Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
School of Medicine, Chang Gung University, Taoyuan, Taiwan.
Sci Rep. 2019 Dec 11;9(1):18840. doi: 10.1038/s41598-019-55414-1.
Schizophrenia's pathogenesis remains elusive. Cognitive dysfunction is the endophenotype and outcome predictor of schizophrenia. The LIM and SH3 domain protein (LASP1) protein, a component of CNS synapses and dendritic spines, has been related to the N-methyl-D-aspartate receptor (NMDAR) dysfunction hypothesis and schizophrenia. A single-nucleotide polymorphism (rs979607) in the LASP1 gene promoter region has been also implicated in schizophrenia susceptibility. The aim of this study was to investigate the role of the LASP1 rs979607 polymorphism in the cognitive functions of patients with schizophrenia. Two hundred and ninety-one Han Taiwanese patients with schizophrenia were recruited. Ten cognitive tests and two clinical rating scales were assessed. The scores of cognitive tests were standardized to T-scores. The genotyping of the LASP1 rs979607 polymorphism was performed using TaqMan assay. Among the 291 patients, 85 were C/C homozygotes of rs979607, 141 C/T heterozygotes, and 65 T/T homozygotes, which fitted the Hardy-Weinberg equilibrium. After adjusting age, gender, and education with general linear model, the C/C homozygotes performed better than C/T heterozygotes in overall composite score (p = 0.023), Category Fluency test (representing processing speed and semantic memory) (p = 0.045), and Wechsler Memory Scale (WMS)-III backward Spatial Span test (p = 0.025), albeit without correction for multiple comparisons for the latter two individual tests. To the best of our knowledge, this is the first study suggesting that the genetic variation of LASP1 may be associated with global cognitive function, category verbal fluency, and spatial working memory of patients with schizophrenia. The finding also lends support to the NMDAR dysfunction hypothesis of schizophrenia. More studies with longitudinal designs are warranted.
精神分裂症的发病机制仍然难以捉摸。认知功能障碍是精神分裂症的内表型和结局预测因子。LIM 和 SH3 结构域蛋白（LASP1）是中枢神经系统突触和树突棘的组成部分，与 N-甲基-D-天冬氨酸受体（NMDAR）功能障碍假说和精神分裂症有关。LASP1 基因启动子区域的单核苷酸多态性（rs979607）也与精神分裂症易感性有关。本研究旨在探讨 LASP1 rs979607 多态性在精神分裂症患者认知功能中的作用。招募了 291 名汉族台湾精神分裂症患者。评估了 10 项认知测试和 2 项临床评定量表。认知测试的分数被标准化为 T 分数。使用 TaqMan 测定法对 LASP1 rs979607 多态性进行基因分型。在 291 名患者中，85 名是 rs979607 的 C/C 纯合子，141 名是 C/T 杂合子，65 名是 T/T 纯合子，符合哈迪-温伯格平衡。在用一般线性模型调整年龄、性别和教育后，C/C 纯合子在总体综合评分（p=0.023）、类别流畅性测试（代表处理速度和语义记忆）（p=0.045）和韦氏记忆量表（WMS）-III 背向空间跨度测试（p=0.025）中的表现优于 C/T 杂合子，尽管后两个单独测试没有进行多次比较的校正。据我们所知，这是第一项表明 LASP1 遗传变异可能与精神分裂症患者的整体认知功能、类别言语流畅性和空间工作记忆有关的研究。这一发现也支持精神分裂症的 NMDAR 功能障碍假说。需要进行更多具有纵向设计的研究。
