A major international study has found that children exposed to antidepressants in the womb may face a higher risk of anxiety and altered brain responses to fear during adolescence. The research, published in Nature Communications, used brain imaging and behavioural analysis in both mice and humans to investigate the effects of perinatal exposure to selective serotonin reuptake inhibitors (SSRIs).
SSRIs, commonly prescribed to treat depression and anxiety, are used by approximately 6% of pregnant women. While the medications are considered important for maternal mental health, their long-term impact on the developing brain has remained poorly understood.
In the animal portion of the study, newborn mice were given fluoxetine, a common SSRI, during a period equivalent to the third trimester in humans. As adults, these mice exhibited exaggerated fear responses when exposed to predator odours. Functional brain scans revealed significantly increased activation in areas associated with fear and emotion regulation, such as the amygdala and hypothalamus.
In parallel, the researchers analysed brain scans and behavioural data from thousands of children enrolled in the Adolescent Brain Cognitive Development (ABCD) Study in the US. The findings showed that adolescents who had been exposed to SSRIs in utero displayed greater anxiety, depression, and internalising behaviours compared to their peers. Brain imaging revealed amplified activity in the amygdala, hippocampus, and insula when viewing fearful faces – patterns closely matching the responses seen in the mice.
Importantly, the study controlled for a range of potential confounders, including maternal depression, socioeconomic factors, and substance use during pregnancy. Even after adjusting for these variables, the association between prenatal SSRI exposure and altered fear responses remained strong.
The researchers also explored whether the observed brain changes might help explain behavioural symptoms. They found that heightened amygdala activity was linked to increased anxiety and depressive symptoms in the children and predicted mental health difficulties one year later. This suggests that alterations in brain circuitry may play a mediating role in how SSRI exposure translates into emotional challenges.
Although animal studies have long suggested that serotonin plays a crucial role in early brain development, this study is one of the first to demonstrate that SSRI-related changes in brain function are conserved across species. The findings support the idea that increased serotonin levels during key developmental windows may disrupt the maturation of fear and emotion circuits.
The researchers acknowledge that the decision to prescribe SSRIs during pregnancy is complex. Untreated maternal depression carries its own risks for both mother and child, including preterm birth and impaired bonding. But they argue that more research is needed to develop alternative interventions that safeguard both maternal mental health and fetal neurodevelopment.
