Perinatal SSRI exposure impacts innate fear circuit activation and behavior in mice and humans

Giulia Zanni, Milenna T. Dijk, Martha Caffrey Cagliostro, Pradyumna Sepulveda, Nicolò Pini, Ariel L. Rose, Alexander L. Kesin, Claudia Lugo-Candelas, Priscila Dib Goncalves, Alexandra S. MacKay, Kiyohito Iigaya, Praveen Kulkarni, Craig F. Ferris, Myrna M. Weissman, Ardesheer Talati, Mark S. Ansorge () and Jay A. Gingrich
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Giulia Zanni: Columbia University
Milenna T. Dijk: Columbia University
Martha Caffrey Cagliostro: Columbia University
Pradyumna Sepulveda: Columbia University
Nicolò Pini: Columbia University
Ariel L. Rose: Columbia University
Alexander L. Kesin: Columbia University
Claudia Lugo-Candelas: Columbia University
Priscila Dib Goncalves: Columbia University
Alexandra S. MacKay: Columbia University
Kiyohito Iigaya: Columbia University
Praveen Kulkarni: Northeastern University
Craig F. Ferris: Northeastern University
Myrna M. Weissman: Columbia University
Ardesheer Talati: Columbia University
Mark S. Ansorge: Columbia University
Jay A. Gingrich: Columbia University

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Before assuming its role in the mature brain, serotonin modulates early brain development across phylogenetically diverse species. In mice and humans, early-life SSRI exposure alters the offspring’s brain structure and is associated with anxiety and depression-related behaviors beginning in puberty. However, the impact of early-life SSRI exposure on brain circuit function is unknown. To address this question, we examined how developmental SSRI exposure changes fear-related brain activation and behavior in mice and humans. SSRI-exposed mice showed increased defense responses to a predator odor, and stronger fMRI amygdala and extended fear-circuit activation. Likewise, adolescents exposed to SSRIs in utero exhibited higher anxiety and depression symptoms than unexposed adolescents and also had greater activation of the amygdala and other limbic structures when processing fearful faces. These findings demonstrate that increases in anxiety and fear-related behaviors as well as brain circuit activation following developmental SSRI exposure are conserved between mice and humans. These findings have potential implications for the clinical use of SSRIs during human pregnancy and for designing interventions that protect fetal brain development.

Date: 2025
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DOI: 10.1038/s41467-025-58785-4

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