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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 Pcorr=0.000), and there was marginal statistical difference in anticipatory pleasure experience between the SZ and MDD groups (Pcorr=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. |
