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Jane Pei-Chen Chang,1,* Kuo-Hao Huang,1,* Chieh-Hsin Lin,2,3 Hsien-Yuan Lane1,3,4 1Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan; 2Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; 4Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Chieh-Hsin LinDepartment of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Road, Niaosong District, Kaohsiung 833, TaiwanTel +886-7-7317123 ext. 8753Fax +886-7-7326817Email cyndi36@gmail.com Hsien-Yuan LaneDepartment of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, TaiwanTel +886-4-22062121 ext. 1074Fax +886-4-2236-1230Email hylane@gmail.comBackground: 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 DISC1 gene and M24 (rs1421292) of the G72 gene, are strongly associated with pathogenesis and pathophysiology of schizophrenia. This study examined these two SNPs’ effects on visual learning in schizophrenia patients.Methods: Two hundred seventy-one patients (mean age, 37.0 years [SD = 9.3]; 159 men) with chronic schizophrenia were genotyped for the DISC1 Ser704Cys and G72 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.Results: The DISC1 Ser carriers excelled DISC1 Cys/Cys homozygotes in visual learning (p=0.004, effect size: 0.43), but not in other cognitive functions. G72 M24 A-allele carriers and G72 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.Conclusion: The findings suggest that genetic variations in DISC1 Ser704Cys and G72 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 DISC1-G72 interaction.Keywords: attention, DISC1, G72, visual and verbal learning, schizophrenia |
