Multiple Causes Suspected : Brain May Have Key Role in Development of Ulcers

When Austrialian gastroenterologist Barry Marshall gulped down a vial of bacteria five years ago, he not only resurrected the idea of self-experimentation but laid the foundation for the germ theory of ulcers.

The campylobacter cocktail caused stomach cramping, bad breath and an erosion of stomach tissue, giving the first scientific hints of a bacterial role in the development of ulcers, one of the most common gastrointestinal diseases.

But Dr. Daniel Hernandez, a gastroenterologist at USC, thinks that something far more subtle may be at work.

Stress Implicated

While stress has been implicated for years as the most common factor in the cause of the raw, penetrating sores made ever more painful by the continual bath of strong stomach acids, Hernandez has begun to look to the brain for clues.

In his laboratory, where ulcer-afflicted rats are monitored daily, he has developed promising evidence that ulcer formation may be directly related to brain chemistry, a hypothesis that he estimates is more than 200 years old.

Hernandez and his colleagues have identified an area of the lower brain stem as the site of specific hormonal activity that stimulates stomach acid secretion, lending credence to his notion that ulcers may be inextricably tied to neurochemistry.

“The classical approach to the cause of gastric ulcers has been to look at the stomach itself mainly because that is the site where the actual disease occurs,” explained Hernandez, an associate professor in the department of gastroenterology at USC’s School of Medicine.

“So because of that, a great deal of interest has been generated in specific studies to determine what mechanisms in the stomach cells may be involved in the onset of gastric ulcers.

Mechanism Elusive

“Evidence that the brain is involved in producing stress ulcers has existed for more than 200 years.

“But the specifics as to how they’re formed or the mechanisms involved in the onset have remained elusive,” he said.

Hernandez and his team have isolated thyrotropin-releasing hormone (TRH) and the site in the brain stem related to its activity. They have concluded, at least in rat studies, that TRH can precipitate ulcers.

This is not to say that researchers will abandon the germ origin idea.

“It’s a good hypothesis,” said Dr. Richard McCallum, chief of gastroenterology at the University of Virginia, Charlottesville. “There’s a lot of good scientific data to support it but it still needs some tightening up.”

‘No Single Cause’

Dr. Gary B. Glavin, a specialist in the study of ulcers at the University of Manitoba in Winnipeg, Canada, said because ulcers are a multifaceted disease, any of the new theories of ulcer formation may be correct.

“There’s no question that these theories can exist side by side,” he said comparing work exploring a bacterial cause and experiments such as those being conducted by Hernandez. “This is not a disease that has a single cause.”

Indeed, studies conducted at Johns Hopkins University in Baltimore by Dr. Solomon Snyder also suggest that brain chemistry may play a role in the development of ulcers in either the stomach or duodenum, the upper section of the small intestine that connects to the stomach.

Snyder’s investigations of patients with Parkinson’s disease, a degenerative neurological disorder characterized by low levels of the neurotransmitter dopamine, reveal a higher than usual incidence of gastrointestinal ulcers.

But schizophrenics, who produce a higher than usual level of the same brain chemical, have a lower than normal rate of ulcers, the studies show.

“My hypothesis is that the actual etiology or cause of ulcers resides in the brain and this contention is based on the function of the nerves that control the gastrointestinal tract,” Hernandez said.

Ulcers, for years, have posed a dilemma for medical science because they can bleed and in cases of massive hemorrhaging result in death. Treatment has included an adjustment in diet and administration of medicines that inhibit production of gastric acid, which can erode the protective mucous lining of the stomach.

In some extreme instances surgery is the preferred method of treatment. It involves severing the vagus nerve, which originates in the brain stem and is associated with gastrointestinal function.

New Treatments Seen

Hernandez said if studies continue to reveal that ulcers are related to brain chemistry, possibly as a response to emotional stress, then scientists might eventually produce synthetic TRH analogs to block its function.

“This would be a first step,” he said.

But Glavin noted that there are at least a half dozen receptor sites on acid-secreting stomach cells, suggesting that an array of analogs may be the eventual method of chemically treating ulcers.

Both researchers say the number of cases of ulcers has been on the decline in recent years in all but two populations: the very young and the very old.

Apparently infants and the elderly hospitalized for great lengths of time develop ulcers in higher than usual numbers, research indicates.

“It is the emotional stress of being hospitalized that many believe causes the problem,” Glavin said.