title: Kynurenine and Tryptophan Levels in Patients With Schizophrenia and Elevated Antigliadin Immunoglobulin G Antibodies.
abstract: Several studies have reported an association between nonceliac gluten sensitivity and schizophrenia. Immune and kynurenine (KYN) pathways have also been implicated in the pathophysiology of schizophrenia, and certain proinflammatory immune mediators may increase KYN and reduce tryptophan (TRP) levels.
  
  
  
  We measured serum antigliadin immunoglobulin G (IgG), KYN, and TRP in 950 patients with schizophrenia. Patients with antibody level at the 90th percentile or higher of control participants (21.9% of all patients) were classified as having elevated antigliadin IgG. Independent t tests and linear regression models were used to compare TRP, KYN, and KYN-TRP ratio (indicator of TRP metabolism) between patients with and those without elevated antigliadin IgG. The correlation between antigliadin IgG and TRP, KYN, and the ratio was also evaluated in the patients.
  
  
  
  KYN and KYN-TRP ratio were higher in patients with elevated antigliadin IgG (geometric mean [standard deviation {SD}] = 2.65 [0.25] µmol/L versus 2.25 [0.23] µmol/L [p < .001] and 0.05 [0.26] versus 0.04 [0.25; p = .001] respectively), findings robust to adjustment for potential demographic and clinical confounders. Antigliadin IgG positively correlated with KYN and KYN-TRP ratio (r = 0.12, p < .001; r = 0.11, p = .002). TRP did not differ between the two groups and did not correlate with antigliadin IgG.
  
  
  
  Our results connect nonceliac gluten sensitivity with the KYN pathway of TRP metabolism in psychotic illness and hint toward potential individualized treatment targets.
authors.affiliation: From the Mood and Anxiety Program (Okusaga, Postolache) and Child and Adolescent Psychiatry Division, Department of Psychiatry (Reeves), University of Maryland School of Medicine, Baltimore, Maryland; Department of Psychiatry and Behavioral Sciences (Okusaga), The University of Texas Health Science Center at Houston, Houston, Texas; Division of Biological Chemistry (Fuchs), Biocenter Innsbruck Medical University, Innsbruck, Austria; Department of Psychiatry (Hartmann, Rujescu), University of Halle-Wittenberg, Germany; University of South Florida (Groer), Tampa, Florida; Department of Public Health (Cook), Mercyhurst University, Erie, Pennsylvania; Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC; Stearns-Yoder; Hoisington, Brenner, Postolache), Denver, Colorado; Military and Veteran Microbiome Consortium for Research and Education (Stearns-Yoder, Hoisington, Lowry, Brenner, Postolache), Denver, Colorado; Department of Microbiology and Immunology (Pandey), Medical University of South Carolina, Charleston, South Carolina; Maryland Psychiatric Research Center, Department of Psychiatry (Kelly), University of Maryland School of Medicine, Baltimore, Maryland; Johns Hopkins University (Eaton), Baltimore, Maryland; Civil and Environmental Engineering Department (Hoisington), United States Air Force Academy, Colorado Springs, Colorado; Department of Integrative Physiology and Center for Neuroscience (Lowry), University of Colorado Boulder, Boulder, Colorado; Departments of Psychiatry, Neurology, and Physical Medicine and Rehabilitation (Brenner), University of Colorado, Anschutz Medical Campus, Aurora, Colorado; Veterans Integrated Service Network (VISN) 5, Mental Illness Research Education and Clinical Center (MIRECC; Postolache), Baltimore, Maryland.
authors.forename: Olaoluwa
authors.initials: O
authors.lastname: Okusaga
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Gloria
authors.initials: G
authors.lastname: Reeves
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.forename: Annette M
authors.initials: AM
authors.lastname: Hartmann
authors.forename: Bettina
authors.initials: B
authors.lastname: Konte
authors.forename: Marion
authors.initials: M
authors.lastname: Friedl
authors.forename: Maureen
authors.initials: M
authors.lastname: Groer
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Cook
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Stearns-Yoder
authors.forename: Janardan P
authors.initials: JP
authors.lastname: Pandey
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Kelly
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hoisington
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
authors.forename: William W
authors.initials: WW
authors.lastname: Eaton
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Brenner
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: Teodor T
authors.initials: TT
authors.lastname: Postolache
mesh_terms: D000328:Adult; D005260:Female; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007737:Kynurenine / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000097:blood* / Q000276:immunology*; D014364:Tryptophan / Q000097:blood*
chemical_list: D007074:Immunoglobulin G; D007737:Kynurenine; D014364:Tryptophan; D005903:Gliadin