GPR56/ADGRG1 与抗抑郁治疗反应相关。
GPR56/ADGRG1 is associated with response to antidepressant treatment.
机构信息
Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada.
Aix-Marseille Univ, AP-HM, CNRS, INT, Inst Neurosci Timone, Hôpital Sainte Marguerite, Pôle de psychiatrie, Marseille, France.
出版信息
Nat Commun. 2020 Apr 2;11(1):1635. doi: 10.1038/s41467-020-15423-5.
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.
目前尚不清楚为何许多抑郁症患者对抗抑郁治疗没有反应。在三个接受血清素-去甲肾上腺素再摄取抑制剂治疗的抑郁症患者队列中（N=424），我们发现，有反应者而非无反应者的血液中 GPR56mRNA 增加。在一小部分研究对象中，我们还发现，死于自杀的抑郁症患者的大脑前额叶皮层（PFC）中的 GPR56 下调。在小鼠中，我们发现慢性应激引起的血液和前额叶皮层（PFC）中 Gpr56 下调，伴有类似抑郁的行为，而抗抑郁治疗可以逆转这种情况。Gpr56 在小鼠 PFC 中的敲低与抑郁样行为、执行功能障碍和对抗抑郁治疗的反应不良有关。GPR56 肽激动剂具有抗抑郁作用，并上调 AKT/GSK3/EIF4 通路。我们的研究结果揭示了 GPR56 在抗抑郁反应中的潜在作用。
Zotero 插件