TY - JOUR
T1 - Kynurenine and Tryptophan Levels in Patients with Schizophrenia and Elevated Antigliadin Immunoglobulin G Antibodies
AU - Okusaga, Olaoluwa
AU - Fuchs, Dietmar
AU - Reeves, Gloria
AU - Giegling, Ina
AU - Hartmann, Annette M.
AU - Konte, Bettina
AU - Friedl, Marion
AU - Groer, Maureen
AU - Cook, Thomas B.
AU - Stearns-Yoder, Kelly A.
AU - Pandey, Janardan P.
AU - Kelly, Deanna L.
AU - Hoisington, Andrew J.
AU - Lowry, Christopher A.
AU - Eaton, William W.
AU - Brenner, Lisa A.
AU - Rujescu, Dan
AU - Postolache, Teodor T.
N1 - Funding Information:
This study was supported by a Distinguished Investigator Award (PI Postolache, Co-I Rujescu) from the American Foundation for Suicide Prevention (AFSP) and a Young Investigator Award YIG-0-117-12 from AFSP (PI Cook, Mentor Postolache).
Publisher Copyright:
© Copyright 2016 by the American Psychosomatic Society.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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 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.
AB - 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 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.
KW - antigliadine immunoglobulin antibodies
KW - kynurenine
KW - nonceliac gluten sensitivity
KW - schizophrenia
KW - tryptophan
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U2 - 10.1097/PSY.0000000000000352
DO - 10.1097/PSY.0000000000000352
M3 - Article
C2 - 27359171
AN - SCOPUS:84976599818
VL - 78
SP - 931
EP - 939
JO - Psychosomatic Medicine
JF - Psychosomatic Medicine
SN - 0033-3174
IS - 8
ER -