HLA-DQ Gluten Sensitivity in People with Schizophrenia

(HLA-DQ) Gluten Sensitivity in People with Schizophrenia

. (antibody response to dietary gluten peptides) Project: Molecular Characterization of Gluten Sensitivity in Schizophrenia  Armin Alaedini, PhD (Columbia University) Abstract: Genetic, immunologic, and environmental factors are believed to contribute to the etiopathogenesis of schizophrenia (SZ). Among various immune abnormalities, increased antibody response to dietary gluten has been found to be associated with SZ in recent studies. However, little is known about the molecular specificity of the anti-gluten immune response and its pathogenic relevance in the disease process. Our preliminary data show that the immune response to gluten in SZ is significantly different from celiac disease, the prototype of gluten sensitivity, appearing to involve a distinct mechanism and molecular specificity. The new data provide a strong rationale for in-depth examination of the humoral immune response to gluten in SZ. The current proposal represents a systematic approach to further assess the relevance of gluten in SZ through the following specific aims: 1) To characterize the molecular specificity of the anti-gluten immune response in SZ, and 2) To map the epitope specificity of the observed anti-gluten antibody response in SZ. The information that is expected to emerge if the aims of the proposed project are achieved will 1) offer novel biomarkers that may help in the identification of specific subsets of SZ patients or individuals at risk of developing SZ, 2) support closer examination of gluten exclusion diet as a treatment option in the identified patient subset(s), 3) offer novel clues about the pathogenic relevance of gluten in SZ and other neuropsychiatric conditions.

2012, Sept. Celiac disease and schizophrenia.  Brown JS Jr.  Am J Psychiatry. Sept. 2012

2012, July  Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia, Severance EG, Gressitt KL, Halling M, Stallings CR, Origoni AE, Vaughan C, Khushalani S, Alaedini A, Dupont D, Dickerson FB, Yolken RH, Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, epub July 16, 2012

2012, July  Proteomic, genomic and translational approaches identify CRMP1 (Collapsin response mediator protein 1) for a role in schizophrenia and its underlying Traits  Human Molecular Genetics, July 13, 2012 *

2012, June  Gastrointestinal Inflammation and associated immune activation in schizophrenia, Severance EG, Kannan G, Gressitt KL, Xiao J, Alaedini A, Pletnikov MV, Yolken RH.,  Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, Schizophrenia Research June, 2012

2012, March Markers of gluten sensitivity in acute mania: a longitudinal study, Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Yolken R, The Stanley Research Program at Sheppard Pratt, Baltimore, MD, USA, March 3, 2012  Abstract: Increased levels of antibodies to gliadin, which is derived from the wheat protein gluten, have been reported in schizophrenia and bipolar disorder in cross-sectional studies.  Among the individuals with mania, elevated levels at follow-up were significantly associated with re-hospitalization in the 6-month follow-up period. The monitoring and control of gluten sensitivity may have significant effects on the management of individuals hospitalized with acute mania.

2011, Jan. The environment and susceptibility to schizophreniaBrown AS, Dept. of Psychiatry, College of Physicians and Surgeons of Columbia University, NY, NY, Progress in Neurobiology Jan. 2011 Abstract: … Animal models, including maternal immune activation, have yielded evidence suggesting that these exposures cause brain and behavioral phenotypes that are analogous to findings observed in patients with schizophrenia
2010, May Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia, Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Leister F, Yang S, Krivogorsky B, Alaedini A, Yolken R. Stanley Research Program at Sheppard Pratt, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21204, USA, May 14, 2010  Conclusion: Individuals with recent-onset psychosis and with multi-episode schizophrenia who have increased antibodies to gliadin may share some immunologic features of celiac disease, but their immune response to gliadin differs from that of celiac disease.

2009, Dec. Neural basis of psychosis-related behavior in the infection model of schizophrenia Meyer U, Feldon J. Laboratory of Behavioural Neurobiology, ETH Zurich, Schorenstrasse 16, Schwerzenbach 8603, Switzerland, Behav Brain Res. 2009 Dec 7

2009, Oct.  Immune Influence on Adult Neural Stem Cell Regulation and Function Pamela A. Carpentier, Theo D. Palmer Neuron. Author manuscript; available in PMC Neuron. 2009 October 15

2009, Sept. Novel immune response to gluten in individuals with schizophrenia, Samaroo D, Dickerson F, Kasarda DD, Green PH, Briani C, Yolken RH, Alaedini A., Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, United States, E pub Sept. 11, 2009 (Schizophrenia Research May, 2010), Abstract: …findings indicate that the anti-gliadin immune response in schizophrenia has a different antigenic specificity from that in celiac disease and is independent of the action of transglutaminase enzyme and HLA-DQ2/DQ8. Meanwhile, the presence of elevated levels of antibodies to specific gluten proteins points to shared immunologic abnormalities in a subset of schizophrenia patients…

2009, Feb. Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literatureBryan D Kraft1 and Eric C Westman, Nutr Metab (Lond). 2009

1995, Mar. Specific IgA antibody increases in schizophrenia Karl L. ReicheltaJohan Landmark, Biological Psychiatry, 15 March 1995  “More schizophrenics than controls showed IgA antibody levels above the upper normal limit to gliadin, beta-lactoglobulin, and casein.” Department of Pediatric Research, Rikshospitalet, University of Oslo, Norway

1991 Reichelt KL (1991) Peptides in Schizophrenia. Biol Psychiatry 29: 515–516. doi: 10.1016/0006-3223(91)90283-RFind this article online

1980,  Diet (gluten) and schizophrenia, Ross-Smith P, Jenner FA, Journal of Human Nutrition, April, 1980  

1979  Dohan FC (1979) Schizophrenia and neuroactive peptides from food. Lancet 1: 1031. doi: 10.1016/S0140-6736(79)92780-6Find this article online

1976  The possible pathogenic effect of cereal grains in schizophrenia, Dohan FC, Acta Neurol (Napoli). , Mar-Apr, 1976

1976  Wheat gluten as a pathogenic factor in schizophrenia, Singh MM, Kay SR, Science, Jan, 1976, Abstract: Schizophrenics maintained on a cereal grain-free and milk-free diet and receiving optimal treatment with neuropleptics showed an interruption or reversal of their therapeutic progress during a period of “blind” wheat gluten challenge. The exacerbation of the disease process was not due to variations in neuroleptic doses. After termination of the gluten challenge, the course of improvement was reinstated. The observed effects seemed to be due to a primary schizophrenia-promoting effect of wheat gluten.   http://www.sciencemag.org/

1976  Letter: Gluten and schizophrenia, Singh MM, Kay SR, Lancet. Sep. 1976

1973  Schizophrenia, cereal grains, and celiac disease, Dohan FC, Del Medical Journal, Oct, 1973

1973  Relapsed schizophrenics: earlier discharge from the hospital after cereal-free, milk-free diet, Dohan FC, Grasberger JC, Am J Psychiatry. Jun. 1973

1970  Coeliac disease and schizophrenia. Dohan FC (1970)  Lancet 1: 897–898. Find this article online .
1969  Is celiac disease a clue to the pathogenesis of schizophrenia?, Dohan FC, Mental Hygeine, Oct. 1969
1969  Relapsed schizophrenics: more rapid improvement on milk and cereal-free diet, Dohan FC, Grasberger JC, Lowell FM, Johnston HT Jr, Arbegast AW., Br J Psychiatry. May. 1969


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