Antigliadin Antibodies (AGA IgG) Are Related to Neurochemistry in Schizophrenia.

Laura M Rowland,Katrina Rodriguez,Fang Liu,Frank Gaston,Deanna L Kelly,Haley K Demyanovich,S Andrea Wijtenburg,William W Eaton,Daniela Cihakova,L Elliot Hong,Monica V Talor,Robert R Mcmahon

doi:10.3389/fpsyt.2017.00104

Laura M Rowland, Katrina Rodriguez + Show 10 more

Open Access

https://doi.org/10.3389/fpsyt.2017.00104

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Abstract

Inflammation may play a role in schizophrenia; however, subgroups with immune regulation dysfunction may serve as distinct illness phenotypes with potential different treatment and prevention strategies. Emerging data show that about 30% of people with schizophrenia have elevated antigliadin antibodies of the IgG type, representing a possible subgroup of schizophrenia patients with immune involvement. Also, recent data have shown a high correlation of IgG-mediated antibodies between the periphery and cerebral spinal fluid in schizophrenia but not healthy controls, particularly AGA IgG suggesting that these antibodies may be crossing the blood–brain barrier with resulting neuroinflammation. Proton magnetic resonance spectroscopy (MRS) is a non-invasive technique that allows the quantification of certain neurochemicals in vivo that may proxy inflammation in the brain such as myoinositol and choline-containing compounds (glycerophosphorylcholine and phosphorylcholine). The objective of this exploratory study was to examine the relationship between serum AGA IgG levels and MRS neurochemical levels. We hypothesized that higher AGA IgG levels would be associated with higher levels of myoinositol and choline-containing compounds (glycerophosphorylcholine plus phosphorylcholine; GPC + PC) in the anterior cingulate cortex. Thirty-three participants with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder had blood drawn and underwent neuroimaging using MRS within 9 months. We found that 10/33 (30%) had positive AGA IgG (≥20 U) similar to previous findings. While there were no significant differences in myoinositol and GPC + PC levels between patients with and without AGA IgG positivity, there were significant relationships between both myoinositol (r = 0.475, p = 0.007) and GPC + PC (r = 0.36, p = 0.045) with AGA IgG levels. This study shows a possible connection of AGA IgG antibodies to putative brain inflammation as measured by MRS in schizophrenia.

Highlights

Several emerging lines of evidence suggest that the etiology and pathophysiology of schizophrenia may be related to inflammatory processes
Despite the accumulating evidence of the evidence of AGA IgG antibodies in a subset of schizophrenia, little work has shown the connection of these antibodies with brain inflammation
To the best of our knowledge, this is the first study to show a relationship between peripheral AGA IgG and anterior cingulate cortex (ACC) myoinositol and GPC + PC levels

Summary

Introduction

Several emerging lines of evidence suggest that the etiology and pathophysiology of schizophrenia may be related to inflammatory processes Data contributing to this hypothesis include prenatal maternal infection and the subsequent pro-inflammatory response [1,2,3]. A subset of individuals with schizophrenia may be sensitive to inflammation due to immune activation to specific antigens, and this may contribute to the illness pathophysiology. This is in line with the fact that studies on inflammatory markers are not elevated in all people with schizophrenia and why inconsistent results have been shown in cross-sectional cytokine studies. This study found a high correlation of IgG-mediated antibodies (e.g., antibodies to gliadin) between the periphery and CSF in schizophrenia but not healthy controls

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