A new approach to fighting depression and anxiety

Most of us have experienced the effects that our moods and emotions have on our gastrointestinal tract, from the “flutter” in our stomachs caused by nervousness to loss of appetite when we feel depressed.

A new study in animals shows that targeting antidepressants to cells in the intestine may not only be an effective treatment for mood disorders such as depression and anxiety, but may also help patients and their children. It has been suggested that cognitive, gastrointestinal, and behavioral side effects may be lower than current treatments. .

“Antidepressants like Prozac and Zoloft, which increase serotonin levels, are important first-line treatments and help many patients, but they can sometimes cause side effects that patients cannot tolerate. , suggesting that these problems may be avoided by restricting the drug to interact only with intestinal cells.” '' said Mark Ansorge, associate professor of clinical neurobiology at Columbia University Valléros College of Physicians and Surgeons, who led the study with New York University director Kara Margolis. Associate Professor of Molecular Pathology at the Pain Research Center and New York University School of Dentistry.

Antidepressants that raise serotonin (called selective serotonin reuptake inhibitors, or SSRIs) pose unique problems for pregnant mothers. This is because the drug crosses the placenta and has been linked to mood, cognitive, and gastrointestinal problems from early childhood onwards.

However, untreated depression in pregnant women also carries risks to children. SSRIs, which selectively increase serotonin in the gut, may be a better alternative. ”

Mark Ansorge, Associate Professor of Clinical Neurobiology, Columbia University Vagelos College of Physicians and Surgeons

How do SSRI antidepressants work?

For more than 30 years, SSRIs have been the first-line pharmacological treatment for anxiety and depression. They are also commonly prescribed to treat gastrointestinal issues that occur concurrently with these mood disorders.

SSRIs promote serotonin signaling, and the drug's effects on mood are thought to be due to increased serotonin signaling in the brain, where serotonin helps relay messages.

Serotonin is also produced outside the brain, primarily in cells lining the gut. “In fact, 90 percent of our bodies' serotonin is in our gut,” says Margolis, who is also an associate professor of pediatrics and cell biology at New York University Grossman School of Medicine. Therefore, SSRIs increase serotonin signaling in the gut as well as the brain, raising the possibility that increased serotonin signaling in the gut influences gut-brain communication and ultimately mood. .

Researchers tested this possibility in mice using a combination of genetic engineering, surgery and drugs.

Increased serotonin in the gut reduces anxiety and depressive behavior in mice

To determine whether targeting serotonin in the intestine affects mood, researchers engineered mice to amplify serotonin signaling in the intestine, allowing it to be selectively delivered to the intestine. It imitates SSRIs. They found that animals with increased serotonin signaling in the gut exhibited less anxiety- and depression-like behavior than their unaffected littermates.

“These results suggest that SSRIs produce their therapeutic effects by acting directly in the intestine,” Enzorge says.

The animals also showed none of the cognitive or gastrointestinal side effects commonly seen in patients taking SSRIs or in mice with increased systemic serotonin signaling.

“Based on what we know about the interactions between the brain and the gut, we expected to see some effect. However, enhanced serotonin signaling in the intestinal epithelium was not noticeable. “It was surprising even to us to see it produce such strong antidepressant and anxiety-reducing effects without any side effects,” says Ensorge.

“There may be benefits in selectively targeting antidepressants to the intestinal epithelium,” Margolis added. “Systemic treatment may not be necessary to elicit the drug's effects.”

Researchers also discovered that the vagus nerve is required for the gut's antidepressant and anxiety-reducing effects. The vagus nerve has long been known to play an important role in brain-gut communication, mostly top-down communication from the brain to the gut. Here, researchers discovered that another direction is important: vagal nerve signaling from the gut to the brain.

What are the better antidepressant options during pregnancy?

SSRI treatment poses challenges during pregnancy. This is because several studies have found that exposure in utero can have negative effects on mood, behavior, and cognitive development from infancy onwards. Ensorge's previous animal studies had similar results, identifying behavioral changes in offspring exposed to SSRIs for short periods of time during development.

This new study adds to the evidence that exposure to antidepressants that target serotonin in the womb has negative effects on children. Researchers looked at more than 400 mothers and babies and found that children exposed to such antidepressants were three times more likely to develop constipation in the first year of life.

Ansorge and Margolis caution that pregnant people currently taking SSRIs should not discontinue treatment based on these or other findings. “Maternal depression and anxiety can have many undesirable effects on the development of the fetus and child, so appropriate treatment and monitoring is necessary for the benefit of both mother and child,” Dr. Anzorge said. I say.

Researchers are currently working on developing selective SSRIs that target the gut, which could be a better option for treating depression and anxiety, especially in pregnant women.

“Our findings show that it may be possible to effectively treat depression and anxiety in mothers without exposing their children to infection, and we hope to develop drugs that can help achieve that.” “We're working on delivery technology,” Ansorge said.