GPR56/ADGRG1 is associated with response to antidepressant treatment
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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 also 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 behaviour, and can be reversed by antidepressant treatment. Gpr56 knockdown in mouse PFC was is associated with depressive-like behaviors, executive dysfunction and poor response to antidepressant treatment. GPR56 peptide agonists had antidepressant-like effects and up-regulated AKT/GSK3/EIF4 pathways. Our findings uncover a potential role of GPR56 in antidepressant response.
ORGANISM(S): Homo sapiens
PROVIDER: GSE146446 | GEO | 2020/03/31
REPOSITORIES: GEO
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