Depression may cause constipation

Serotonin Deficiency as a Common Cause of Constipation and Depression

New York (USA) - Every third person with chronic constipation also suffers from depression. There is also a known connection between degenerative brain diseases and impaired bowel function. One reason for this connection could be the insufficient production of the messenger substance serotonin in nerve cells of the intestine and brain, American doctors are now reporting in the specialist journal "Gastroenterology". In experiments with mice, they were able to successfully treat both chronic constipation and depressive behavior using an active ingredient that increases serotonin levels. Clinical studies have yet to show whether the therapy can be transferred to humans.

"The intestine is often referred to as the body's 'second brain'," says Kara Gross Margolis of Columbia University in New York. “The intestinal nervous system contains more neurons than the spinal cord, and many of the neurotransmitters used are the same as those in the brain.” So it would not be surprising if the intestinal and brain malfunctions had the same cause. The neurotransmitter serotonin affects both mood and bowel function. Serotonin production in the brain is lower in patients with depressive disorders than in healthy people. This could be due to a defective enzyme that is responsible for the production of serotonin. In fact, an altered gene has been found in people with major depression that could be responsible for this malfunction.

Margolis and her colleagues worked with mice that carried a similar gene mutation, which resulted in 60 to 80 percent lower serotonin levels in the brain and a serotonin deficiency in the nervous system of the intestine. The consequences were a reduced number of intestinal neurons, impaired intestinal motility and constipation. In addition, the animals showed characteristics of depressive behavior. To compensate for the serotonin deficiency, the researchers gave the mice a precursor of the neurotransmitter (5-hydroxytryptophan) with the food, which can be converted to serotonin independently of the defective enzyme. Since this precursor is very unstable, a dosage form has been developed that delays the release of the active ingredient over a longer period of time.

The treatment stimulated the formation of new intestinal neurons, improved bowel function and normalized depressive behavior. “The number of neurons in the intestine also decreases with age, and that could be a cause of constipation in older people,” says Margolis. A new type of therapy would therefore be conceivable in which the serotonin level is increased so that new neurons can develop. The researchers are now planning clinical trials to test the effectiveness of their treatment for people with either treatment-resistant depression or chronic constipation.

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