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Unexpected Health Risks Found in Celiac Patients


 

Children diagnosed with celiac disease usually experience complete remission once they are started on a gluten-free diet, and thus early diagnosis can be beneficial. But early diagnosis may have adverse effects as well. A large British study has found that a diagnosis of celiac disease in childhood, as opposed to adulthood, is associated with threefold higher mortality–largely due to suicide, accidents, and violence.

The findings are “really surprising and unexpected,” according to Dr. Stefano Guandalini, chief of pediatric gastroenterology and director of the Celiac Disease Program at the University of Chicago. As one of the reviewers of the British study, he said he is confident that the increased mortality is more than a chance finding, but the reasons for it are open to interpretation. “One certainly cannot ignore this report; it's a well-done study,” he said in an interview.

The investigators analyzed data on a cohort of 625 celiac patients and found that those who were diagnosed in childhood (47%) had mortality rates three times higher than would be expected in the general, age-matched population, “with the main cause of the increase being deaths from accidents, suicide, and violence,” reported Dr. Masoud Solaymani-Dodoran and colleagues from the University of Nottingham (England). This increase was not seen in the cohort diagnosed in adulthood (Am. J. Gastroenterol. 2007;102:864-70).

“One explanation for this could be the psychological status of the children and possible changes in their risk-taking behaviors,” said Dr. Solaymani-Dodoran in an interview. The median age at diagnosis was 1.5 years in study subjects diagnosed in childhood (compared with 46 years in those diagnosed as adults), with the threefold increased mortality risk remaining through adolescence and beyond, to more than 25 years after diagnosis.

The Effect of Nonadherence

“Unfortunately [the researchers] had no available data to tell us what percentage of the subjects was on a gluten-free diet,” Dr. Guandalini said in an interview. Nonadherence with the diet has been reported, in other studies, in up to 60% of celiac patients during the rebellious teenage years.

This could explain the increased mortality, he suggested, because in some celiac patients, dietary lapses can have a dramatic effect on the brain. Gluten restriction is recommended, both to relieve the myriad and varied symptoms of celiac disease–ranging from dental to dermatologic to neurologic–and to reduce the potential long-term effects of prolonged exposure, including osteoporosis and malignancies.

“My speculation is that most of these deaths occurred in people who were not following the diet, and this caused the behavioral and psychiatric milieu that would lead to that kind of outcome,” he said.

Finnish authors have suggested that exposure to gluten in adolescents with celiac disease can impair the availability of tryptophan “and the possible consequent serotonergic dysfunction may play a role in vulnerability to depressive disorders” (BMC Psychiatry 2005;5:14-9). They noted that five of nine newly diagnosed, untreated adolescent celiac patients had depressive disorders and abnormal tryptophan levels, all of which improved after gluten was removed from their diets.

“I am personally convinced that eating gluten if you have celiac disease really induces serious changes in brain chemistry that would make you inclined to aggressive, depressive behavior and therefore expose you to this risk,” said Dr. Guandalini, who has seen such psychiatric effects in a celiac patient as young as 5 years old.

The Impact of Adherence

“We know adherence [to the diet] and depression and anxiety are related,” said Jessica Edwards George, Ph.D., psychologist and researcher at The Celiac Center at Beth Israel Deaconess Medical Center in Boston. But the relationship between adherence and psychological symptoms is not well understood, she said in an interview. Just as poor adherence is linked with psychiatric pathology, so too is good adherence–an aspect highlighted by the British authors.

“The actual process of labeling a child with celiac disease and requiring them to adhere to a gluten-free diet may be, in some way, detrimental,” they wrote. “As treatments go, taking a gluten-free diet must rank as one of the most intrusive for a child–more so than something like, for example, epilepsy or asthma,” coauthor Dr. Richard Logan said in an interview. “We wondered what were the psychological effects on a child of being brought up with a condition whose treatment has such a profound effect on daily life–something I suspect most adult gastroenterologists overlook.”

The psychological research on adults regarding this question leaves little open to debate: “There's a lot of anger and frustration about the rigidity of the diet, as well as the fact that it is chronic,” said Sharon Jedel, Psy.D., a clinical psychologist at Rush University's adult celiac disease program in Chicago. Furthermore, “a child doesn't necessarily have the developmental capacities to cope the way an adult might.”

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