In research involving animals, enhancing serotonin levels in gut cells has been shown to diminish anxiety and depression-like behaviors without leading to cognitive or gastrointestinal side effects.
Many of us know how moods and emotions can impact our digestive system, experiencing sensations like “butterflies” in our stomachs when nervous or a lack of appetite when feeling down.
A recent study on animals indicates that focusing antidepressant treatments on gut cells could effectively address mood disorders such as depression and anxiety, potentially resulting in fewer cognitive, gastrointestinal, and behavioral side effects for both patients and their children compared to existing treatments.
“Medications like Prozac and Zoloft, which increase serotonin, are essential first-line therapies and benefit many individuals. However, they can sometimes cause side effects that are hard for patients to manage. Our research suggests that limiting the drugs’ action to intestinal cells might help mitigate these problems,” explains Mark Ansorge, associate professor of clinical neurobiology at Columbia University Vagelos College of Physicians and Surgeons and co-leader of the study alongside Kara Margolis, Director of the NYU Pain Research Center and an associate professor of molecular pathobiology at the NYU College of Dentistry.
For mothers-to-be, the use of SSRIs (selective serotonin reuptake inhibitors), which increase serotonin, presents challenges because these drugs can cross the placenta and are linked with various mood, cognitive, and gastrointestinal issues in children later on.
Ansorge notes, “However, ignoring a pregnant woman’s depression can also pose risks for the child. An SSRI that specifically targets serotonin in the gut might present a safer alternative.”
How do SSRIs function?
SSRIs have been the primary pharmacological option for managing anxiety and depression for over three decades. They are also frequently prescribed for gastrointestinal problems that often accompany these mood disorders.
These medications enhance serotonin signaling, with their impact on mood believed to originate from elevated serotonin activity in the brain, where serotonin transmits messages.
Notably, serotonin is also generated outside the brain, primarily in cells lining the intestines. “Actually, 90% of our body’s serotonin is found in the gut,” states Margolis, who also serves as an associate professor of pediatrics and cell biology at NYU Grossman School of Medicine. As a result, SSRIs enhance serotonin activity not only in the brain but also in the gut, raising the possibility that boosting serotonin signaling in the gut might influence gut-brain interactions and ultimately affect mood.
The research team explored this idea in mice by utilizing a combination of genetic modifications, surgical procedures, and pharmaceuticals.
Boosting gut serotonin alleviates anxiety and depressive behaviors in mice
To assess whether enhancing serotonin in the gut influences mood, the researchers modified mice to increase serotonin signaling in the gut, effectively simulating an SSRI administered solely to that area. The results showed that mice with heightened serotonin activity in the gut displayed significantly fewer anxiety and depressive-like behaviors compared to their untreated counterparts.
“These findings suggest that SSRIs may achieve therapeutic effects by acting directly in the gut,” Ansorge states.
Furthermore, the mice exhibited none of the cognitive or gastrointestinal side effects commonly observed in humans taking SSRIs or in mice with increased serotonin activity across their bodies.
“Given what we understand about brain-gut interactions, we anticipated some effects. However, the fact that enhanced serotonin signaling in the gut epithelium could lead to such substantial antidepressant and anxiety-reducing effects without any notable side effects surprised even us,” Ansorge mentions.
Margolis adds, “There might be benefits to specifically targeting antidepressants to the gut lining. Systemic treatment may not be essential for obtaining the advantages of these drugs.”
The study also revealed that the vagus nerve is vital for the gut’s effects on alleviating depression and anxiety. While the vagus nerve is well known for its role in brain-to-gut communication, the researchers highlighted the significance of gut-to-brain signaling in this context.
A potentially safer antidepressant option during pregnancy?
Pregnant women face challenges when considering SSRI treatments, as some research suggests that in utero exposure to these drugs might adversely affect a child’s mood, behavior, and cognitive development later on. Ansorge’s earlier animal studies have revealed similar findings, noting behavior changes in offspring that had even brief exposure to SSRIs during their development.
The current study reinforces the notion that in utero exposure to serotonin-targeting antidepressants can negatively influence children. The researchers evaluated over 400 mothers and infants, discovering that children exposed to such medications during pregnancy had a threefold increase in the likelihood of experiencing constipation within their first year.
Both Ansorge and Margolis advise that pregnant individuals currently using SSRIs should not stop their medications based on this and other findings. “Maternal depression and anxiety can significantly impact fetal and child development and should be managed appropriately for the benefit of both mother and child,” Ansorge stresses.
The research team is now focused on developing a selective SSRI that targets the gut, which could provide a more suitable option for treating depression and anxiety, particularly among pregnant women.
According to Ansorge, “Our results suggest that we could effectively treat a mother’s depression or anxiety without putting the child at risk, and we’re actively working on drug delivery technologies that could help us achieve this goal.”