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.
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.
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Buranee
B
Kanchanatawan
Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Sunee
S
Sirivichayakul
Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Kiat
K
Ruxrungtham
Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
André F
AF
Carvalho
IDRPHT, Research Department, Talence, France.|GEMAC, Saint Jean d'Illac, France.
Michel
M
Geffard
Faculty of Health Sciences, University College of Southeast Norway, Drammen, Norway.
Heidi
H
Ormstad
CRC Scotland & London, Eccleston Square, London, UK.
George
G
Anderson
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.
Michael
M
Maes
D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010848:Picolinic Acids / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000494:pharmacology*; D012559:Schizophrenia / Q000378:metabolism*; D014977:Xanthurenates / Q000494:pharmacology*; D055815:Young Adult
D007070:Immunoglobulin A; D010848:Picolinic Acids; D014977:Xanthurenates; C028330:xanthurenic acid; D017378:Quinolinic Acid; C030614:picolinic acid
Cytokines; IDO; Immune; Inflammation; Kynurenine; Oxidative stress; Schizophrenia