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GPR56/ADGRG1 is associated with response to antidepressant treatment

Author

Listed:
  • Raoul Belzeaux

    (McGill University
    Hôpital Sainte Marguerite, Pôle de psychiatrie
    Fondation FondaMental)

  • Victor Gorgievski

    (CNRS (Integrative Neuroscience and Cognition Center, UMR 8002)
    Université Paris Descartes, Sorbonne Paris Cité)

  • Laura M. Fiori

    (McGill University)

  • Juan Pablo Lopez

    (McGill University)

  • Julien Grenier

    (Université Paris Descartes)

  • Rixing Lin

    (McGill University)

  • Corina Nagy

    (McGill University)

  • El Chérif Ibrahim

    (Hôpital Sainte Marguerite, Pôle de psychiatrie
    Fondation FondaMental)

  • Eduardo Gascon

    (Hôpital Sainte Marguerite, Pôle de psychiatrie)

  • Philippe Courtet

    (Fondation FondaMental
    Lapeyronie Hospital, CHU Montpellier)

  • Stéphane Richard-Devantoy

    (McGill University)

  • Marcelo Berlim

    (McGill University)

  • Eduardo Chachamovich

    (McGill University)

  • Jean-François Théroux

    (McGill University)

  • Sylvie Dumas

    (Oramacell)

  • Bruno Giros

    (McGill University)

  • Susan Rotzinger

    (University Health Network, Krembil Research Institute, University of Toronto)

  • Claudio N. Soares

    (Centre for Depression and Suicide Studies
    Department of Psychiatry, Queen’s University, Kingston)

  • Jane A. Foster

    (University Health Network, Krembil Research Institute, University of Toronto)

  • Naguib Mechawar

    (McGill University)

  • Gregory G. Tall

    (University of Michigan)

  • Eleni T. Tzavara

    (Fondation FondaMental
    CNRS (Integrative Neuroscience and Cognition Center, UMR 8002)
    Université Paris Descartes, Sorbonne Paris Cité)

  • Sidney H. Kennedy

    (University Health Network, Krembil Research Institute, University of Toronto
    Centre for Depression and Suicide Studies)

  • Gustavo Turecki

    (McGill University)

Abstract

It remains unclear why many patients with depression do not respond to antidepressant treatment. In three cohorts of individuals with depression and treated with serotonin-norepinephrine reuptake inhibitor (N = 424) we show that responders, but not non-responders, display an increase of GPR56 mRNA in the blood. In a small group of subjects we also show that GPR56 is downregulated in the PFC of individuals with depression that died by suicide. In mice, we show that chronic stress-induced Gpr56 downregulation in the blood and prefrontal cortex (PFC), which is accompanied by depression-like behavior, and can be reversed by antidepressant treatment. Gpr56 knockdown in mouse PFC is associated with depressive-like behaviors, executive dysfunction and poor response to antidepressant treatment. GPR56 peptide agonists have antidepressant-like effects and upregulated AKT/GSK3/EIF4 pathways. Our findings uncover a potential role of GPR56 in antidepressant response.

Suggested Citation

  • Raoul Belzeaux & Victor Gorgievski & Laura M. Fiori & Juan Pablo Lopez & Julien Grenier & Rixing Lin & Corina Nagy & El Chérif Ibrahim & Eduardo Gascon & Philippe Courtet & Stéphane Richard-Devantoy &, 2020. "GPR56/ADGRG1 is associated with response to antidepressant treatment," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15423-5
    DOI: 10.1038/s41467-020-15423-5
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    Cited by:

    1. Saurabh Thapliyal & Isabel Beets & Dominique A. Glauser, 2023. "Multisite regulation integrates multimodal context in sensory circuits to control persistent behavioral states in C. elegans," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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