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Antidepressant use and infection during pregnancy associated with neurological disorders

Antidepressant use and infection during pregnancy associated with neurological disorders

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Summary: A combination of antidepressant use 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 to increase the risk of lifelong neurodevelopmental changes in babies’ brains, such as those linked to autism, new research from the University of Virginia School of Medicine shows.

A team of UVA neuroscientists found that commonly 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 causes harmful changes in the placenta and decidua – the direct link between mother and child – and affects the developing brain.

“Our findings suggest that [SSRIs] can have deleterious effects when mixed with infection, inflammation, etc.,” said senior researcher John Lukens, Ph.D., of the UVA Department of Neurology and its Center for Brain Immunology and Glia (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 spread of widespread use of SSRIs in the developing world.”

SSRIs during pregnancy

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

Lukens and his colleagues discovered 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 offspring during pregnancy.

The offspring of mothers exposed to inflammation later show sex-specific behavioral changes, such as behaviors seen in people 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 signatures in the placenta that correlate with neurological changes in the adult offspring of mothers who faced an immune challenge during pregnancy,” said researcher Christine Zengeler, first author of a new scientific paper outlining the findings.

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

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

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

SSRIs are commonly used during pregnancy, being prescribed to 80% of pregnant women who need medication for depression. Image is in the public domain

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

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

The researchers noted that SSRIs are important tools for dealing with depression and stressed that pregnant women should not stop taking them without consulting their doctors. Instead, the scientists are calling for additional studies, possibly in humans, 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 may themselves disrupt offspring neurodevelopment, contributing to adverse behavioral and cognitive outcomes,” the researchers wrote. “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 the journal Brain, behavior and immunity. Lukens’ lab also recently made a discovery that may hold the 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
Image: Image is in the public domain

See also

This shows a depressed woman

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


Summary

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

Disturbance of intrauterine the environment can dramatically alter the neurodevelopmental trajectory of the offspring. Insults common in modern human life, such as infection, toxins, high-fat diet, prescription drugs, and others, are increasingly associated with behavioral changes in prenatally exposed offspring.

Although appreciation of the potential consequences these triggers may have on embryonic development is growing, there is scant information regarding how the crucial maternal-fetal interface (MFI) responds to these various insults and how it may relate to neurodevelopmental changes in the offspring.

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

The main MFI compartments, the decidua and the placenta, responded in different ways to MIA. MFIs exposed to MIA were also found to have impaired sex-specific gene expression and elevated serotonin levels. We found that MIA-exposed offspring had sex-related behavioral changes and that microglia were not transcriptionally affected.

Furthermore, the combination of maternal inflammation in the presence of pharmacological serotonin reuptake inhibition further transforms MFI physiology and offspring neurobiology, similarly affecting immune and serotonin signaling pathways.

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


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