Related Experiment Video
Updated: Dec 25, 2025

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
Published on: June 6, 2025
GPR56/ADGRG1 is associated with response to antidepressant treatment
Raoul Belzeaux1,2,3, Victor Gorgievski4,5, Laura M Fiori1
1Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada.
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.
Related Concept Videos
G-protein Coupled Receptors
Antidepressant Drugs: MAOIs and Other Agents
Antidepressant Drugs: Overview
Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists

