谷氨酸通路基因多态性交互作用与快感缺失的关联研究

Relationship between polymorphic interaction of glutamate pathway genes and anhedonia

目的·探究谷氨酸通路基因-基因交互作用与快感缺失的关联。方法·纳入2017年1月-2020年8月在上海交通大学医学院附属精神卫生中心门诊及病房招募的279例精神分裂症(schizophrenia,SZ)患者、236例重型抑郁障碍(major depression disorder,MDD)患者,以及在社区招募的236例健康对照(healthy control,HC)为研究对象。收集并比较3组被试的一般人口学资料及临床特征。采用时间性愉快体验量表(Temporal Experience of Pleasure Scale,TEPS)中文版评估3组的愉快体验能力。采用广义多因子降维(generalized multifactor dimensionality reduction,GMDR)法建立谷氨酸通路基因(NOS1AP、GSK3β、DAOA、DISC1及GRIN2A)单核苷酸多态性(single nucleotide polymorphism,SNP)交互作用模型,依据该模型将SZ及MDD患者分为高风险组和低风险组,并对其愉快体验能力的差异进行组间比较,以分析基因-基因交互作用对快感缺失的影响。结果·年龄、受教育年限在3组间的差异具有统计学意义,首发年龄、病程在SZ、MDD组间的差异具有统计学意义(均P=0.000)。3组被试在总体愉快体验、期待性愉快体验及即时性愉快体验间差异均具有统计学意义(均P=0.000);SZ、MDD组患者的总体愉快体验、期待性及即时性愉快体验均低于HC组(均P_(校正)=0.000),且SZ与MDD组在期待性愉快体验上具有边缘性统计学差异(P_(校正)=0.051)。通过GMDR建模发现,由DAOA-rs3916965与DISC1-rs821577组成的2位点交互作用模型对SZ患者总体愉快体验能力具有预测作用(P=0.003),由NOS1AP-rs1858232和GRIN2A-rs1014531组成的2位点交互作用模型对MDD患者期待性愉快体验能力具有预测作用(P=0.037);且SZ高风险组患者的总体愉快体验能力、MDD高风险组患者的期待性愉快体验能力均分别低于其低风险组(t=3.443,P=0.000;t=3.471,P=0.001)。结论·谷氨酸通路基因多态性交互作用可能参与了快感缺失的发生。

Objective·To explore the association between gene-gene interaction of glutamate pathway and anhedonia.Methods·A total of 279 patients with schizophrenia(SZ)and 236 patients with major depression disorder(MDD)recruited in the outpatient department and ward of Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 236 healthy controls(HC)recruited in the community from January 2017 to August 2020 were included in the study.General demographic data and clinical characteristics of the three groups were collected and compared.The Chinese version of Temporal Experience of Pleasure Scale(TEPS)was used to evaluate the pleasure experience ability of the three groups.Generalized multifactor dimensionality reduction(GMDR)method was used to establish the interaction model of the single nucleotide polymorphism(SNP)in glutamate pathway genes(NOS1AP,GSK3β,DAOA,DISC1 and GRIN2A).According to the interaction model,SZ and MDD patients were divided into high-risk group and low-risk group,and the differences in pleasure experience ability were compared between the two groups,so as to analyze the effect of gene-gene interaction on anhedonia.Results·There were significant differences in age and years of education among the three groups,and in age of onset and duration of illness between SZ and MDD groups(all P=0.000).There were significant differences among the three groups of participants in terms of overall pleasure experience,anticipatory pleasure experience and consummatory pleasure experience(all P=0.000);the overall pleasure experience,anticipatory pleasure experience and consummatory pleasure experience in the SZ and MDD group were lower than those in the HC group(all P_(corr)=0.000),and there was marginal statistical difference in anticipatory pleasure experience between the SZ and MDD groups(P_(corr)=0.051).Through GMDR modeling,it was found that the 2-loci interaction model composed of DAOA-rs3916965 and DISC1-rs821577 had a predictive effect on the overall pleasure experience ability of SZ patients(P=0.003),and the 2-loci interaction model composed of NOS1AP-rs1858232 and GRIN2A-rs1014531 had a predictive effect on the anticipatory pleasure experience ability of MDD patients(P=0.037);moreover,the overall pleasure experience ability of patients in the SZ high-risk group and anticipatory pleasure experience ability of patients in MDD high-risk groups were lower than those in their low-risk groups(t=3.443,P=0.000;t=3.471,P=0.001).Conclusion·The interaction of glutamate pathway gene polymorphisms may be involved in the occurrence of anhedonia.