Coeliac Disease (Gluten intolerance) and Schizophrenia

Coeliac Disease

• Coeliac disease (CD) is a gastro-intestinal (GI) disorder caused by an autoimmune reaction to gluten (a protein found in wheat and some other cereal grains). Formal diagnosis rests on specific damage to the gut lining being revealed via surgical biopsy. As this procedure is highly invasive, symptoms may be present for years before the diagnosis is finally made.
• A gluten-free diet is the standard treatment for CD. This is effective in reducing the GI symptoms such as diarrhoea, malabsorption and weight loss. Gluten avoidance also appears to prevent further intestinal damage but does not reverse this, so the earlier a diagnosis is made, the better.
• Until recently, CD was thought to affect only around 1 in 1500 of the general population. Blood tests can now identify the antibodies involved, however, and have shown that these are present in around 1 in 200 people. Although many of these people have no obvious gut-related symptoms that might lead to investigation of CD – some studies have raised the possibility that the presence of these antibodies might in some cases be linked with otherwise unexplained neurological symptoms.

Gluten Intolerance and Schizophrenia

• A controlled clinical trial published by Dohan in 1966 first suggested that a gluten-free diet could reduce symptoms in some patients with schizophrenia. Subsequent studies failed to replicate these findings, and although case reports have continued to provide some support for this idea, there was little systematic investigation until recently.
• Debate was re-opened by Eaton et al (2004) who studied case records from 7997 psychiatric patients in Denmark, each matched by sex and year of birth with 25 control subjects. Taking into account other known risk factors, they found that the chances of developing schizophrenia were 3.2 times higher than expected in people with a history of CD. No significant increase in risk for schizophrenia was found for two other auto-immune gastro-intestinal conditions (ulcerative colitis and Crohn’s disease).
• This study considered only CD occurring before the diagnosis of schizophrenia, and diagnosed via hospitals or specialist clinics. Classical clinical symptoms of CD affect only a fraction (less than one in seven) of people who test positive for the gluten-related antibodies involved, so the authors acknowledge that CD was almost certainly underestimated in this study. They also emphasised that although the risk relationship found here was strong, it could account for only a small proportion of cases of either disorder, because both CD and schizophrenia are rare.
• Criticisms of the conclusions drawn, and a response by Eaton were published in a subsequent issue of the BMJ.
• Since then, one UK study based on data from the GP research register found no evidence for an increased risk of schizophrenia in people with CD, Crohn's disease or Ulcerative Colitis (West et al 2006).. There appear to be no data yet on the prevalence of positive antibody reactions to gluten (indexing 'silent' as well as overt CD) in schizophrenia patients versus controls.
• Without further data, it is difficult to disagree with the conclusions of Eaton et al (2004): “Removal of gluten from the diet is not dangerous or expensive and is an effective treatment for coeliac disease. Failure of replication in earlier clinical trials of gluten withdrawal (in schizophrenia) may have been the result of sampling fluctuation since coeliac disease is rare. New screening tests for coeliac disease are inexpensive and carry minimal risk and discomfort. An important question is the degree to which removal of gluten from the diet will alleviate symptoms in the small proportion of people with schizophrenia who screen positively for coeliac disease but do not show its classical symptoms”

References and Further information

Further information on this and related topics is available from the following sources (accessible via this web site)

• Eaton et al (2004). Coeliac disease and schizophrenia. BMJ, 328:438-9.
• Campbell and Foley (2004). Coeliac disease and schizophrenia: data do not support hypothesis BMJ, 328(7446): 1017; author reply by Eaton, 2004BMJ, 328(7446):1017.
• West et al (2006). Risk of schizophrenia in people with coeliac disease, ulcerative colitis and Crohn's disease: a general population-based study. Aliment Pharmacol Ther. 23(1): 71-4.
• Luostarinen et al (2003). Neuromuscular and sensory disturbances in patients with well treated coeliac disease. J Neurol Neurosug Psychiat, 70(4): 490-4.
• Volta et al (2002). Clinical findings and anti-neuronal antibodies in coeliac disease with neurological disorders. Scand J Gastroenterol. 2002 Nov;37(11):1276-81.
• Wills & Unsworth (2002). The neurology of gluten sensitivity: separating the wheat from the chaff. Curr Opin Neurol. 2002 Oct;15(5):519-23.
• De Santis et al (1997). Schizophrenic symptoms and SPECT abnormalities in a coeliac patient: regression after a gluten-free diet. J Intern Med. 242(5): 421-3.
• For further information on Coeliac Disease, see also Coeliac UK a UK-registered charity.
• For further information on Schizophrenia, contact the Schizophrenia Association of Great Britain, also a UK-registered charity.