注意缺陷多动障碍患儿药物治疗前后microRNA表达量与临床症状的关系

张帆; 朱萍; 吴丽慧

doi:10.7499/j.issn.1008-8830.2020.02.013

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中国当代儿科杂志 ›› 2020, Vol. 22 ›› Issue (2) : 152-157. DOI: 10.7499/j.issn.1008-8830.2020.02.013

论著·临床研究

注意缺陷多动障碍患儿药物治疗前后microRNA表达量与临床症状的关系

张帆¹, 朱萍¹, 吴丽慧^1,2

作者信息 +

Association of microRNA expression before and after drug therapy with clinical symptoms in children with attention deficit hyperactivity disorder

ZHANG Fan¹, ZHU Ping¹, WU Li-Hui^1,2

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摘要

目的探讨注意缺陷多动障碍（ADHD）儿童药物治疗前后microRNA表达量与临床症状的关系。方法选取2017年5月至2018年10月初诊为ADHD儿童80例为研究对象，将愿意接受药物治疗的儿童随机分为盐酸哌甲酯治疗组（n=31）和盐酸托莫西汀治疗组（n=33），不愿接受治疗的作为未治疗组（n=16），随访中盐酸哌甲酯组脱落10例，盐酸托莫西汀组脱落13例。另随机选取同时期行健康体检儿童60例作为健康对照组。ADHD儿童在首诊、随访3个月、6个月时进行SNAP-V评分，并采集ADHD及健康对照组儿童血清样本以荧光定量PCR法检测miR-4655-3p和miR-7641的相对表达量。结果重复测量方差分析结果显示，注意力不足症状SNAP-V评分在两治疗组和未治疗组中，以及两种miRNA相对表达量在两治疗组和健康对照组中均存在分组与时间因素差异，且分组与时间因素均存在交互作用（P < 0.05）。多动冲动症状SNAP-V评分在两治疗组和未治疗组中存在时间因素差异（P < 0.05），而分组因素差异无统计学意义，且时间因素与分组因素无交互作用（P > 0.05）。经药物治疗的ADHD儿童注意力不足症状SNAP-V评分与miRNA-4655-3p和miRNA-7641相对表达量均呈负相关（分别r=-0.314、-0.495，P < 0.05）。结论药物治疗可显著改善ADHD儿童的临床症状；血清中miR-4655-3p和miR-7641的表达水平可能作为ADHD的诊断及疗效评估的分子指标。

Abstract

Objective To study the association of microRNA expression before and after drug therapy with clinical symptoms in children with attention deficit hyperactivity disorder (ADHD). Methods A total of 80 previously untreated children with ADHD who were diagnosed from May 2017 to October 2018 were enrolled. The children who were willing to receive drug therapy were randomly divided into concerta-treated group with 31 children and strattera-treated group with 33 children. The children who were unwilling to receive treatment were enrolled as the untreated group with 16 children. A total of 60 children who underwent physical examination during the same period of time were enrolled as the healthy control group. SNAP-V score was determined at initial diagnosis and 3 and 6 months of follow-up. Serum samples were collected from the children with ADHD and the healthy control group. Quantitative real-time PCR was used to measure the relative expression of miR-4566-3p and miR-7641. Results The repeated measures analysis of variance showed that the SNAP-V score of attention deficit symptoms were different among the two treatment groups and the untreated group at the first visit and 3 months and 6 months after treatment (P < 0.05). There were significant differences in the relative expression of the two miRNAs among the two treatment groups and the healthy control group at the first visit and 3 months and 6 months after treatment (P < 0.05). The SNAP-V score of attention deficit symptoms and the relative expression of the two miRNAs were different in different time points in the subjects (P < 0.05). There were interactions between grouping and time factors in the SNAP-V score of attention deficit symptoms and the relative expression of the two miRNAs (P < 0.05). The SNAP-V score of hyperactive impulsive symptoms was different in different time points in the two treatment groups and the untreated group (P < 0.05), but the significant difference in the score was not observed between two treatment groups and the untreated group (P > 0.05), and there was no interaction between the time factor and the grouping factor (P > 0.05). The SNAP-V score of attention deficit symptoms was negatively correlated with the relative expression of miRNA-4655-3p and miRNA-7641 (r=-0.314, -0.495 respectively; P < 0.05) in ADHD children after drug treatment. Conclusions Drug therapy can significantly improve the clinical symptoms of children with ADHD. The expression of miR-4655-3p and miR-7641 in serum can be used as biomarkers for the diagnosis and outcome evaluation of ADHD.

导出引用

张帆, 朱萍, 吴丽慧. 注意缺陷多动障碍患儿药物治疗前后microRNA表达量与临床症状的关系[J]. 中国当代儿科杂志. 2020, 22(2): 152-157 https://doi.org/10.7499/j.issn.1008-8830.2020.02.013

ZHANG Fan, ZHU Ping, WU Li-Hui. Association of microRNA expression before and after drug therapy with clinical symptoms in children with attention deficit hyperactivity disorder[J]. Chinese Journal of Contemporary Pediatrics. 2020, 22(2): 152-157 https://doi.org/10.7499/j.issn.1008-8830.2020.02.013

参考文献

[1] Polanczyk GV, Willcutt EG, Salum GA, et al. ADHD prevalence estimates across three decades:an updated systematic review and meta-regression analysis[J]. Int J Epidemiol, 2014, 43(2):434-442.
[2] Zhou F, Wu F, Zou S, et al. Dietary, nutrient patterns and blood essential elements in chinese children with ADHD[J]. Nutrients, 2016, 8(6). pii:E352.
[3] Tandon PS, Sasser T, Gonzalez ES, et al. Physical activity, screen time, and sleep in children with ADHD[J]. J Phys Act Health, 2019, 16(6):416-422.
[4] Song M, Lauseng D, Lee S, et al. Enhanced physical activity improves selected outcomes in children with ADHD:systematic review[J]. West J Nurs Res, 2016, 38(9):1155-1184.
[5] 陈美英, 张斌. 《精神障碍诊断与统计手册第五版》双相障碍分类和诊断标准的循证依据[J]. 中华脑科疾病与康复杂志(电子版), 2014, 4(4):207-211.
[6] Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay[J]. Nat Rev Genet, 2010, 11(9):597-610.
[7] Lewis BP, Shih IH, Jones-Rhoades MW, et al. Prediction of mammalian microRNA targets[J]. Cell, 2003, 115(7):787-798.
[8] Omran A, Elimam D, Shalaby S, et al. MicroRNAs:a light into the "black box" of neuropediatric diseases?[J]. Neuromolecular Med, 2012, 14(4):244-261.
[9] Wright C, Gupta CN, Chen J, et al. Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia[J]. Transl Psychiatry, 2016, 6:e724.
[10] Perkins DO, Jeffries CD, Jarskog LF, et al. MicroRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder[J]. Genome Biol, 2007, 8(2):R27.
[11] Wu LH, Peng M, Yu M, et al. Circulating microRNA let-7d in attention-deficit/hyperactivity disorder[J]. Neuromolecular Med, 2015, 17(2):137-146.
[12] Wu L, Zhao Q, Zhu X, et al. A novel function of microRNA let-7d in regulation of galectin-3 expression in attention deficit hyperactivity disorder rat brain[J]. Brain Pathol, 2010, 20(6):1042-1054.
[13] Wu LH, Cheng W, Yu M, et al. Nr3C1-Bhlhb2 axis dysregulation is involved in the development of attention deficit hyperactivity[J]. Mol Neurobiol, 2017, 54(2):1196-1212.
[14] 朱萍, 潘景, 张帆, 等. 与ADHD相关的外周循环microRNA芯片筛选及分析[J]. 医学研究杂志, 2019, 48(5):59-63.
[15] Piovesana AM, Harrison JL, Ducat JJ. The development of a motor-free short-form of the Wechsler Intelligence Scale for Children-Fifth Edition[J]. Assessment, 2019, 26(8):1564-1572.
[16] Munkvold LH, Manger T, Lundervold AJ. Conners' continuous performance test (CCPT-II) in children with ADHD, ODD, or a combined ADHD/ODD diagnosis[J]. Child Neuropsychol, 2014, 20(1):106-126.
[17] Austerman J. ADHD and behavioral disorders:assessment, management, and an update from DSM-5[J]. Cleve Clin J Med, 2015, 82(11 Suppl 1):S2-S7.
[18] Sugrue D, Bogner R, Ehret MJ, et al. Methylphenidate and dexmethylphenidate formulations for children with attention-deficit/hyperactivity disorder[J]. Am J Health Syst Pharm, 2014, 71(14):1163-1170.
[19] Türkoğlu S, Çetin FH. Atomoxetine in the treatment of adolescent with trichotillomania and attention-deficit/hyperactivity disorder[J]. Clin Neuropharmacol, 2018, 41(2):84-85.
[20] Hechtman L. ADHD medication treatment and risk of psychosis[J]. Lancet Psychiatry, 2019, 6(8):632-633.
[21] Fineberg SK, Kosik KS, Davidson BL. MicroRNAs potentiate neural development[J]. Neuron, 2009, 64(3):303-309.
[22] Tabrez S, Jabir NR, Shakil S, et al. A synopsis on the role of tyrosine hydroxylase in Parkinson's disease[J]. CNS Neurol Disord Drug Targets, 2012, 11(4):395-409.
[23] Jiang Y, Liu J, Chen L, et al. Serum secreted miR-137-containing exosomes affects oxidative stress of neurons by regulating OXR1 in Parkinson's disease[J]. Brain Res, 2019, 1722:146331.
[24] 吴静静. 血浆microRNA作为早期诊断锰中毒性帕金森综合征生物标志物的研究[D]. 南宁:广西医科大学, 2019.