A common clinical association among individuals suffering from depression is that many also suffer from gastrointestinal distress such as low gut motility and constipation. Though some antidepressants are known to cause constipation, medication side effects do not explain all cases. Now, a new study from investigators at Columbia University Medical Center study suggests that some forms of depression and gut distress arise from the same glitch in neuronal chemistry—low serotonin. Findings from the new study were published recently in Gastroenterology through an article titled “Effects of Serotonin and Slow-release 5-HTP on Gastrointestinal Motility in a Mouse Model of Depression.”
This new study, which was conducted in mice, shows 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. Surprisingly, however, the research team also found that a new treatment, which raises serotonin in the gut and the brain, may alleviate both conditions.
“Ultimately, many patients with depression are faced with limited treatment options and have to suffer from prominent GI dysfunction,” explained senior study investigator Kara Gross Margolis, MD, associate professor of pediatrics at Columbia University Medical Center.
Up to a third of people with depression have chronic constipation, and a few studies report that people with a depression rate their accompanying bowel difficulties as one of the biggest factors reducing their quality of life. Moreover, 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.
“The gut is often called the body’s ‘second brain,” Margolis noted. “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.”
Because 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 current 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 GI tract.
“Basically, the mice were constipated,” Margolis stated, “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).
An experimental drug treatment used by the research team showed some promising results as it raised serotonin levels in the gut’s neurons and alleviated constipation in the mice. The new treatment—slow-release drug-delivery of 5-HTP, a precursor of serotonin—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 that new 5-HTP slow-release therapies could treat related brain-gut conditions simultaneously.
“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 concluded. “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. 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.”
