A global team directed by Duke-NUS school of medicine has uncovered a possible link involving autistic-like behaviors in adult mice and subjection to a prevalent antidepressant in the womb. Additionally, they discovered a treatment that helped to improve loss of memory and social interactions, base on the new research published in the journal Molecular Brain.
Antidepressants are typically recommended for managing major depression and post-traumatic stress disorder, which includes pregnant women. Among the most frequently recommended antidepressants is fluoxetine, a serotonin reuptake inhibitor (SRI). Fluoxetine can traverse the placenta as well as being found in breast milk. Very little may be known about its safety when pregnant, and not enough studies have been performed on its long-term impacts on children.
“Many human association studies have been conducted to investigate connections between antidepressant exposure during pregnancy and children with autism and attention deficit disorder (ADHD). But they have not been able to pinpoint a causal relationship,” claimed Associate Professor Hyunsoo Shawn Je, from Duke-NUS’ Neuroscience and Behavioral Disorders (NBD) Programme, a senior and affiliated composer of the research.
The group from Duke-NUS, as well as their collaborators in South Korea and Singapore, explored adult mice born to mothers given fluoxetine (sold in the brands Prozac and Sarafem) over a 15-day time frame that corresponds to the second trimester in humans, compared to those born to mothers provided standard saline as controls. They found key variations in behavior. For instance, the unexposed mice regularly explored all three arms of a Y-shaped maze over a ten-minute time frame and, during the courses of multiple arm entries, mice commonly enter a much less visited arm, whilst the fluoxetine-subjected ones were less likely to investigate unvisited arm.
In a second test, the mice were exposed to two juvenile mice, one after the other. The moment the second new mouse was presented, mice that were never exposed to fluoxetine were more inclined to only sniff the freshly introduced mouse, acknowledging they had already come across the first mouse. But the fluoxetine-subjected group sniffed both mice, meaning that there was weakened social novelty understanding.
The team then analyzed nerve signal relaying in the prefrontal cortex, an integral part of the brain linked to moderating social behavior. They found weakened transmission as a result of a hyperactive serotonin receptor. Treating fluoxetine-subjected mice with a substance that hinders the receptor eased their behavioral issues and increased their working memory.
The team next would like to analyze autistic children born to mothers given antidepressants utilizing positron emission tomography (PET) scans, an imaging strategy applied to observe metabolic functions within the body. If they also show increased serotonin receptor activity in the same area of the brain, the team intends to test whether FDA-approved serotonin receptor blockers can stabilize 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,” noted Professor Patrick Casey, Senior Vice Dean for Research at Duke-NUS. “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.”