Kynurenine and Tryptophan Levels in Patients With Schizophrenia With Elevated Antigliadin Immunoglobulin G Antibodies

Olaoluwa Okusaga, Dietmar Fuchs, Gloria Reeves, Ina Giegling, Annette M. Hartmann, Bettina Konte, Marion Friedl, Maureen Groer, Thomas B. Cook, Kelly A. Stearns-Yoder, Janardan P. Pandey, Deanna L. Kelly, Andrew J. Hoisington, Christopher A. Lowry, William W Eaton, Lisa A. Brenner, Dan Rujescu, Teodor T. Postolache

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: 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. METHODS: We thus 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. RESULTS: 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. CONCLUSIONS: Our results connect nonceliac gluten sensitivity with the KYN pathway of TRP metabolism in psychotic illness and hint toward potential individualized treatment targets.

Original languageEnglish (US)
JournalPsychosomatic Medicine
DOIs
StateAccepted/In press - Jun 29 2016

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Applied Psychology
  • Arts and Humanities (miscellaneous)
  • Developmental and Educational Psychology

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    Okusaga, O., Fuchs, D., Reeves, G., Giegling, I., Hartmann, A. M., Konte, B., Friedl, M., Groer, M., Cook, T. B., Stearns-Yoder, K. A., Pandey, J. P., Kelly, D. L., Hoisington, A. J., Lowry, C. A., Eaton, W. W., Brenner, L. A., Rujescu, D., & Postolache, T. T. (Accepted/In press). Kynurenine and Tryptophan Levels in Patients With Schizophrenia With Elevated Antigliadin Immunoglobulin G Antibodies. Psychosomatic Medicine. https://doi.org/10.1097/PSY.0000000000000352