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Research Paper

Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study

Deanna L. Kelly, Haley K. Demyanovich, Katrina M. Rodriguez, Daniela Čiháková, Monica V. Talor, Robert P. McMahon, Charles M. Richardson, Gopal Vyas, Heather A. Adams, Sharon M. August, Alessio Fasano, Nicola G. Cascella, Stephanie M. Feldman, Fang Liu, MacKenzie A. Sayer, Megan M. Powell, Heidi J. Wehring, Robert W. Buchanan, James M. Gold, William T. Carpenter and William W. Eaton
J Psychiatry Neurosci July 01, 2019 44 (4) 269-276; DOI: https://doi.org/10.1503/jpn.180174
Deanna L. Kelly
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Haley K. Demyanovich
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Katrina M. Rodriguez
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Daniela Čiháková
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Monica V. Talor
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Robert P. McMahon
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Charles M. Richardson
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Gopal Vyas
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Heather A. Adams
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Sharon M. August
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Alessio Fasano
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Nicola G. Cascella
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Stephanie M. Feldman
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Fang Liu
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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MacKenzie A. Sayer
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Megan M. Powell
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Heidi J. Wehring
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Robert W. Buchanan
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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James M. Gold
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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William T. Carpenter Jr.
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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William W. Eaton
From the Maryland Psychiatric Research Center (MPRC), School of Medicine, University of Maryland, College Park, MD (Kelly, McMahon, August, Feldman, Liu, Powell, Wehring, Buchanan, Gold, Carpenter); the Department of Orthopedics, School of Medicine, University of Maryland, College Park, MD (Demyanovich); the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Rodriguez, Eaton); the Department of Pathology, Division of Immunology, Immune Disorders Laboratory, Johns Hopkins University, Baltimore, MD (Čiháková, Talor); the Spring Grove Hospital Center, Baltimore, MD (Richardson, Vyas, Adams); the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA (Fasano); the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD (Cascella); the Department of Psychology, Kent State University, Kent, OH (Sayer)
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Abstract

Background: Approximately one-third of people with schizophrenia have elevated levels of antigliadin antibodies of the immunoglobulin G type (AGA IgG) — a higher rate than seen in healthy controls. We performed the first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA IgG.

Methods: In this pilot feasibility study, 16 participants with schizophrenia or schizoaffective disorder who had elevated AGA IgG (≥ 20 U) but were negative for celiac disease were admitted to an inpatient unit for a 5-week trial. All participants received standardized gluten-free meals and were randomized in a double-blind fashion to receive a shake containing 10 g of gluten flour or 10 g of rice flour each day. Participants were rated for psychiatric, cognitive and gastrointestinal symptoms at baseline and end point.

Results: Of the 16 participants, 14 completed the 5-week trial (2 discontinued early for administrative reasons). Compared with participants on the gluten-containing diet, participants on the gluten-free diet showed improvement on the Clinical Global Impressions scale (Cohen d = −0.75) and in negative symptoms (Cohen d = −0.53). We noted no improvement in positive or global cognitive symptoms, but did observe an improvement in attention favouring the gluten-free diet (Cohen d = 0.60). Robust improvements in gastrointestinal adverse effects occurred in the gluten-free group relative to the gluten-containing group. Adverse effects were similar between groups.

Limitations: This study was limited by its small sample size; larger studies are needed.

Conclusion: This feasibility study suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder.

  • Received September 26, 2018.
  • Revision received December 17, 2018.
  • Accepted January 7, 2019.
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Journal of Psychiatry and Neuroscience: 44 (4)
J Psychiatry Neurosci
Vol. 44, Issue 4
1 Jul 2019
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Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study
Deanna L. Kelly, Haley K. Demyanovich, Katrina M. Rodriguez, Daniela Čiháková, Monica V. Talor, Robert P. McMahon, Charles M. Richardson, Gopal Vyas, Heather A. Adams, Sharon M. August, Alessio Fasano, Nicola G. Cascella, Stephanie M. Feldman, Fang Liu, MacKenzie A. Sayer, Megan M. Powell, Heidi J. Wehring, Robert W. Buchanan, James M. Gold, William T. Carpenter, William W. Eaton
J Psychiatry Neurosci Jul 2019, 44 (4) 269-276; DOI: 10.1503/jpn.180174

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Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study
Deanna L. Kelly, Haley K. Demyanovich, Katrina M. Rodriguez, Daniela Čiháková, Monica V. Talor, Robert P. McMahon, Charles M. Richardson, Gopal Vyas, Heather A. Adams, Sharon M. August, Alessio Fasano, Nicola G. Cascella, Stephanie M. Feldman, Fang Liu, MacKenzie A. Sayer, Megan M. Powell, Heidi J. Wehring, Robert W. Buchanan, James M. Gold, William T. Carpenter, William W. Eaton
J Psychiatry Neurosci Jul 2019, 44 (4) 269-276; DOI: 10.1503/jpn.180174
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