Mediating effect of genome-wide DNA methylation on suicidal ideation induced by stressful events.

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Psychiatric Genetics Pub Date : 2023-02-01 DOI:10.1097/YPG.0000000000000331

Vincenzo De Luca, Nzaar Al-Chalabi, Zanib Chaudhary, Jessica Qian, Carol Borlido, Araba Chintoh, Philip Gerretsen, Ariel Graff, Gary Remington, Marcos Sanches, Marco Battaglia

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引用次数: 0

Abstract

Objective: Schizophrenia is a debilitating disease that is associated with higher rates of death by unnatural causes including suicide. Exposure to stressful events is an important risk factor for suicidal ideation (SI); however, the mechanisms that link stress, SI, and suicide remain unclear. Epigenetic processes are involved in both vulnerability to suicidal behavior and stress. Therefore, we sought to study the relationship between epigenetic modifications and suicidal behavior and stress.

Methods: This pilot study was conducted on 39 patients diagnosed with schizophrenia (54% men and age 45.5 ± 12.7). We analyzed the effects of (a) stress exposure and (b) the mediation of DNA methylation [via an epigenetic wide association study (EWAS) of more than 450 000 CpG sites across the genome] on SI severity.

Results: The top CpG site mediating the effect of global stress exposure on SI was cg27660192 located in an intergenic region on chromosome 11, exerting a facilitating effect on worsening SI through DNA hypomethylation.

Conclusion: These preliminary results indicate that DNA methylation in peripheral tissues can shed light on the complex relationship between stress and SI in schizophrenia.

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全基因组DNA甲基化对应激事件诱导的自杀意念的中介作用。

目的:精神分裂症是一种使人衰弱的疾病，与包括自杀在内的非自然原因死亡率较高有关。暴露于压力事件是自杀意念(SI)的重要危险因素;然而，将压力、自杀和自杀联系起来的机制仍不清楚。表观遗传过程涉及自杀行为和压力的脆弱性。因此，我们试图研究表观遗传修饰与自杀行为和压力之间的关系。方法:本初步研究纳入39例精神分裂症患者(男性54%，年龄45.5±12.7岁)。我们分析了(a)应激暴露和(b) DNA甲基化介导[通过对基因组中超过45万个CpG位点的表观遗传广泛关联研究(EWAS)]对SI严重程度的影响。结果:介导全局胁迫对SI影响的CpG位点顶端为cg27660192，位于11号染色体的基因间区，通过DNA低甲基化对SI恶化起促进作用。结论:这些初步结果提示外周组织DNA甲基化可能揭示精神分裂症患者应激与SI之间的复杂关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychiatric Genetics 医学-神经科学

CiteScore

2.30

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： The journal aims to publish papers which bring together clinical observations, psychological and behavioural abnormalities and genetic data. All papers are fully refereed. Psychiatric Genetics is also a forum for reporting new approaches to genetic research in psychiatry and neurology utilizing novel techniques or methodologies. Psychiatric Genetics publishes original Research Reports dealing with inherited factors involved in psychiatric and neurological disorders. This encompasses gene localization and chromosome markers, changes in neuronal gene expression related to psychiatric disease, linkage genetics analyses, family, twin and adoption studies, and genetically based animal models of neuropsychiatric disease. The journal covers areas such as molecular neurobiology and molecular genetics relevant to mental illness. Reviews of the literature and Commentaries in areas of current interest will be considered for publication. Reviews and Commentaries in areas outside psychiatric genetics, but of interest and importance to Psychiatric Genetics, will also be considered. Psychiatric Genetics also publishes Book Reviews, Brief Reports and Conference Reports.