Genetic variables of the glutamatergic system associated with treatment-resistant depression:A review of the literature  

作　　者：Estela Saez Leire Erkoreka Teresa Moreno-Calle Belen Berjano Ana Gonzalez-Pinto Nieves Basterreche Aurora Arrue 

机构地区：[1]Department of Psychiatry,Barrualde-Galdakao Integrated Health Organization,Osakidetza-Basque Health Service,Galdakao 48960,Spain [2]Mental Health Network Group,Biocruces Bizkaia Health Research Institute,Barakaldo 48903,Spain [3]Department of Neurosciences,University of the Basque Country UPV/EHU,Leioa 48940,Spain [4]Department of Psychiatry,Araba Integrated Health Organization,Osakidetza-Basque Health Service,CIBERSAM,Vitoria-Gasteiz 01004,Spain [5]Severe Mental Disorders Group,Bioaraba Health Research Institute,Vitoria-Gasteiz 01009,Spain [6]Zamudio Hospital,Bizkaia Mental Health Network,Osakidetza-Basque Health Service,Zamudio 48170,Spain [7]Integrative Research Group in Mental Health,Biocruces Bizkaia Health Research Institute,Barakaldo 48903,Spain [8]Neurochemical Research Unit,Bizkaia Mental Health Network,Osakidetza-Basque Health Service,Barakaldo 48903,Spain

出　　处：《World Journal of Psychiatry》2022年第7期884-896,共13页世界精神病学杂志

摘　　要：Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide.Up to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,can be defined as treatment-resistant depression(TRD).The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment.Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD.Specifically,the N-methyl-D-aspartic acid receptor(NMDAR)andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR),which are targeted by ketamine and esketamine,are proposed as promising pathways.A literature search was performed to identify studies on the genetics of the glutamatergic system in depression,focused on variables related to NMDARs and AMPARs.Our review highlights GRIN2B,which encodes the NR2B subunit of NMDAR,as a candidate gene in the pathogenesis of TRD.In addition,several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation.These genes encoding glutamatergic receptors could,therefore,be candidate genes for understanding the etiopathogenesis of TRD,as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.

关 键 词：GENETICS N-methyl-D-aspartic acid receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor Treatment-resistant depression KETAMINE Esketamine 

分 类 号：R749.4[医药卫生—神经病学与精神病学]