Researchers have found a potential link between autism-like behavior in adult mice and exposure to a common antidepressant in the womb.
They also identified a treatment that helped improve memory loss and social interactions, according to the new study in the journal Molecular Brain.
Doctors commonly prescribe antidepressants for treating major depression and post-traumatic stress disorder, including in pregnant women. One of the most commonly prescribed antidepressants is fluoxetine, a serotonin reuptake inhibitor. Fluoxetine can cross the placenta and scientists have also detected it in breast milk. Little is known about its safety during pregnancy, and not enough studies have taken place on its long-term effects on offspring.
“Many human association studies have been conducted to investigate connections between antidepressant exposure during pregnancy and children with autism and attention deficit disorder. But they have not been able to pinpoint a causal relationship,” says senior and corresponding author Hyunsoo Shawn Je, associate professor from the Duke-NUS neuroscience and behavioral disorders program.
The team and their collaborators in South Korea and Singapore investigated adult mice born to mothers treated with fluoxetine (sold under the brand names Prozac and Sarafem) over a 15-day time period that corresponds to the second trimester in humans, in comparison with those born to mothers given normal saline as controls.
The researchers found key differences in behavior. For example, the unexposed mice normally explored all three arms of a Y-shaped maze over a ten-minute time period and, over the courses of multiple arm entries, mice usually enter a less recently visited arm, while the fluoxetine-exposed ones were less inclined to explore an unvisited arm.
In a second experiment, the researchers introduced the mice to two juvenile mice, one after the other. When the second new mouse was introduced, mice that were not exposed to fluoxetine were more likely to only sniff the newly introduced mouse, recognizing that they had already met the first mouse. But the fluoxetine-exposed group sniffed both mice, indicating that they had impaired social novelty recognition.
The team then examined nerve signal transmission in the prefrontal cortex, a part of the brain involved in moderating social behavior. They found that an overactive serotonin receptor impaired transmission. Treating fluoxetine-exposed mice with a compound that blocks the receptor alleviated their behavioral problems and improved their working memory.
The team next wants to examine children with autism born to mothers who took with antidepressants using positron emission tomography scans, an imaging technique used to observe metabolic processes in the body. If they also show enhanced serotonin receptor activity in the same area of the brain, the team plans to test whether FDA-approved serotonin receptor blockers can normalize their behaviors.
“The consensus among experts is that the rise in the number of people diagnosed with autism around the world is likely due to more awareness and testing rather than an increase in the prevalence of autism,” notes Patrick Casey, professor and senior vice dean for research.
“This collaborative study by our researchers offers a compelling case for a link between autism and antidepressant exposure in the womb in an animal model, and a possible mechanism that could potentially be exploited for future therapies.”