GPR56/ADGRG1 is associated with response to antidepressant treatment.
Adult
Animals
Antidepressive Agents
/ administration & dosage
Cohort Studies
Depressive Disorder, Major
/ drug therapy
Female
Glycogen Synthase Kinase 3
/ metabolism
Humans
Male
Mice
Mice, Inbred C57BL
Middle Aged
Prefrontal Cortex
/ drug effects
Receptors, G-Protein-Coupled
/ genetics
Selective Serotonin Reuptake Inhibitors
/ administration & dosage
Treatment Outcome
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 04 2020
02 04 2020
Historique:
received:
05
02
2019
accepted:
10
03
2020
entrez:
4
4
2020
pubmed:
4
4
2020
medline:
25
7
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32242018
doi: 10.1038/s41467-020-15423-5
pii: 10.1038/s41467-020-15423-5
pmc: PMC7118175
doi:
Substances chimiques
ADGRG1 protein, human
0
Antidepressive Agents
0
GPR56 protein, mouse
0
Receptors, G-Protein-Coupled
0
Serotonin Uptake Inhibitors
0
Glycogen Synthase Kinase 3
EC 2.7.11.26
Banques de données
ClinicalTrials.gov
['NCT00635219', 'NCT00599911', 'NCT01140906', 'NCT02209142']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1635Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM120110
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS103946
Pays : United States
Organisme : CIHR
ID : FDN148374
Pays : Canada
Organisme : CIHR
ID : EGM141899
Pays : Canada
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