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童年不良经历与精神障碍患者基因的甲基化

Adverse Childhood Experiences and Methylation of the Gene in Patients with Psychotic Disorders.

作者信息

Misiak Błażej, Karpiński Paweł, Szmida Elżbieta, Grąźlewski Tomasz, Jabłoński Marcin, Cyranka Katarzyna, Rymaszewska Joanna, Piotrowski Patryk, Kotowicz Kamila, Frydecka Dorota

机构信息

Department of Psychiatry, Wroclaw Medical University, Pasteura 10 Street, 50-367 Wroclaw, Poland.

Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1 Street, 50-368 Wroclaw, Poland.

出版信息

J Clin Med. 2020 Nov 24;9(12):3792. doi: 10.3390/jcm9123792.

Abstract

Altered methylation of the gene has been observed in various mental disorders and attributed to the effects of adverse childhood experiences (ACEs). However, the level of methylation has not been investigated in patients with psychotic disorders. Therefore, in this study we aimed to determine the methylation in patients with psychosis and controls, taking into account the effects of ACEs. Participants were 85 patients with psychotic disorders, including first-episode psychosis (FEP) patients and acutely relapsed schizophrenia (SCZ-AR) patients, as well as 56 controls. The level of four CpG sites at the gene was determined in the peripheral blood leukocytes using pyrosequencing. After controlling for potential confounding factors, the level of methylation at one out of four tested CpG sites was significantly lower in FEP patients compared to other groups of participants. Significant main effects of parental antipathy and sexual abuse on the level of methylation were observed at the differentially methylated CpG site. Participants reporting this category of ACEs had significantly lower levels of methylation at this CpG site. Lower levels of methylation were associated with better cognitive performance and higher functional capacity in patients with psychosis. In controls, lower methylation of was related to worse performance of immediate memory and language skills. Our findings suggest that hypomethylation of the appears at early stages of psychosis and might be associated with a history of ACEs as well as less severe clinical manifestation.

摘要

已在多种精神障碍中观察到该基因甲基化的改变,并将其归因于童年不良经历(ACEs)的影响。然而,尚未对精神病性障碍患者的该基因甲基化水平进行研究。因此,在本研究中,我们旨在确定精神病患者和对照组中该基因的甲基化情况,并考虑ACEs的影响。参与者包括85例精神病性障碍患者,其中有首发精神病(FEP)患者和急性复发型精神分裂症(SCZ - AR)患者,以及56名对照。使用焦磷酸测序法测定外周血白细胞中该基因四个CpG位点的水平。在控制潜在混杂因素后,FEP患者中四个检测的CpG位点之一的甲基化水平与其他参与者组相比显著降低。在差异甲基化的CpG位点观察到父母反感和性虐待对该基因甲基化水平有显著的主要影响。报告此类ACEs的参与者在该CpG位点的甲基化水平显著较低。较低的甲基化水平与精神病患者更好的认知表现和更高的功能能力相关。在对照组中,该基因较低的甲基化与即时记忆和语言技能较差的表现有关。我们的研究结果表明,该基因的低甲基化出现在精神病的早期阶段,可能与ACEs病史以及不太严重的临床表现有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/7759816/00a38817a6af/jcm-09-03792-g001.jpg

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