title: Deficit Schizophrenia Is Characterized by Defects in IgM-Mediated Responses to Tryptophan Catabolites (TRYCATs): a Paradigm Shift Towards Defects in Natural Self-Regulatory Immune Responses Coupled with Mucosa-Derived TRYCAT Pathway Activation.
abstract: Deficit schizophrenia is accompanied by mucosa-associated activation of the tryptophan catabolite (TRYCAT) pathway, as indicated by increased IgA responses to noxious (NOX) TRYCATs, but not regulatory or protective (PRO) TRYCATs, suggesting increased neurotoxic, excitotoxic, inflammatory, and oxidative potential. No previous studies examined IgM-mediated autoimmune responses to the TRYCAT pathway in deficit versus nondeficit schizophrenia. We measured IgM responses to NOX TRYCATs, namely, quinolinic acid (QA), 3-OH-kynurenine (3HK), picolinic acid (PA), and xanthurenic (XA) acid, and PRO TRYCATs, including kynurenic acid (KA) and anthranilic acid (AA), in 40 healthy controls and 40 deficit and 40 nondeficit schizophrenic patients. We computed the IgM responses to NOX (QA + PA + 3HK + XA)/PRO (AA + KA) ratio and ∆ differences in IgA - IgM TRYCAT values and NOX/PRO ratio. Deficit schizophrenia is characterized by significantly attenuated IgM responses to all TRYCATs and NOX/PRO ratio and highly increased ∆IgA - IgM NOX/PRO ratio as compared to nondeficit schizophrenia and healthy controls. The negative symptoms of schizophrenia are significantly and positively associated with increased IgM responses directed against the KA/3HK ratio and ∆IgA - IgM NOX/PRO ratio. The findings support the view that deficit schizophrenia is a distinct subtype of schizophrenia that may be significantly discriminated from nondeficit schizophrenia. Deficit schizophrenia is accompanied by a highly specific defect in IgM isotype-mediated regulatory responses directed to the TRYCAT pathway. Lowered IgM regulatory responses together with mucosa-derived activation of the TRYCAT pathway may contribute to neuroprogression, negative symptoms, and deficit schizophrenia. All in all, a highly specific defect in the compensatory (anti-)inflammatory reflex system (CIRS), namely, natural IgM-mediated regulatory responses, may underpin deficit schizophrenia.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Buranee
authors.initials: B
authors.lastname: Kanchanatawan
authors.affiliation: Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Sunee
authors.initials: S
authors.lastname: Sirivichayakul
authors.affiliation: Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: IDRPHT, Research Department, Talence, France.|GEMAC, Saint Jean d'Illac, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Geffard
authors.affiliation: CRC Scotland & London, Eccleston Square, London, UK.
authors.forename: George
authors.initials: G
authors.lastname: Anderson
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. dr.michaelmaes@hotmail.com.|IMPACT Strategic Research Center, Deakin University, Geelong, Australia. dr.michaelmaes@hotmail.com.|Department of Psychiatry, Faculty of Medicine, State University of Londrina, Londrina, Brazil. dr.michaelmaes@hotmail.com.|Revitalis, Waalre, The Netherlands. dr.michaelmaes@hotmail.com.|Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria. dr.michaelmaes@hotmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008660:Metabolism / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D017378:Quinolinic Acid / Q000494:pharmacology; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D012565:Schizophrenic Psychology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014364:Tryptophan / Q000097:blood / Q000276:immunology*; D014977:Xanthurenates / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D007075:Immunoglobulin M; D014977:Xanthurenates; C028330:xanthurenic acid; D014364:Tryptophan; D017378:Quinolinic Acid; D007736:Kynurenic Acid
keywords: Cytokines; IDO; Immune; Inflammation; Kynurenine; Oxidative stress