Young pregnant woman sitting on bed and holding head to represent being pregnant with opioid use disorder, which can increase risk of birth malformations.
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Reporting in Nature Communications, researchers from the University of Colorado (CU) Anschutz Medical Campus have unveiled the direct impact of antidepressant use during pregnancy on fetal brain development.

Led by assistant professor in the department of pharmacology at CU Anschutz Won Chan Oh, PhD, the study sheds light on the consequences of serotonin manipulation, particularly through drugs like fluoxetine (commonly known as Prozac or Sarafem), on the formation of the prefrontal cortex, a region critical for high-order cognitive functions.

“While it is known that serotonin plays a role in the brain development, the mechanisms responsible for this influence, specifically in the prefrontal cortex, have been unclear. The prefrontal cortex, the most evolved brain region, plays a central role in highest-order cognition, which is why we focused our study on finding the answer from this brain area,” Oh said in a press statement.

For the study, Oh, along with neuroscience PhD candidate Roberto Ogelman, investigated the complex mechanisms underlying serotonin’s role in shaping nascent and immature excitatory synaptic connections within this crucial brain region.

Their findings underscore a pivotal link between serotonin dysregulation during early development and the heightened risk of various mental health disorders later in life. Notably, the research marks the first empirical demonstration of how fluoxetine exposure during pregnancy directly impacts the developing prefrontal cortex, as fluoxetine can permeate the placenta and even enter breast milk.

By investigating serotonin levels in mice brains, the researchers uncovered a connection between serotonin signaling and synaptic plasticity—the brain’s ability to adapt and learn. According to the researchers serotonin has a dual role: not only crucial for overall brain function but also instrumental in shaping individual neural connections essential for learning and cognitive flexibility.

“Understanding this correlation has the potential to help with early intervention and the development of new therapeutics for neurodevelopmental disorders involving serotonin dysregulation,” said Oh, emphasizing the potential implications of the findings for clinical practice.

The researchers suggested that healthcare professionals should engage in comprehensive discussions with pregnant patients, weighing the benefits of pharmacological interventions against potential risks and exploring non-pharmacological alternatives for managing perinatal depression.

Moving forward, the scientists aim to extend their investigations to investigate fluoxetine’s impact on the developing teenage brain, holding promise for advancing our understanding of neurodevelopmental disorders associated with serotonin dysregulation and paving the way for tailored interventions and novel therapeutics.

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