Antidepressant use, infection during pregnancy linked to neurodevelopmental changes in infants

A new study from the University of Virginia School of Medicine suggests that antidepressant use during pregnancy may combine with inflammation to increase the risk of lifelong neurodevelopmental changes in babies’ brains, such as those linked to autism.

A team of UVA neuroscientists has discovered that widely used antidepressants known as selective serotonin reuptake inhibitors (SSRIs) can interact strongly with inflammation in the mother’s body from infections or other sources. In lab mice, this interaction caused deleterious changes in the placenta and decidua (the direct connection between mother and child) and affected the developing brain.

“Our findings show that [SSRIs] “When mixed with infection, inflammation, etc., it can have harmful consequences,” said senior researcher John Lukens of the UVA Department of Neuroscience and the Center for Brain Immunology and Glia (BIG) and the UVA Brain Institute. Our results may help explain the increase in autism prevalence over the past 20 years, as this time coincides with widespread SSRI use in the developing world.”

SSRIs in pregnancy

SSRIs are commonly used during pregnancy and are prescribed to 80% of pregnant women who need depression medication. Medications are widely recognized as a safe option for managing depression in pregnant women, but there is some evidence that they may increase the chance of preterm birth and the risk of neurological problems and other health problems in children.

Lukens and collaborators found that SSRIs can interact with the mother’s immune system to produce a strong inflammatory reaction at the “mother-fetal interface,” the physical connection between mother and offspring during pregnancy.

Children of mothers exposed to inflammation subsequently showed gender-based behavioral changes seen in people with autism, such as decreased communication and decreased interest in social interactions. Such mouse models are widely used as an important autism research tool.

“We identified inflammatory signatures in the placenta that are associated with neurological changes in the adult offspring of mothers who encounter an immune challenge during pregnancy,” said researcher Kristine Zengeler, first author of a new scientific paper summarizing the findings. “These signatures can be used to help identify biomarkers and druggable targets to help alleviate the neurodevelopmental consequences of prenatal environmental stressors, such as an immune response.”

Previous research has shown that infections, autoimmune disorders, and other conditions that alter the mother’s immune status during pregnancy can affect neurodevelopment. UVA researchers believe that SSRIs can interact with this inflammation and amplify it, leading to permanent brain changes.

The results make sense, the researchers say, because of how SSRIs change serotonin in the body. Serotonin is an important mood stabilizer—often thought of as a “feel-good” chemical in the brain—but it’s also a vital regulator of the body’s immune response. Developing babies only receive serotonin from their mothers through the placenta in the early stages of pregnancy, so disruption of maternal serotonin levels can have consequences for the baby as well.

Researchers have found that inflammation alone and in combination with SSRIs alters serotonin levels in the placenta in opposite directions. “We found that mothers who encountered an immune challenge during pregnancy showed a completely different signature in the placenta when they took an SSRI compared to mothers who did not take an SSRI,” Zengeler said. Said. “This highlights the importance of considering the entire prenatal environment, as drugs designed to reduce inflammation can have unexpected consequences on the baby when combined with other modulators such as SSRIs.”

The researchers emphasized that SSRIs are important tools in the fight against depression, emphasizing that pregnant women should not stop taking them without consulting their doctor. Instead, the scientists ultimately call for additional studies in human subjects to determine how the drugs may affect the mother and child, and to better understand the interactions of SSRIs and inflammation.

“Untreated maternal stress, depression, and anxiety, in and of themselves, can impair the neurodevelopment of the offspring, contributing to adverse behavioral and cognitive outcomes,” the researchers write. “Therefore, it will be extremely important to consider both the relative benefits and potential consequences of SSRIs as a therapeutic option during pregnancy.”

Published Findings

The researchers published their findings in the scientific journal Brain, Behavior and Immunity. The team consisted of Zengeler, Daniel A. Shapiro, Katherine R. Bruch, Catherine R. Lammert, Hannah Ennerfelt and Lukens. The researchers did not report any financial interests in the study.

Lukens’ lab also recently made a discovery that may hold the key to boosting the brain’s ability to fight Alzheimer’s disease and multiple sclerosis.

The lab’s most recent research was supported by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke, grant R01NS106383; National Institute of Mental Health, grant R21MH120412-01; Simons Foundation Autism Research Initiative, pilot award 515305; and the Owens Family Foundation. In addition, members of the research team were supported by Cell and Molecular Biology Education Grants 1T32GM139787-01-35 and T32GM008136, Wagner Fellowships, Double Hoo Awards, and a Harrison Fellowship.

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