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GPR56/ADGRG1 is associated with response to antidepressant treatment

Raoul Belzeaux 1, 2, 3 Victor Gorgievski 4 Laura Fiori 5 Juan Pablo Lopez 5 Julien Grenier 6 Rixing Lin 5 Corina Nagy 5 El Chérif Ibrahim 2, 3 Eduardo Gascon 2 Philippe Courtet 3, 7 Stéphane Richard-Devantoy 5 Marcelo Berlim 5 Eduardo Chachamovich 5 Jean-François Théroux 5 Sylvie Dumas 8 Bruno Giros 5 Susan Rotzinger 9 Claudio Soares 10 Jane Foster 9 Naguib Mechawar 5 Gregory Tall 11 Eleni Tzavara 3, 4, 12 Sidney Kennedy 13 Gustavo Turecki 5
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.
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Submitted on : Friday, April 3, 2020 - 12:23:25 PM
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Raoul Belzeaux, Victor Gorgievski, Laura Fiori, Juan Pablo Lopez, Julien Grenier, et al.. GPR56/ADGRG1 is associated with response to antidepressant treatment. Nature Communications, Nature Publishing Group, 2020, 11, ⟨10.1038/s41467-020-15423-5⟩. ⟨hal-02530966⟩

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