New study may explain why gut distress accompanies depression

Gastrointestinal distress is common for patients with depression, and the two conditions may arise from the same glitch in neuron chemistry, low serotonin, according to a new study published in the journal Gastroenterology.

The study, conducted in mice, showed that a shortage of serotonin in the neurons of the gut can cause constipation, just as a serotonin shortage in the brain can lead to depression. The study also found that a treatment that raises serotonin in the gut and the brain may alleviate both conditions.

Up to a third of people with depression have chronic constipation, and a few studies report that people with depression rate their accompanying bowel difficulties as one of the biggest factors reducing their quality of life. Severe constipation can obstruct the gastrointestinal tract and cause serious pain. The condition leads to 2.5 million physician visits and 100,000 hospitalizations each year.

Though some antidepressants are known to cause constipation, medication side effects do not explain all cases. Similarities between the gut and the brain suggest the two conditions may also share a common cause, the study says.

Since low levels of serotonin in the brain have been linked to depression and serotonin is also used by neurons in the gut, the researchers studied mice to determine if a serotonin shortage also plays a role in constipation. The mice used in the study carry a genetic mutation, linked to severe depression in people, that impairs the ability of neurons in the brain and the gut to make serotonin.

The serotonin shortage in the gut, the researchers found, reduced the number of neurons in the gut, led to a deterioration of the gut's lining, and slowed the movement of contents through the gastrointestinal tract. The authors developed a treatment, a slow-release drug-delivery of 5-HTP, a precursor of serotonin, which works in part by increasing the number of GI neurons in adult mice.

The discovery of this connection between a brain and a gastrointestinal disorder suggests 5-HTP slow-release therapies could treat related brain-gut conditions simultaneously. The study also shows that neurogenesis in the gut is possible and can correct abnormalities in the gut. Neurogenesis may help treat other types of constipation.

An immediate-release version of 5-HTP is available as a supplement, but it has not been proved scientifically to work and physiologically it should not, as it is too short-acting. 5-HTP is the immediate precursor to serotonin. Once ingested, 5-HTP is converted to serotonin, but the serotonin is rapidly inactivated before it can work effectively.

The slow-release version of 5-HTP used in the current study produces constant administration of 5-HTP, according to the study abstract, which has been demonstrated to remedy the limitations of currently available immediate-release 5-HTP.