Chang Jane Pei-Chen, Huang Kuo-Hao, Lin Chieh-Hsin, Lane Hsien-Yuan
Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan.
Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Neuropsychiatr Dis Treat. 2020 Mar 20;16:771-780. doi: 10.2147/NDT.S235675. eCollection 2020.
Visual learning plays an important role in general populations and patients with schizophrenia. Genetic influences on visual learning remain unknown. Two functional single nucleotide polymorphisms (SNPs), Ser704Cys of the gene and M24 (rs1421292) of the gene, are strongly associated with pathogenesis and pathophysiology of schizophrenia. This study examined these two SNPs' effects on visual learning in schizophrenia patients.
Two hundred seventy-one patients (mean age, 37.0 years [SD = 9.3]; 159 men) with chronic schizophrenia were genotyped for the Ser704Cys and M24 SNPs and assessed for visual learning with Visual Reproduction II (delayed reproduction) of Wechsler Memory Scale - III (WMS-III). For comparison, verbal learning (using Word list II of WMS-III) and attention (by Continuous Performance Test) were also measured.
The Ser carriers excelled Cys/Cys homozygotes in visual learning (p=0.004, effect size: 0.43), but not in other cognitive functions. M24 A-allele carriers and M24 T/T homozygotes performed similarly (effect size: 0.07). In SNP-SNP interaction analysis, the patients with Ser carrier_T/T had better visual learning than those with Cys/Cys_T/T (p=0.004, effect size: 0.70) and those with Cys/Cys_A-allele carrier (p=0.003, effect size: 0.65). Education had a positive effect (p=0.007), while negative symptoms had a negative effect (p<0.001) on visual learning.
The findings suggest that genetic variations in Ser704Cys and M24 affect visual learning in schizophrenia patients. The effect sizes of SNP-SNP interaction surpassed the sum (0.50) of effect sizes from two individual genes, suggesting synergistic interaction.
视觉学习在普通人群和精神分裂症患者中都起着重要作用。基因对视觉学习的影响尚不清楚。两个功能性单核苷酸多态性(SNP),即基因的Ser704Cys和基因的M24(rs1421292),与精神分裂症的发病机制和病理生理学密切相关。本研究探讨了这两个SNP对精神分裂症患者视觉学习的影响。
对271例慢性精神分裂症患者(平均年龄37.0岁[标准差=9.3];159例男性)进行基因分型,检测基因的Ser704Cys和基因的M24 SNP,并使用韦氏记忆量表第三版(WMS-III)的视觉再现II(延迟再现)评估视觉学习能力。为了进行比较,还测量了言语学习(使用WMS-III的单词列表II)和注意力(通过连续性能测试)。
基因的Ser携带者在视觉学习方面优于Cys/Cys纯合子(p=0.004,效应大小:0.43),但在其他认知功能方面则不然。M24 A等位基因携带者和M24 T/T纯合子表现相似(效应大小:0.07)。在SNP-SNP相互作用分析中,Ser携带者_T/T的患者比Cys/Cys_T/T的患者(p=0.004,效应大小:0.70)和Cys/Cys_A等位基因携带者的患者(p=0.003,效应大小:0.65)具有更好的视觉学习能力。教育对视觉学习有积极影响(p=0.007),而阴性症状对视觉学习有负面影响(p<0.001)。
研究结果表明,基因Ser704Cys和M24的基因变异会影响精神分裂症患者的视觉学习。SNP-SNP相互作用的效应大小超过了两个单个基因效应大小之和(0.50),表明存在协同相互作用。