Quinolinic Acid is Associated with Cognitive Deficits in Schizophrenia but Not Major Depressive Disorder

Overview

Journal Sci Rep

Specialty Science

Date 2021 May 12

PMID 33976271

Citations 15

Authors

Flurin Cathomas

Karoline Guetter

Erich Seifritz

Federica Klaus

Stefan Kaiser

Affiliations

Soon will be listed here.

Abstract

Tryptophan and its catabolites (TRYCATs) have been suggested to link peripheral immune system activation and central neurotransmitter abnormalities with relevance to the etio-pathophysiology of schizophrenia (SZ) and major depressive disorder (MDD). The relationship to different psychopathological dimensions within these disorders however remains to be elucidated. We thus investigated potential group differences of tryptophan, kynurenine, kynurenic acid, 3-hydroxy kynurenine and quinolinic acid in the plasma of 19 healthy controls (HC), 45 patients with SZ and 43 patients with MDD and correlated plasma proteins with the "motivation and pleasure" dimension and cognition. After correcting for the covariates age, sex, body mass index, smoking and medication, patients with MDD showed lower kynurenine and 3-hydroxy kynurenine levels compared to HC. Quinolinic acid correlated negatively with composite cognitive score in patients with SZ, indicating that more severe cognitive impairments were associated with increased plasma levels of quinolinic acid. No correlations were found in patients with MDD. These results indicate that MDD and SZ are associated with dysregulation of the kynurenine pathway. Quinolinic acid might be specifically implicated in the pathophysiology of cognitive deficits in patients with SZ. Further studies are needed to determine whether TRYCATs are causally involved in the etiology of these neuropsychiatric disorders.

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References

Colle R, Masson P, Verstuyft C, Feve B, Werner E, Boursier-Neyret C . Peripheral tryptophan, serotonin, kynurenine, and their metabolites in major depression: A case-control study. Psychiatry Clin Neurosci. 2019; 74(2):112-117. DOI: 10.1111/pcn.12944. View

Wallwork R, Fortgang R, Hashimoto R, Weinberger D, Dickinson D . Searching for a consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia. Schizophr Res. 2012; 137(1-3):246-50. PMC: 3351536. DOI: 10.1016/j.schres.2012.01.031. View

McGrath J, Saha S, Chant D, Welham J . Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev. 2008; 30:67-76. DOI: 10.1093/epirev/mxn001. View

Myint A, Schwarz M, Verkerk R, Mueller H, Zach J, Scharpe S . Reversal of imbalance between kynurenic acid 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. View

Juckel G, Schaub D, Fuchs N, Naumann U, Uhl I, Witthaus H . Validation of the Personal and Social Performance (PSP) Scale in a German sample of acutely ill patients with schizophrenia. Schizophr Res. 2008; 104(1-3):287-93. DOI: 10.1016/j.schres.2008.04.037. View

Myint A, Kim Y . Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression. Med Hypotheses. 2003; 61(5-6):519-25. DOI: 10.1016/s0306-9877(03)00207-x. View

Meier T, Drevets W, Wurfel B, Ford B, Morris H, Victor T . Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder. Brain Behav Immun. 2015; 53:39-48. PMC: 4783304. DOI: 10.1016/j.bbi.2015.11.003. View

Halverson T, Orleans-Pobee M, Merritt C, Sheeran P, Fett A, Penn D . Pathways to functional outcomes in schizophrenia spectrum disorders: Meta-analysis of social cognitive and neurocognitive predictors. Neurosci Biobehav Rev. 2019; 105:212-219. DOI: 10.1016/j.neubiorev.2019.07.020. View

Lux V, Kendler K . Deconstructing major depression: a validation study of the DSM-IV symptomatic criteria. Psychol Med. 2010; 40(10):1679-90. PMC: 3010198. DOI: 10.1017/S0033291709992157. View

10.

Addington D, Addington J, Schissel B . A depression rating scale for schizophrenics. Schizophr Res. 1990; 3(4):247-51. DOI: 10.1016/0920-9964(90)90005-r. View

11.

Whiteford H, Degenhardt L, Rehm J, Baxter A, Ferrari A, Erskine H . Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013; 382(9904):1575-86. DOI: 10.1016/S0140-6736(13)61611-6. View

12.

Ogyu K, Kubo K, Noda Y, Iwata Y, Tsugawa S, Omura Y . Kynurenine pathway in depression: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2018; 90:16-25. DOI: 10.1016/j.neubiorev.2018.03.023. View

13.

Barch D . Neuropsychological abnormalities in schizophrenia and major mood disorders: similarities and differences. Curr Psychiatry Rep. 2009; 11(4):313-9. PMC: 3836606. DOI: 10.1007/s11920-009-0045-6. View

14.

Raison C, Dantzer R, Kelley K, Lawson M, Woolwine B, Vogt G . CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression. Mol Psychiatry. 2009; 15(4):393-403. PMC: 2844942. DOI: 10.1038/mp.2009.116. View

15.

Savitz J . The kynurenine pathway: a finger in every pie. Mol Psychiatry. 2019; 25(1):131-147. PMC: 6790159. DOI: 10.1038/s41380-019-0414-4. View

16.

Schwieler L, Samuelsson M, Frye M, Bhat M, Schuppe-Koistinen I, Jungholm O . Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients. J Neuroinflammation. 2016; 13(1):51. PMC: 4772340. DOI: 10.1186/s12974-016-0517-7. View

17.

Zhou Y, Zheng W, Liu W, Wang C, Zhan Y, Li H . Cross-sectional relationship between kynurenine pathway metabolites and cognitive function in major depressive disorder. Psychoneuroendocrinology. 2018; 101:72-79. DOI: 10.1016/j.psyneuen.2018.11.001. View

18.

Hayasaka Y, Purgato M, Magni L, Ogawa Y, Takeshima N, Cipriani A . Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials. J Affect Disord. 2015; 180:179-84. DOI: 10.1016/j.jad.2015.03.021. View

19.

Erhardt S, Schwieler L, Imbeault S, Engberg G . The kynurenine pathway in schizophrenia and bipolar disorder. Neuropharmacology. 2016; 112(Pt B):297-306. DOI: 10.1016/j.neuropharm.2016.05.020. View

20.

Haroon E, Welle J, Woolwine B, Goldsmith D, Baer W, Patel T . Associations among peripheral and central kynurenine pathway metabolites and inflammation in depression. Neuropsychopharmacology. 2020; 45(6):998-1007. PMC: 7162907. DOI: 10.1038/s41386-020-0607-1. View