系统性红斑狼疮患者的自杀行为:系统文献回顾和遗传连锁不平衡分析。

Suicidal behavior in patients with systematic lupus erythematosus: Systematic literature review and genetic linkage disequilibrium analysis.

机构信息

Division of Rheumatology, Department of Medicine, University of Cyprus Medical School, Nicosia, Cyprus.

Department of Medicine, University of Cyprus Medical School, Nicosia, Cyprus.

出版信息

Semin Arthritis Rheum. 2022 Jun;54:151997. doi: 10.1016/j.semarthrit.2022.151997. Epub 2022 Mar 19.

Abstract

BACKGROUND

Previous studies suggested that patients with Systematic Lupus Erythematosus (SLE) have a higher risk of suicidal behavior, including suicidal ideation, attempt and complete suicide. Systematic data describing the SLE patients' clinical characteristics and risk factors of suicidal behavior are lacking.

OBJECTIVES

To determine the magnitude of suicidal behavior among SLE patients and to examine predictors associated with suicidal behavior. An additional aim was to identify common genes or coinherited single nucleotide polymorphisms (SNP) implicated in suicidal behavior and SLE.

METHODS

We conducted a systematic literature review based on PRISMA guidelines using the online databases PubMed/Medline, EMBASE and Web of Science, from inception to August 2021. Full-text original articles that examined the relationship between SLE patients with suicidal behavior were eligible for our review. Two reviewers independently reviewed articles to assess eligibility using the Newcastle-Ottawa Scale and the Joanna Briggs Institute criteria. Systematic reviews, metanalysis, narrative review, case reports, case series, including less than 10 patients, and conference abstracts, were excluded. All registered genome-wide association study (GWAS) data in the GWAS catalog database for SLE and psychiatric traits (suicidal behavior, depression, anxiety, psychosis) were downloaded for further analysis. Special in silico tools were used to examine if any genetic polymorphisms (SNPs) that predispose for SLE or psychiatric traits can be inherited together as a single haplotype. This could be posing a risk factor for a coexisting psychiatric condition in SLE patients.

RESULTS

Of the 64 articles identified, 22 were relevant to the study question; cross-sectional (n = 8) and prospective cohorts (n = 6) were the most frequently retrieved studies. Among the 27,106 SLE patients with SLE, 802 had suicidal behavior (2.9%), and of those, 87.9% were female. Suicide attempt occurred in 573/802 (71.4%) and complete suicide in 18/802 (3%). Major depressive disorder was the most frequently reported coexisting psychiatric condition associated with suicidal behavior, followed by psychosis and social phobia. In addition, several clinical manifestations were linked to suicidal behavior, particularly neuropsychiatric lupus, serositis, mucocutaneous, and renal involvement. Further, high scores in disease activity and damage indices were associated with suicidal behavior. A haplotype in chromosomal region 6p21.33 was found to contain a combination of risk alleles predisposing for SLE and depression, the most common psychiatric disorder associated with suicidal behavior.

CONCLUSION

Suicide behavior in SLE patients was associated with depression, neuropsychiatric lupus, active disease and damage. Further evidence supports a genetic origin of psychiatric symptoms in SLE patients. Awareness of these findings can guide clinicians to recognize suicide behavior promptly and prevent suicide attempts.

摘要

背景

先前的研究表明,红斑狼疮(SLE)患者自杀行为的风险较高,包括自杀意念、自杀企图和自杀完成。缺乏描述 SLE 患者临床特征和自杀行为相关危险因素的系统数据。

目的

确定 SLE 患者自杀行为的程度,并研究与自杀行为相关的预测因素。另一个目的是确定与自杀行为和 SLE 相关的常见基因或共遗传的单核苷酸多态性(SNP)。

方法

我们按照 PRISMA 指南进行了系统的文献综述,使用在线数据库 PubMed/Medline、EMBASE 和 Web of Science,从成立到 2021 年 8 月。符合我们综述的是检查 SLE 患者自杀行为之间关系的全文原始文章。两位审查员使用纽卡斯尔-渥太华量表和 Joanna Briggs 研究所标准独立审查文章,以确定其合格性。系统评价、荟萃分析、叙述性评论、病例报告、病例系列,包括少于 10 例患者的研究,以及会议摘要,均被排除在外。从 GWAS 目录数据库中下载了 SLE 和精神疾病特征(自杀行为、抑郁、焦虑、精神病)的所有已注册全基因组关联研究(GWAS)数据,以进行进一步分析。使用特殊的计算工具来检查是否可以将导致 SLE 或精神疾病特征的任何遗传多态性(SNP)作为单个单倍型遗传。这可能会成为 SLE 患者同时存在精神疾病的危险因素。

结果

在确定的 64 篇文章中,有 22 篇与研究问题相关;横断面(n=8)和前瞻性队列(n=6)是最常检索到的研究。在 27106 名 SLE 患者中,有 802 名患有自杀行为(2.9%),其中 87.9%为女性。自杀企图发生在 573/802 例(71.4%),完全自杀发生在 18/802 例(3%)。与自杀行为最常相关的同时存在的精神疾病是重度抑郁症,其次是精神病和社交恐惧症。此外,几种临床表现与自杀行为相关,特别是神经精神狼疮、浆膜炎、黏膜皮肤和肾脏受累。此外,疾病活动度和损伤指数高与自杀行为相关。在染色体 6p21.33 区域发现的单倍型包含一组导致 SLE 和抑郁症的风险等位基因,抑郁症是与自杀行为最相关的常见精神疾病。

结论

SLE 患者的自杀行为与抑郁症、神经精神狼疮、活动期疾病和损伤有关。进一步的证据支持 SLE 患者精神症状的遗传起源。了解这些发现可以指导临床医生及时识别自杀行为,预防自杀企图。

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