Summary: The combination of antidepressant use and inflammatory infections during pregnancy increases the risk of neurodevelopmental disorders, including autism, in children, according to a new study.

Source: University of Virginia

Antidepressant use during pregnancy, combined with inflammation, increases the risk of lifelong neurodevelopmental changes in the baby’s brain, such as those associated with autism, according to a new study from the University of Virginia School of Medicine.

A team of UVA neuroscientists found that antidepressants commonly known as selective serotonin reuptake inhibitors (SSRIs) can strongly interact with inflammation in the mother’s body from infections or other sources. In laboratory mice, this direct interaction between mother and child caused deleterious changes in plasma and decidua, affecting the developing brain.

“Our findings indicate [SSRIs] “Combined with infection, inflammation, and so on, it can have dire consequences,” said John Lukens, Ph.D., senior researcher in UVA’s Department of Neuroscience and Center for Brain Immunology and Glia (BIG) and UVA Brain. Institute.

“Our results may help to explain the increase in the prevalence of autism over the past 20 years, as this period coincided with the widespread use of SSRIs in the developing world.”

SSRIs during pregnancy

SSRIs are commonly used during pregnancy, with 80% of pregnant women requiring depression medication prescribed. The drugs are considered a safe option for managing depression in pregnant women, although there is some evidence that they may increase the risk of premature birth and increase the risk of neurological problems and other health problems in children.

Lukens and colleagues found that SSRIs can interact with the mother’s immune system to trigger a strong inflammatory response at the “maternal-fetal interface,” the physical connection between mother and child during pregnancy.

Offspring of mothers exposed to the tumor later showed sex-specific behavioral changes similar to those seen in people with autism, such as decreased communication and a decreased need for social interactions. Such mouse models are widely used as an important autism research tool.

“We have identified inflammatory signatures in plasma that correlate with neurological changes in the adult child of mothers exposed to immunosuppression during pregnancy,” said Christine Zengeler, first author of a new scientific paper describing the findings.

“These signatures can be used to identify biomarkers and potential drug targets to reduce the neurodevelopmental consequences of prenatal environmental stressors, such as immune responses.”

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

According to the researchers, the results make sense because of how SSRIs change serotonin in the body. Serotonin is an important mood regulator – often thought of as the “feel good” chemical in the brain – but it is also a critical regulator of the body’s immune response. Growing infants receive serotonin from their mothers only through the placenta in the early stages of pregnancy, so a violation of maternal serotonin levels can have consequences for the baby as well.

This shows a pregnant woman
SSRIs are commonly used during pregnancy, with 80% of pregnant women requiring depression medication prescribed. The image is in the public domain.

The researchers found that inflammation alone and in combination with SSRIs changed plasma serotonin levels in opposite directions. “We found that mothers who developed immune dysfunction during pregnancy showed a completely different signature when they were on SSRIs compared to mothers who were not on SSRIs,” Zangler said.

“This highlights the importance of considering the overall prenatal environment, as drugs designed to reduce inflammation can have unexpected effects on the baby if combined with other modulators, such as SSRIs.”

The researchers suggest that SSRIs are useful tools for managing depression and caution that pregnant women should not stop taking them without consulting their doctors. Instead, the scientists call for more studies in human subjects to ultimately better understand how the drugs affect mother and child and the interaction of SSRIs and inflammation.

“Untreated maternal stress, depression, and anxiety can all contribute to negative behavioral and cognitive outcomes and impair their children’s neurodevelopment,” the researchers concluded. “Therefore, it is important to consider both the relative benefits and potential side effects of SSRIs as a treatment option during pregnancy.”

The researchers published their findings in the journal Brain, behavior and immunity. The Lukens lab also recently made a discovery that may help boost the brain’s resistance to Alzheimer’s disease and multiple sclerosis.

So pregnancy and neurodevelopmental research news

Author: Press office
Source: University of Virginia
Contact: Press Office – University of Virginia
Image: The image is in the public domain.

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This shows different brain cells in the organoid

Preliminary study: Open Access.
SSRI treatment improves the effects of maternal inflammation on uterine physiology and reproductive neurobiology” by Christine E. Zengeler et al. Brain, Behavior and Immunology


SSRI treatment improves the effects of maternal inflammation on uterine physiology and reproductive neurobiology

b In the womb Environment can significantly alter the course of children’s neurodevelopment. Insults such as infections, toxins, high-fat diets, prescription drugs, and other insults in modern human life have been linked to behavioral changes in prenatally vulnerable offspring.

While there is a growing appreciation of the potential effects of these triggers on fetal development, there is a paucity of information on how the critical maternal-fetal interface (MFI) responds to these various insults and how it relates to neurodevelopmental changes in the offspring.

Here, we found that MFI responds to inflammatory conditions and altered serotonergic tone in pregnant mice. Maternal immune activation (MIA) triggered an acute inflammatory response in MFI mediated by interferon signaling at the expense of normal growth-related transcriptional programs.

The main components of MFI, the decidua and placenta, each responded differently to MIA. MFIs exposed to MIA had sex-dependent disruption of gene expression and elevated serotonin levels. We found that children exposed to MIA had sex-specific behavioral changes and that microglia were transcriptionally unaffected.

Furthermore, the combination of maternal inflammation in the presence of pharmacological inhibition of serotonin reuptake alters MFI physiology and seed neurobiology and affects immunity and serotonin signaling in a similar manner.

Collectively, these findings highlight the complexities of assessing diverse environmental influences on placental physiology and neural development.

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