A popular medication for depression and anxiety could be associated with long-term abnormalities in the brains of children whose mothers take the drug while pregnant.
A fetus’s brain develops according to a precise schedule. If the process is disrupted, causing a developmental step to happen too early or too late, it can interfere with how the brain is structured and how it eventually functions.
This mistiming in the brain’s wiring during key development windows can create vulnerabilities that may lead to mental health or neurological disorders, even if the symptoms do not appear until much later in life.
Scientists from Italy and Finland gave the antidepressant medication, fluoxetine, known as Prozac, to pregnant and nursing rats and then studied their offspring.
The study found male rats exposed to the drug in utero and female rats exposed through their mother’s milk also saw changes in genes that control critical periods of brain development, leading to an increased vulnerability to neurological and psychiatric conditions later on.
In male mice exposed to fluoxetine in the womb, the brain’s key development window opened early and mood-related issues, such as a loss of pleasure, were observed.
Female rats exposed after birth through breastfeeding showed a later window of opening and future memory deficits.
Researchers found the drug’s strongest impact was in the hippocampus, the brain’s central hub for memory and emotional regulation. This may explain why exposed individuals later developed issues with memory and mood.
Antidepressants, including fluoxetine (Prozac), are considered a safe option for many pregnant women. A 2020 US study found that about five percent of women used them during early pregnancy (stock)
These outcomes were linked to molecular changes in the brain, specifically, altered genes that trigger and halt the timing of development in the hippocampus and other brain regions.
Treatments designed to correct this abnormal timing could help prevent the disorders from developing in the first place, the researchers said.
Pregnant mother rats were divided into three groups: the prenatal group received fluoxetine in their drinking water only during pregnancy, while the postnatal group received fluoxetine while nursing. The control group drank plain water the entire time.
When their offspring were adolescents and then as adults, scientists conducted a test that measured their pleasure response to a stimulus, specifically sugar water.
All of the adolescent rats, whether they were exposed to Prozac or not, behaved normally. They preferred the sugar water, showing that their ability to feel pleasure was intact at that age.
But in adulthood, the rats exposed to fluoxetine in utero lost their preference for the sugar water. They drank almost as much plain water as sweet water.
This new behavior, called anhedonia, is a core symptom of depression. It signifies a loss of the ability to feel pleasure.
The drug exposure had reprogrammed their brain’s reward system, which did not become apparent until they were fully grown.
Fluoxetine, the antidepressant known as Prozac, is used by over 5.7 million Americans for depression and anxiety. It has been a fundamental and widely trusted medication since the 1990s (stock)
Another test introduced rats to two objects that they sniffed and familiarized themselves with. Then, scientists replaced one of the familiar objects with a new one to measure a rat’s ability to recognize what it had seen before.
Rats with good memory should investigate the new object more. As adolescents, all the rats performed normally. However, major disparities became apparent when the rats matured into adulthood.
Unlike normal rats, females exposed to the drug through their mother’s milk did not prefer a new object over a familiar one, indicating a failure to form or recall memories.
The adult rats in the placebo group behaved as expected and demonstrated normal memory.
Scientists concluded that females exposed to fluoxetine through their mother’s milk grew up to have memory problems, while males exposed in the womb grew up to have a loss of pleasure.
The researchers then conducted analyses of the rats’ brains to see changes in brain structure and connectivity.
They found the physical cause for the behavioral shifts. The early drug exposure had thrown the brain’s precise developmental wiring instructions into chaos.
Exposure to antidepressants disrupted the development of key brain cells that help filter information, as well as the structures that protect those cells, making it harder to distinguish important stimuli like a familiar object or a sweet taste.
The chart shows that between 2021 and 2023, 13.1 percent of Americans aged 12 and older experienced depression. The rate was highest among adolescents (19.2 percent) and lowest among adults 60 and older (8.7 percent), showing that depression decreases with age
The graph shows that rates of depression in the US have risen significantly, climbing from 8. percent in 2013-2014 to 13.1 percent in 2021-2023. The increase was seen in both males and females
Scientists determined that this effectively rewired the male brains for depression and the female brains for memory loss, creating a lasting vulnerability that only became evident in adulthood.
Antidepressants are generally thought of as safe during pregnancy. According to a 2020 study based in the US, antidepressants were used in approximately one in 20 pregnancies during the first trimester.
One of the most commonly used medications was fluoxetine. Overall, 5.7 million Americans take the drug.
Fluoxetine belongs to a family of medications called selective serotonin reuptake inhibitors (SSRIs), which increase the number of receptors in the brain that latch on to serotonin, a key neurotransmitter for regulating mood.
Serotonin delivers ‘feel-good’ signals between brain cells before being reabsorbed. SSRIs block this reabsorption, allowing more serotonin to remain active and improving communication and mood.
Newborns exposed to Prozac in the womb may experience temporary withdrawal symptoms like jitters and breathing difficulties, and face a slightly higher risk of preterm birth, low birth weight, and potential heart issues.
But for many pregnant women with depression, the benefits of taking an SSRI outweigh the known risks. Untreated depression itself carries significant risks for both the mother and her baby.
Untreated depression in pregnancy raises the risk of pre-term birth, low birth weight and intrauterine growth restriction, a condition where a fetus does not grow adequately in the womb.
It can also contribute to problems as a child gets older. Children born to mothers with untreated depression are more likely to struggle with controlling their impulses, have trouble making friends and face difficulties with learning, behavior and managing their emotions.
At the same time, the latest study, published in the journal Molecular Psychiatry, suggests that taking fluoxetine during pregnancy could potentially alter a child’s brain development and increase their risk for mental health conditions later in life.
However, the researchers stress that these findings, while concerning, need to be confirmed in human studies before they can influence medical guidelines.
