GPR56/ADGRG1 is associated with response to antidepressant treatment.

TitleGPR56/ADGRG1 is associated with response to antidepressant treatment.
Publication TypeJournal Article
Year of Publication2020
AuthorsBelzeaux 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
JournalNat Commun
Date Published2020 04 02
KeywordsAdult, 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 JournalNat Commun
PubMed ID32242018
PubMed Central IDPMC7118175
Grant ListR01 GM120110 / GM / NIGMS NIH HHS / United States
R01 NS103946 / NS / NINDS NIH HHS / United States
FDN148374 / / CIHR / Canada
EGM141899 / / CIHR / Canada