Nature communications · 2020
GPR56/ADGRG1 is associated with response to antidepressant treatment.
СтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.