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GPR56/ADGRG1 is associated with response to antidepressant treatment

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Belzeaux, Raoul | Gorgievski, Victor | Fiori, Laura, M | Lopez, Juan Pablo | Grenier, Julien | Lin, Rixing | Nagy, Corina | Ibrahim, El Chérif | Gascon, Eduardo | Courtet, Philippe | Richard-Devantoy, Stéphane | Berlim, Marcelo | Chachamovich, Eduardo | Théroux, Jean-François | Dumas, Sylvie | Giros, Bruno | Rotzinger, Susan | Soares, Claudio, N | Foster, Jane, A | Mechawar, Naguib | Tall, Gregory, G | Tzavara, Eleni, T | Kennedy, Sidney, H | Turecki, Gustavo

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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