Gluten Sensitivity in Schizophrenia


Topping the list of nutritional orthomolecular therapies is the elimination of gluten. This is recommended for cases of schizophrenia, depression, anxiety, ADD, and OCD.

The West is the Best … a common saying but few know that along with the cultural diversity of Westernization came an agricultural mono-cropping boom. The food industry launched widespread availability of low cost wheat and gluten containing products into our local grocery stores. Wheat-derived gluten-based fillers bulk up foods and add structural elasticity. The list of gluten-filled products is endless … junk food, candy, gravy, meat, pasta, pizza, bread, etcetera. Too much of one thing however, is not good for the body. Gluten protein overload had to be dealt with by the end-user, us, the consumer. An immune response from the individual consumer was inevitable. Our metabolisms, especially if genetically predisposed, often refuse to accept constant bombardment of big proteins. Large proteins such as gluten (or dairy’s casein and whey) are just as much not considered a part of ‘self’ as are the proteins of pathogenic bacteria which trigger mild to severe immune responses. Immune responses vary, some are immediate and others not uncommonly are delayed. This is the accepted basic premise behind food allergies including gluten. Food allergies are also called food sensitivities, food intolerances, or in the context of mental health, brain or cerebral allergies. The treatment is dietary elimination and gluten diets are simple and effective if you implement good purchasing and cooking habits and, limit your intake of the more processed gluten-free products.

Abstract 1

Cascella NG, Kryszak D, Bhatti B, Gregory P, Kelly DL, Mc Evoy JP, Fasano A, Eaton WW. Prevalence of celiac disease and gluten sensitivity in the United States clinical antipsychotic trials of intervention effectiveness study population. Schizophr Bull. 2011 Jan; 37(1): 94-100. Epub 2009 Jun 3. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 144, Baltimore, MD 21287, USA. PubMed free full text article.

Celiac disease (CD) and schizophrenia have approximately the same prevalence, but epidemiologic data show higher prevalence of CD among schizophrenia patients. The reason for this higher co-occurrence is not known, but the clinical knowledge about the presence of immunologic markers for CD or gluten intolerance in schizophrenia patients may have implications for treatment. Our goal was to evaluate antibody prevalence to gliadin (AGA), transglutaminase (tTG), and endomysium (EMA) in a group of individuals with schizophrenia and a comparison group. AGA, tTG, and EMA antibodies were assayed in 1401 schizophrenia patients who were part of the Clinical Antipsychotic Trials of Intervention Effectiveness study and 900 controls. Psychopathology in schizophrenia patients was assessed using the Positive and Negative Symptoms Scale (PANSS). Logistic regression was used to assess the difference in the frequency of AGA, immunoglobulin A (IgA), and tTG antibodies, adjusting for age, sex, and race. Linear regression was used to predict PANSS scores from AGA and tTG antibodies adjusting for age, gender, and race. Among schizophrenia patients, 23.1% had moderate to high levels of IgA-AGA compared with 3.1% of the comparison group (χ(2) = 1885, df = 2, P < .001.) Moderate to high levels of tTG antibodies were present in 5.4% of schizophrenia patients vs 0.80% of the comparison group (χ(2) = 392.0, df = 2, P < .001). Adjustments for sex, age, and race had trivial effects on the differences. Regression analyses failed to predict PANSS scores from AGA and tTG antibodies. Persons with schizophrenia have higher than expected titers of antibodies related to CD and gluten sensitivity.

Point 1

So there is medical recognition that a severe mental illness population of schizophrenics, in this example, have a definate biochemical imbalance with the way that their bodies deal with wheat, rye, and barley proetins. 

The IgG Elisa Gluten antibody screen, if done here, may have shown greater prevalence of food intolerance among schizophrenics. In clinic I only do IgG/IgE Elisa  antibodies measures if patients want to see results on paper before doing diet changes. Thew down side to testing is that it has limitations and every 4 or 5 patients tested will show negative results due to the complexity of the immune system but, just because the test didn’t show it, doesn’t mean it doesn’t exist and affect the patient profoundly. 

So I encourage gluten elimination because its actually more accurate. If you simply commit to elimination diet for 3 weeks you will see if you feel better (mental state, digestion, energy) and, when you re-introduce gluten, if your symptoms come back, and this is reproducable (i.e. even inadvertant consumption of gluten provokes negative responses), its diagnostic. I see a trend of about 50+% of schizophrenics having some degree of gluten sensitivity and this is typically determined easily by a simple elimination diet trial.


Abstract 2

Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Leister F, Yang S, Krivogorsky B, Alaedini A, Yolken R. Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia. Biol Psychiatry. 2010 Jul 1;68(1):100-4. Epub 2010 May 14. (Stanley Research Program at Sheppard Pratt, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21204, USA.)

BACKGROUND: Increased immune sensitivity to gluten has been reported in schizophrenia. However, studies are inconsistent about this association.

METHODS: The sample of 471 individuals included 129 with recent-onset psychosis, 191 with multi-episode schizophrenia, and 151 controls. Immunoglobulin (Ig)G and IgA antibodies to gliadin and to tissue transglutaminase, and IgG antibodies to deamidated gliadin were measured. Quantitative levels of antibodies in the psychiatric groups were compared with controls. All participants were categorized as to whether their levels of antibodies met standardized cutoffs for celiac disease. HLA DQ2 and HLA DQ8 alleles were detected by real-time polymerase chain reaction.

RESULTS: Individuals with recent-onset psychosis had increased levels of IgG (odds ratio [OR] 5.50; 95% confidence interval [CI] 2.65-11.42) and IgA (OR 2.75; 95% CI 1.31-5.75) antibodies to gliadin compared with control subjects. Individuals with multi-episode schizophrenia also had significantly increased levels of IgG antibodies to gliadin (OR 6.19; 95% CI 2.70-14.16). IgG antibodies to deamidated gliadin and IgA antibodies to tissue transglutaminase were not elevated in either psychiatric group, and fewer than 1% of individuals in each of the groups had levels of these antibodies predictive of celiac disease. There were no significant differences in the distribution of the HLA DQ2/8 alleles among the groups.

CONCLUSIONS: 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.

Point 2

Gliadin is a big protein and it is found in oats and, it is structurally similar in to gluten. Here in this research we see IgG gliadin antibody tests showing significant elevations in schizophrenia. This shows that gliadin food intolerance is a real entity in schizophrenia. Gliadin is therefore important to eliminate in schizophrenic populations. Indeeed, I see a majority of schizophrenic cases with gluten intolerance who also need to avoid gliadin (oats).  The Gluten IgG or IgE antibody test was unfortunately not assessed here. This important research effort tells us that gliadin is associated with but not necessarily a causative factor of schizophrenia. If the patient feels better eliminating oats then I say this is a step in the right direction. I have patients that become psychotic quickly after eating gluten or gliadin containing products and this negative response reinforces their need to avoid foods (negative reinforcement behaviour) containing these big proteins. Negative responses not only keep my patients compliant, but it also puts them in a position to acheive greater mental health.  

Abstract 3

Dohan FC. Genetic hypothesis of idiopathic schizophrenia: its exorphin connection. Schizophr Bull. 1988;14(4):489-94. (Medical College of Pennsylvania, Eastern Pennsylvania, Psychiatric Institute, Philadelphia 19129.)

This brief overview proposes a testable oligogenic model of the inheritance of susceptibility to idiopathic schizophrenia: “abnormal” genes at each of a few complementary loci. The model is based on my assumptions as to the likely genetic abnormalities at possibly four or five interacting loci that would permit exorphins, the opioid peptides from some food proteins, especially glutens and possibly caseins, to go from gut to brain and cause symptoms of schizophrenia. Exorphins may reach the brain cerebrospinal fluid (CSF) in harmful amounts because of their genetically increased, receptor-mediated transcellular passage across the gut epithelial barrier plus decreased catabolism by genetically defective enzymes. A schizophrenia-specific, genetically enhanced affinity for exorphins by opioid receptors influencing dopaminergic and other neurons would permit sustained dysfunction at low CSF exorphin concentrations. Tests of each postulated genetic abnormality are suggested. This model is supported by a variety of evidence, including a significant effect of gluten or its absence on relapsed schizophrenic patients, the high correlation of changes in first admission rates for schizophrenia with changes in grain consumption rates, and the rarity of cases of schizophrenia where grains and milk are rare.

Point 3

The clinical trials mentioned in this article show clear psychotic worsening with exposure to gluten and psychotic improvement without exposure to gluten. The geographic distribution of schizophrenia is not uniform and we see more schizophrenia in areas of the world where grain consumption is higher.

As a side note it is important to recognize dairy allergies as well, not only in schizophrenia, but also in depression, anxiety, ADD, and OCD. I find significant dairy intolerance in about 10 to 20% of my schizophrenic cases as determined by diet elimination.