Une étude de Columbia établit un lien entre l'utilisation d'ISRS pendant la grossesse et la dépression chez les adolescents

Columbia University researchers have uncovered concerning evidence about the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, suggesting a potential link to increased depression and anxiety rates in adolescents. In a study that began nearly 20 years ago, the team experimented with mouse models to explore serotonin’s role in depression. They genetically modified mice to delete a serotonin reuptake protein, expecting similar effects to those of Prozac, an SSRI. However, the results surprised them: the modified mice displayed increased symptoms of depression and anxiety, contradicting their initial hypothesis.

Professor Jay Gingrich, who led the research, noted, “By deleting the gene, we did what Prozac does by increasing serotonin signaling. Yet, these mice seemed to demonstrate behaviors akin to being on ‘anti-Prozac.'” This unexpected behavior prompted further investigation into the timing of serotonin signaling.

In a follow-up study, conducted with colleague Mark Ansorge, the team found that early exposure to Prozac, simulating the third trimester in humans, led to anxious and depressed behaviors in mice later in life. Their findings were echoed in human studies, showing higher rates of depression in children exposed to SSRIs in utero compared to those who were not. “These children appeared to be normal during early childhood, but their depression rates surged during adolescence, mirroring our mouse studies,” Gingrich stated.

A major challenge in human studies is isolating the effects of SSRIs from maternal depression. Ansorge explained, “The severity of the mother’s depression could increase the child’s likelihood of developing similar issues.” To address this, the researchers examined the brain’s fear circuits in both mice and children. They hypothesized that specific activity patterns would emerge in the brains of those exposed to SSRIs.

Using an animal MRI machine, they recorded brain activity in mice exposed to predator odors. Results indicated that SSRI-exposed mice had significantly heightened activity in their fear circuits. The team then analyzed data from the Adolescent Brain Cognitive Development study, which provided MRI data on children’s reactions to disturbing images. They found similar patterns in SSRI-exposed children, unlike those whose mothers had depression but did not take SSRIs.

Ansorge remarked, “This distinct response indicates a unique mechanism at play in the SSRI-exposed children. They exhibit markedly different brain activity.”

Despite the compelling findings, the research has faced skepticism. Gingrich noted that while some clinicians advocate for SSRIs to support pregnant women with anxiety or depression—due to concerns about bonding with their infants—this research raises questions about potential negative impacts on fetal development.

Gingrich cautioned against immediate changes in clinical practice, stating, “It is premature to advise pregnant women to stop taking SSRIs. A thorough understanding of both risks and benefits is necessary before making any recommendations.”

He suggested that switching to alternative antidepressants, such as those targeting norepinephrine, might be an option, as preliminary results indicate these do not produce the same adverse effects observed with SSRIs in animal models.

The researchers are now focused on further analyzing brain circuit function and connectivity in both mice and humans. They aim to pinpoint when changes arise and how they affect brain structure and function. Additionally, they are exploring a new drug that targets the gut’s serotonin transporter, which may offer antidepressant effects without reaching the brain, potentially serving as a safer option for pregnant women.

Gingrich also noted an ongoing study in Quebec, monitoring mothers’ mental health during pregnancy to discern differences in depression severity between those who continue SSRIs and those who discontinue. The results could either support or challenge their recent findings.

As the team continues their research, they hope to clarify the long-term effects of in utero SSRI exposure and improve clinical guidance for managing maternal mental health during pregnancy.