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Deficit, but Not Nondeficit, Schizophrenia Is Characterized by Mucosa-Associated Activation of the Tryptophan Catabolite (TRYCAT) Pathway with Highly Specific Increases in IgA Responses Directed to Picolinic, Xanthurenic, and Quinolinic Acid

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Abstract

Evidence suggests that activation of the tryptophan catabolite (TRYCAT) pathway is involved in the pathophysiology of schizophrenia. However, no previous study examined whether TRYCAT pathway activation is associated with deficit schizophrenia. We measured IgA responses to TRYCATs, namely quinolinic acid, picolinic acid, kynurenic acid, xanthurenic acid, and anthranilic acid and 3-OH-kynurenine, in 40 healthy controls and in schizophrenic patients with (n = 40) and without (n = 40) deficit, defined according to the Schedule for the Deficit Syndrome (SDS). Primary deficit schizophrenia is accompanied by an activated TRYCAT pathway as compared to controls and nondeficit schizophrenia. Participants with deficit schizophrenia show increased IgA responses to xanthurenic acid, picolinic acid, and quinolinic acid and relatively lowered IgA responses to kynurenic and anthranilic acids, as compared to patients with nondeficit schizophrenia. Both schizophrenia subgroups show increased IgA responses to 3-OH-kynurenine as compared to controls. The IgA responses to noxious TRYCATs, namely xanthurenic acid, picolinic acid, quinolinic acid, and 3-OH-kynurenine, but not protective TRYCATS, namely anthranilic acid and kunyrenic acid, are significantly higher in deficit schizophrenia than in controls. The negative symptoms of schizophrenia are significantly and positively associated with increased IgA responses directed against picolinic acid and inversely with anthranilic acid, whereas no significant associations between positive symptoms and IgA responses to TRYCATs were found. In conclusion, primary deficit schizophrenia is characterized by TRYCAT pathway activation and differs from nondeficit schizophrenia by a highly specific TRYCAT pattern suggesting increased excitotoxicity, cytotoxicity, and neurotoxicity, as well as inflammation and oxidative stress. The specific alterations in IgA responses to TRYCATs provide further insight for the biological delineation of deficit versus nondeficit schizophrenia.

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Acknowledgements

This research has been supported by the Asahi Glass Foundation, Chulalongkorn University Centenary Academic Development Project, and IDRPHT and Gemac, France.

Author’s Contributions

All the contributing authors have participated in the manuscript. MM and BK designed the study. BK recruited patients and completed diagnostic interviews and rating scales measurements. All authors contributed to interpretation of the data and writing of the manuscript. MM carried out the statistical analyses.

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Authors and Affiliations

  1. Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Buranee Kanchanatawan & Michael Maes

  2. Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Sunee Sirivichayakul & Kiat Ruxrungtham

  3. Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil

    André F. Carvalho

  4. IDRPHT, Research Department, Talence, France

    Michel Geffard

  5. GEMAC, Saint Jean d’Illac, France

    Michel Geffard

  6. Faculty of Health Sciences, University College of Southeast Norway, Drammen, Norway

    Heidi Ormstad

  7. CRC Scotland & London, Eccleston Square, London, UK

    George Anderson

  8. IMPACT Strategic Research Center, Deakin University, Geelong, Australia

    Michael Maes

  9. Department of Psychiatry, Faculty of Medicine, State University of Londrina, Londrina, Brazil

    Michael Maes

  10. Revitalis, Waalre, the Netherlands

    Michael Maes

  11. Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria

    Michael Maes

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  1. Buranee Kanchanatawan
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Correspondence to Michael Maes.

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The study was conducted according to Thai and international ethics and privacy laws. Approval for the study was obtained from the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, which is in compliance with the International Guideline for Human Research protection as required by the Declaration of Helsinki, The Belmont Report, CIOMS Guideline, and International Conference on Harmonization in Good Clinical Practice (ICH-GCP).

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Kanchanatawan, B., Sirivichayakul, S., Ruxrungtham, K. et al. Deficit, but Not Nondeficit, Schizophrenia Is Characterized by Mucosa-Associated Activation of the Tryptophan Catabolite (TRYCAT) Pathway with Highly Specific Increases in IgA Responses Directed to Picolinic, Xanthurenic, and Quinolinic Acid. Mol Neurobiol 55, 1524–1536 (2018). https://doi.org/10.1007/s12035-017-0417-6

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