GPR56/ADGRG1 is associated with response to antidepressant treatment Academic Article uri icon

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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.

authors

  • 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
  • Mechawar, Naguib
  • Tall, Gregory G
  • Tzavara, Eleni T
  • Kennedy, Sidney H
  • Turecki, Gustavo

publication date

  • December 2020