Department of Psychological Sciences, University of Missouri, Columbia, MO 65211, USA.
Department of Psychological Sciences, University of Missouri, Columbia, MO 65211, USA; Department of Applied Behavioral Science, University of Kansas, Lawrence, KS 66045, USA.
Psychiatry Res. 2019 Sep;279:47-54. doi: 10.1016/j.psychres.2019.06.025. Epub 2019 Jun 18.
Individuals with schizophrenia have higher lifetime rates of substance use disorders than the general population, and research suggests high comorbidity rates may be partially explained by shared genetic influences related to common underlying etiology. Moreover, deficits in executive functions are thought to be central to the diagnosis of schizophrenia and are likewise associated with alcohol and tobacco use. The current study examined the associations between schizophrenia polygenic risk scores and tobacco and alcohol use and the mediation of these associations by executive function sub-domains. Results from the Psychiatric Genomics Consortium's meta-analysis of genome-wide association studies of schizophrenia were used to calculate polygenic risk scores in a sample of moderate drinkers. Schizophrenia risk scores were significantly associated with shifting-specific executive function deficits and tobacco use phenotypes. However, risk scores were not significantly associated with alcohol use and executive functions were not significantly associated with either tobacco or alcohol use. These findings extend previous research by suggesting that genetic risk for schizophrenia may be associated with specific sub-domains of executive function as well as smoking. The lack of a relation with alcohol use suggests genetic factors related to schizophrenia and executive functioning may not influence drinking in a non-disordered, social-drinking sample.
精神分裂症患者的物质使用障碍终身发生率高于普通人群，研究表明，高共病率可能部分可以用与常见潜在病因相关的共同遗传影响来解释。此外，执行功能缺陷被认为是精神分裂症诊断的核心，同样与酒精和烟草使用有关。本研究考察了精神分裂症多基因风险评分与烟草和酒精使用之间的关联，以及执行功能子领域对这些关联的中介作用。使用精神分裂症全基因组关联研究的精神分裂症基因组联盟荟萃分析的结果，在中度饮酒者样本中计算多基因风险评分。精神分裂症风险评分与转换特定的执行功能缺陷和吸烟表型显著相关。然而，风险评分与酒精使用不显著相关，执行功能与吸烟或酒精使用也不显著相关。这些发现通过表明精神分裂症的遗传风险可能与特定的执行功能子领域以及吸烟有关，扩展了之前的研究。与酒精使用无关表明，与精神分裂症和执行功能相关的遗传因素可能不会影响非紊乱、社交性饮酒样本的饮酒行为。
