退伍军人创伤后应激障碍患者中儿茶酚-O-甲基转移酶(COMT)ValMet基因多态性与认知功能之间的显著关联。
Significant association between catechol-O-methyltransferase (COMT) ValMet polymorphism and cognitive function in veterans with PTSD.
作者信息
Havelka Mestrovic Ana, Tudor Lucija, Nikolac Perkovic Matea, Nedic Erjavec Gordana, Kovacic Petrovic Zrnka, Svob Strac Dubravka, Konjevod Marcela, Pivac Nela
机构信息
Rochester Institute of Technology Croatia, Zagreb, Croatia.
Rudjer Boskovic Institute, Division of Molecular Medicine, Zagreb, Croatia.
出版信息
Neurosci Lett. 2018 Feb 14;666:38-43. doi: 10.1016/j.neulet.2017.12.033. Epub 2017 Dec 14.
Core features of posttraumatic stress disorder (PTSD) are cognitive disturbances. Enzyme catechol-O-methyltransferase (COMT) degrades dopamine primarily in prefrontal cortex. Its functional polymorphism, COMT ValMet, affects COMT activity and dopamine availability and is associated with disturbances in cognition. The hypothesis was that PTSD subjects will have worse working memory than healthy controls and that the carriers of the COMT Met allele will show better cognitive performance compared to Val/Val carriers in PTSD and controls subjects. The aim of this study was to assess the differences in cognitive functioning between PTSD and control subjects and to evaluate the association between COMT ValMet polymorphism and cognitive function determined using the Rey-Osterrieth complex figure (ROCF) copy, immediate and delayed test. The study included 323 male Caucasian participants of Croatian origin: 205 male combat veterans with PTSD and 118 control subjects. A significant association between the COMT ValMet and the ROCF immediate and delayed scores in veterans with PTSD was found. We confirmed, on ethnically homogenous groups of veterans with matched combat experience, that controls had higher ROCF immediate and delayed test scores than veterans with PTSD. In PTSD subjects, the Met carriers of the COMT ValMet performed better (i.e. had higher ROCF scores) than Val/Val homozygotes on both ROCF immediate recall and delayed recall test. Our results provide the first evidence that the presence of one or two Met alleles of the COMT ValMet might act as a protective variant in working memory tasks in combat exposed veterans with PTSD.
创伤后应激障碍(PTSD)的核心特征是认知障碍。儿茶酚-O-甲基转移酶(COMT)主要在前额叶皮质降解多巴胺。其功能多态性COMT ValMet会影响COMT活性和多巴胺可用性,并与认知障碍相关。研究假设为,PTSD患者的工作记忆比健康对照者更差,并且在PTSD患者和对照者中,COMT Met等位基因携带者相比Val/Val纯合子将表现出更好的认知表现。本研究的目的是评估PTSD患者与对照者在认知功能上的差异,并评估COMT ValMet多态性与使用雷-奥斯特里思复杂图形(ROCF)复制、即时和延迟测试所确定的认知功能之间的关联。该研究纳入了323名克罗地亚裔男性白种人参与者:205名患有PTSD的男性退伍军人和118名对照者。发现PTSD退伍军人中COMT ValMet与ROCF即时和延迟得分之间存在显著关联。在具有匹配战斗经历的种族同质退伍军人组中,我们证实对照者的ROCF即时和延迟测试得分高于患有PTSD的退伍军人。在PTSD患者中,COMT ValMet的Met携带者在ROCF即时回忆和延迟回忆测试中的表现均优于Val/Val纯合子(即具有更高的ROCF得分)。我们的结果首次证明,COMT ValMet的一个或两个Met等位基因的存在可能在患有PTSD的参战退伍军人的工作记忆任务中起到保护变异的作用。