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药物治疗的躁狂型精神病性双相障碍患者与健康对照者的 microRNAome 分析。

A miRNome analysis of drug-free manic psychotic bipolar patients versus healthy controls.

机构信息

Department of Pathophysiology and Transplantation, Medical Genetics, Università degli Studi di Milano, Milan, Italy.

Department of Psychiatry, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Via F. Sforza 35, 20122, Milan, Italy.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2020 Oct;270(7):893-900. doi: 10.1007/s00406-019-01057-2. Epub 2019 Aug 17.

Abstract

The lifetime presence of psychotic symptoms is associated with more clinical severity, poorer outcome and biological changes in patients affected by bipolar disorder (BD). Epigenetic mechanisms have been evoked to explain the onset of psychotic symptoms in BD as well as the associated biological changes. The main objective of the present study was to evaluate the expression profiles of circulating microRNAs (miRNAs) in drug-free manic psychotic bipolar patients versus healthy controls (HC), to identify possible non-invasive molecular markers of the disorder. 15 drug-free manic psychotic bipolar patients and 9 HC were enrolled and 800 miRNAs expression profile was measured by Nanostring nCounter technology on plasma samples and validated through qPCR. Overall, twelve miRNAs showed a significantly altered expression between the two groups (p < 0.05). Functional annotation of predicted miRNAs targets by MultiMIR R tool showed repression in bipolar patients of genes with a role in neurodevelopment and neurogenesis, and upregulation of genes involved in metabolism regulation. We identified a signature of circulating miRNA characteristic of manic psychotic bipolar patients, suggesting a possible role in neurodevelopment and metabolic processes regulation.

摘要

精神病症状的终身存在与更严重的临床症状、更差的预后以及受双相情感障碍 (BD) 影响的患者的生物学变化有关。已经提出了表观遗传机制来解释 BD 中精神病症状的发作以及相关的生物学变化。本研究的主要目的是评估无药物治疗的躁狂精神病性双相情感障碍患者与健康对照 (HC) 之间循环 microRNAs (miRNAs) 的表达谱,以确定该疾病的可能非侵入性分子标志物。纳入了 15 名无药物治疗的躁狂精神病性双相情感障碍患者和 9 名 HC,并通过纳米字符串 nCounter 技术测量血浆样本中的 800 个 miRNAs 表达谱,并通过 qPCR 进行验证。总体而言,两组之间有 12 个 miRNAs 的表达明显改变(p<0.05)。MultiMIR R 工具对预测 miRNAs 靶标的功能注释表明,在双相情感障碍患者中,与神经发育和神经发生相关的基因受到抑制,而与代谢调节相关的基因则受到上调。我们确定了一个具有特征性的循环 miRNA 特征,表明其在神经发育和代谢过程调节中可能发挥作用。

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