Sun Ning, Yang Chunxia, He Xiaoting, Liu Zhifen, Liu Sha, Li Xinrong, Wang Yanfang, Jin Ruihua, Zhang Kerang
Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.
Nursing College of Shanxi Medical University, Taiyuan, People's Republic of China.
Neuropsychiatr Dis Treat. 2020 Jun 19;16:1543-1554. doi: 10.2147/NDT.S247787. eCollection 2020.
Patients suffering from major depressive disorder (MDD) commonly demonstrate lower performance across multiple cognitive domains. Cognitive impairment is an intrinsic characteristic of MDD status and is often influenced by genetic factors. microRNAs (miRNAs or miRs) have been shown to have important implications in the etiology of MDD. Therefore, we aimed to identify and analyze the impact of expression and genetic variation of miR-34b/c on cognitive dysfunction in MDD.
First, we analyzed miR-34c-5p expression in 48 cases of MDD and 54 healthy controls in a Chinese population using qRT-PCR. We assessed the relationship between the level of miR-34c-5p expression and cognitive performance by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Trail Making Test (TMT). Second, in order to characterize allelic effects of miR-34b/c on cognitive performance in MDD patients, we performed genetic association analysis of single-nucleotide polymorphism (SNP) loci of the MIR34B/C genes with cognitive function in a second group consisting of 531 MDD patients and 267 healthy controls.
We found a significant negative correlation between the level of miR-34c-5p expression and both the language and delayed memory index scores in patients with MDD. We also found a significant positive correlation between the level of miR-34c-5p expression and the time required to complete tests A and B of the TMT. The interaction between the rs2187473 genotype and the disease was significant for both immediate memory and delayed memory. In the patient group, the rs2187473 CC genotype was significantly associated with higher performance on immediate memory ( = 6.683, p < 0.05) and delayed memory tasks ( = 4.221, p < 0.05).
Our findings suggest that changes in miR-34c expression level have important impacts on cognitive function in patients with MDD. In particular, the polymorphism rs2187473 is a potential genetic risk factor for cognitive function in MDD, which may be of clinical use.
患有重度抑郁症（MDD）的患者通常在多个认知领域表现出较低的水平。认知障碍是MDD状态的一个内在特征，并且常常受到遗传因素的影响。微小RNA（miRNA或miR）已被证明在MDD的病因学中具有重要意义。因此，我们旨在识别并分析miR-34b/c的表达和基因变异对MDD患者认知功能障碍的影响。
首先，我们使用qRT-PCR分析了48例中国MDD患者和54例健康对照者中miR-34c-5p的表达。我们通过可重复神经心理状态评估量表（RBANS）和连线测验（TMT）评估了miR-34c-5p表达水平与认知表现之间的关系。其次，为了表征miR-34b/c对MDD患者认知表现的等位基因效应，我们在由531例MDD患者和267例健康对照组成的第二组中，对MIR34B/C基因的单核苷酸多态性（SNP）位点与认知功能进行了基因关联分析。
我们发现MDD患者中miR-34c-5p表达水平与语言和延迟记忆指数得分均呈显著负相关。我们还发现miR-34c-5p表达水平与完成TMT测试A和B所需时间呈显著正相关。rs2187473基因型与疾病之间的相互作用对即时记忆和延迟记忆均具有显著意义。在患者组中，rs2187473 CC基因型与即时记忆（= 6.683，p < 0.05）和延迟记忆任务（= 4.221，p < 0.05）的较高表现显著相关。
我们的研究结果表明，miR-34c表达水平的变化对MDD患者的认知功能具有重要影响。特别是，多态性rs2187473是MDD患者认知功能的一个潜在遗传危险因素，这可能具有临床应用价值。
