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 |
| Journal | Nat Commun |
| Volume | 11 |
| Issue | 1 |
| Pagination | 1635 |
| Date Published | 2020 04 02 |
| ISSN | 2041-1723 |
| 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 |
| 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. |
| DOI | 10.1038/s41467-020-15423-5 |
| Alternate Journal | Nat Commun |
| PubMed ID | 32242018 |
| 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 |
