Plasma levels of quinolinic acid and kynurenic acid in patients with major mental illnesses

  • Received 27.12.2025
  • Revised 16.04.2026
  • Accepted 26.05.2026
  • Published 29.05.2026
  • 80 Views
  • Retrieved from Vol. 12, No. 1, 2026
  • Pages 6-13

Clarifying antipsychotic effects on kynurenine-pathway metabolites may improve understanding of their role in major mental illnesses. Therefore, this study aimed to assess plasma quinolinic and kynurenic acid levels in patients with major mental illnesses. 85 adults comprising 55 treatment-experienced patients with major mental illnesses; schizophrenia, bipolar and depression, and 30 controls were enrolled into this study. The plasma levels of quinolinic acid and kynurenic acid were determined using Enzyme Linked Immunosorbent Assay. Plasma quinolinic acid level was significantly lower in patients with major mental illnesses (14.52 (7.16-48.24) mg/mL) compared with the controls (157.79 (68.64-464.05)  mg/mL). In contrast, plasma kynurenic acid level was higher in patients with major mental illnesses (243.96 (210.65-283.05)  μmol/L) compared with the controls (215.36 (185.67-243.65)  μmol/L). After stratification into groups, patients with schizophrenia (22.86 (7.62-53.14) mg/mL), bipolar (15.34 (8.37-48.21) mg/mL) and depression (6.18 (2.66-43.05)  mg/mL) had significantly lower quinolinic acid levels compared with the controls (157.79 (68.64-464.05)  mg/mL). However, kynurenic acid levels were only significantly elevated in patients with schizophrenia (247.0 (208.34-290.22 μmol/L) and bipolar (243.20 (212.85-291.12) μmol/L) compared with the controls (215.36 (185.67-243.65) μmol/L). The plasma levels of quinolinic acid and kynurenic acid did not differ significantly among patients with schizophrenia, bipolar disorder, and depression. Treated patients with major mental illnesses exhibited a kynurenine metabolite profile indicative of reduced neurotoxicity and enhanced neuroprotection. These metabolites may serve as potential biomarkers for monitoring treatment effects

antipsychotics; inflammation; tryptophan metabolism; mental health disorders; neuroprotection

https://doi.org/10.63341/ijmmr/1.2026.06
  1. Akinlade KS, Adedokun KA, Rahamon SK, Lasebikan VO. Elevated levels of visfatin and fetuin-A in patients with major mental disorders. Clin Transl Res. 2020;8(1):49–53.
  2. Badawy AA. Kynurenine pathway and human systems. Exp Gerontol. 2020;129:110770. DOI: 10.1016/j.exger.2019.110770
  3. Marković M, Petronijević N, Stašević M, Stašević Karličić I, Velimirović M, Stojković T, et al. Decreased plasma levels of kynurenine and KA in previously treated and first-episode antipsychotic-naive schizophrenia patients. Cells. 2023;12(24):2814. DOI: 10.3390/cells12242814
  4. Kuuskmäe C, Philips MA, Kilk K, Haring L, Kangro R, Seppo I, et al. Kynurenine pathway dynamics in patients with schizophrenia spectrum disorders across the disease trajectory. Psychiatry Res. 2023;328:115423. DOI: 10.1016/j.psychres.2023.115423
  5. Li M, Wu Y, Xu Y, Huang X, Gao K, Hu N, et al. Peripheral tryptophan-kynurenine pathway dysfunction in first-episode schizophrenia. Sci Rep. 2025;15(1):2432. DOI: 10.1038/s41598-025-86390-4
  6. Pan Y, Xu P, Sun X. Associations between Kynurenine pathway metabolites and cognitive dysfunction in major depressive disorder. PLoS One. 2025;20(8):e0328886. DOI: 10.1371/journal.pone.0328886
  7. Colle R, Chappell K, El Asmar K, Fève B, Chanson P, David DJ, et al. Plasma kynurenine pathway metabolite levels increase in depressed patients after antidepressant treatment. Brain Behav Immun. 2025;129:92–9. DOI: 10.1016/j.bbi.2025.05.025
  8. Hebbrecht K, Morrens M, Giltay EJ, van Nuijs ALN, Sabbe B, van den Ameele S. The role of kynurenines in cognitive dysfunction in bipolar disorder. Neuropsychobiology. 2022;81(3):184–91. DOI: 10.1159/000520152
  9. Yavuz Ataşlar E, Altınbaş K. A comprehensive examination of circadian rhythm and tryptophan pathway parameters: Assessing their role in predicting bipolar disorder in patients, siblings, and controls. Chronobiol Int. 2025;42(6):755–69. DOI: 10.1080/07420528.2025.2509623
  10. Brum M, Nieberler M, Kehrwald C, Knopf K, Brunkhorst-Kanaan N, Etyemez S, et al. Phase-and disorder-specific differences in peripheral metabolites of the kynurenine pathway in major depression, bipolar affective disorder and schizophrenia. World J Biol Psychiatry. 2023;24(7):564–77. DOI: 10.1080/15622975.2023.2169348
  11. World Medical Association. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects [Internet]. [cited 23 November 2025]. Available from: https://www.wma.net/what-we-do/medical-ethics/declaration-of-helsinki/
  12. Diagnostic and statistical manual of mental disorders: DSM-5. Washington: American Psychiatric Association Publishing; 2013. 96 P. DOI: 10.1176/appi.books.9780890425596
  13. Sales PMG, Schrage E, Coico R, Pato M. Linking nervous and immune systems in psychiatric illness: A meta-analysis of the kynurenine pathway. Brain Res. 2023;1800:148190. DOI: 10.1016/j.brainres.2022.148190
  14. Savitz J, Drevets WC, Smith CM, Victor TA, Wurfel BE, Bellgowan PS, et al. Putative neuroprotective and neurotoxic kynurenine pathway metabolites are associated with hippocampal and amygdalar volumes in subjects with major depressive disorder. Neuropsychopharmacology. 2015;40:463–71. DOI: 10.1038/npp.2014.194
  15. Skorobogatov K, Autier V, Foiselle M, Richard JR, Boukouaci W, Wu CL, et al. Kynurenine pathway abnormalities are state-specific but not diagnosis-specific in schizophrenia and bipolar disorder. Brain Behav Immun Health. 2023;27:100584. DOI: 10.1016/j.bbih.2022.100584
  16. Fellendorf FT, Manchia M, Squassina A, Pisanu C, Dall'Acqua S, Sut S, et al. Is poor lithium response in individuals with bipolar disorder associated with increased degradation of tryptophan along the kynurenine pathway? Results of an exploratory study. J Clin Med. 2022;11(9):2517. DOI: 10.3390/jcm11092517
  17. Patlola SR, Donohoe G, McKernan DP. Anti-inflammatory effects of 2nd generation antipsychotics in patients with schizophrenia: A systematic review and meta-analysis. J Psychiatr Res. 2023;160:126–36. DOI: 10.1016/j.jpsychires.2023.01.042
  18. Cathomas F, Guetter K, Seifritz E, Klaus F, Kaiser S. Quinolinic acid is associated with cognitive deficits in schizophrenia but not major depressive disorder. Sci Rep. 2021;11:9992. DOI: 10.1038/s41598-021-89335-9
  19. Trepci A, Sellgren CM, Pålsson E, Brundin L, Khanlarkhani N, Schwieler L, et al. Central levels of tryptophan metabolites in subjects with bipolar disorder. Eur Neuropsychopharmacol. 2021;43:52–62. DOI: 10.1016/j.euroneuro.2020.11.018
  20. Myint AM, Schwarz MJ, Verkerk R, Mueller HH, Zach J, Scharpé S, et al. Reversal of imbalance between KA and 3-hydroxykynurenine by antipsychotics in medication-naïve and medication-free schizophrenic patients. Brain Behav Immun. 2011;25(8):1576–81. DOI: 10.1016/j.bbi.2011.05.005
  21. Wurfel BE, Drevets WC, Bliss SA, McMillin JR, Suzuki H, Ford BN, et al. Serum KA is reduced in affective psychosis. Transl Psychiatry. 2017;7(5):e1115. DOI: 10.1038/tp.2017.88
  22. Marx W, McGuinness AJ, Rocks T, Ruusunen A, Cleminson J, Walker AJ, et al. The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: A meta-analysis of 101 studies. Mol Psychiatry. 2021;26(8):4158–78. DOI: 10.1038/s41380-020-00951-9