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

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.

Keywords: Genetics; Suicidal behavior; Suicidal ideation; Suicide; Suicide attempted; Systemic lupus erythematosus.