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Association Between Side Effects and Blood microRNA Expression Levels and Their Targeted Pathways in Patients With Major Depressive Disorder Treated by a Selective Serotonin Reuptake Inhibitor, Escitalopram: A CAN-BIND-1 Report.
International Journal of Neuropsychopharmacology ( IF 4.8 ) Pub Date : 2020-02-01 , DOI: 10.1093/ijnp/pyz066
Antoine Yrondi 1 , Laura M Fiori 1 , Benicio N Frey 2 , Raymond W Lam 3 , Glenda M MacQueen 4 , Roumen Milev 5 , Daniel J Müller 6, 7 , Jane A Foster 6 , Sidney H Kennedy 6, 8 , Gustavo Turecki 1
Affiliation  

INTRODUCTION Antidepressant drugs are effective therapies for major depressive disorder; however, they are frequently associated with side effects. Although there is some evidence for a relationship between genetic variation and side effects, little is known regarding the role of dynamic molecular factors as moderators of side effects. The aim of this study was to assess microRNA (miRNA) changes associated with side effects during escitalopram treatment and their downstream effects on target gene expression. METHODS A total 160 patients with major depressive disorder from the CAN-BIND-1 cohort were included. Side effects were assessed with the Toronto Side Effect Scale after 2 weeks of treatment with escitalopram. We assessed the relationship between side effects and changes in peripheral expression of miRNAs between baseline and week 2. For miRNA whose expression changed, we used target prediction algorithms to identify putative messenger RNA (mRNA) targets and assessed their expression. RESULTS Nausea was experienced by 42.5% of patients. We identified 45 miRNAs whose expression changed on initiation of escitalopram treatment, of which 10 displayed a negative association with intensity of nausea (miR15b-5p, miR17-5p, miR20a-5p, miR20b-5p, miR103a-3p, miR103b, miR106a-5p, miR182-5p, miR185-5p, and miR660-5p). Additionally, we found negative associations between 4 microRNAs (miR20a-5p, miR106a-5p, miR185-5p, miR660-5p) and mRNA targets. The expression of the miR185-5p target, CAMK2δ was significantly decreased [log 2 mean = -0.048 (0.233)] between weeks 0 and 2 (P = .01)]. CONCLUSIONS We identified an overexpression of miR185-5p during escitalopram treatment of major depressive disorder, which was negatively associated with intensity of nausea, and identified a potential mRNA target that may mediate this effect.

中文翻译:

选择性5-羟色胺再摄取抑制剂Escitalopram治疗的重度抑郁症患者的副作用与血液microRNA表达水平及其靶向途径之间的关联:CAN-BIND-1报告。

引言抗抑郁药是治疗严重抑郁症的有效方法。但是,它们经常与副作用相关。尽管有一些证据表明遗传变异与副作用之间存在关系,但关于动态分子因子作为副作用调节剂的作用知之甚少。这项研究的目的是评估与依他普仑治疗期间的副作用及其对靶基因表达的下游影响相关的微小RNA(miRNA)变化。方法包括来自CAN-BIND-1队列的160例重度抑郁症患者。依他普仑治疗2周后,用多伦多副作用量表评估副作用。我们评估了基线与第2周之间副作用与miRNA外周表达变化之间的关系。对于表达发生变化的miRNA,我们使用靶标预测算法来识别推定的信使RNA(mRNA)靶标并评估其表达。结果42.5%的患者经历了恶心。我们鉴定了45种在依他普仑治疗开始后表达发生变化的miRNA,其中10种与恶心强度呈负相关(miR15b-5p,miR17-5p,miR20a-5p,miR20b-5p,miR103a-3p,miR103b,miR106a-5p ,miR182-5p,miR185-5p和miR660-5p)。此外,我们发现4种microRNA(miR20a-5p,miR106a-5p,miR185-5p,miR660-5p)与mRNA靶标之间存在负相关。在第0周和第2周之间,miR185-5p靶标CAMK2δ的表达显着降低[log 2均值= -0.048(0.233)](P = 0.01)。
更新日期:2020-04-17
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