Coeliac disease in primary care

E.V. O'Flaherty raises the interesting observation that coeliac
disease may present as psychosis.[1] Both O'Flaherty's commentary and
Jones' editorial [2], however, omit other neuropsychiatric clinical
manifestations and their possible causes. In an attempt to explain them, I
will summarize two theories. The first involves a direct nutritional
consequence and the latter a shared genetic susceptibility.

In severe malabsorption, there are diminished amino acid precursors
for neurotransmitter synthesis. Notably, altered serotonin and melatonin
may result from decreased bio-available tryptophan. Also, catecholamines
(e.g., dopamine, epinephrine, norepinephrine) are underexpressed in
tyrosine deficiency. Pynnonen et al. followed nine adolescents with
coeliac disease and noted significantly lower tryptophan levels in
patients also with depression.[3] Moreover, a gluten-free diet mitigated
many of the psychiatric symptoms--suggesting a direct nutritional
relationship without permanent pathology.

Newer theories have delved more into the convergence of genetic
etiology and a pathogenesis between coeliac disease and behavioral and
neurological disorders.

A general population cohort study in Sweden showed an increased risk
for non-affective psychosis in individuals with coeliac disease.[4] This
may be explained by an interesting hypothesis that the disease process
permits psychosis-inducing agents to enter the circulation, thereby
inciting schizophrenia and other mental conditions. Wei and Hemmings
suggest that transmembrane barrier proteins (such as DQB1 and CLDN5,
associated with coeliac disease) are the causal genes for schizophrenia
susceptibility in coeliac disease.[5]

The authors of the altered barrier protein theory specifically
address the potential for psychosis-inducing compounds. However, many
"idiopathic" neuropathologies are theorized to be due to gluten
sensitivity, including cerebellar ataxia and peripheral neuropathy.
Recently, anti-ganglioside antibodies have been linked to neurological
impairment.[6] Gluten-free diets do not eradicate the neurological
involvement, suggesting a more permanent pathology. A solid pathway has
yet to be identified. Perhaps the absorption of otherwise undigested
"foreign" compounds illicits a humoral immune response. The antibodies may
have affinity to the gangliosides and other neuronal structures, or these
structures may house the absorbed foreign compound causing their
destruction. In any event, we need further research on the impact of
coeliac disease on the mind.

References

1. O'Flaherty EV. Coeliac disease may manifest itseslf as psychosis.
eBMJ 2007.

2. Jones R. Coeliac disease in primary care. BMJ 2007;334:704-5.

3. Pynnonen PA et al. Gluten-free diet may alleviate depressive and
behavioural symptoms in adolescents with coeliac disease: a prospective
follow-up case-series study. BMC Psychiatry 2005;17;5:14.

4. Ludvigsson JF et al. Coeliac disease and risk of schizophrenia
and other psychosis: a general population cohort study. Scand J
Gastroenterol 2007;42(2):179-85.

5. Wei J and Hemmings GP. Gene, gut and schizophrenia: the meeting
point for the gene-environment interaction in developing schizophrenia.
Med Hypotheses 2005;64(3):547-52.

6. Volta U et al. Anti-ganglioside antibodies in coeliac disease
with neurological disorders. Dig Liver Dis 2006;38(3):183-7.

Competing interests:
None declared