Relationship between polymorphic interaction of glutamate pathway genes and anhedonia

doi:10.3969/j.issn.1674-8115.2024.05.005

Abstract

Abstract:

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.

Key words: anhedonia, glutamate pathway, generalized multifactor dimensionality reduction (GMDR), interaction effect

CLC Number:

R749

HUANG Xinxin, LIU Chao, LÜ Qinyu, HU Guoqin, BAO Chenxi, ZHANG Yao, YI Zhenghui. Relationship between polymorphic interaction of glutamate pathway genes and anhedonia[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(5): 576-583.

Figures/Tables 5

TrendMD

References 29

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Item	SZ group (n=279)	MDD group (n=236)	HC group (n=236)	χ²/Z/F value	P value
Gender/n(%)				4.757	0.093
Male	146 (52.3)	104 (44.1)	125 (53.0)
Female	133 (47.7)	132 (55.9)	111 (47.0)
Age/year	24.5 (19.0, 31.0)^①,④	27.0 (22.0, 33.0)^②	32.0 (24.0, 57.3)	76.941	0.000
Years of education/year	12.0 (9.4, 15.0)^①,④	15.0 (12.0, 15.0)^②	16.0 (12.6, 17.0)	78.504	0.000
Age of onset/year	19.0 (16.0, 24.0)	25.0 (20.0, 31.0)	‒	-7.125	0.000
Duration of illness/month	23.0 (7.5, 60.0)	6.0 (2.0, 24.0)	‒	-6.712	0.000
Number of episodes	1.0 (1.0, 1.0)	1.0 (1.0, 1.0)	‒	-0.309	0.757
TEPS total score/score	72.3±13.3^①	66.8±16.0^②,③	81.7±12.9	26.028	0.000
Anticipatory	34.0 (30.0, 38.0)^①	30.0 (24.0, 37.0)^②	37.0 (33.0, 43.0)	34.729	0.000
Abstract anticipatory	18.0 (14.0, 20.0)^①	15.0 (11.5, 19.0)^②,③	20.0 (18.0, 22.0)	51.744	0.000
Contextual anticipatory	16.0 (14.0, 19.0)	15.0 (13.0, 19.0)^②	18.0 (14.8, 21.0)	9.606	0.008
Consummatory	39.0 (34.0, 44.0)^①	38.0 (30.5, 42.5)^②	44.0 (38.8, 50.0)	34.277	0.000
Abstract consummatory	24.5±5.3^①	22.5±6.3^②,③	27.7±4.6	20.481	0.000
Contextual consummatory	14.0 (11.5, 17.0) ^①	15.0 (11.5, 16.5)^②	17.0 (14.0, 19.0)	22.299	0.000

Item	SZ group (n=279)	MDD group (n=236)	HC group (n=236)	χ²/Z/F value	P value
Gender/n(%)				4.757	0.093
Male	146 (52.3)	104 (44.1)	125 (53.0)
Female	133 (47.7)	132 (55.9)	111 (47.0)
Age/year	24.5 (19.0, 31.0)^①,④	27.0 (22.0, 33.0)^②	32.0 (24.0, 57.3)	76.941	0.000
Years of education/year	12.0 (9.4, 15.0)^①,④	15.0 (12.0, 15.0)^②	16.0 (12.6, 17.0)	78.504	0.000
Age of onset/year	19.0 (16.0, 24.0)	25.0 (20.0, 31.0)	‒	-7.125	0.000
Duration of illness/month	23.0 (7.5, 60.0)	6.0 (2.0, 24.0)	‒	-6.712	0.000
Number of episodes	1.0 (1.0, 1.0)	1.0 (1.0, 1.0)	‒	-0.309	0.757
TEPS total score/score	72.3±13.3^①	66.8±16.0^②,③	81.7±12.9	26.028	0.000
Anticipatory	34.0 (30.0, 38.0)^①	30.0 (24.0, 37.0)^②	37.0 (33.0, 43.0)	34.729	0.000
Abstract anticipatory	18.0 (14.0, 20.0)^①	15.0 (11.5, 19.0)^②,③	20.0 (18.0, 22.0)	51.744	0.000
Contextual anticipatory	16.0 (14.0, 19.0)	15.0 (13.0, 19.0)^②	18.0 (14.8, 21.0)	9.606	0.008
Consummatory	39.0 (34.0, 44.0)^①	38.0 (30.5, 42.5)^②	44.0 (38.8, 50.0)	34.277	0.000
Abstract consummatory	24.5±5.3^①	22.5±6.3^②,③	27.7±4.6	20.481	0.000
Contextual consummatory	14.0 (11.5, 17.0) ^①	15.0 (11.5, 16.5)^②	17.0 (14.0, 19.0)	22.299	0.000

Candidate gene	SNP	Chromosome	Position	Alleles	MAF	Feature
NOS1AP	rs12742393	1q23.3	162224586	C/A	0.32	Intron2
	rs1415259		162085309	C/T	0.42	Intron1
	rs1415263		162166043	C/T	0.48	Intron2
	rs1858232		162303838	G/A	0.33	Intron5
	rs348624		162335256	C/T	0.25	Synonymous_exon9
	rs6680461		162255286	G/T	0.39	Intron2
GSK3β	rs334558	3q13.33	119813282	G/A	0.40	5′-flanking
	rs6779828		119775147	C/T	0.28	Intron1
DAOA	rs3916965	13q33.2	106103360	C/T	0.36	Intergenic region
	rs778294		106142235	C/T	0.22	Synonymous_exon4
	rs947267		106139662	G/T	0.49	Intron3
DISC1	rs1538979	1q42.2	231896868	C/T	0.24	Intron4
	rs821577		232067057	G/T	0.38	Intron9
	rs821633		232148933	C/T	0.41	Intron11
	rs999710		232010943	G/A	0.40	Intron9
GRIN2A	rs1014531	16p13.2	9855794	G/A	0.27	3′-UTR
	rs1420040		9850397	G/A	0.42	3′-UTR

Candidate gene	SNP	Chromosome	Position	Alleles	MAF	Feature
NOS1AP	rs12742393	1q23.3	162224586	C/A	0.32	Intron2
	rs1415259		162085309	C/T	0.42	Intron1
	rs1415263		162166043	C/T	0.48	Intron2
	rs1858232		162303838	G/A	0.33	Intron5
	rs348624		162335256	C/T	0.25	Synonymous_exon9
	rs6680461		162255286	G/T	0.39	Intron2
GSK3β	rs334558	3q13.33	119813282	G/A	0.40	5′-flanking
	rs6779828		119775147	C/T	0.28	Intron1
DAOA	rs3916965	13q33.2	106103360	C/T	0.36	Intergenic region
	rs778294		106142235	C/T	0.22	Synonymous_exon4
	rs947267		106139662	G/T	0.49	Intron3
DISC1	rs1538979	1q42.2	231896868	C/T	0.24	Intron4
	rs821577		232067057	G/T	0.38	Intron9
	rs821633		232148933	C/T	0.41	Intron11
	rs999710		232010943	G/A	0.40	Intron9
GRIN2A	rs1014531	16p13.2	9855794	G/A	0.27	3′-UTR
	rs1420040		9850397	G/A	0.42	3′-UTR

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