Deanna L. Kelly, PharmD; Haley K. Demyanovich, MPS; Katrina M. Rodriguez, MHS; Daniela Čiháková, PhD; Monica V. Talor, MSc; Robert P. McMahon, PhD; Charles M. Richardson, MD; Gopal Vyas, DO; Heather A. Adams, PsyD; Sharon M. August, MA; Alessio Fasano, MD; Nicola G. Cascella, MD; Stephanie M. Feldman, MSW; Fang Liu, MS; MacKenzie A. Sayer, BS; Megan M. Powell, BA; Heidi J. Wehring, PharmD; Robert W. Buchanan, MD; James M. Gold, PhD; William T. Carpenter, Jr., MD; William W. Eaton, PhD
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 glutencontaining 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.
Submitted Sep. 26, 2018; Revised Dec. 17, 2018; Accepted Jan. 7, 2019; Published online on Mar. 27, 2019
Acknowledgements: The authors thank the clinical and research team of the Treatment Research Program (TRP) at the Maryland Psychiatric Research Center (MPRC). The authors thank the nursing staff, who were instrumental in helping to maintain a gluten-free environment and helping with blood draws for screening, and the Outpatient Research Program (ORP) at the MPRC for their help in recruitment and screening. They also thank the many students, residents and fellows who spent countless hours with participants that helped with cooking classes and study integrity. They thank numerous students and trainees for their help over the years with the study, manuscript preparation and data analysis. Lastly, the authors thank the Research Pharmacist for his work in the preparation of the intervention materials. Preliminary data were presented at the Schizophrenia International Research Society Meeting in Florence, Italy, in April 2018.
Affiliations: 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).
Funding: This study was funded by NIMH R34 (NIMH R34 MH100776; PIs: Eaton and Kelly). Preparation of this paper was supported by NIMH grant R01 MH113617; PIs: Kelly and Eaton. Clinical Trials.gov NCT01927276.
Competing interests: D. Kelly served as an advisor to Lundbeck and HLS Therapeutics. A. Fasano is the founder and a stock holder of Alba Therapeutics. R. Buchanan served on the advisory boards for Astellas Pharma, Avanir, Boehringer Ingelheim-RCV, ITI, Inc., Lundbeck and Roche. He was a consultant for Takeda and Upsher-Smith Laboratories and on the DSMB for Pfizer. W. Carpenter has served as an advisor to Boehringer Ingelheim, Allergan, Health Analytics and Teva. All other authors have nothing to disclose.
Contributors: D. Kelly, H. Demyanovich, D. Čiháková, M. Talor, R. McMahon, A. Fasano, N. Cascella and W. Eaton conceived and designed the study. D. Kelly, H. Demyanovich, K. Rodriguez, M. Talor, C. Richardson, G. Vyas, H. Adams, S. August, S. Feldman, M. Sayer and M. Powell acquired the data, which D. Kelly, H. Demyanovich, R. McMahon, F. Liu, H. Wehring, R. Buchanan, J. Gold, W. Carpenter and W. Eaton analyzed. D. Kelly, H. Demyanovich, D. Čiháková, M. Talor, R. McMahon, H. Adams, M. Sayer, H. Wehring, R. Buchanan, J. Gold, W. Carpenter and W. Eaton wrote the article, which D. Kelly, H. Demyanovich, K. Rodriguez, D. Čiháková, M. Talor, C. Richardson, G. Vyas, H. Adams, S. August, A. Fasano, N. Cascella, S. Feldman, F. Liu, M. Powell, H. Wehring, R. Buchanan, J. Gold, W. Carpenter and W. Eaton reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Correspondence to: D. Kelly, Maryland Psychiatric Research Center, University of Maryland School of Medicine, PO Box 21247, Baltimore, MD, 21228; firstname.lastname@example.org