Department of Internal Medicine, Yasuj University of Medical Sciences, Yasuj, Iran; Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
J Psychiatr Res. 2019 Feb;109:185-192. doi: 10.1016/j.jpsychires.2018.12.013. Epub 2018 Dec 8.
Attention-deficit/hyperactivity disorder (ADHD), a common psychiatric disorder, is identified by abnormal levels of impulsivity, inattention, and hyperactivity. MiRNAs play important roles in neural network development of the brain. Circulating miRNAs (cmiRNAs) are offered as promising noninvasive markers for psychiatric disorders. In this study, the expression level of neurologically relevant miRNAs was evaluated in serum samples of ADHD individuals.
RNA extraction was performed for 60 subjects with ADHD and 60 healthy controls, and the cDNAs were synthesized for all the miRNAs. The expression level of 84 cmiRNAs was then examined in 4 ADHD subjects and 4 controls. The altered expression of 10 cmiRNAs was further evaluated in validation cohort comprising 56 ADHD and 56 control samples by qPCR. The diagnostic power of the miRNAs was determined by use of Receiver-operating characteristic (ROC) analysis. The cmiRNAs target genes were predicted using DIANA mirPath software and gene ontology enrichment analysis was performed using Cytoscape CLUGO.
Initially, 10 miRNAs showed differential expression in ADHD individuals. Further analysis confirmed four miRNAs (hsa-miR-101-3p, hsa-miR-130a-3p, hsa-miR-138-5p and hsa-miR-195-5p) upregulated and one miRNA (hsa-miR-106b-5p) downregulated. These miRNAs showed significant predictive values for discriminating ADHD individuals. Enrichment analysis highlighted the involvement of the deregulated cmiRNAs in many canonical neurobiological pathways and mechanisms.
Our report is the first comprehensive study on the expression profiling of miRNAs in serum of ADHD subjects. These findings suggest a set of cmiRNAs as potential noninvasive biomarkers for ADHD.
注意力缺陷多动障碍（ADHD）是一种常见的精神疾病，其特征为冲动、注意力不集中和多动等行为异常。miRNA 在大脑神经网络发育中发挥重要作用。循环 miRNA（cmicroRNA）作为精神疾病的潜在非侵入性标志物备受关注。本研究评估了 ADHD 患者血清样本中与神经相关 miRNA 的表达水平。
对 60 例 ADHD 患者和 60 例健康对照者进行 RNA 提取，并合成所有 miRNA 的 cDNA。对 4 例 ADHD 患者和 4 例对照者的 84 个 cmicroRNA 表达水平进行检测。通过 qPCR 对包含 56 例 ADHD 患者和 56 例对照者的验证队列中 10 个差异表达的 miRNA 进行进一步评估。使用受试者工作特征（ROC）分析确定 miRNA 的诊断效能。使用 DIANA mirPath 软件预测 cmicroRNA 的靶基因，并使用 Cytoscape CLUGO 进行基因本体论富集分析。
初步研究发现 10 个 miRNA 在 ADHD 患者中存在差异表达。进一步分析证实，有 4 个 miRNA（hsa-miR-101-3p、hsa-miR-130a-3p、hsa-miR-138-5p 和 hsa-miR-195-5p）上调，1 个 miRNA（hsa-miR-106b-5p）下调。这些 miRNA 对区分 ADHD 患者具有显著的预测价值。富集分析突出了失调 cmicroRNA 参与了许多经典的神经生物学途径和机制。
本研究是首次对 ADHD 患者血清中 miRNA 表达谱进行的全面研究。这些发现提示一组 cmicroRNA 可能作为 ADHD 的潜在非侵入性生物标志物。
