Study provides first evidence of direct impact of serotonin on prefrontal cortex development

A new study published in Natural communications provides direct evidence that antidepressant use during pregnancy may impact a child’s brain development and contribute to the risk of mental health disorders later in life.

The study, led by researchers at the University of Colorado Anschutz Medical Campus, focused on the effect of fluoxetine, commonly used in medications such as Prozac and Sarafem to treat depression and depression perinatal, on a developing prefrontal cortex.

Since fluoxetine works by increasing serotonin levels in the brain, researchers have examined the impact of serotonin on the development of the prefrontal cortex in the fetus.

“Although serotonin is known to play a role in brain development, the mechanisms responsible for this influence, particularly in the prefrontal cortex, remain unclear. The prefrontal cortex, the most evolved brain region, plays a role central in high-level cognition, which is why we focused our study on finding the answer in this area of ​​the brain,” said lead author Won Chan Oh, Ph.D., assistant professor in the Department in Pharmacology from CU Anschutz.

Oh and his student, Roberto Ogelman, who has a Ph.D. in neuroscience. candidate, discovered that serotonin directly influences nascent and immature excitatory synaptic connections in the prefrontal cortex, which, if disrupted or dysregulated during early development, can contribute to various mental health disorders.

“Our research reveals the specific processes at the synaptic level that explain how serotonin contributes to the development of this important brain region during early exposure to fluoxetine,” adds Oh. “We are the first to provide experimental evidence of the direct impact of serotonin on the development of the prefrontal cortex when fluoxetine is taken during pregnancy, because fluoxetine not only crosses the placental barrier but also passes into breast milk. “

To study this effect, researchers examined the impact of serotonin deficiency and excess on brain development in mice. They discovered that serotonin is not only involved in overall brain function, but also plays a specific role in influencing how individual connections between neurons change and adapt, thereby contributing to the ability of the brain to learn and adapt.

“Understanding this correlation could potentially contribute to early intervention and the development of new treatments for neurodevelopmental disorders involving serotonin dysregulation,” Oh said.

Researchers say health care professionals should be involved in decision-making regarding individualized care for pregnant women, including discussing the benefits and side effects of antidepressants and possible nonpharmacologic interventions for postpartum depression.

The researchers plan to continue studying the impact of fluoxetine, next examining its impact on a developing adolescent’s brain.