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
The use of antidepressants during pregnancy may combine with inflammation to increase the risk of lifelong neurodevelopmental changes in babies’ brains, such as those linked to autism, according to new research from the University of Medicine School of Medicine. the University of Virginia.
A team of UVA neuroscientists have found that commonly used antidepressants known as selective serotonin reuptake inhibitors (SSRIs) can powerfully interact with inflammation in the mother’s body due to infections or other sources. In lab mice, this interaction caused harmful changes in the placenta and decidua – the direct link between mother and child – and affected the developing brain.
“Our results suggest that [SSRIs] can have deleterious consequences when mixed with infection, inflammation, etc. said lead researcher John Lukens, Ph.D., of the UVA Department of Neuroscience and its Center for Cerebral and Glial Immunology (BIG), as well as the UVA Brain Institute.
“Our findings could help explain the increase in autism prevalence over the past 20 years, as this period coincides with the rollout of widespread use of SSRIs in developing countries.”
SSRIs during pregnancy
SSRIs are commonly used during pregnancy, being prescribed to 80% of pregnant women who need medication for depression. Medication is widely considered a safe option for managing depression in pregnant women, although there is some evidence that it may increase the risk of preterm labor as well as 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 produce a strong inflammatory response at the “maternal-fetal interface,” the physical connection between mother and offspring during pregnancy.
The offspring of the inflammation-exposed mothers then showed sex-based behavioral changes, similar to behaviors seen in autistic people, such as reduced communication and reduced interest in social interactions. These mouse models are widely used as an important autism research tool.
“We identified inflammatory signatures in the placenta that correlated with neurological changes in the adult offspring of mothers who encountered an immune challenge during pregnancy,” said researcher Kristine Zengeler, first author of a new scientific paper. describing the results.
“These signatures could be used to help identify biomarkers and drug targets to help mediate 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. According to UVA researchers, SSRIs may interact with this inflammation and amplify it, leading to permanent brain changes.
The findings make sense, the researchers say, because of how SSRIs alter 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 mother via the placenta in the early stages of pregnancy, so disruption of serotonin levels in the mother can also have consequences for the baby.
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 experienced an immune challenge during pregnancy showed a totally different signature in the placenta when they were on SSRIs compared to mothers who weren’t on SSRIs,” Zengeler said.
“This underscores the importance of considering the entire prenatal environment, as drugs designed to dampen inflammation can have unintended 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 their doctor. Instead, scientists are calling for additional studies, possibly in human subjects, to determine how the drugs may affect mother and child and to better understand the interactions of SSRIs and inflammation.
“Untreated maternal stress, depression, and anxiety alone can impair neurodevelopment in offspring, contributing to adverse behavioral and cognitive outcomes,” the researchers write. “It will therefore be of utmost importance to consider both the relative benefits and the potential consequences of SSRIs as a treatment 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 disease and multiple sclerosis.
About this pregnancy and neurodevelopment research news
Author: Press office
Source: University of Virginia
Contact: Press Office – University of Virginia
Image: Image is in public domain
Original research: Free access.
“SSRI treatment alters the effects of maternal inflammation on in utero physiology and neurobiology of the offspring” by Kristine E. Zengeler et al. Brain, behavior and immunology
SSRI treatment alters effects of maternal inflammation on in utero physiology and neurobiology of offspring
The disturbances of the in utero the environment can drastically change the neurodevelopmental trajectory of the offspring. Insults commonly encountered in modern human life such as infections, toxins, high fat diets, prescription drugs and others are increasingly linked to behavioral alterations in children exposed before birth.
While appreciation of the potential consequences these triggers may have on embryo development is widening, there is little information about how the crucial mother-fetus interface (MFI) responds to these various insults. and how it may be related to changes in the neurological development of offspring.
Here, we found that MFI responds to both an inflammatory state and impaired serotonergic tone in pregnant mice. Maternal immune activation (MIA) elicited an acute inflammatory response in the IMF dominated by interferon signaling that occurred at the expense of ordinary developmentally related transcriptional programs.
The main compartments of the IMF, the decidua and the placenta, each responded distinctly to MIA. MFIs exposed to MIA were also found to disrupt sex-specific gene expression and increased serotonin levels. We found that offspring exposed to MIA exhibited sex-related behavioral changes and microglia were unaffected by transcription.
Moreover, the combination of maternal inflammation in the presence of pharmacological inhibition of serotonin reuptake further transformed the physiology of the IMF and the neurobiology of the offspring, impacting both the immune and signaling pathways. serotonin.
Taken together, these results highlight the complexity of assessing various environmental impacts on placental physiology and neurodevelopment.
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