Perinatal SSRI Exposure Impacts Innate Fear Circuit Activation and Behavior in Mice and Humans

Serotonin shapes brain structure and function during early development across phylogenetically diverse species. In mice and humans, perinatal SSRI exposure produces brain alterations and increases anxiety/depression-related behaviors in the offspring. It remains unclear whether shared brain circuit changes underlie the behavioral impact of perinatal SSRIs across species. We examine how developmental SSRI-exposure in mice and humans changes fear-related brain activation and behavior. SSRI-administered mice showed increased defense responses to a predator odor that were associated with stronger fMRI-based fear circuit activation when compared to saline controls. Similarly, human adolescents exposed to SSRIsin uteroshowed greater activation of fear brain structures and exhibited higher anxiety and depressive symptoms than unexposed adolescents. Perinatal SSRI enhances innate fear-related responses and fear brain circuit activation that are conserved across species.One Sentence SummarySince SSRI use in pregnancy is common, we determined the effects of altered serotonin signaling during development in mice and humans.