The gut is considered to be our second brain; In fact, both organs maintain a relationship that explains why good intestinal health is key to emotional and psychological well-being. A new study has now found new connections between the gut and the brain that show promise for the development of more targeted treatments for depression and anxiety, and could also help prevent digestive problems in children by reducing their prenatal exposure to antidepressants.
The study has been published in the journal Gastroenterology and shows that increasing serotonin in the intestinal epithelium (the thin layer of cells that lines the small and large intestine) improves symptoms of anxiety and depression in animal studies. Researchers also found that in humans, using antidepressants during pregnancy increases the risk of babies becoming constipated in the first year of life.
“Our findings suggest that there may be an advantage in targeting antidepressants selectively to the intestinal epithelium, as systemic treatment may not be necessary to obtain the benefits of the drugs, but may be contributing to digestive problems in children exposed during pregnancy. “said Kara Margolis, director of the Pain Research Center at New York University who led the study along with Mark Ansorge, associate professor of clinical neurobiology at Columbia University.
Connection between serotonin in the gut and mood
Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), are indicated for depression, anxiety, and personality disorders. These medications are considered safe, but they can have side effects such as gastrointestinal problems and anxiety, especially at the beginning of treatment with an SSRI, which can cause patients to discontinue treatment. Antidepressants also pose problems during and after pregnancy due to their ability to cross the placenta and breast milk.
SSRIs work by blocking a protein called the serotonin transporter, which raises serotonin levels in the brain. However, the vast majority of the body’s serotonin is produced in the intestine, and the serotonin transporter also lines the intestines. “In the case of psychiatric medications that act on receptors in the brain, many of those same receptors are found in the intestine, so the effects on the development and function of the intestine must be taken into account,” Margolis explained. .
To better understand the connection between serotonin in the gut and mood and gastrointestinal disorders, researchers studied several mouse models in which the serotonin transporter was deleted or blocked. Previous studies led by Margolis revealed that mice bred to lack the serotonin transporter throughout the body, as well as mice that were exposed to SSRIs during and after pregnancy, experienced changes in the development of the digestive system and dysfunction in intestinal motility .
In the new study, the researchers looked at the role of serotonin in the gut specifically by studying mice that lacked the serotonin transporter in the intestinal epithelium, either during development (mimicking exposure to an SSRI during pregnancy) or in adulthood. early (similar to taking an SSRI as an adult).
“Restricting an antidepressant to inhibit the serotonin transporter only in the intestinal epithelium could avoid these adverse effects and limit transmission of the drug during pregnancy and lactation”
Removal of the serotonin transporter from the intestinal epithelium increased serotonin levels and produced improvements in anxiety and depression symptoms in both groups of mice. It also protected them from adverse effects on digestion and motility that were found in previous research in which the serotonin transporter was missing or blocked throughout the body.
The researchers also determined that the vagus nerves (a key communication pathway between the digestive system and the brain) are the pathway by which serotonin in the intestinal epithelium modulates mood. By disrupting this communication in mice in one direction (gut to brain), improvements in anxiety and depression were eliminated.
To explore whether blocking the serotonin transporter in humans leads to digestive problems similar to those seen in mice, the researchers also looked at the use of antidepressants during pregnancy. They studied more than 400 pairs of mothers (a quarter of whom were taking antidepressants [ISRS] or SNRI) and their babies, and followed them during pregnancy and during the children’s first year of life. The use of antidepressants during pregnancy significantly increased the risk of a child suffering from functional constipation, a very common GDI that can be painful, during their first year of life.
“We found that by the time they were one year old, 63% of children exposed to antidepressants during pregnancy were constipated, compared to 31% of children whose mothers were not taking medication,” said Larissa Takser, a professor of pediatrics. from the University of Sherbrooke in Quebec and one of the authors of the study. “This finding suggests a possible connection between serotonin levels in utero and intestinal development, and opens new doors to examine previously unstudied properties of SSRIs.”
The researchers strongly caution that these findings should not change clinical practice or influence whether mothers continue taking SSRIs during pregnancy due to the risk of constipation in their children, given the known risks of untreated maternal depression and anxiety. “These are not clinical guidelines, but rather a call for more research into the connection between SSRIs, serotonin and the gut,” Margolis said. “It is recommended that mothers and doctors together consider treatment options that have been shown to be successful, including medications and cognitive behavioral therapy.”
Taken together, the findings in mice and humans reveal a promising avenue for future studies: the intestinal epithelium as a new and potentially safer target for the treatment of mood disorders, particularly in pregnant women.
“Systemic blockade of the serotonin transporter appears to play a role in the development of digestive problems in both mice and humans. However, restricting an antidepressant to inhibit the serotonin transporter only in the intestinal epithelium could prevent these adverse effects and limit the transmission of the drug during pregnancy and lactation,” concludes Margolis.
