Abstract: Background　The pathogenesis of schizophrenia is associated with dopamine D2 receptor（DRD2）gene polymorphism. Cognitive dysfunction is a major symptom of schizophrenia，and may be associated with the risk of developing schizophrenia. However，there are few studies about the association of first-episode schizophrenia with DRD2 gene polymorphism and cognitive function. Objective　To examine the association of first-episode schizophrenia with DRD2 rs2514218 and cognitive function. Methods　Seventy-five patients with first-episode schizophrenia（patient group） and 75 healthy subjects（control group） who were treated at the Hebei Provincial Mental Health Center from 2018—2019 were recruited. The Chinese version of MATRICS Consensus Cognitive Battery（MCCB），including seven domains measuring cognitive functions（speed of processing，attention/vigilance，working memory，verbal learning，visual learning，reasoning and problem solving，and social cognition）：Trail Making Test：Part A（TMT-A），Continuous Performance Test（CPT），Brief Visuospatial Memory Test-Revised（BVMT-R），Hopkins Verbal Learning Test-Revised（HVLT-R），and Stroop Color Word Test（SCWT）. All participants were genotyped for DRD2 rs2514218. Results　Except for dropouts，the remaining 74 patients and 73 controls were finally included. These two groups had no significant differences in genotype distribution and allele frequencies of DRD2 rs2514218（P>0.05）. The patient group had lower average scores of TMT-A，CPT，BVMT-R，and HVLT-R，as well as less number of correct responses for SCWT than control group（P<0.01）. Multivariate logistic regression analysis found that scores of TMT-A〔OR=0.888，95%CI（0.817，0.965），P=0.005〕，CPT〔OR=0.856，95%CI（0.790，0.928），P<0.001〕，BVMT-R〔OR=0.882，95%CI（0.817，0.952），P=0.001〕 and HVLT-R〔OR=0.807，95%CI（0.734，0.888），P<0.001〕 were associated with schizophrenia，and the direction of these associations was negative. Conclusion　First-episode schizophrenia patients had impaired cognitive functions. The risk of first-episode schizophrenia was not associated with DRD2 rs2514218 SNP，but had association with some cognitive functions. Poorer speed of processing，attention/vigilance，visual learning and memory，visual learning and memory were associated with higher risk of developing schizophrenia.

Key words: Schizophrenia；Polymorphism, single nucleotide；Cognition；Genes, DRD2；Cognitive dysfunction

摘要： 背景　精神分裂症的发病机制与D2受体（DRD2）基因多态性有关，其主要症状之一是认知功能障碍，认知功能又与精神分裂症的患病风险有关，但目前关于首发精神分裂症与DRD2基因多态性和认知功能关系的研究很少。目的　探讨首发精神分裂症与DRD2基因rs2514218位点多态性与认知功能的关系。方法　选取2018—2019年就诊于河北省精神卫生中心治疗的首发精神分裂症患者75例（患者组）和健康受试者75例（对照组），采用中文版MATRICS共识认知成套测验（MCCB），包括连线测试A（TMT-A）、持续操作测验（CPT）、简易视觉空间记忆测验修订版（BVMT-R）、霍普金斯词语学习测验修订版（HVLT-R）、Stroop色词测验进行认知功能评定，分别测量认知的7个分领域，包括信息处理速度、注意/警觉能力、工作记忆、词语学习、视觉学习、推理及问题解决和社会认知，并进行基因型分析。结果　研究剔除脱落样本，最终成功入组首发精神分裂症患者74例（患者组）和健康受试者73例（对照组）。患者组和对照组的DRD2基因rs2514218位点基因型分布和等位基因频率比较，差异均无统计学意义（P>0.05）；在认知功能评估上，患者组TMT-A评分、CPT评分、BVMT-R评分、HVLT-R评分、Stroop 色词测验个数均低于对照组，差异有统计学意义（P<0.01）。经多因素Logistic回归分析结果显示，TMT-A评分〔OR=0.888，95%CI（0.817，0.965），P=0.005〕、CPT评分〔OR=0.856，95%CI（0.790，0.928），P<0.001〕、BVMT-R评分〔OR=0.882，95%CI（0.817，0.952），P=0.001〕及HVLT-R评分〔OR=0.807，95%CI（0.734，0.888），P<0.001〕与精神分裂症的患病风险呈负相关，且是精神分裂症患病的影响因素。结论　健康人群的认知功能优于首发精神分裂症人群；并且精神分裂症的患病风险与DRD2基因rs2514218位点多态性无关，但与部分认知功能有关，信息处理速度、注意/警觉能力、视觉学习和记忆能力、词语学习和记忆能力等部分认知功能越差患精神分裂症的风险越高。

关键词: 精神分裂症；多态性, 单核苷酸；认知；基因, DRD2；认知功能障碍