Depression and Cognitive Impairment in Newly Diagnosed Systemic Lupus Erythematosus

Petri, Michelle; Naqibuddin, Mohammad; Carson, Kathryn A.; Wallace, Daniel J.; Weisman, Michael H.; Holliday, Stephen L.; Sampedro, Margaret; Padilla, Patricia A.; Brey, Robin L.

doi:10.3899/jrheum.091366

Cited by 104 publications

(89 citation statements)

References 40 publications

(34 reference statements)

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“…Depression was improved by an approximate average of 9 points (post-intervention) and 5 points (four months post-intervention) on the BDI-II in intervention participants, which is greater than the minimum clinically significant change suggested for interpreting change scores in lupus trials[42–44]. Overall, depression findings were consistent with other studies that have observed higher depression scores in SLE cases compared with controls[43, 45].…”

Section: Discussionsupporting

confidence: 83%

An intervention to reduce psychosocial and biological indicators of stress in African American lupus patients: The balancing lupus experiences with stress strategies study

Williams¹,

Penfield²,

Kamen³

et al. 2014

OJPM

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Objective Very little is known about the impact of psychosocial stress on African American lupus patients. Due to the exposure of African Americans to a unique trajectory of stressors throughout life, it may be critical to understand the relationship between psychosocial stress and underlying biological mechanisms that influence disease activity and pathology in this high risk group. Methods The Balancing Lupus Experiences with Stress Strategies (BLESS) study piloted the validated “Better Choices, Better Health” Chronic Disease Self-Management Program (CDSMP) in 30 African-American lupus patients participating in the SLE Clinic Database Project at the Medical University of South Carolina (MUSC). Measures of psychosocial and biological indicators of stress were collected in all of the patients in each of the study conditions before and after intervention activities, as well as four months post-intervention, to assess the effectiveness of the program in reducing perceived and biological indicators of stress. Results Participation in the workshops had large effects upon depression (d=1.63 and d = 1.68), social/role activities limitations (d =1.15), health distress (d =1.13 and d = 0.78), fatigue (d =1.03), pain (d =0.96), and lupus self-efficacy (d =0.85). Neither the differences in cortisol or DHEA levels pre- and post-intervention were found to be significantly different between intervention participants and controls. Conclusion The intervention workshops acted to reduce perceived stress and improve quality of life. Our findings imply that comparable, if not more significant gains in relevant health indicators are possible in African American patients when provided the opportunity to participate in CDSMP’s.

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Section: Discussionsupporting

confidence: 83%

An intervention to reduce psychosocial and biological indicators of stress in African American lupus patients: The balancing lupus experiences with stress strategies study

Williams¹,

Penfield²,

Kamen³

et al. 2014

OJPM

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“…47, p=0.07), functional relevance of NMNAT2 to SLE pathogenesis remains inconclusive and (4) although we observed correlation between SMG7 and SMG7-AS1 transcript levels, how SMG7 expression is regulated by its local lncRNA need further investigation.…”

Section: Discussionmentioning

confidence: 82%

Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production

et al. 2016

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Objectives Following up the SLE GWAS identification of NMNAT2 at rs2022013, we fine-mapped its 150kb flanking regions containing NMNAT2 and SMG7 in a 15,292 case-control multi-ancestry population and tested functions of identified variants. Methods We performed genotyping using custom array, imputation by IMPUTE 2.1.2, and allele specific functions using qRT-PCR and luciferase reporter transfections. SLE PBMCs were cultured with siRNAs to measure antinuclear antibody (ANA) and cyto/chemokine levels in supernatants using ELISA. Results We confirmed association at NMNAT2 in European American (EA) and Amerindian/Hispanic ancestries, and identified independent signal at SMG7 tagged by rs2702178 in EA only (P=2.4×10−8, OR=1.23 [95%CI=1.14–1.32]). In complete linkage disequilibrium with rs2702178, rs2275675 in the promoter region robustly associated with SMG7 mRNA levels in multiple expression quantitative trait locus datasets. Its risk allele was dose-dependently associated with decreased SMG7 mRNA levels in PBMCs of 86 SLE patients and 119 controls (P=1.1×10−3 and 6.8×10−8, respectively) and conferred reduced transcription activity in transfected HEK-293 and Raji cells (P=0.0035 and 0.0037, respectively). As a critical component in the nonsense-mediated mRNA decay pathway, SMG7 could regulate autoantigens including RNP and Sm. We showed SMG7 mRNA levels in PBMCs correlated inversely with ANA titers of SLE patients (r=−0.31, P=0.01), and SMG7 knockdown increased levels of ANA IgG and CCL19 in SLE PBMCs (P=2.0×10−5 and 2.0×10−4, respectively). Conclusions We confirmed NMNAT2 and identified independent SMG7 association with SLE. The inverse relationship between levels of the risk-allele associated SMG7 mRNAs and ANA suggested the novel contribution of mRNA surveillance pathway to SLE pathogenesis.

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“…As in human SLE where depression and other kinds of NP manifestations can appear early in the time course of the disease [15,89], authors found that depressive-like behavior is exhibited by MRL-lpr mice (stock #006825) already at 8-weeks of age, at a time when there was no other apparent organ involvement [90]. Thus, these mice demonstrate increased immobility in the forced-swim test, which is usually accepted as an indicator of depression in rodents if strength, motor coordination and general locomotion are otherwise normal (mice's motor function had been evaluated and revealed no impairment in the beam-walking as well as in open field tests).…”

Section: The Mrl-lpr Mouse Modelmentioning

confidence: 98%

“…NP manifestations seem not to be correlated with lupus flares [12], further confounding diagnosis and emphasizing the necessity to rule out other potential etiologies such as medication-induced (corticosteroid) psychiatric symptoms, infections, or metabolic abnormalities [13,14] to establish a possible diagnosis. While lupus patients with long duration of disease hold concurrently several factors that may provoke NP manifestations, affective, cognitive and mood disorders can be found in patients with newly diagnosed disease [15]. Disruption of blood brain barrier (BBB), brain pathology, and the presence of auto-antibodies (autoAbs) are central components of NPSLE.…”

Section: Introductionmentioning

confidence: 99%

Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

Jeltsch-David

Muller

2014

Autoimmunity Reviews

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Mouse models of autoimmunity, such as (NZB×NZW)F1, MRL/MpJ-Fas(lpr) (MRL-lpr) and BXSB mice, spontaneously develop systemic lupus erythematosus (SLE)-like syndromes with heterogeneity and complexity that characterize human SLE. Despite their inherent limitations, such models have highly contributed to our current understanding of the pathogenesis of SLE as they provide powerful tools to approach the human disease at the genetic, cellular, molecular and environmental levels. They also allow novel treatment strategies to be evaluated in a complex integrated system, a favorable context knowing that very few murine models that adequately mimic human autoimmune diseases exist. As we move forward with more efficient medications to treat lupus patients, certain forms of the disease that requires to be better understood at the mechanistic level emerge. This is the case of neuropsychiatric (NP) events that affect 50-60% at SLE onset or within the first year after SLE diagnosis. Intense research performed at deciphering NP features in lupus mouse models has been undertaken. It is central to develop the first lead molecules aimed at specifically treating NPSLE. Here we discuss how mouse models, and most particularly MRL-lpr female mice, can be used for studying the pathogenesis of NPSLE in an animal setting, what are the NP symptoms that develop, and how they compare with human SLE, and, with a critical view, what are the neurobehavioral tests that are pertinent for evaluating the degree of altered functions and the progresses resulting from potentially active therapeutics.

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Depression and Cognitive Impairment in Newly Diagnosed Systemic Lupus Erythematosus

Abstract: Depression, a modifiable risk factor, is associated with significantly poorer function in several cognitive domains in patients newly diagnosed with SLE. Treatment of depression when the CDS score is greater than 6 may improve cognitive functioning and should be further studied.

Cited by 104 publications

References 40 publications

An intervention to reduce psychosocial and biological indicators of stress in African American lupus patients: The balancing lupus experiences with stress strategies study

An intervention to reduce psychosocial and biological indicators of stress in African American lupus patients: The balancing lupus experiences with stress strategies study

Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production

Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

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