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

Author

Listed:
  • Giulia Zanni

    (Columbia University
    New York State Psychiatric Institute)

  • Milenna T. Dijk

    (Columbia University
    New York State Psychiatric Institute)

  • Martha Caffrey Cagliostro

    (Columbia University
    Northeastern University)

  • Pradyumna Sepulveda

    (Columbia University)

  • Nicolò Pini

    (Columbia University
    New York State Psychiatric Institute)

  • Ariel L. Rose

    (Columbia University
    New York State Psychiatric Institute)

  • Alexander L. Kesin

    (Columbia University
    New York State Psychiatric Institute)

  • Claudia Lugo-Candelas

    (Columbia University
    New York State Psychiatric Institute)

  • Priscila Dib Goncalves

    (Columbia University)

  • Alexandra S. MacKay

    (Columbia University
    New York State Psychiatric Institute)

  • Kiyohito Iigaya

    (Columbia University
    New York State Psychiatric Institute
    Columbia University
    Columbia University)

  • Praveen Kulkarni

    (Northeastern University)

  • Craig F. Ferris

    (Northeastern University)

  • Myrna M. Weissman

    (Columbia University
    New York State Psychiatric Institute
    Columbia University)

  • Ardesheer Talati

    (Columbia University
    New York State Psychiatric Institute)

  • Mark S. Ansorge

    (Columbia University
    New York State Psychiatric Institute)

  • Jay A. Gingrich

    (Columbia University
    New York State Psychiatric Institute)

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.

Suggested Citation

  • 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. MacK, 2025. "Perinatal SSRI exposure impacts innate fear circuit activation and behavior in mice and humans," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58785-4
    DOI: 10.1038/s41467-025-58785-4
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    References listed on IDEAS

    as
    1. Christopher Genovese & Larry Wasserman, 2002. "Operating characteristics and extensions of the false discovery rate procedure," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 64(3), pages 499-517, August.
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