Gluten-brain Connection

The Celiac Disease of Mental Illness

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(derived in large part from a lecture James V. Croxton, M.A. summer 2002)

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Although often referred to as “wheat allergy,” Celiac Disease (also called Celiac Sprue) is not an “allergy” but rather an intolerance to the protein in gluten, a substance found in wheat and other grains. For susceptible people, gluten injures the small intestinal lining (called “villi”) that takes in nourishment. The mental disorders that Celiac brings to a child and adult are due to both the malnutrition caused by the damage to the small intestine and to the by-products of gluten metabolism.

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Professor F. C. Dohan of the University of Pennsylvania was the first researcher to use this concept, beginning in the late 1960’s. He quoted from earlier researchers in his article published in The Biological Basis of Schizophrenia (Hemmings, ed; MTP Press; London, 1980).
 
Celiac disease may present with psychiatric symptoms, which, in association with other symptoms, may be of diagnostic help… Kaser (1961) described celiac  children as showing definite symptoms in all cases. The children are conspicuously quiet, turned, inward, often weepy, often discontented or surly and apparently lack all joy in living. They can take on negativistic and schizoid characteristics and may execute ceaseless stereotyped movements. Paulley wrote in 1959: many (adult celiacs) showed extreme obsessional neuroses, suffering delusions, frequently believing they had cancer. Paranoid ideas were also frequent and many were considered psychotic or near psychotic.

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In the 1960’s and 70’s it was thought that there were only about five infants out of 10,000 born with this strongly genetic disorder.  The idea that that very small could account for many of the large number of schizophrenics in the general population did not appear reasonable. So the “celiac model” for explaining the development of schizophrenia did not catch on.  The incidence of this disease has changed, however, and estimates now are stated to be as high as 1 in 250 in the American population.

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If the increase in celiac disease is real, it might be because there is more gluten being consumed: “gluten enteropathy” is another term for this illness.  Gluten is useful in cooking because it promotes a resistant, “chewy” mouth-feel to many foods including baked goods.  Also, as the amount of convenience foods increases (such as pizza) we probably consume more foods with gluten-containing grains as ingredients. Another factor exists which does not have to do with our food intake: the diagnostic criteria for celiac disease have changed over the years.  Twenty and thirty years ago, the “gold standard” for diagnosing this illness was to do a biopsy of the small intestine. Now it is being realized that there are individuals with celiac disease who do not have typical intestinal biopsies that show atrophy of the villi or other signs of tissue damage in the gut-wall.

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A different factor in the celiac model emerged in the late 1990’s based on newly appreciation roles of glial cells in the brain – those cells which make up about one-half of the brain’s mass.  Before the last decade the glia were characterized as “support cell” with no clear functions.  It is now appreciated that glia are capable of being activated as immune system agents.  Glia do engage in “signaling” activity (sending “messages” to each other and perhaps even to neurons).  Glia have “conversations” with each other and have the potential for neuronal signaling.

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This change in appreciation of glial cells’ importance is a bit like “not seeing the forest for the trees.” Consider the brain’s neurons are like the trees in a forest, they have received the bulk of research over the years.  The other entities in the forest (the underbrush, the ferns, the ground-cover plants) were harder to see and had more subtle effects on the total system.  (Actually, glial cells did not take the early stains well and were much more difficult to see and to study.)  Today we are more sensitive to the challenge of understanding the complexities of the brain as an ecosystem.

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Recent successes with two kinds of therapy provide some indirect support for the connection of celiac disease with mental illness.  Gluten-free diets (sometimes combined with dairy-free) have been used for autism, depression and schizophrenia.  When troublesome proteins, especially alpha-gliadin in gluten and casein in milk are avoided, marked improvement has been reported by a number of individuals with these brain biochemistry disorders.  The other therapy is to use essential fatty acids (emphasizing Omega 3, “cold-water fish” oils) with the same illnesses.  The NIH has funded studies for these therapies.

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Many adult celiacs who have not been diagnosed and are not following a strict gluten-free diet have some of the same symptoms as persons diagnosed with schizophrenia and other mental, psychological, or emotional disorders.  Perhaps those symptoms- some of which were present to a lesser degree in childhood- are exacerbations of the earlier, weaker ones.  Of course a large number of social factors are also relevant and or many seem work against them.  The loss of friends and relatives who no longer show care and affection cannot be ignored.

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In “sensitive” people who are genetically predisposed to this celiac disease, malabsorption of significant nutrients including B vitamins, essential fatty acids, some minerals (calcium and zinc, for instance) compound the mental and emotional component. Malabsorption can stunt the stature of children, slow the maturation rate, create an over-sensitive or irritable brain tissue, and perhaps alter the learning styles (sensory perception issues) of these children. Because gluten enteropathy is, in part, an immune system disorder originating in the wall of the small intestine, any amount of gluten from wheat, rye, barley, and oats keeps the immune system activated, which in turn may result in “spreading” of symptoms.  It is hypothesized that organ systems not apparently involved during childhood become involved as the child ages. What began in the gut seems to move through the body, affecting lung function, the skin, and even the brain. Again, evidence to support such a theory is based on the effect of gluten avoidance – less mucus and bronchial symptoms, clearer skin, improved cognition, stabilization of mood, etc.

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In addition to the biochemical and immune effect of gluten, the loss of nutrients would result in loss of some of the supportive tissue (glial cells) which would lead to larger cerebral ventricles (they would expand by default into areas where the glia have been lost), deeper sulci (the crevices apparent in the cortical surface of the brain), narrower gyri (the humps on the cortical surfaces), and perhaps the disarrangement of neurons positioned in infancy and early childhood.

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Since the fats and oils we eat become both structural and functional components of the “barrier” membranes in our bodies, such as the cell membranes, gut wall and the blood-brain barrier, another result of lipid malabsorption could be a less-reliable blood-brain barrier. In those parts of the brain where the blood-barrier is purposely “thin,” such as areas close to the middle of the brain (parts of the hypothalamus and the pituitary gland – the paraventricular regions) the insufficient or imbalanced lipid components certainly would be expected to affect many functions. These areas of the brain have much to do with basic motives and behaviors dealing with food intake, thirst, sexuality, sleep regulation, etc.

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Another factor is related to the concept “cerebral allergy.”  This is a concept supported by just a few hundred medical doctors and psychiatrists. It became increasingly apparent in the 1990s that there are immune system defenses in the brain, and that the microglia can be recruited and even reprogrammed to do the work. Experiments show that microglia can be stimulated to “change roles” and produce a cascade of cytokines (the “cell-movers” that can produce, maintain and increase the inflammation response. Because we cannot feel brain tissue – it is not “engineered” to signal to us its own changes – hence there is no pain, itching, etc. Inflammation involves swelling, increased blood flow, increased temperature, itching or pain or both – none of this can be felt in the brain unless severe. This must be one of the strongest reasons for people with brain-based disorders denying that anything is wrong with their brains.

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The cerebral allergy concept depended on the assumptions of clinicians who believed that brain tissue is subject to “local Inflammation” and that this caused unusual or abnormal symptoms. The “allergens” could be proteins in foods such as alpha-gliadin in wheat, volatile gases such as fumes of toluene, certain chemicals in perfumes or cosmetics, and so on. The symptoms could be very diverse: unusual behaviors (paralleling symptoms of toxic psychosis), altered motivations (changes in hunger or sexuality), sudden emotional upsets (intense, unreasonable jealousy or inexplicable grief), etc. Any of these, along with altered perceptions and thinking, can happen. Neurons and glia function differently (“abnormally”) when disturbed by heat, pressure, pH changes and cytokine effects.

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In this hypothesis, celiac disease could be a specific kind of cerebral allergy, with ongoing disruption in gut tissue, and increasingly intense and diverse symptoms involving depression, paranoia, hallucinations and delusions (but not all of these at once). The good news is that celiac disease, when identified early enough, is controlled with a very careful diet. You never get over the illness, but you also never get over being glad you found out what it was.

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From an informal survey of about 20 people with gluten related sensitivity, >90% reported improvement from a gluten-free diet.  All spoke of delayed learning prior to a gluten free diet either in themselves or their children.  Some of the physiological, cognitive, and emotional symptoms they reported with dietary avoidance of gluten included:

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• Improved ability to learn

• Improved interest in school

• Improved concentration

• No more meds for depression problems

• No more avoidance of meeting people

• Expected full recovery of ataxia problems (inability to coordinate muscle movements)

• Improved gross motor skills (was delayed in some cases)

• Improved physical growth (was smaller than expected)

• Went from bottom of class to the top of his class after 3 months on diet

• Found a “hunger” for learning after avoiding gluten

• Improved mood with less “crossness” and “crankiness”

• Improved development to catch up with peers

• Improved intellect with definite increases in intelligence

• Grade point average went from 2.5 to 3.9

• Many have acquired college degrees with high gpa after going gluten-free

• Came alive academically

• Improved ability to meet daily challenges

• Improved speed of learning (“quicker” in her studies)

• Absenteeism no longer a problem

• Lots of stories about coming out of withdrawn state socially to an outgoing one — running for student council, more motivated in doing well and meeting people

• Increased well-being and better brain chemistry

• No more “brain fog”

• Improved in reading (“noticeable”)

• Improved temperaments in children

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Before going gluten-free, students had the following difficulties/complaints:

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• Daydreaming in school

• Difficulty in finishing sentences and finding words

• Speech delay

• In and out of Special Education classes

• Delays in walking and talking

• Delayed puberty including menarche

• Vitamin deficiencies

• Non-epileptic seizures

• Arthritis and osteopenia

• Short term and long term memory was not good

• Many reports of struggles with school but score high in intelligence

• Misdiagnosis of fibromyalgia

• Visual and auditory delusions

• Anxiety problems, tummy aches

• Temporary dyslexia

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1. K. Horvath, MD, PhD, et al; Gastroenterology, April 1996: “First Epidemiological Study of Gluten Intolerance in the United States”

2. Etty Benveniste, PhD.; American Journal of Physiology 263, 1992: “Inflammatory Cytokines within the central nervous system: sources, function, and mechanism of action”

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P.S. – There is a urine test (IAG – AAL #6500) that may give some insight into gluten and casein intolerance based on the metabolic by-products of these grain and dairy components.  It can be helpful in identifying hidden gluten in the diet or patients who might be susceptible to the metabolic effects of gluten and dairy.