Research & Education

New Research on the Link Between Depression and Constipation

Constipation is uncomfortable. Depression can be downright disabling. So imagine the compromised quality of life for people living with both. In fact. According to a Columbia University press release announcing new findings about the connection between these two issues, as much as a third of people with depression experience chronic constipation, and some of these individuals describe their “bowel difficulties as one of the biggest factors reducing their quality of life.”

It’s long been believed that some cases of depression result from low serotonin in the brain. Being that serotonin also plays a key role in gut motility and that the gut is heavily reliant on neurotransmitters for proper function (it’s often called “the second brain”), low serotonin may be contributing to constipation, at least in some individuals.

Researchers at Columbia and Duke Universities looked more closely at this, using mice with a genetic mutation that impairs serotonin production in both the brain and the gut. (The mutation is in the enzyme tryptophan hydroxylase 2, which is the rate-limiting step in the biosynthesis of tryptophan.) The mutation reduces serotonin levels by 60–80% in the central nervous system and induces depressive symptoms in the mice. Affected mice show fewer neurons in the gut, deterioration of the gut lining, and slower bowel transit time.

In their study, “Effects of Serotonin and Slow-release 5-HTP on Gastrointestinal Motility in a Mouse Model of Depression,” researchers gave the mice a slow-release form of 5-HTP, the precursor to serotonin, and this resulted in an increase in the number of neurons in the gut—actually, the number was restored to normal. Gut serotonin levels were also increased, and perhaps the most encouraging finding—if future research shows this translates to humans with constipation—is that gut motility returned to normal. This is one of the first studies to show that neurogenesis in the gut is possible, which may have encouraging implications for treating constipation in general, and in the elderly in particular, who typically experience a loss of GI neurons during aging.

Obviously, 5-HTP has long been available as a supplement. The difference here is that the immediate-release form has not been shown to be effective for GI issues, but the slow-release form may get around this obstacle by providing a more constant supply of the compound. However, there are conflicts of interest that are worth noting among the researchers. Some of the study authors have a patent or a pending patent application on slow-release 5-HTP drugs and hold equity in a company founded to develop these drugs. This may have no implications in terms of bias in the study findings, but it’s important to be aware of nonetheless.

Depression and constipation are both conditions that may be caused by a number of factors besides low serotonin. Reduced serotonin synthesis is especially interesting as an etiological factor because it’s a single element that contributes to both. Hypothyroidism is another issue that should be explored when depression and chronic constipation occur together, particularly if other signs and symptoms of suboptimal thyroid home levels are present. Iodine is the nutrient that comes to mind first when thinking about hypothyroidism, but there are important roles for iron and vitamin A, too.

It’s important to be aware that conventional thyroid testing, which often includes only TSH or TSH and T4, may miss patients who do, indeed, have altered thyroid hormone levels. (See here for a past article looking at this issue.) Regarding constipation, we’ve previously explored lifestyle changes that can help improve bowel function and regularity. Fiber is a contentious issue for those with constipation. It makes sense on the surface that increasing stool bulk should “get things moving,” but this advice sometimes backfires and actually makes things worse. For those with constipation caused by low serotonin or some other factor that slows transit time, adding additional material to be excreted means that more stool may accumulate and stagnate in the colon—exactly the opposite of what anyone with chronic constipation would want to experience. (Magnesium citrate is often helpful for alleviating constipation.)

As always in functional medicine, it’s critical to uncover the root causes of physiological dysfunction and address those, rather than masking the symptoms. For patients with constipation and depression secondary to low serotonin, new forms of 5-HTP may be beneficial, but research remains to be done to substantiate this in humans.