Association Between Systemic Lupus Disease Activity and Sleep Quality among Sample of Females with or without Depression at Baghdad Teaching Hospital View PDF

The Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disease that is associated with the production of a variety of autoantibodies directed against native DNA and other cellular constituents [1]. It is a prototypic disease with heterogeneous clinical manifestations that may involve many different organ systems [2]. The systems commonly involved include skin, joints and muscle, brain and peripheral nervous system, lungs, heart, kidneys, gastrointestinal tract, serous membranes, and components of the blood [3]. Prevalence rates of SLE vary widely in the literature. Reported prevalence frequencies worldwide range from 20-240 per 100,000 persons, Caucasian and African American patients, reported prevalence of 72.1-74.4 per 100,000 persons, African American women had the highest rates [4]. Iraqi patients reported prevalence of 53.6 per 100,000 persons and higher rates for women with 88.7 per 100,000 persons [5,6]. Ninety percent of patients are women of reproductive age [7]. The female: male ratio is approximately 6–10:1, while in both children and elderly patients, the female: male ratio is approximately 2-3:1 [8]. Interactions between susceptible genes and environmental factors result in abnormal immune responses which vary between individuals. Those responses may include: Abnormal activation of innate immunity (dendritic cells, monocyte and macrophages) and adaptive immunity cells (T and B lymphocytes) [9], and ineffective regulatory CD4+ and CD8+T cells and B cells can be attributed to inappropriate clearance of immune complexes and apoptotic cells [10]. Sleep is first and foremost a behavior, which is characterized by changes in body posture and eye state, which is dimensionally evaluated by self-report, behavioral, physiological, cellular, and genetic analysis, whereas such analysis is used to differentiate arousal states along a continuum from fully awake to deep sleep [11]. Sleep divided into wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep [12]. Depression is a state of low mood and aversion to activity that affect persons’ emotions, thoughts, behaviors and sense of well-being [13]. A person who is depressed usually experiences several feelings of sadness or emptiness, hopeless, anhedonia (a decrease or loss of ability to take pleasure in ordinary activities), guilt, irritability, angry, lowered self-esteem and worthlessness, reduced energy and vitality, social isolation, slowness of thought or action, recurrent thoughts of death or suicide, loss of appetite or overeating, constipation or diarrhea, disturbed sleep or insomnia and decreased libido [14-16]. Depression is the most common mood disorder [17]. Overlap of depression and specific autoimmune diseases in the same individuals at a higher frequency than chance, investigating the relationship between depression and autoimmune diseases will inform theories that the etiology of depression involves immune processes [18]. The link between lupus and depression is controversial but it is known that negative life events, low socioeconomic status, lupus disease activity and lupus treatment may be contributing to depression. The psychiatric symptoms of lupus may vary from mild personality disorders to severe psychosis. Depression is the most frequent mental change in lupus (studies cited about half of lupus patients develop depression) [19,20].

Study Design and Setting

A cross-sectional study was conductedat Rheumatology Unit, Baghdad Teaching Hospital, during the period from the 1^st of January to the 31^st of October 2018.

Patients Collection

A total of 61 Iraqi female patients attending the Rheumatology Unit at Baghdad Teaching Hospital, were evaluated.A brief interview (20-30 min) was conducted in a private quiet room in order to take the illness history of each patient prior to enrollment. All patients enrolleddiagnosed with SLE (by the Consultant Rheumatologists) after fulfilling at least 4 criteria of the ACR revised criteriafor SLEand after fulfilling at least 4 criteria or biopsy-proven lupus nephritis with positive ANA or Anti-DNA of theSLICC criteriafor SLE. The patients were diagnosed with depression (by the Consultant Psychiatrists) after having at least 5 of the DSM-5 criteria for depression.

Inclusion Criteria

Female patients were diagnosed with SLE with disease onset after the age of 18 years regardless the disease duration was evaluated for sleep quality according to the PSQI scoring and depression according to the DSM-5 criteria. Because mostof the persons with SLE are females, for clarity and feasibility, we studied females only.

Exclusion Criteria

• Chronic medical diseases including end-stage renal disease, ischemic heart disease, hypertension, diabetes mellitus and active neoplastic disease.
• Overlap, mixed connective tissue diseases and antiphospholipid syndrome.
• Pregnancy and lactation.
• Substance abuse including smoking and alcohol.

Data Collection

• Data were collected using a data collection sheet containing questionnaires for the patients. The questionnaires included general demographic data: name, age, height, weight, body mass index, marital status (single, married, widow, divorced), education (illiterate, read & write, primary school, secondary school, college, postgraduate), employment (unemployed, employed, retired, housewife) and household crowding index.
• Data for SLE evaluation included disease duration and disease activity.Disease activity was evaluated by using SLEDAI which based on clinical and laboratory variables, scores may range from no flare ≤3, mild or moderate flare >3-12, and severe flare >12.
• Sleep quality was evaluated by using data collection questionnaire, derived from Pittsburgh Sleep Quality Index (PSQI) a widely used and standardized questionnaire,19 questions are combined into seven clinically derived component scores, each exploring a different sleep feature, The seven component scores are then added in order to obtain a global score rating from 0-21, with a global score ≥5 points was defined as poor sleep quality. The following PSQI-derived data were also analyzed: increased sleep latency (>30 min) (component 2), difficulty in maintaining sleep and early morning awakening (component 5).
• Depression was evaluated by using data collection questionnaire, derived from DSM-5 criteria which is anine-question questionnaire to assess depressive symptoms during the previous two weeks, with a global score≥5 points.

Ethical Issue, Approval and Official Permission

Prior to data collection, a verbal consent was taken from all patients to participate in the study. The study protocol was reviewed; approval and official permission were obtained from the Ministry of Higher Education and Scientific Research, Baghdad University, College of Medicine to conduct the present study.

Statistical Analysis

All statistical procedures, analysis and tests were applied using the statistical package for social sciences (SPSS) version 25. Descriptive statistics presented as mean, standard deviation, median, inter-quartile range (IQR), frequencies and percentages. Continuous variables were tested for normal distribution using the histogram, normal distribution curve and for dataset smaller than 2000 elements, the Shapiro-Wilk test was used. The total PSQI and DSM-5 appeared to be normally distributed with minimal skewness but both passed the Shapiro-Wilk testing, while SLEDAI appeared to have large skewness and did not pass the Shapiro-Wilk test (i.e. it was not normally distributed). Independent student’s t test was used to compare two means of normally distributed variable. The Mann-Whitney U test used to compare SLEDAI across two subgroups. The Kruskal-Wallis test (one-way ANOVA on ranks) used to compare SLEDAI of the patients in the 4 subgroups according to combination of sleep quality and depression. The bivariate Pearson’s correlation test used to assess the correlation among DSM-5, PSQI and SLEDAI as continuous variables, and because the SLEDAI was not normally distributed, Pearson’s Bivariate correlation test used with Bootstrapping. Level of significance was set at 0.05 below which the difference or correlation considered to be significant.

A total of 61 SLE patients were enrolled in this cross-sectional study, with a mean age of 33.6 (±10.2), moreover, 26 patients (42.6%) aged 20-29 years. Married patients were 39 (63.9%). Level of education of the patients ranged from illiterate to postgraduate with higher proportion of the patients had secondary level of education and below. Housewives patients were 48 (78.7%). Obese patients were 21 (34.4%). Crowding index ranged between 1 to more than 3, and majority, (82%), of the patients with crowding index of less than 3, as shown in the table (Table 1).

Table 1: Demographic characteristics of SLE patients (Number=61).

The below table shows the clinical disease related variables of SLE patients, the disease duration ranged betweenless than 3 years in some patients to more than 8 years in others; where the median duration of SLE was 3 (IQR: 2-7) years (Table 2).

Table 2: Disease related variables of SLE patients (No.=61).

According to the SLEDAI, it was ranged from 1-42 with a mean of 12.87±9.83 and median of 8.0 (IQR: 5.0-19.0), the disease was inactive in 7 patients (11.5 %), mild or moderate flare in28 patients (45.9%) and severe flare in 26 patients (42.6%).

Assessment of the patients according to the DSM-5 criteria for diagnosis of depressionrevealed that 26 patients (42.6%) were depressed compared to 35patients (57.4%) were not, as shown in the figure (Figure 1).

The assessment of sleep quality of the studied group according to the 7 components of the PSQI score, are shown in the table (Table 3).

Table 3: Distribution of the sleep quality related difficulties of different PSQI components.

The total PSQI ranged between 0 to 18 with a mean of 6.31±2.29 and median (IQR) of 5.0 (3.0-9.0). Moreover, according to the cutoff point (5.0 point) of the total PSQI, Poor sleep quality (PSQI≥5) was reported in 36 patients (59.0%) while the remaining 25 patients (41.0%) had a total PSQI of <5 (Good sleep quality), as shown in the figure (Figure 2).

The mean disease activity index (SLEDAI) of patients with poor sleep quality (SQ) was 15.8±1.8, while that of patients with good SQ was 8.6±1.3. The comparison of SQ subgroups, using the Mann-Whitney U test revealed that patients with poor SQ had significantly higher levels of SLEDAI than those with good SQ, indicated that poor sleep quality associated with more active disease, (P value=0.005). Secondly, the SLEDAI was compared with depression, where patients with depression had significantly higher disease activity index, and the mean SLEDAI of patients with poor and good SQ was 18.8±2.1 vs. 8.5=1.1, respectively, (P value<0.001), as shown in the below table (Table 4).

Table 4: Comparison of mean SLEDAI across the sleep quality and depressioncategories of SLE patients (No.=61).

From other point of view, for more precise assessment of the correlation between SQ and depression from one side and disease activity from the other side, bivariate Pearson’s correlation test was used for the testing of the correlation between total PSQI, DSM-5 and SLEDAI, and because SLEDAI was not-normally distributed the bivariate Pearson’s correlation test used with bootstrapping, then the correlation results were evaluated and revealed a direct significant correlation between SLEDAI and each of PSQI (R=0.417, P value=0.001) and DSM-5 (R=0.440, P value<0.001), moreover, a significant direct correlation was found between DSM-5 and PSQI (R=0.512, P value<0.001), as shown in (Table 5) (Figures 4 and 5).

Table 5: Results of bivariate Pearson’s correlation test of the intercorrelation of SLEDAI, DSM-5 and PSQI of SLE patients (No.=61).

SLE patients were categorized according to their SQ and presence or absence of depression, as shown in the below table, where 4 subgroups had been generated; 21 patients had Poor SQ with Depression, 15 patients had Poor SQ without Depression, 5 patients had Good SQ with Depression and 20 patients had Good SQ without Depression (Table 6).

Table 6: Comparison of mean SLEDAI across the SQ-Depression combined subgroups.

Further comparison was made according to the 4 combined subgroups, this comparison revealed that patients who had Poor SQ with Depression had the highest mean SLEDAI (21.0±2.3) and was significantly higher than the SLEDAI levels of patients who had Poor SQ without Depression, Good SQ without Depression, and Good SQ with Depression, (P value< 0.05), while no significant differences had been found among other subgroups in SLEDAI, (P value>0.05).

As it shown in the table, higher body mass index was significantly associated with higher SLEDAI (P value=0.009) (Table 7). Longer duration of SLE was significantly associated with higher PSQI (P value=0.001).Other variables showed no significant association with DSM-5, PSQI and SLEDAI, (P value>0.05).

Table 7: Results of Bivariate correlation tests of the demographic variables and each of SLEDAI, DSM-5 and PSQI of SLE patients (No.=61).

There are several reports available concerning prevalence of poor sleep quality in SLE [21]. To the best of our knowledge there were no previous reports about poor sleep quality among Iraqi patients with SLE. The purpose of this study was to evaluate sleep quality in lupus women with or without depression. In the current study sleep quality was evaluated by using PSQI score, SLE patients had statistically high scores in subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, and daytime dysfunction. These results are in line with Mirbagher L, et al. (2016), Abad VC, et al. (2008) and Chandrasekhara PK, et al. (2009) [22-24]. In the present study, poor sleep quality was reported in (59%) of SLE patients. These results were like Tench CM, et al. (2009) (British study) which reported poor sleep quality in 60% of SLE female patients [25]. As well as Palagini L, et al. (2014) (Italian study) which demonstrated the presence of poor sleep quality in almost two-thirds of the SLE cohort [26]. The similarities between these studies were all enrolled a small sample size and used PSQI score in their samples. Poor sleep quality was high in SLE studies and lupus disease activity may be the contributing factor. The second part of this study was aimed at identifying the relationship between depression and sleep quality in the SLE cohort. The depressed mood might play an important role in the pathogenesis of poor sleep quality in SLE and sleep disturbances are frequently associated with depression and in the absence of sleep complaints, a diagnosis of depression should be made with caution. In the present study, depression was reported in (42.6%) of SLE women. This finding was agreed to the results of Palagini L, et al. (2014) (Italian study) in which the prevalence of depressive symptoms was about 35% of SLE patients [26]. Despite of we were used DSM-5, while Palagini L, et al. (2014) were used Beck depression inventory (BDI) [26]. This result was close to another study, Meszaros ZS, et al. (2012) (American study) in which depression was present in up to 39% of SLE patients [27]. In both studies the enrolled patients were adults of any age who fulfilled the ACR criteria for SLE. The current study was comparable to Adeli AM, et al. (2016) (Iranian study) which reported that depression prevalence in SLE was 33.3% [28]. This is a little bit difference probably because of Adeli AM, et al. (2016) were studied the prevalence of cognitive disorders in SLE patients rather than focusing on depression only, another difference that we were used DSM-5, while they used BDI and finally our patients were suffered from a more stressful environment that play a key role on the impact of sleep quality. Iraqi people are being exposed to a great deal of violence and threats range from vehicle-borne bombings to displacement crisis, kidnappings and murders by Islamic State in Iraq and Al Sham (ISIS) and organized criminal gangs [28].

In Iraq, depression has been reported in few previous studies. Salman S, et al. (1995) observed that neuropsychiatric manifestation in SLE were present in 34.6% and depression is seen in 9.6% [29]. This is much less than the (42.6%) that found in our study, possible explanation of this difference maybe related to difference in sample size, data measurement, long periods of time between the two studies (23 years) and increasing stressful events, and probably due to the fact that we have concentrated more on depression than other neuropsychiatric manifestations.

The present study demonstrated that a high disease activity and longer disease duration were contributed significantly to poor sleep quality. This findings was agree with studies done byCosta DD, et al. (2005), Mirbagher L, et al. (2016), Chandrasekhara PK, et al. (2009), and Palagini L, et al. (2014) [22,24,26,30]. This result may show that living with a chronic disease has an impact on sleep quality.

The other predictors of poor sleep quality in the present study was a higherbody mass index was significantly associated with higher SLEDAI (P value=0.009) and this result was like Zonana NA, et al. (2008) (American study) which reported that obesity and metabolic syndrome were related with pain and functional status suggesting disease activity [31].

While other demographic variables including age, marital status, education, occupation, crowding index showed no significant association with sleep quality, depressive symptoms and disease activity (P value>0.05), the probable explanation that we studied only women and our sample was dominant for married and housewives and the majority of them their crowding index was less than 3. These results were agreeing to the studies done by Costa DD, et al. (2005), Chandrasekhara PK, et al. (2009) and Palagini L, et al. (2014) but disagree regarding age with Mirbagher L, et al. (2016) (Iranian study) which reported that old age was a determinant of poor sleep quality [22,24,26,30]. This difference may be because the majority (two thirds) of our sample were younger than 40 years and may be related to the difference in sample size.

Poor sleep quality among SLE women in the current study was (59%). Depression among SLE women in the current study was (42.6%). Higher scores of SLE disease activity index was associated with poor sleep quality and depressive symptoms. These results highlight the need to assess sleep quality in SLE population. The PSQI (a brief, self-administered instrument) could be used in a clinical setting to measure sleep complaints in SLE. Early depression screening for SLE patients for early management.

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