Wang Dong Mei, Zhu Rong Rong, Tian Yang, Uludag Kadir, Chen Jia Jing, Zhou Hui Xia, Wang Li, Kosten Thomas R, Zhang Xiang Yang
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.
Antioxidants (Basel). 2022 Oct 4;11(10):1981. doi: 10.3390/antiox11101981.
The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity, Ala-9Val polymorphism and cognitive dysfunction in unmedicated first-episode (UMFE) SZ patients, which has not been examined. We recruited 234 UMFE SZ patients and 232 healthy controls (HC) and evaluated them with Repeated Battery for the Assessment of Neuropsychological Status (RBANS), plasma MnSOD activity and Ala-9Val (rs4880) polymorphism. In addition, we used the Positive and Negative Syndrome Scale (PANSS) to assess the severity of patients' psychopathological symptoms. Compared with HC, UMFE patients showed extensive cognitive impairment on RBANS, and had higher MnSOD activity. Ala-9Val polymorphism was not associated with SZ susceptibility and cognitive impairment, but only affected MnSOD activity in patients. Moreover, only in SZ patients with Val homozygotes, MnSOD activity was significantly correlated with cognitive impairment, especially in RBANS total score, visuospatial/constructional and attention index scores. Our results suggest that cognitive impairment is associated with MnSOD activity in patients with first-episode SZ, which may be regulated by Ala-9Val polymorphism.
促氧化剂与抗氧化剂之间的失衡被认为是导致包括精神分裂症（SZ）在内的许多退行性疾病衰老和认知障碍的原因。作为线粒体中清除超氧自由基的首个抗氧化酶，锰超氧化物歧化酶（MnSOD）的活性及其Ala-9Val功能多态性已被发现与精神分裂症有关。在本研究中，我们探讨了未用药的首发（UMFE）精神分裂症患者中MnSOD活性、Ala-9Val多态性与认知功能障碍之间的关联，此前尚未对此进行过研究。我们招募了234例UMFE精神分裂症患者和232名健康对照（HC），并用重复成套神经心理状态评估量表（RBANS）、血浆MnSOD活性和Ala-9Val（rs4880）多态性对他们进行评估。此外，我们使用阳性和阴性症状量表（PANSS）来评估患者精神病理症状的严重程度。与HC相比，UMFE患者在RBANS上表现出广泛的认知障碍，且MnSOD活性更高。Ala-9Val多态性与精神分裂症易感性和认知障碍无关，仅影响患者的MnSOD活性。此外，仅在Val纯合子的精神分裂症患者中，MnSOD活性与认知障碍显著相关，尤其是在RBANS总分、视觉空间/构建和注意力指数得分方面。我们的结果表明，首发精神分裂症患者的认知障碍与MnSOD活性有关，这可能受Ala-9Val多态性的调节。
