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惊恐障碍中艾司西酞普兰治疗反应的全基因组DNA甲基化和基因表达的初步研究。

Pilot study of genome-wide DNA methylation and gene expression for treatment response to escitalopram in panic disorder.

作者信息

Zou Zhi-Li, Zhang Yuan, Huang Yu-Lan, Wang Jin-Yu, Zhou Bo, Chen Hua-Fu

机构信息

Department of Psychosomatic Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 611731, Sichuan Province, China.

Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan Province, China.

出版信息

World J Psychiatry. 2023 Aug 19;13(8):524-532. doi: 10.5498/wjp.v13.i8.524.

Abstract

BACKGROUND

Antidepressants, particularly selective serotonin reuptake inhibitors, are currently considered the first-line treatment for panic disorder (PD). However, little is known about the relationship between the biomarkers that may predict better treatment.

AIM

To compare genome-wide methylation and gene expression patterns between responsive and non-responsive patients with PD after 4 wk of escitalopram treatment.

METHODS

Thirty patients with PD were enrolled in this study (responders = 13; non-responders = 17). All patients were assessed using the PD Severity Scale-Chinese version before and after treatment. The Illumina Infinium MethylationEPIC (850k) BeadChip for genome-wide methylation screening and mRNA sequencing was used in all patients with PD.

RESULTS

A total of 701 differentially methylated positions (DMPs) were found between responders and non-responders (|Δβ| ≥ 0.06, < 0.05), and the hyper- and hypomethylated CpG sites were 511 (72.9%) and 190 (27.1%), respectively. Relative to non-responders, there were 59 differential transcripts, of which 20 were downregulated and 39 were upregulated ( < 0.05). However, no differentially expressed genes were identified by mRNA sequencing after correcting for multiple testing (|log2(FC)| > 1, > 0.05).

CONCLUSION

This preliminary study showed that DMPs might be associated with the treatment response to escitalopram in PD; however, these DMPs need to be verified in large samples.

摘要

背景

抗抑郁药,尤其是选择性5-羟色胺再摄取抑制剂,目前被认为是惊恐障碍(PD)的一线治疗药物。然而,对于可能预测更好治疗效果的生物标志物之间的关系,人们知之甚少。

目的

比较艾司西酞普兰治疗4周后,PD反应性和无反应性患者之间的全基因组甲基化和基因表达模式。

方法

30例PD患者纳入本研究(反应者=13例;无反应者=17例)。所有患者在治疗前后均使用中文版PD严重程度量表进行评估。所有PD患者均使用Illumina Infinium MethylationEPIC(850k)芯片进行全基因组甲基化筛查和mRNA测序。

结果

反应者与无反应者之间共发现701个差异甲基化位点(DMPs)(|Δβ|≥0.06,P<0.05),其中高甲基化和低甲基化的CpG位点分别为511个(72.9%)和190个(27.1%)。相对于无反应者,有59个差异转录本,其中20个下调,39个上调(P<0.05)。然而,在进行多重检验校正后,mRNA测序未发现差异表达基因(|log2(FC)|>1,P>0.05)。

结论

这项初步研究表明,DMPs可能与PD患者对艾司西酞普兰的治疗反应有关;然而,这些DMPs需要在大样本中进行验证。

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