Abstract
Background
Systemic lupus erythematosus (SLE) is a chronic autoimmune illness defined by involvement of several systems and a variety of clinical symptoms among them the neuropsychiatric manifestations. The purpose of the study was to evaluate the presence of depression and to assess overall health in individuals with SLE, as well as their relation to SLE disease activity and damage. Sixty adult SLE patients were enrolled, along with sixty age and sex-matched controls. For the presence of major depression, all patients were examined using the Beck Depression Inventory (BDI-II) and the General Health Questionnaire (GHQ-12) for mental distress. Antinuclear antibody, anti-ds DNA, complements 3 and 4, and anti-ribosomal P antibody were performed for SLE patients. The SLEDAI-2 K and SLEDDI were assessed.
Results
The 60 patients were 52 (86.7%) females and 8 (13.3%) men, with a mean age of 32.5 ± 11.5 years and disease duration of 3.57 ± 3.55 years. Patients with depression accounted for 43 (71.6%) of the total, whereas controls accounted for just 14 (23.3%). Patients with substantial depression had significantly higher SLEDAI-2 K, SLEDDI, and illness duration than those without major depression (p = 0.047, p = 0.043, and p = 0.033, respectively). The patients’ mean GHQ-12 score was 17 ± 5.96, whereas the control group's was 10.0 ± 67.30, with a p value of 0.002. SLEDAI-2 K, SLEDDI, and depression score had a substantial positive association (p = 0.001, p = 0.042), while BDI-II and GHQ-12 had a significant positive correlation (p 0.001).
Conclusions
Depression and psychological distress were both common in SLE patients. Depression severity was linked to illness duration, activity, and damage.
Similar content being viewed by others
Background
Systemic lupus erythematosus (SLE) is a chronic autoimmune illness defined by involvement of several systems with variety of clinical manifestations as a result of autoantibody production and immune complex deposition. During their reproductive years, females are nine times more likely than males to be afflicted [1].
In patients with SLE, neuropsychiatric SLE (NPSLE) refers to a diverse range of neurological and psychiatric symptoms caused by involvement of the central, peripheral, and autonomic nervous systems [2, 3]. Seizures, mood disorder, psychosis, headache, neuropathy, and stroke were among the neuropsychiatric symptoms of SLE documented in Egyptian patients [4]. Cognitive impairment was also discovered to be a common symptom in SLE Egyptian patients [5].
Prevalence, initiation time, complexity, resolution rates, and recurrence of neuropsychiatric episodes vary [6]. The majority of the events are linked to a decrease in self-reported health-related quality of life [7]. In a recent research of Egyptian SLE patients, quality of life was shown to be severely impaired, particularly in those who were obese [8].
Mood disorders, particularly depression, are common in SLE patients and are important neuropsychiatric manifestations of the illness, in addition to their high incidence and possible deleterious influence on disease progression [9].
SLE depression is complex, with neurotransmitter dysfunction and immunological activation (lymphocyte abnormalities and cytokine production) being two possible causes [10, 11]. Depression exacerbates pain, tiredness, psychological stress, and reduces treatment adherence in SLE patients, resulting in a considerable worsening in quality of life and job disability [12, 13].
The goal of this study was to evaluate the occurrence of depression and its contributing factors, as well as overall health assessment in patients with SLE, and to determine their relation with disease activity and damage.
Methods
Sixty adult SLE patients who met the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria were included in this research [14]. Patients were recruited from the Rheumatology Unit of Alexandria University Hospital’s Internal Medicine Department. As controls, sixty healthy adults were enlisted who were age and sex matched to the patients. Exclusion criteria included patients with history of depression prior to the onset of SLE, uncooperative patients, antiphospholipid syndrome, other autoimmune rheumatic diseases, and pregnant lupus patients. After receiving clearance from the institutional ethics committee, the study was carried out in accordance with the Declaration of Helsinki’s ethical criteria, and each subject gave their informed consent.
Age, gender, domicile, marital status, educational level, and work status of the participants were all taken into account. All SLE patients had a history taking, a clinical examination, and a disease activity evaluation using the SLE disease activity index (SLEDAI-2 k) [15], with scores ranging from “inactive” (scores ≤ 4) to mild-moderate (5–9) to high (≥ 10). The Systemic Lupus Collaborating Clinics/ACR damage index (SLICC/ACR DI) was also used to quantify disease damage [16].
Complete blood count, creatinine, urinary protein to creatinine ratio (PCR), alanine transaminase, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were performed.
Serological tests included antinuclear antibodies (ANA), anti-double-stranded DNA (anti-ds DNA), anti-ribosomal-p antibody, and complement C3 and C4 were among the laboratory tests performed for the patients.
The Beck Depression Inventory Score (BDI-II) was applied to assess the presence of depression in the patients and control group, and we used the Arabic version (Additional file 1), which is one of the most extensively used tools for measuring depression symptoms and severity [17]. It has 13 items, each of which is assessed on a four-point Likert scale ranging from 0 (not likely to happen) to 3 (always or mostly happen). The total number of components in the patient's score ranges from 0 to 39. There are four levels of depression: no depression (0 to 4), mild cases (5 to 7), moderate instances (8 to 15), and severe cases (≥ 16).
The General Health Questionnaire-12 (GHQ-12) [18] was used to conduct psychometric testing for general health and psychological distress. The GHQ-12 is a 12-item questionnaire with a score range of 1 to 36, with mild cases falling between (1 to 12), moderate cases (13 to 24), and severe cases (25 to 36).
Statistical analysis
IBM-SPSS statistical program version 22 was used to analyze the data. The Mann-Whitney or Student t-test was used to analyze continuous data, while the chi-square test was employed to assess categorical ones. The Spearman coefficient was used to determine the correlation between quantitative variables. Logistic regression analysis was used to determine risk factor for presence of depression among SLE patients. The significance of the acquired results was assessed at a 5% level. The p value of 0.05 was used to determine statistical significance.
Results
The 60 patients had a mean age of 32.5 ± 11.5 years and illness duration of 3.57 ± 3.55 years, with 52 (86.7%) females and 8 (13.3%) men (F to M 6.5:1). Table 1 shows the socio-demographic characteristics of SLE patients and controls. Table 2 shows the patients’ clinical features and immunological profiles. In terms of SLE disease activity, 11 patients had inactive disease, 32 patients had mild-moderate disease activity, and 17 patients had high disease activity.
The neuropsychiatric manifestations were observed in 15 patients (25%) and included seizures 3 patients (20%), cranial neuropathy 2 patients (13.4%), psychosis 3 patients (20%), cognitive dysfunction 4 patients (26.6%), headache 3 patients (20%), and peripheral neuropathy 2 patients (13.4%).
The medications that were used by the patients included the following: hydroxychloroquine 52 patients (86.6%), glucocorticoids 48 patients (80%), azathioprine 21 (35%), mycophenolate mofetil 9 patients (15%), cyclophosphamide 12 patients (20%), methotrexate 5 patients (8.4%), and cyclosporin 4 patients (6.7%).
According to the BDI-II, 43 (71.6%) of patients experienced depression, with a mean score of 14.94 ± 7.3, whereas 14 (23.3%) of the control group's had depression, with mean score of 7.1 ± 3.62 (Fig. 1), with a p value of 0.0019.
The SLE patients with depression were classified as following: 17 patients with high disease activity (10 patients in severe depression, 5 patients in moderate depression and 2 patients in mild depression), while 24 patients with mild-moderate activity (2 patients in severe depression, 12 patients in moderate depression and 10 patients in mild depression) and 2 patients were inactive disease had mild depression. Based on the degree of their depression, the patients were separated into three groups: there were 14 individuals with mild depression, 17 with moderate depression, and 12 with severe depression. In addition, there was a substantial distinction between the two groups as regard GHQ-12 with p value = 0.0021 (Fig. 2).
The sociodemographic status of SLE patients with and without depression did not differ substantially, although they did differ considerably in terms of illness duration, SLEDAI-2 K, and SLEDDI (p = 0.033, p = 0.047, and p = 0.043, respectively).
SLEDAI-2 K had a substantial positive connection with BDI-II and GHQ-12 scores (p 0.001, p 0.001), as shown in Fig. 3. SLEDDI was also shown to be associated with depression score (p = 0.042) and GHQ-12 severity (p = 0.026). Furthermore, there was a significant positive connection between the BDI-II and GHQ-12 (p < 0.001).
Anti-ribosomal P antibody testing was positive in 23.3% of SLE patients in this investigation, with a mean titer of 46.48 U/ml. Furthermore, there was a high statistical correlation between anti-ribosomal P antibody and depression score (p = 0.0472), as well as SLEDAI-2 K (p = 0.001).
Multivariate regression analysis was done to determine the predictors of depression in SLE patients. We found that disease activity, damage, and disease duration were significant predictors for depression (Table 3).
Discussion
SLE has a significant influence on people's quality of life, posing several obstacles, particularly for young people who are frequently impacted. Involvement of the central nervous system (CNS) in SLE is linked to a variety of neurological and psychiatric symptoms and is one of the leading causes of morbidity and disability [19, 20].
The majority of the SLE patients in this study reported significant depressive symptoms. According to the BDI-II score, 43/60 (71.6%) of the patients had depression, while only 14/60 (23.3%) of the control group had depression. This is consistent with Raafat et al. [21], who found that 64% of their study patients had depression, while Stoll et al. [22] found that the prevalence of depression was as low as 16%. Our sample had a larger proportion of patients with depression than previous research, which might be related to different methodology, different evaluation tools, patient samples, sample sizes, and different social and economic factors and cultural backgrounds.
GHQ-12 has become one of the most commonly used tools for detecting psychological distress. It carries advantage when compared to other version like GHQ-28, being brief, easily scored. In addition to level of symptoms present (Likert type scoring). It is composed of positive and negative phrased items that cover the multiple dimension of mental health including social dysfunction, anxiety, depression, and loss of confidence [23].
Patients with depression had a higher SLEDAI-2 K score than those without, and there was a strong positive connection between SLEDAI-2 K score and depression severity. These findings back up the theory that disease activity may be a risk factor for the presence and severity of depression in SLE patients. This was in line with the findings of Zakeri et al. [24], who found that 60% of patients reported depression, with the severity of depression being related to disease activity. Nery et al. [25] likewise came up with similar results.
Patients with higher disease activity are more likely to experience impairments in daily living activities, which can contribute to depression and a deterioration in health-related quality of life (HRQOL) [26]. This might be explained by the two-dimentional assosiaction between chronic illness activity influeces emotional condition, or by the fact that depression induces more disease activity, as documented by Beckerman et al. [27].
Anti-ribosomal P antibody testing was positive in 23.3 % of the patients in this research, and there was a significant correlation with depression score (p = 0.0472). This is in line with the findings of Arnett et al. [28], who discovered strong links between lupus psychosis and depression and serum anti-ribosomal P antibodies. Furthermore, Reichlin et al. [29] and Schneebaum et al. [30] have verified the anti-ribosomal P antibody’s capacity to distinguish people who have nervous system involvement owing to SLE illness from those who have it as a consequence of therapy or merely as an associated condition.
Disease activity, damage, and disease duration were all found to be predictors of depression in SLE patients in regression analysis. Higher disease activity at baseline was predictive of depression, psychosis, and cognitive impairment, according to Mikdashi et al. [31]. Stoll et al. [22] also showed a high total SLICC/ACR DI score during the first years of disease is a strong predictor of depression and other neuropsychiatric manifestations.
Conclusions
Depression is quite common among SLE patients. Disease activity, damage, and disease duration were all found to be predictive of the occurrence and severity of depression. Anti-ribosomal P antibody was found to be positive in considerable number of patients with a significant correlation with depression score. The early identification and treatment of depression may have a significant influence on the patient's quality of life.
Availability of data and materials
Data is available from Ahmed Shaaban (corresponding author).
Abbreviations
- ANA:
-
Antinuclear antibodies
- anti-ds DNA:
-
Anti-double-stranded DNA
- BDI-II:
-
Beck Depression Inventory
- CNS:
-
Central nervous system
- CRP:
-
C-reactive protein
- ESR:
-
Erythrocyte sedimentation rate
- GHQ-12:
-
General Health Questionnaire
- HRQOL:
-
Health-related quality of life
- NPSLE:
-
Neuropsychiatric SLE
- PCR:
-
Protein to creatinine ratio
- SLE:
-
Systemic lupus erythematosus
- SLEDAI-2 k:
-
SLE disease activity index
- SLICC/ACR DI:
-
Systemic Lupus Collaborating Clinics/ACR damage index
- SLICC:
-
Systemic Lupus International Collaborating Clinics
- SLEDDI:
-
Systemic lupus erythematosus disease damage index
References
D'Cruz DP, Khamashta MA, Hughes GR (2007) Systemic lupus erythematosus. Lancet 369(9561):587–596. https://doi.org/10.1016/s0140-6736(07)60279-7
Jeltsch-David H, Muller S (2014) Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers. Nat Rev Neurol 10(10):579–596. https://doi.org/10.1038/nrneurol.2014.148
Hanly JG (2004) ACR classification criteria for systemic lupus erythematosus: limitations and revisions to neuropsychiatric variables. Lupus 13(11):861–864. https://doi.org/10.1191/0961203304lu2024oa
Mani A, Shenavandeh S, Sepehrtaj SS, Javadpour A (2015) Memory and learning functions in patients with systemic lupus erythematosus: a neuropsychological case-control study. Egypt. Rheumatol 37(4, Supplement):S13–S17. https://doi.org/10.1016/j.ejr.2015.02.004
El-Shafey AM, Abd-El-Geleel SM, Soliman ES (2012) Cognitive impairment in non-neuropsychiatric systemic lupus erythematosus. Egypt Rheumatol 34(2):67–73. https://doi.org/10.1016/j.ejr.2012.02.002
Hanly JG, Kozora E, Beyea SD, Birnbaum J (2019) Review: Nervous system disease in systemic lupus erythematosus: current status and future directions. Arthritis Rheumatol 71(1):33–42. https://doi.org/10.1002/art.40591
Ahn GY, Kim D, Won S, Song ST, Jeong HJ, Sohn IW et al (2018) Prevalence, risk factors, and impact on mortality of neuropsychiatric lupus: a prospective, single-center study. Lupus 27(8):1338–1347. https://doi.org/10.1177/0961203318772021
Rizk A, Gheita TA, Nassef S, Abdallah A (2012) The impact of obesity in systemic lupus erythematosus on disease parameters, quality of life, functional capacity and the risk of atherosclerosis. Int J Rheum Dis 15(3):261–267. https://doi.org/10.1111/j.1756-185X.2011.01698.x
Palagini L, Mosca M, Tani C, Gemignani A, Mauri M, Bombardieri S (2013) Depression and systemic lupus erythematosus: a systematic review. Lupus 22(5):409–416. https://doi.org/10.1177/0961203313477227
Dantzer R (2006) Cytokine, sickness behavior, and depression. Neurol Clin 24(3):441–460. https://doi.org/10.1016/j.ncl.2006.03.003
Maes M, Berk M, Goehler L, Song C, Anderson G, Gałecki P et al (2012) Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways. BMC Med 10:66. https://doi.org/10.1186/1741-7015-10-66
Huang X, Magder LS, Petri M (2014) Predictors of incident depression in systemic lupus erythematosus. J Rheumatol 41(9):1823–1833. https://doi.org/10.3899/jrheum.140111
Ward MM, Lotstein DS, Bush TM, Lambert RE, van Vollenhoven R, Neuwelt CM (1999) Psychosocial correlates of morbidity in women with systemic lupus erythematosus. J Rheumatol 26(10):2153–2158
Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR et al (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64(8):2677–2686. https://doi.org/10.1002/art.34473
Gladman DD, Ibañez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29(2):288–291
Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E, Gordon C et al (1997) The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus. Arthritis Rheum 40(5):809–813. https://doi.org/10.1002/art.1780400506
Kühner C, Bürger C, Keller F, Hautzinger M (2007) Reliability and validity of the Revised Beck Depression Inventory (BDI-II). Results from German samples. Nervenarzt 78(6):651–656. https://doi.org/10.1007/s00115-006-2098-7
Salama-Younes M, Montazeri A, Ismaïl A, Roncin C (2009) Factor structure and internal consistency of the 12-item General Health Questionnaire (GHQ-12) and the Subjective Vitality Scale (VS), and the relationship between them: a study from France. Health Qual Life Outcomes 7:22. https://doi.org/10.1186/1477-7525-7-22
Chiewthanakul P, Sawanyawisuth K, Foocharoen C, Tiamkao S (2012) Clinical features and predictive factors in neuropsychiatric lupus. Asian Pac J Allergy Immunol 30(1):55–60
Hanly JG, Urowitz MB, Sanchez-Guerrero J, Bae SC, Gordon C, Wallace DJ et al (2007) Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum 56(1):265–273. https://doi.org/10.1002/art.22305
Raafat HA, El Refai RM, Alrasheed HA, El Din MN (2015) Major depression and disease activity among systemic lupus erythematosus Egyptian females. Egypt. Rheumatol 37(4, Supplement):S1–S6. https://doi.org/10.1016/j.ejr.2015.09.007
Stoll T, Kauer Y, Büchi S, Klaghofer R, Sensky T, Villiger PM (2001) Prediction of depression in systemic lupus erythematosus patients using SF-36 Mental Health scores. Rheumatology (Oxford) 40(6):695–698. https://doi.org/10.1093/rheumatology/40.6.695
Hystad SW, Johnsen BH (2020) The dimensionality of the 12-item general health questionnaire (GHQ-12): comparisons of factor structures and invariance across samples and time. Front Psychol 11:1300. https://doi.org/10.3389/fpsyg.2020.01300
Zakeri Z, Shakiba M, Narouie B, Mladkova N, Ghasemi-Rad M, Khosravi A (2012) Prevalence of depression and depressive symptoms in patients with systemic lupus erythematosus: Iranian experience. Rheumatol Int 32(5):1179–1187. https://doi.org/10.1007/s00296-010-1791-9
Nery FG, Borba EF, Hatch JP, Soares JC, Bonfá E, Neto FL (2007) Major depressive disorder and disease activity in systemic lupus erythematosus. Compr Psychiatry 48(1):14–19. https://doi.org/10.1016/j.comppsych.2006.04.002
Doria A, Rinaldi S, Ermani M, Salaffi F, Iaccarino L, Ghirardello A et al (2004) Health-related quality of life in Italian patients with systemic lupus erythematosus. II. Role of clinical, immunological and psychological determinants. Rheumatology (Oxford) 43(12):1580–1586. https://doi.org/10.1093/rheumatology/keh392
Beckerman NL, Auerbach C, Blanco I (2011) Psychosocial dimensions of SLE: implications for the health care team. J Multidiscip Healthc 4:63–72. https://doi.org/10.2147/jmdh.s19303
Arnett FC, Reveille JD, Moutsopoulos HM, Georgescu L, Elkon KB (1996) Ribosomal P autoantibodies in systemic lupus erythematosus. Frequencies in different ethnic groups and clinical and immunogenetic associations. Arthritis Rheum 39(11):1833–1839. https://doi.org/10.1002/art.1780391109
Reichlin M (2003) Ribosomal P antibodies and CNS lupus. Lupus 12(12):916–918. https://doi.org/10.1191/0961203303lu502oa
Schneebaum AB, Singleton JD, West SG, Blodgett JK, Allen LG, Cheronis JC et al (1991) Association of psychiatric manifestations with antibodies to ribosomal P proteins in systemic lupus erythematosus. Am J Med 90(1):54–62. https://doi.org/10.1016/0002-9343(91)90506-s
Mikdashi J, Handwerger B (2004) Predictors of neuropsychiatric damage in systemic lupus erythematosus: data from the Maryland lupus cohort. Rheumatology (Oxford) 43(12):1555–1560. https://doi.org/10.1093/rheumatology/keh384
Acknowledgements
We would like to thank the patients and the control group for participating in this research.
Funding
There was no particular grant for this research from any governmental, private, or non-profit funding bodies.
Author information
Authors and Affiliations
Contributions
Ahmed Shaaban: software, writing original draft. Manal Tayel: supervision, conceptualization. Eman Hassan: conceptualization, methodology. Medhat Salah: methodology, resources. Mohamed Ibrahim: investigations. Walaa Saide: software, investigations. The author(s) read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
After receiving clearance from the institutional ethics committee, the study was carried out in accordance with the Declaration of Helsinki’s ethical criteria, and each subject gave written informed consent.
Consent for publication
All authors revised the manuscript and approved the publication.
Competing interests
The authors declare that they have no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Shaaban, A., Tayel, M., Hassan, E. et al. Evaluation of depression and general health assessment among systemic lupus erythematosus patients in relation to disease activity and damage. Egypt Rheumatol Rehabil 49, 15 (2022). https://doi.org/10.1186/s43166-022-00113-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s43166-022-00113-5