Antidepressant use and infections during pregnancy associated with neurodevelopmental disorders

Abstract: The combination of taking antidepressants and infections that lead to inflammation during pregnancy increases the risk of neurodevelopmental disorders including autism in children, a new study reports.

Source: University of Virginia

Antidepressant use during pregnancy may combine with inflammation and increase the risk of lifelong neurodevelopmental changes in the baby’s brain, such as those associated with autism, new research from the University of Virginia School of Medicine suggests.

A team of UVA neuroscientists has found that commonly used antidepressants known as selective serotonin reuptake inhibitors (SSRIs) can have a powerful effect on inflammation in the mother’s body caused by infections or other sources. In laboratory mice, this interaction caused harmful changes in the placenta and decidua — the direct link between mother and child — and affected brain development.

“Our findings suggest that [SSRIs] it can have adverse effects when mixed with infection, inflammation, etc.,” said senior researcher Dr. John Lukens of UVA’s Department of Neuroscience and its Center for Brain and Glia Immunology (BIG), as well as UVA Brain. Institute.

“Our results may help explain the rise in autism prevalence over the past 20 years, as this time coincides with the widespread use of SSRIs in developing countries.”

SSRIs during pregnancy

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

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

The offspring of mothers exposed to inflammation later showed gender-specific behavioral changes similar to those seen in individuals with autism, such as reduced communication and reduced interest in social interactions. Such mouse models are widely used as an important tool for autism research.

“We identified inflammatory markers in the placenta that were correlated with neurological changes in the adult offspring of mothers who faced an immune challenge during pregnancy,” said researcher Kristine Zengeler, first author of a new scientific paper presenting the findings.

“These signatures could be used to help identify biomarkers and drug targets to ameliorate the neurodevelopmental consequences of prenatal environmental stressors, such as the 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. SSRIs, the UVA researchers believe, may interact with and exacerbate this inflammation, leading to permanent brain changes.

The results make sense, the researchers say, because of the way SSRIs change serotonin in the body. Serotonin is an important mood regulator—it’s 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 infants only receive serotonin from their mothers via the placenta early in pregnancy, so disruption of serotonin levels in the mother can have consequences for the baby as well.

The researchers found that inflammation alone and in combination with SSRIs alter placental serotonin levels, but in opposite directions. “We found that mothers who were immunologically challenged during pregnancy showed a completely different signature in the placenta when they were on SSRIs compared to mothers who weren’t on SSRIs,” Zengeler said.

“This highlights the importance of considering the entire prenatal environment, as drugs designed to reduce inflammation can lead to unexpected consequences for the baby if combined with other modulators, such as SSRIs.”

The researchers noted that SSRIs are important tools for managing depression and stressed that pregnant women should not stop taking them without consulting a doctor. Instead, scientists are calling for additional studies, possibly in humans, to determine how the drugs may affect mother and child and to better understand the interactions between SSRIs and inflammation.

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

The researchers published their findings in a journal Brain, behavior and immunity. Lukens’ lab also recently made a discovery that could be key to boosting the brain’s ability to fight Alzheimer’s and multiple sclerosis.

About this pregnancy and neurodevelopmental research news

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

Original research: Open access.
“SSRI treatment modifies the effects of maternal inflammation on in utero physiology and offspring neurobiology” by Kristine E. Zengeler et al. Brain, behavior and immunology

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Abstract

SSRI treatment modifies the effects of maternal inflammation on in utero physiology and offspring neurobiology

Perturbations on in the womb the environment can dramatically alter the neurodevelopmental trajectory of the offspring. Insults frequently encountered in modern human life, such as infections, toxins, high-fat diets, prescription drugs, and others, are increasingly associated with behavioral changes in prenatally exposed offspring.

While the potential consequence these triggers can have on embryonic development is increasingly understood, there is insufficient information on how the key maternal-fetal interface (MFI) responds to these different insults and how this may be linked to changes in the neurodevelopment of the offspring.

Here, we found that MFI responds to both the inflammatory state and altered serotonergic tone in pregnant mice. Maternal immune activation (MIA) triggered an acute inflammatory response in MFI dominated by interferon signaling that came at the expense of normal transcriptional programs associated with development.

The main compartments of the MFI, the decidua and the placenta, each responded differently to MIA. MFIs exposed to MIA were also found to have disrupted sex-specific gene expression and increased serotonin levels. We found that MIA-exposed offspring had sex-specific behavioral changes and that microglia were not transcriptionally affected.

Moreover, the combination of maternal inflammation in the presence of pharmacological inhibition of serotonin reuptake further transformed MFI physiology and offspring neurobiology, both affecting immune and serotonin signaling pathways.

Overall, these findings highlight the complexity of assessing the various environmental influences on placental physiology and neurodevelopment.