Mouse Study Probes Why GI Issues Often Accompany Depression
Many people with depression suffer from gastrointestinal problems, and now new research suggests that for some, the two conditions may arise from the same issue: low serotonin.
The study, conducted in mice, is published in the journal Gastroenterology.
As many as one in three people with depression have chronic constipation, and a few studies report that individuals with depression rate their accompanying bowel problems as one of the biggest factors reducing their quality of life.
Severe constipation can obstruct the GI tract and cause serious pain. The condition leads to 2.5 million physician visits and 100,000 hospitalizations each year. And while some antidepressants are known to cause constipation, medication side effects do not explain all cases.
“Ultimately, many patients with depression are faced with limited treatment options and have to suffer with prominent GI dysfunction,” said study leader Kara Gross Margolis, M.D., associate professor of pediatrics at Columbia University Vagelos College of Physicians and Surgeon.
Similarities between the gut and the brain suggest the two conditions may share a root cause.
“The gut is often called the body’s ‘second brain,'” Margolis said. “It contains more neurons than the spinal cord and uses many of the same neurotransmitters as the brain. So it shouldn’t be surprising that the two conditions could be caused by the same process.”
Since a shortage of serotonin in the brain is 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 in the study carried 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 findings show that a serotonin shortage in the gut 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 GI tract.
“Basically, the mice were constipated,” Margolis says, “and they showed the same kind of GI changes we see in people with constipation.” (In previous studies, these same mice also showed depressive symptoms).
Encouragingly, an experimental drug treatment invented by two of the study’s co-authors, Marc Caron, PhD, and Jacob Jacobsen, PhD, of Duke University, raised serotonin levels in the gut’s neurons and alleviated constipation in the mice.
The treatment, which involved a slow-release drug-delivery of 5-HTP (a precursor of serotonin), worked in part by increasing the number of GI neurons in adult mice.
The discovery of this link between the brain and GI problems suggests that new 5-HTP slow-release therapies could treat related brain-gut conditions simultaneously.
The study is also one of the first to demonstrate that neurogenesis in the gut is possible and can fix abnormalities in the gut. “Though it’s been known for many years that neurogenesis occurs in certain parts of the brain, the idea that it occurs in the gut nervous system is relatively new,” Margolis said.
Neurogenesis may help treat other types of constipation. “We see a reduction of neurons in the GI tract with age, and that loss is thought to be a cause of constipation in the elderly,” Margolis said. “The idea that we may be able to use slow-release 5-HTP to treat conditions that require the development of new neurons in the gut may open a whole new avenue of treatment.”
The commonly available immediate-release 5-HTP supplement is too short-acting for this issue, Margolis says. 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 study produces consistent administration of 5-HTP which has been shown to fix the limitations of immediate-release 5-HTP.
Clinical studies are already planned for testing a slow-release 5-HTP drug in people with treatment-resistant depression as well as a 5-HTP drug for constipation.
Pedersen, T. (2019). Mouse Study Probes Why GI Issues Often Accompany Depression. Psych Central. Retrieved on September 28, 2020, from https://psychcentral.com/news/2019/05/08/mouse-study-probes-why-gi-issues-often-accompany-depression/145595.html