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Abstract

Background

Systemic lupus erythematosus (SLE) patients are a high-risk population for suicide. Glutamatergic neurosystem genes have been implicated in the neurobiology of depression in SLE and suicidal behaviour in general. However, the role of glutamate receptor gene polymorphisms in suicidal behaviour among SLE patients remains unclear in the context of established clinical and psychosocial factors. We aimed to investigate the association of NR2A gene polymorphism with suicidal ideation in SLE while accounting for the interaction between clinical and psychosocial factors.

Methods

A total of 130 SLE patients were assessed for mood disorders (MINI International Neuropsychiatric Interview), severity of depression (Patient Health Questionnaire-9), suicidal behaviour (Columbia-Suicide Severity Rating Scale), socio-occupational functioning (Work and Social Adjustment Scale), recent life events (Social Readjustment Rating Scale) and lupus disease activity (SELENA-SLE Disease Activity Index). Eighty-six out of the 130 study participants consented for NR2A genotyping.

Results

Multivariable logistic regression showed nominal significance for the interaction effect between the NR2A rs2072450 AC genotype and higher severity of socio-occupational impairment with lifetime suicidal ideation in SLE patients (p = 0.038, odds ratio = 1.364, 95% confidence interval = 1.018–1.827). However, only the association between lifetime mood disorder and lifetime suicidal ideation remained significant after Bonferroni correction (p < 0.001, odds ratio = 33.834, 95% confidence interval = 7.624–150.138).

Conclusions

Lifetime mood disorder emerged as a more significant factor for suicidal ideation in SLE compared with NR2A gene polymorphism main and interaction effects. Clinical implications include identification and treatment of mood disorders as an early intervention for suicidal behaviour in SLE. More adequately-powered gene–environment interaction studies are required in the future to clarify the role of glutamate receptor gene polymorphisms in the risk stratification of suicidal behaviour among SLE patients.

Keywords

Glutamate receptor gene–environment interaction suicidal ideation neuropsychiatric systemic lupus erythematosus

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References

Unterman

Nolte

Boaz

et al.

Neuropsychiatric syndromes in systemic lupus erythematosus: A meta-analysis. Semin Arthritis Rheum 2011; 41: 1–11.

Palagini

Mosca

Tani

et al.

Depression and systemic lupus erythematosus: A systematic review. Lupus 2013; 22: 409–416.

Hajduk

Nowicka-Sauer

Smoleńska

et al.

Prevalence and correlates of suicidal thoughts in patients with neuropsychiatric lupus. Lupus 2016; 25: 185–192.

O’Carroll

Berman

Maris

et al.

Beyond the Tower of Babel: A nomenclature for suicidology. Suicide Life Threat Behav 1996; 26: 237–252.

Harris

Barraclough

Winslow

. Suicide as an outcome for medical disorders. Medicine 1994; 73: 281–296.

Karassa

Magliano

Isenberg

. Suicide attempts in patients with systemic lupus erythematosus. Ann Rheum Dis 2003; 62: 58–60.

Matsukawa

Sawada

Hayama

et al.

Suicide in patients with systemic lupus erythematosus: A clinical analysis of seven suicidal patients. Lupus 1994; 3: 31–35.

Ishikura

Morimoto

Tanaka

et al.

Factors associated with anxiety, depression and suicide ideation in female outpatients with SLE in Japan. Clin Rheumatol 2001; 20: 394–400.

Xie

L-F

Chen

P-L

Pan

H-F

et al.

Prevalence and correlates of suicidal ideation in SLE inpatients: Chinese experience. Rheumatol Int 2012; 32: 2707–2714.

10.

Mok

Chan

Cheung

EFC

et al.

Suicidal ideation in patients with systemic lupus erythematosus: Incidence and risk factors. Rheumatology 2014; 53: 714–721.

11.

Lee

Perlis

Jung

J-Y

et al.

Multi-locus genome-wide association analysis supports the role of glutamatergic synaptic transmission in the etiology of major depressive disorder. Transl Psychiatry 2012; 2: e184–e184.

12.

Efthimiou

Blanco

. Pathogenesis of neuropsychiatric systemic lupus erythematosus and potential biomarkers. Mod Rheumatol 2009; 19: 457–468.

13.

Sokolowski

Ben-Efraim

Wasserman

et al.

Glutamatergic GRIN2B and polyaminergic ODC1 genes in suicide attempts: Associations and gene–environment interactions with childhood/adolescent physical assault. Mol Psychiatry 2013; 18: 985–992.

14.

Lapteva

Nowak

Yarboro

et al.

Anti-N‐methyl‐D‐aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum 2006; 54: 2505–2514.

15.

Omdal

Brokstad

Waterloo

et al.

Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors. Eur J Neurol 2005; 12: 392–398.

16.

DiazGranados

Ibrahim

Brutsche

et al.

Rapid resolution of suicidal ideation after a single infusion of an NMDA antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry 2010; 71: 1605–1605.

17.

Phelps

Brutsche

Moral

et al.

Family history of alcohol dependence and initial antidepressant response to an N-methyl-D-aspartate antagonist. Biol Psychiatry 2009; 65: 181–184.

18.

Schumann

Johann

Frank

et al.

Systematic analysis of glutamatergic neurotransmission genes in alcohol dependence and adolescent risky drinking behavior. Arch Gen Psychiatry 2008; 65: 826–838.

19.

Zarate

Mathews

Furey

. Human biomarkers of rapid antidepressant effects. Biol Psychiatry 2013; 73: 1142–1155.

20.

Tan

Cohen

Fries

et al.

The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

21.

Sheehan

Lecrubier

Sheehan

et al.

The Mini-International Neuropsychiatric Interview (MINI): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998; 59: 22–33.

22.

Kroenke

Spitzer

Williams

. The PHQ‐9. J Gen Intern Med 2001; 16: 606–613.

23.

Hyphantis

Paika

Almyroudi

et al.

Personality variables as predictors of early non-metastatic colorectal cancer patients’ psychological distress and health-related quality of life: A one-year prospective study. J Psychosom Res 2011; 70: 411–421.

24.

Sherina

Arroll

Goodyear-Smith

. Criterion validity of the PHQ-9 (Malay version) in a primary care clinic in Malaysia. Med J Malaysia 2012; 67: 309–315.

25.

Posner

Brent

Lucas

et al.

Columbia-Suicide Severity Rating Scale (C-SSRS), New York: New York State Psychiatric Institute, 2008.

26.

Holmes

Rahe

. The social readjustment rating scale. J Psychosom Res 1967; 11: 213–218.

27.

Abdul

. Life changes stress of Malay students in the United States. Jurnal Psikologi Malaysia 1986; 2: 129–139.

28.

Chan

Shah

Maniam

. Predictors of suicidal ideation among depressed inpatients in a Malaysian sample. Suicidol Online 2012; 3: 33–41.

29.

Mundt

Marks

Shear

et al.

The Work and Social Adjustment Scale: A simple measure of impairment in functioning. Br J Psychiatry 2002; 180: 461–464.

30.

Sousa

Rojjanasrirat

. Translation, adaptation and validation of instruments or scales for use in cross‐cultural health care research: A clear and user‐friendly guideline. J Eval Clin Pract 2011; 17: 268–274.

31.

Petri

Buyon

Kalunian

et al.

Revision of the SELENA flare index. Arthritis Rheum 2009; 60: S339–S339.

32.

Dudbridge

. Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data. Hum Hered 2008; 66: 87–98.

33.

. Statistical analysis of genetic interactions. Genet Res 2010; 92: 443–459.

34.

Cox

. Interaction. Int Stat Rev 1984; 52: 1–24.

35.

Chen

Wang

Schwender

et al.

Joint testing of genotypic and gene-environment interaction identified novel association for BMP4 with non-syndromic CL/P in an Asian population using data from an International Cleft Consortium. PloS One 2014; 9: e109038–e109038.

36.

SNP rs2072450 [Homo sapiens], www.ncbi.nlm.nih.gov/snp/?term=rs2072450, 2016 (accessed 13 August 2017).

37.

Zakeri

Shakiba

Narouie

et al.

Prevalence of depression and depressive symptoms in patients with systemic lupus erythematosus: Iranian experience. Rheumatol Int 2012; 32: 1179–1187.

38.

Maniam

Marhani

Firdaus

et al.

Risk factors for suicidal ideation, plans and attempts in Malaysia—Results of an epidemiological survey. Compr Psychiatry 2014; 55: S121–S125.

39.

Lee

Fung

Tsang

et al.

Lifetime prevalence of suicide ideation, plan, and attempt in metropolitan China. Acta Psychiatr Scand 2007; 116: 429–437.

40.

World Health Organization. Preventing suicide: A global imperative, http://apps.who.int/iris/bitstream/10665/131056/1/9789241564779_eng.pdf (2014, accessed 13 August 2017).

41.

Futrell

Schultz

Millikan

. Central nervous system disease in patients with systemic lupus erythematosus. Neurology 1992; 42: 1649–1649.

42.

Tang

K-T

Hsieh

C-W

Hsieh

T-Y

et al.

Suicide attempts in patients with systemic lupus erythematosus: A single-center experience and literature review. Psychosomatics 2015; 56: 190–195.

43.

Baker

Pope

Fortin

et al.

Work disability in systemic lupus erythematosus is prevalent and associated with socio-demographic and disease related factors. Lupus 2009; 18: 1281–1288.

44.

Mok

Cheung

et al.

Risk and predictors of work disability in Chinese patients with systemic lupus erythematosus. Lupus 2008; 17: 1103–1107.

45.

Olfson

Shea

Feder

et al.

Prevalence of anxiety, depression, and substance use disorders in an urban general medicine practice. Arch Fam Med 2000; 9: 876–876.

46.

Wang

Alexanderson

Runeson

et al.

Are all-cause and diagnosis-specific sickness absence, and sick-leave duration risk indicators for suicidal behaviour? A nationwide register-based cohort study of 4.9 million inhabitants of Sweden. Occup Environ Med 2014; 71: 12–20.

47.

Wang

Björkenstam

Alexanderson

et al.

Trajectories of work-related functional impairment prior to suicide. PloS One 2015; 10: e0139937–e0139937.

48.

Gordon

Isenberg

Lerstrøm

et al.

The substantial burden of systemic lupus erythematosus on the productivity and careers of patients: A European patient-driven online survey. Rheumatology 2013; 52: 2292–2301.

49.

Reinstatler

Youssef

. Ketamine as a potential treatment for suicidal ideation: A systematic review of the literature. Drugs R D 2015; 15: 37–43.

50.

Park

. An introduction to logistic regression: From basic concepts to interpretation with particular attention to nursing domain. J Korean Acad Nurs 2013; 43: 154–164.

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Suicidal ideation in systemic lupus erythematosus: NR2A gene polymorphism,clinical and psychosocial factors

Abstract

Background

Methods

Results

Conclusions

Keywords

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References

Supplementary Material