title: Genetic modulation of working memory deficits by ankyrin 3 gene in schizophrenia.
abstract: Neuropsychological endophenotype approach is an emerging strategy in schizophrenia research to understand and identify the functional importance of genetically transmitted, brain-based deficits present in this disorder. Accumulating evidence indicated that working memory deficit is a core neuropsychological dysfunction in schizophrenia and a primary endophenotype indexing the liability to develop schizophrenia. Genetic variation in ankyrin 3 gene (ANK3) is likely to have widespread cognitive effects. Our previous study has identified a significant association of ANK3 SNPs and schizophrenia. In this study, we aimed to examine whether the schizophrenia-risk SNPs within ANK3 may affect working memory deficits in schizophrenia patients. Herein, we assess the working memory performance in 163 patients with first-episode, antipsychotic-naïve schizophrenia and 42 sex, age-matched healthy subjects using N-back task. Two SNPs rs10761482 and rs10994336 were genotyped among the patients and 209 controls. Our results showed that schizophrenia patients showed significantly poorer performance than healthy controls on N-back task (ps<0.01). After adjusting for the scores of intelligence quotient, memory quotient and the demographic factors, there was a significant genotype effect of the rs10994336 on the accuracy rate and reaction time of 2-back item (p=0.048 and 0.024, respectively). Post-hoc analyses showed that patients with rs10994336T/T genotype had significantly lower accuracy rate and more reaction time at 2-back task than those with T/C and C/C genotypes. The association of SNP rs10994336 with schizophrenia was replicated in our sample (genotypic p=0.024 and allelic p=0.006). However, we did not find any significant association of rs10761482 with schizophrenia and parameters in N-back task. Our results indicated that genetic variation within ANK3 may exert gene-specific modulating effects on working memory deficits in schizophrenia.
authors.affiliation: Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Shanghai Changhai Hospital, Secondary Military Medical University, Shanghai, China.
authors.forename: Zezhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Psychiatry, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Lu
authors.affiliation: Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Genetics, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Yuan
authors.affiliation: Department of Genetics, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yushuny@yahoo.com.
authors.forename: Shunying
authors.initials: S
authors.lastname: Yu
authors.affiliation: Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yirufang@aliyun.com.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Fang
mesh_terms: D000328:Adult; D017487:Ankyrins / Q000235:genetics* / Q000502:physiology; D016022:Case-Control Studies; D058068:Endophenotypes; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008570:Memory, Short-Term / Q000502:physiology; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D055815:Young Adult
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins
keywords: ANK3; First-episode schizophrenia; SNP; Working memory