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

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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.

Original languageEnglish
Pages (from-to)744-752
Number of pages9
JournalLupus
Volume27
Issue number5
DOIs
Publication statusPublished - 1 Apr 2018

Fingerprint

Suicidal Ideation
Systemic Lupus Erythematosus
Psychology
Genes
Mood Disorders
Glutamate Receptors
Suicide
Odds Ratio
Confidence Intervals
Depression
Social Adjustment
Neurobiology
Logistic Models
Genotype
Interviews

Keywords

  • gene–environment interaction
  • Glutamate receptor
  • neuropsychiatric systemic lupus erythematosus
  • NMDA receptors
  • NR2A
  • suicidal ideation

ASJC Scopus subject areas

  • Rheumatology

Cite this

@article{521aca3b178941e885f687b8b86d59d3,
title = "Suicidal ideation in systemic lupus erythematosus: NR2A gene polymorphism, clinical and psychosocial factors",
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 = "gene–environment interaction, Glutamate receptor, neuropsychiatric systemic lupus erythematosus, NMDA receptors, NR2A, suicidal ideation",
author = "Buji, {R. I.} and {Abdul Murad}, {Nor Azian} and Chan, {Lai Fong} and T. Maniam and {Mohamed Said}, {Mohd Shahrir} and Rozita Mohd and Shah, {Shamsul Azhar} and {Mohamad Hussain}, R. and {Abdullah @ Muda}, Noraidatulakma and {A. Jamal}, {A. Rahman} and {Nik Jaafar}, {Nik Ruzyanei}",
year = "2018",
month = "4",
day = "1",
doi = "10.1177/0961203317742711",
language = "English",
volume = "27",
pages = "744--752",
journal = "Lupus",
issn = "0961-2033",
publisher = "SAGE Publications Ltd",
number = "5",

}

TY - JOUR

T1 - Suicidal ideation in systemic lupus erythematosus

T2 - NR2A gene polymorphism, clinical and psychosocial factors

AU - Buji, R. I.

AU - Abdul Murad, Nor Azian

AU - Chan, Lai Fong

AU - Maniam, T.

AU - Mohamed Said, Mohd Shahrir

AU - Mohd, Rozita

AU - Shah, Shamsul Azhar

AU - Mohamad Hussain, R.

AU - Abdullah @ Muda, Noraidatulakma

AU - A. Jamal, A. Rahman

AU - Nik Jaafar, Nik Ruzyanei

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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.

AB - 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.

KW - gene–environment interaction

KW - Glutamate receptor

KW - neuropsychiatric systemic lupus erythematosus

KW - NMDA receptors

KW - NR2A

KW - suicidal ideation

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DO - 10.1177/0961203317742711

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