf TM, Hennings A, Riemer S, Riedel M, et al. Values of cytokines and tryptophan metabolites over a 12 weeks time course in patients with depression and somatoform disorder. Clin Psychopharmacol Neurosci. 2019;17:34.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Krause D, Myint A-M, Schuett C, Musil R, Dehning S, Cerovecki A, et al. High kynurenine (a tryptophan metabolite) predicts remission in patients with major depression to add-on treatment with celecoxib. Front Psychiatry. 2017;8:16.

    PubMed  PubMed Central  Google Scholar 

  69. Kuwano N, Kato TA, Setoyama D, Sato-Kasai M, Shimokawa N, Hayakawa K, et al. Tryptophan-kynurenine and lipid related metabolites as blood biomarkers for first-episode drug-naïve patients with major depressive disorder: an exploratory pilot case-control study. J Affect Disord. 2018;231:74–82.

    CAS  PubMed  Google Scholar 

  70. Lee M, Jayathilake K, Dai J, Meltzer HY. Decreased plasma tryptophan and tryptophan/large neutral amino acid ratio in patients with neuroleptic-resistant schizophrenia: relationship to plasma cortisol concentration. Psychiatry Res. 2011;185:328–33.

    CAS  PubMed  Google Scholar 

  71. Leppik L, Kriisa K, Koido K, Koch K, Kajalaid K, Haring L, et al. Profiling of amino acids and their derivatives biogenic amines before and after antipsychotic treatment in first-episode psychosis. Front Psychiatry. 2018;9:155.

    PubMed  PubMed Central  Google Scholar 

  72. Liu H, Ding L, Zhang H, Mellor D, Wu H, Zhao D, et al. The metabolic factor kynurenic acid of kynurenine pathway predicts major depressive disorder. Front psychiatry. 2018;9:552.

    PubMed  PubMed Central  Google Scholar 

  73. Lucca A, Lucini V, Piatti E, Ronchi P, Smeraldi E. Plasma tryptophan levels and plasma tryptophan/neutral amino acids ratio in patients with mood disorder, patients with obsessive-compulsive disorder, and normal subjects. Psychiatry Res. 1992;44:85–91.

    CAS  PubMed  Google Scholar 

  74. Maes M, De Backer G, Suy E, Minner B. Increased plasma serine concentrations in depression. Neuropsychobiology. 1995;31:10–5.

    CAS  PubMed  Google Scholar 

  75. Maes M, Galecki P, Verkerk R, Rief W. Somatization, but not depression, is characterized by disorders in the tryptophan catabolite (TRYCAT) pathway, indicating increased indoleamine 2, 3-dioxygenase and lowered kynurenine aminotransferase activity. Neuroendocrinol Lett. 2011;32:264–73.

    CAS  PubMed  Google Scholar 

  76. Maes M, Jacobs MP, Suy E, Minner B, Leclercq C, Christiaens F, et al. Suppressant effects of dexamethasone on the availability of plasma L-tryptophan and tyrosine in healthy controls and in depressed patients. Acta Psychiatr Scandinavica. 1990;81:19–23.

    CAS  Google Scholar 

  77. Maes M, Meltzer HY, Scharpè S, Bosmans E, Suy E, De Meester I, et al. Relationships between lower plasma L-tryptophan levels and immune-inflammatory variables in depression. Psychiatry Res. 1993;49:151–65.

    CAS  PubMed  Google Scholar 

  78. Maes M, Verkerk R, Vandoolaeghe E, Van Hunsel F, Neels H, Wauters A, et al. Serotonin-immune interactions in major depression: lower serum tryptophan as a marker of an immune-inflammatory response. Eur Arch Psychiatry Clin Neurosci. 1997;247:154–61.

    CAS  PubMed  Google Scholar 

  79. Maes M, Wauters A, Verkerk R, Demedts P, Neels H, Van Gastel A, et al. Lower serum L-tryptophan availability in depression as a marker of a more generalized disorder in protein metabolism. Neuropsychopharmacology. 1996;15:243–51.

    CAS  PubMed  Google Scholar 

  80. Mauri MC, Ferrara A, Boscati L, Bravin S, Zamberlan F, Alecci M, et al. Plasma and platelet amino acid concentrations in patients affected by major depression and under fluvoxamine treatment. Neuropsychobiology. 1998;37:124–9.

    CAS  PubMed  Google Scholar 

  81. Meier TB, Drevets WC, Wurfel BE, Ford BN, Morris HM, Victor TA, et al. Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder. Brain, Behav, Immun. 2016;53:39–48.

    CAS  Google Scholar 

  82. Moaddel R, Shardell M, Khadeer M, Lovett J, Kadriu B, Ravichandran S, et al. Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects. Psychopharmacology. 2018;235:3017–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Møller S, Kirk L, Honore P. Relationship between plasma ratio of tryptophan to competing amino acids and the response to L-tryptophan treatment in endogenously depressed patients. J Affect Disord. 1980;2:47–59.

    PubMed  Google Scholar 

  84. Møller SE, Group DUA. Plasma amino acid profiles in relation to clinical response to moclobemide in patients with major depression. J Affect Disord. 1993;27:225–31.

    PubMed  Google Scholar 

  85. Moreno FA, Gelenberg AJ, Heninger GR, Potter RL, McKnight KM, Allen J, et al. Tryptophan depletion and depressive vulnerability. Biol psychiatry. 1999;46:498–505.

    CAS  PubMed  Google Scholar 

  86. Moreno J, Gaspar E, López-Bello G, Juárez E, Alcazar-Leyva S, González-Trujano E, et al. Increase in nitric oxide levels and mitochondrial membrane potential in platelets of untreated patients with major depression. Psychiatry Res. 2013;209:447–52.

    CAS  PubMed  Google Scholar 

  87. Mukherjee D, Krishnamurthy VB, Millett CE, Reider A, Can A, Groer M, et al. Total sleep time and kynurenine metabolism associated with mood symptom severity in bipolar disorder. Bipolar Disord. 2018;20:27–34.

    PubMed  Google Scholar 

  88. Myint A, Schwarz MJ, Verkerk R, Mueller H, Zach J, Scharpe S, et al. Reversal of imbalance between kynurenic acid and 3-hydroxykynurenine by antipsychotics in medication-naive and medication-free schizophrenic patients. Brain, Behav, Immun. 2011;25:1576–81.

    CAS  Google Scholar 

  89. Myint AM, Kim YK, Verkerk R, Park SH, Scharpe S, Steinbusch HW, et al. Tryptophan breakdown pathway in bipolar mania. J Affect Disord. 2007;102:65–72.

    CAS  PubMed  Google Scholar 

  90. Myint A-M, Kim YK, Verkerk R, Scharpé S, Steinbusch H, Leonard B. Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord. 2007;98:143–51.

    CAS  PubMed  Google Scholar 

  91. Ogawa S, Koga N, Hattori K, Matsuo J, Ota M, Hori H, et al. Plasma amino acid profile in major depressive disorder: Analyses in two independent case-control sample sets. J Psychiatr Res. 2018;96:23–32.

    PubMed  Google Scholar 

  92. Oxenkrug G, van der Hart M, Roeser J, Summergrad P. Anthranilic acid: a potential biomarker and treatment target for schizophrenia. Ann Psychiatry Ment Health. 2016;4:1059.

    PubMed  PubMed Central  Google Scholar 

  93. Pan J-X, Xia J-J, Deng F-L, Liang W-W, Wu J, Yin B-M, et al. Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: a targeted metabolomics study. Transl Psychiatry. 2018;8:1–10.

    Google Scholar 

  94. Platzer M, Dalkner N, Fellendorf FT, Birner A, Bengesser SA, Queissner R, et al. Tryptophan breakdown and cognition in bipolar disorder. Psychoneuroendocrinology. 2017;81:144–50.

    CAS  PubMed  Google Scholar 

  95. Poletti S, Myint AM, Schüetze G, Bollettini I, Mazza E, Grillitsch D, et al. Kynurenine pathway and white matter microstructure in bipolar disorder. Eur Arch psychiatry Clin Neurosci. 2018;268:157–68.

    PubMed  Google Scholar 

  96. Porter RJ, Gallagher P, Watson S, Smith MS, Young AH. Elevated prolactin responses to L-tryptophan infusion in medication-free depressed patients. Psychopharmacology. 2003;169:77–83.

    CAS  PubMed  Google Scholar 

  97. Potkin SG, Cannon-Spoor HE, DeLisi LE, Neckers LM, Wyatt RJ. Plasma phenylalanine, tyrosine, and tryptophan in schizophrenia. Arch Gen Psychiatry. 1983;40:749–52.

    CAS  PubMed  Google Scholar 

  98. Quintana J. Platelet serotonin and plasma tryptophan decreases in endogenous depression. Clinical, therapeutic, and biological correlations. J Affect Disord. 1992;24:55–62.

    CAS  PubMed  Google Scholar 

  99. Rao ML, Gross G, Strebel B, Bräunig P, Huber G, Klosterkötter J. Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and neuroleptic-treated schizophrenic patients and healthy subjects. Psychiatry Res. 1990;34:243–57.

    CAS  PubMed  Google Scholar 

  100. Rao ML, Gross G, Strebel B, Halaris A, Huber G, Bräunig P, et al. Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia. Biol Psychiatry. 1994;35:151–63.

    CAS  PubMed  Google Scholar 

  101. Ravikumar A, Deepadevi K, Arun P, Manojkumar V, Kurup P. Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders. Neurol India. 2000;48:231.

    CAS  PubMed  Google Scholar 

  102. Reininghaus EZ, McIntyre RS, Reininghaus B, Geisler S, Bengesser SA, Lackner N, et al. Tryptophan breakdown is increased in euthymic overweight individuals with bipolar disorder: a preliminary report. Bipolar Disord. 2014;16:432–40.

    CAS  PubMed  Google Scholar 

  103. Rief W, Pilger F, Ihle D, Verkerk R, Scharpe S, Maes M. Psychobiological aspects of somatoform disorders: contributions of monoaminergic transmitter systems. Neuropsychobiology. 2004;49:24–9.

    CAS  PubMed  Google Scholar 

  104. Roiser JP, Levy J, Fromm SJ, Nugent AC, Talagala SL, Hasler G, et al. The effects of tryptophan depletion on neural responses to emotional words in remitted depression. Biol Psychiatry. 2009;66:441–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Savitz J, Dantzer R, Meier TB, Wurfel BE, Victor TA, McIntosh SA, et al. Activation of the kynurenine pathway is associated with striatal volume in major depressive disorder. Psychoneuroendocrinology. 2015;62:54–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Schwieler L, Samuelsson M, Frye MA, Bhat M, Schuppe-Koistinen I, Jungholm O, et al. Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients. J Neuroinflammation. 2016;13:51.

    PubMed  PubMed Central  Google Scholar 

  107. Sellgren CM, Gracias J, Jungholm O, Perlis RH, Engberg G, Schwieler L, et al. Peripheral and central levels of kynurenic acid in bipolar disorder subjects and healthy controls. Transl Psychiatry. 2019;9:1–9.

    Google Scholar 

  108. Shaw DM, Tidmarsh SF, Karajgi BM. Tryptophan, affective disorder and stress: an hypothesis. J Affect Disord. 1980;2:321–5.

    CAS  PubMed  Google Scholar 

  109. Shovestul BJ, Glassman M, Rowland LM, McMahon RP, Liu F, Kelly DL. Pilot study examining the relationship of childhood trauma, perceived stress, and medication use to serum kynurenic acid and kynurenine levels in schizophrenia. Schizophrenia Res. 2017;185:200.

    Google Scholar 

  110. Song C, Lin A, Bonaccorso S, Heide C, Verkerk R, Kenis G, et al. The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression. J Affect Disord. 1998;49:211–9.

    CAS  PubMed  Google Scholar 

  111. Sorgdrager F, Doornbos B, Penninx B, de Jonge P, Kema IP. The association between the hypothalamic pituitary adrenal axis and tryptophan metabolism in persons with recurrent major depressive disorder and healthy controls. J Affect Disord. 2017;222:32–9.

    CAS  PubMed  Google Scholar 

  112. Sperner-Unterweger B, Miller C, Holzner B, Laich A, Widner B, Fleischhacker WW, et al. Immunologic alterations in schizophrenia: neopterin, L-kynurenine, tryptophan and T-cell subsets in the acute stage of illness. Pteridines. 2002;13:9–14.

    CAS  Google Scholar 

  113. Sublette ME, Galfalvy HC, Fuchs D, Lapidus M, Grunebaum MF, Oquendo MA, et al. Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder. Brain, Behav, Immun. 2011;25:1272–8.

    CAS  Google Scholar 

  114. Szymona K, Zdzisińska B, Karakuła-Juchnowicz H, Kocki T, Kandefer-Szerszeń M, Flis M, et al. Correlations of kynurenic acid, 3-hydroxykynurenine, sIL-2R, IFN-α, and IL-4 with clinical symptoms during acute relapse of schizophrenia. Neurotox Res. 2017;32:17–26.

    CAS  PubMed  Google Scholar 

  115. Teraishi T, Hori H, Sasayama D, Matsuo J, Ogawa S, Ota M, et al. 13 C-tryptophan breath test detects increased catabolic turnover of tryptophan along the kynurenine pathway in patients with major depressive disorder. Sci Rep. 2015;5:15994.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Tortorella A, Monteleone P, Fabrazzo M, Viggiano A, De Luca B, Maj M. Plasma concentrations of amino acids in chronic schizophrenics treated with clozapine. Neuropsychobiology. 2001;44:167–71.

    CAS  PubMed  Google Scholar 

  117. Umehara H, Numata S, Watanabe S-y, Hatakeyama Y, Kinoshita M, Tomioka Y, et al. Altered KYN/TRP, Gln/Glu, and Met/methionine sulfoxide ratios in the blood plasma of medication-free patients with major depressive disorder. Sci Rep. 2017;7:1–8.

    CAS  Google Scholar 

  118. van de Kerkhof NW, Fekkes D, van der Heijden FM, Hoogendijk WJ, Stöber G, Egger JI, et al. Cycloid psychoses in the psychosis spectrum: evidence for biochemical differences with schizophrenia. Neuropsychiatr Dis Treat. 2016;12:1927.

    PubMed  PubMed Central  Google Scholar 

  119. Van der Heijden F, Fekkes D, Tuinier S, Sijben A, Kahn R, Verhoeven W. Amino acids in schizophrenia: evidence for lower tryptophan availability during treatment with atypical antipsychotics? J Neural Transm. 2005;112:577–85.

    PubMed  Google Scholar 

  120. Wei J, Xu H, Ramchand C, Hemmings GP. Low concentrations of serum tyrosine in neuroleptic-free schizophrenics with an early onset. Schizophrenia Res. 1995;14:257–60.

    CAS  Google Scholar 

  121. Wood K, Harwood J, Coppen A. The effect of antidepressant drugs on plasma kynurenine in depressed patients. Psychopharmacology. 1978;59:263–6.

    CAS  PubMed  Google Scholar 

  122. Wu Y, Mai N, Zhong X, Wen Y, Zhou Y, Li H, et al. Kynurenine pathway changes in late-life depression with memory deficit. Psychiatry Res. 2018;269:45–49.

    CAS  PubMed  Google Scholar 

  123. Wu Y, Zhong X, Mai N, Wen Y, Shang D, Hu L, et al. Kynurenine pathway changes in late-life depression. J Affect Disord. 2018;235:76–81.

    CAS  PubMed  Google Scholar 

  124. Wurfel B, Drevets W, Bliss S, McMillin J, Suzuki H, Ford B, et al. Serum kynurenic acid is reduced in affective psychosis. Transl psychiatry. 2017;7:e1115.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Young KD, Drevets WC, Dantzer R, Teague TK, Bodurka J, Savitz J. Kynurenine pathway metabolites are associated with hippocampal activity during autobiographical memory recall in patients with depression. Brain, Behav, Immun. 2016;56:335–42.

    CAS  Google Scholar 

  126. Zhou Y, Zheng W, Liu W, Wang C, Zhan Y, Li H, et al. Cross-sectional relationship between kynurenine pathway metabolites and cognitive function in major depressive disorder. Psychoneuroendocrinology. 2019;101:72–9.

    CAS  PubMed  Google Scholar 

  127. Andreazza AC, Laksono I, Fernandes BS, Toben C, Lewczuk P, Riederer P, et al. Guidelines for the standardized collection of blood-based biomarkers in psychiatry: Steps for laboratory validity–a consensus of the Biomarkers Task Force from the WFSBP. World J Biol Psychiatry. 2019;20:340–51.

    PubMed  PubMed Central  Google Scholar 

  128. Fernandes B, Steiner J, Berk M, Molendijk M, Gonzalez-Pinto A, Turck C, et al. Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: meta-analysis and implications. Mol psychiatry. 2015;20:1108–19.

    CAS  PubMed  Google Scholar 

  129. Haroon E, Welle JR, Woolwine BJ, Goldsmith DR, Baer W, Patel T, et al. Associations among peripheral and central kynurenine pathway metabolites and inflammation in depression. Neuropsychopharmacology. 2020;45:998–1007. https://doi.org/10.1038/s41386-020-0607-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Fernandes BS, Williams LM, Steiner J, Leboyer M, Carvalho AF, Berk M. The new field of ‘precision psychiatry’. BMC Med. 2017;15:80.

    PubMed  PubMed Central  Google Scholar 

  131. Fernandes BS, Borgwardt S, Carvalho AF, Steiner J. Back to the future: on the road towards precision psychiatry. Front Psychiatry. 2020;11:112. https://doi.org/10.3389/fpsyt.2020.00112.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Gostner JM, Becker K, Croft KD, Woodman RJ, Puddey IB, Fuchs D, et al. Regular consumption of black tea increases circulating kynurenine concentrations: a randomized controlled trial. BBA Clin. 2015;3:31–5.

    CAS  PubMed  Google Scholar 

  133. Gualdoni GA, Fuchs D, Zlabinger GJ, Gostner JM. Resveratrol intake enhances indoleamine-2, 3-dioxygenase activity in humans. Pharmacol Rep. 2016;68:1065–8.

    CAS  PubMed  Google Scholar 

  134. Rudzki L, Ostrowska L, Pawlak D, Małus A, Pawlak K, Waszkiewicz N, et al. Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study. Psychoneuroendocrinology. 2019;100:213–22.

    CAS  PubMed  Google Scholar 

  135. Teasdale SB, Ward PB, Samaras K, Firth J, Stubbs B, Tripodi E, et al. Dietary intake of people with severe mental illness: systematic review and meta-analysis. Br J Psychiatry. 2019;214:251–9.

    PubMed  Google Scholar 

  136. Zhu C, Sawrey-Kubicek L, Beals E, Rhodes CH, Houts HE, Sacchi R, et al. Human gut microbiome composition and tryptophan metabolites were changed differently by fast food and Mediterranean diet in four days: A pilot study. Nutr Res. 2020.

  137. Carl GF, Brogan MP, Young BK. Is plasma serine a marker for psychosis? Biol Psychiatry. 1992;31:1130–5.

    CAS  PubMed  Google Scholar 

  138. Domino EF, Krause RR. Free and bound serum tryptophan in drug-free normal controls and chronic schizophrenic patients. Biol Psychiatry. 1974;8:265–79.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

WM is currently funded by an Alfred Deakin Postdoctoral Research Fellowship and a Multiple Sclerosis Research Australia early-career fellowship. WM has previously received funding from the Cancer Council Queensland and university grants/fellowships from La Trobe University, Deakin University, University of Queensland, and Bond University. WM has received industry funding and has attended events funded by Cobram Estate Pty. Ltd. WM has received travel funding from Nutrition Society of Australia. WM has received consultancy funding from Nutrition Research Australia. WM has received speakers honoraria from The Cancer Council Queensland and the Princess Alexandra Research Foundation. BS is supported by a Clinical Lectureship (ICA-CL-2017-03-001) jointly funded by Health Education England (HEE) and the National Institute for Health Research (NIHR). BS is partly funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. BS also holds active grants with the Medical Research Council and Guys and St Thomas Charity (GSTT). JC has received research support from Deakin University. AJW is supported by a Deakin University Dean’s Research Postdoctoral Fellowship, and has received research support previously from the Trisno Family Gift, and Deakin University. MB is supported by a NHMRC Senior Principal Research Fellowship (1059660 and 1156072). MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Lundbeck, Merck, Pfizer, and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Lundbeck Merck, Pfizer and Servier—all unrelated to this work. The views expressed are those of the author(s) and not necessarily those of the (partner organization), the NHS, the NIHR, the Department of Health and Social Care, the MRC, NHMRC, or GSTT. AO is supported by a Future Leader Fellowship (#101160) from the Heart Foundation Australia and Wilson Foundation. She has received research funding from National Health & Medical Research Council, Australian Research Council, University of Melbourne, Deakin University, Sanofi, Meat and Livestock Australia and Woolworths Limited and Honoraria from Novartis. The Food & Mood Centre has received funding from the Fernwood Foundation, the A2 Milk Company and Be Fit Foods – unrelated to this paper. ML is funded by a Deakin University PhD Scholarship and has received research support from BeFit Foods. SGC has received a grant for external rotation during psychiatry training period, from Fundación de Psiquiatría y Salud Mental. SGC has received CME-related honoraria, or consulting fees from Janssen-Cilag, Italfarmaco, Angelini and Lundbeck all unrelated to this work. APC Microbiome Ireland is funded by Science Foundation Ireland (SFI), through the Irish Government’s National Development Plan (grant number SFI/12/RC/2273 P2). GC is supported by the Health Research Board (HRB) (grant no ILP-POR-2017-013). AJM is funded by an Australian Rotary Health/Ten Island Tassie Tag Along Tour Funding Partner PhD Scholarship. TR has received grants, fellowships and research support from University of the Sunshine Coast, Australian Postgraduate Awards, Fernwood Foundation and Be Fit Food. TR received consultancy, honoraria and travel funds from Oxford University Press, the University of Melbourne, the University of Sydney, Bond University, University of Southern Queensland, Dietitians Association of Australia, Nutrition Society of Australia, The Royal Australian and New Zealand College of Psychiatrists, Academy of Nutrition and Dietetics, Black Dog Institute, Australian Rotary Health, Australian Disease Management Association, Department of Health and Human Services, Primary Health Networks, Barwon Health, West Gippsland Healthcare Group, Central West Gippsland Primary Care Partnership, Parkdale College, Positive Schools, City of Greater Geelong and Global Age.

Author information

Author notes

  1. These authors contributed equally: Wolfgang Marx, Amelia J. McGuinness

  2. These authors jointly supervised this work: Brisa S. Fernandes, Jair C. Soares

Authors and Affiliations

  1. Deakin University, IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia

    Wolfgang Marx, Amelia J. McGuinness, Tetyana Rocks, Anu Ruusunen, Jasmine Cleminson, Adam J. Walker, Melissa Lane, Michael Berk, Adrienne O’Neil & Felice Jacka

  2. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland

    Anu Ruusunen

  3. Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland

    Anu Ruusunen

  4. Bipolar and Depression Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain

    Susana Gomes-da-Costa

  5. Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Marsal Sanches, Alexandre P. Diaz, João Quevedo, Jair C. Soares & Brisa S. Fernandes

  6. Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Marsal Sanches, Alexandre P. Diaz, João Quevedo, Jair C. Soares & Brisa S. Fernandes

  7. Institute of Biomedical Sciences and Prospect Clinic for Otorhinolaryngology & Neurology, National Sun Yat-sen University, Kaohsiung, Taiwan

    Ping-Tao Tseng

  8. Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Pao-Yen Lin

  9. Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

    Pao-Yen Lin

  10. Department of Psychiatry and Neurobehavioural Science and APC Microbiome Ireland, University College Cork, Cork, Ireland

    Gerard Clarke

  11. Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK

    Brendon Stubbs

  12. South London and Maudsley NHS Foundation Trust, London, UK

    Brendon Stubbs

  13. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    André F. Carvalho

  14. Centre for Addiction and Mental Health, Toronto, ON, Canada

    André F. Carvalho

Authors
  1. Wolfgang Marx
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amelia J. McGuinness
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tetyana Rocks
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anu Ruusunen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jasmine Cleminson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Adam J. Walker
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Susana Gomes-da-Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Melissa Lane
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marsal Sanches
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alexandre P. Diaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ping-Tao Tseng
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Pao-Yen Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Michael Berk
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Gerard Clarke
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Adrienne O’Neil
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Felice Jacka
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Brendon Stubbs
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. André F. Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. João Quevedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Jair C. Soares
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Brisa S. Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Wolfgang Marx or Brisa S. Fernandes.

Ethics declarations

Conflict of interest

BSF, APD, AFC, BS, JC, MS, ML, SGC, PTT, WM, AJM, TR, AR, AJW, PYL, MB, AON, FJ, and JCS have no conflict of interest regarding this manuscript. GC from APC Microbiome Ireland has conducted studies in collaboration with several companies, including GSK, Pfizer, Cremo, Suntory, Wyeth, Mead Johnson, Nutricia, 4D Pharma, and DuPont. GC has been an invited speaker at meetings organized by Janssen and is receipt of research funding from Pharmavite. GC is not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this report.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Marx, W., McGuinness, A.J., Rocks, T. et al. The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies. Mol Psychiatry 26, 4158–4178 (2021). https://doi.org/10.1038/s41380-020-00951-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-020-00951-9

This article is cited by

Search

Advanced search

Quick links