Okusaga Olaoluwa, Fuchs Dietmar, Reeves Gloria, Giegling Ina, Hartmann Annette M, Konte Bettina, Friedl Marion, Groer Maureen, Cook Thomas B, Stearns-Yoder Kelly A, Pandey Janardan P, Kelly Deanna L, Hoisington Andrew J, Lowry Christopher A, Eaton William W, Brenner Lisa A, Rujescu Dan, Postolache Teodor T
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.
Psychosom Med. 2016 Oct;78(8):931-939. doi: 10.1097/PSY.0000000000000352.
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.
多项研究报告了非乳糜泻麸质敏感与精神分裂症之间的关联。免疫和犬尿氨酸（KYN）途径也与精神分裂症的病理生理学有关，某些促炎免疫介质可能会增加KYN并降低色氨酸（TRP）水平。
我们测量了950例精神分裂症患者的血清抗麦醇溶蛋白免疫球蛋白G（IgG）、KYN和TRP。抗体水平处于对照参与者第90百分位数或更高的患者（占所有患者的21.9%）被归类为抗麦醇溶蛋白IgG升高。采用独立t检验和线性回归模型比较抗麦醇溶蛋白IgG升高和未升高的患者之间的TRP、KYN和KYN-TRP比值（TRP代谢指标）。还评估了患者中抗麦醇溶蛋白IgG与TRP、KYN及比值之间的相关性。
抗麦醇溶蛋白IgG升高的患者中KYN和KYN-TRP比值更高（几何均值[标准差{SD}]分别为2.65[0.25]µmol/L对2.25[0.23]µmol/L[p<.001]以及0.05[0.26]对0.04[0.25；p=.001]），这些结果在对潜在人口统计学和临床混杂因素进行调整后依然稳健。抗麦醇溶蛋白IgG与KYN和KYN-TRP比值呈正相关（r=0.12，p<.001；r=0.11，p=.002）。两组之间的TRP没有差异，且与抗麦醇溶蛋白IgG无相关性。
我们的结果将非乳糜泻麸质敏感与精神病性疾病中TRP代谢的KYN途径联系起来，并提示了潜在的个体化治疗靶点。
