GPR56/ADGRG1 is associated with response to antidepressant treatment.
|Title||GPR56/ADGRG1 is associated with response to antidepressant treatment.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Belzeaux R, Gorgievski V, Fiori LM, Lopez JPablo, Grenier J, Lin R, Nagy C, Ibrahim EChérif, Gascon E, Courtet P, Richard-Devantoy S, Berlim M, Chachamovich E, Théroux J-F, Dumas S, Giros B, Rotzinger S, Soares CN, Foster JA, Mechawar N, Tall GG, Tzavara ET, Kennedy SH, Turecki G|
|Date Published||2020 04 02|
|Keywords||Adult, Animals, Antidepressive Agents, Cohort Studies, Depressive Disorder, Major, Female, Glycogen Synthase Kinase 3, Humans, Male, Mice, Mice, Inbred C57BL, Middle Aged, Prefrontal Cortex, Receptors, G-Protein-Coupled, Serotonin Uptake Inhibitors, Treatment Outcome|
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.
|Alternate Journal||Nat Commun|
|PubMed Central ID||PMC7118175|
|Grant List||R01 GM120110 / GM / NIGMS NIH HHS / United States |
R01 NS103946 / NS / NINDS NIH HHS / United States
FDN148374 / / CIHR / Canada
EGM141899 / / CIHR / Canada