Lupus (2015) 0,
1–8
http://lup.sagepub.com
PAPER
Active disease is independently associated with more severe anxiety rather than depressive symptoms in patients with systemic lupus erythematosus SH Tay, PPM Cheung and A Mak Division of Rheumatology, University Medicine Cluster, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Objective: The inter-correlation between and co-existence of depression and anxiety may engender inconsistency in addressing the relationship between the severity of depression and disease activity of systemic lupus erythematosus (SLE). We aimed at identifying whether lupus disease activity is independently associated with depression and anxiety in lupus patients. Methods: Adult lupus patients were assessed for the severity of depressive and anxiety symptoms and lupus disease activity by using the Hospital Anxiety and Depression Scale (HADS) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), respectively. Age- and gender-matched healthy controls (HCs) were recruited for comparison. Prevalence and severity of depressive and anxiety symptoms were compared between lupus patients and HCs. Independent relationships between the severity of anxiety (HADS-Anxiety) and depressive (HADS-Depression) symptoms, and SLEDAI were studied with regression models. Results: In total, 110 lupus patients and 110 HCs were studied. Lupus patients had significantly higher HADS scores than HCs (10.82 6.5 vs 7.34 4.9, p < 0.001). Significantly more lupus patients had anxiety (40.9 vs 21.8%, p ¼ 0.002) and depressive symptoms (15.5 vs 6.4%, p ¼ 0.025) than HCs. Multiple linear regression analyses revealed that SLEDAI (b ¼ 0.160, p ¼ 0.016), calcineurin inhibitor non-use (b ¼ –1.929, p ¼ 0.041) and past cyclophosphamide non-use (b ¼ –1.603, p ¼ 0.039) independently predicted HADS-Anxiety amongst lupus patients even after adjusting for HADS-Depression. Conversely, SLEDAI (b ¼ 0.014, p ¼ 0.834) lost its significant univariate correlation with HADS-Depression after controlling for HADS-Anxiety and other covariates. Conclusion: Anxiety is more common in lupus patients than in HCs, and its severity is independently associated with more active SLE regardless of the presence or absence of concomitant depression. Lupus (2015) 0, 1–8. Key words: Mood; anxiety; depression; disease activity; SLE
Introduction Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune condition which potentially affects major organ systems including the central nervous system (CNS).1 Along with headache, cognitive dysfunction and cerebrovascular disease, depression and anxiety disorders are amongst the commonest CNS manifestations in patients
Correspondence to: Anselm Mak, National University of Singapore Division of Rheumatology, Department of Medicine, University Medicine Cluster, Level 10, #10-086, NUHS Tower Block, 1 E Kent Ridge Road, 119228 Singapore. Email: [email protected] Received 23 November 2014; accepted 21 May 2015
with SLE.2–5 In addition to the higher prevalence of depression and anxiety in lupus patients than in the general population,6,7 depression and anxiety entail substantial physical and psychosocial burden amongst patients with SLE.8,9 The negative physical and psychosocial impact of depression on lupus patients which has been commonly described included poor sleep quality10 and health-related quality of life (HRQoL),11–13 fatigue,14 fibromyalgia,15,16 sexual dysfunction,17 lupus-related organ damage18 and suicidal ideation.19 Lupusrelated organ damage, high cumulative glucocorticoids,20 bodily pain,21 fibromyalgia,22 fatigue21 and poor HRQoL20 have been shown to be associated with more severe anxiety symptoms amongst adult patients with SLE.
! The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at FLORIDA ATLANTIC UNIV on September 2, 2015
10.1177/0961203315591026
Anxiety, depression and disease activity in SLE SH Tay et al.
2
As a psychological reaction to the disease or a potential biological effect of proinflammatory cytokines and lupus-related autoantibodies on the CNS, it is logical to hypothesize that patients with active SLE are vulnerable to more severe depressive and anxiety symptoms. Although a number of studies supported the presence of a psychobiological relationship between lupus disease activity and depression,2,23,24 several studies have refuted such a relationship.25–29 While different characteristics amongst study populations, divergent assessment methods and tools for depression adopted in different studies may partly contribute to the inconsistency,30 one of the major caveats which has been overlooked in previous studies attempting to address disease activity and depression is the intrinsic inter-correlation between and the co-existence of depression and anxiety.20,31 Since depression and anxiety symptoms are closely related, anxiety symptoms should be considered as a potential confounder in the relationship between disease activity of SLE and depression. In this study, we aimed at (1) identifying the prevalence of symptoms of depression and anxiety in patients with SLE and confirming whether lupus patients had more severe depressive and anxiety symptoms than a group of age- and gendermatched healthy controls (HCs) and (2), exploring whether disease activity of SLE is an independent predictor for depression and anxiety after adjusting for confounders, including anxiety and depression, respectively, in multiple regression models. A point of note is, in order to enhance a more clear-cut assessment of the relationship between lupusrelated depression and/or anxiety and SLE Disease Activity Index (SLEDAI), patients with anxiety and/or depressive disorders prior to the diagnosis of SLE would be excluded. Such exclusion would help minimize the prevalence of anxiety and depression which was much less likely to be related to SLE.
Materials and methods Participants Patients who attended the lupus clinic of the National University Hospital (NUH), Singapore, and fulfilled the American College of Rheumatology (ACR) 1997 revised classification criteria for SLE32 were recruited for two ongoing projects aiming at studying cardiovascular disease and the relationship between vitamin D and cognitive function in patients with SLE (The vitamin
D/SLE study). HCs matched for age (4 years) and gender who were mainly nursing staff of the NUH medical clinic and their relatives without acute and/ or chronic medical conditions, and past or current psychiatric conditions, were recruited for comparison. Lupus patients with existing or past history of idiopathic or iatrogenic endocrinopathy, and cerebrovascular and cardiovascular diseases were excluded. Patients with history of anxiety and/or depression, as well as other major psychiatric conditions including schizophrenia, bipolar disorder, psychosis, dementia and autism prior to the diagnosis of SLE, and those who were or had been on psychotropic agents were also excluded. In order to test our hypothesis that SLE disease activity is related to psychiatric symptoms, we did not exclude lupus patients with any neuropsychiatric manifestations because their psychiatric symptoms were likely related to the inflammatory effect of SLE. Assessment of depression, anxiety and lupus disease activity and damage For all participants, the severity of anxiety and depressive symptoms was assessed by the Hospital Anxiety and Depression Scale (HADS).20,33 HADS is a formally validated, reliable and widely utilized psychological measure of medical patients with chronic illnesses in hospital and clinic settings.33 This is a 14-item questionnaire which comprises two seven-item subscales for measuring the severity of anxiety (HADS-Anxiety) and that of depression (HADS-Depression) and scores between 0 and 21 for each subscales. A score of 8 on either subscale is conventionally considered to define clinical anxiety and depression, with sensitivity and specificity above 80% and 90%, respectively.34 In patients with SLE, disease activity and damage were assessed by the SLEDAI and the Systemic Lupus International Collaborating clinics/ACR damage index (SLICC), respectively.35,36 All the demographics, clinical and laboratory data were collected via clinical interview and electronic medical record review. Written informed consent was obtained from all the participants prior to recruitment. Statistical analyses Values were expressed as meanstandard deviation (SD) unless otherwise specified. Normality of data was checked by the Kolmogorov-Smirnov test. Continuous variables between the SLE and HC groups were compared by using Student’s t-test or Mann-Whitney U test where appropriate while
Lupus Downloaded from lup.sagepub.com at FLORIDA ATLANTIC UNIV on September 2, 2015
Anxiety, depression and disease activity in SLE SH Tay et al.
3
comparisons between discrete variables were made by the 2 test. Univariate linear regression analysis was used to determine the relationships between the severity of depression (and severity of anxiety) and demographic as well as clinical variables. Multiple regression models were constructed to identify potential demographic and clinical variables which were independently associated with the severity of depression (and severity of anxiety). Only variables with p < 0.2 in the univariate analysis were entered into the multiple regression models by using the forced entry approach. To ascertain the validity of the regression equations, only independent variables of tolerance >0.4, which indicates minimal multi-collinearity, were accepted into the final regression model.37 All statistical analyses were performed with SPSS (SPSS version 22.0, Chicago, IL, USA). A twotailed p value of
1–8
http://lup.sagepub.com
PAPER
Active disease is independently associated with more severe anxiety rather than depressive symptoms in patients with systemic lupus erythematosus SH Tay, PPM Cheung and A Mak Division of Rheumatology, University Medicine Cluster, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Objective: The inter-correlation between and co-existence of depression and anxiety may engender inconsistency in addressing the relationship between the severity of depression and disease activity of systemic lupus erythematosus (SLE). We aimed at identifying whether lupus disease activity is independently associated with depression and anxiety in lupus patients. Methods: Adult lupus patients were assessed for the severity of depressive and anxiety symptoms and lupus disease activity by using the Hospital Anxiety and Depression Scale (HADS) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), respectively. Age- and gender-matched healthy controls (HCs) were recruited for comparison. Prevalence and severity of depressive and anxiety symptoms were compared between lupus patients and HCs. Independent relationships between the severity of anxiety (HADS-Anxiety) and depressive (HADS-Depression) symptoms, and SLEDAI were studied with regression models. Results: In total, 110 lupus patients and 110 HCs were studied. Lupus patients had significantly higher HADS scores than HCs (10.82 6.5 vs 7.34 4.9, p < 0.001). Significantly more lupus patients had anxiety (40.9 vs 21.8%, p ¼ 0.002) and depressive symptoms (15.5 vs 6.4%, p ¼ 0.025) than HCs. Multiple linear regression analyses revealed that SLEDAI (b ¼ 0.160, p ¼ 0.016), calcineurin inhibitor non-use (b ¼ –1.929, p ¼ 0.041) and past cyclophosphamide non-use (b ¼ –1.603, p ¼ 0.039) independently predicted HADS-Anxiety amongst lupus patients even after adjusting for HADS-Depression. Conversely, SLEDAI (b ¼ 0.014, p ¼ 0.834) lost its significant univariate correlation with HADS-Depression after controlling for HADS-Anxiety and other covariates. Conclusion: Anxiety is more common in lupus patients than in HCs, and its severity is independently associated with more active SLE regardless of the presence or absence of concomitant depression. Lupus (2015) 0, 1–8. Key words: Mood; anxiety; depression; disease activity; SLE
Introduction Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune condition which potentially affects major organ systems including the central nervous system (CNS).1 Along with headache, cognitive dysfunction and cerebrovascular disease, depression and anxiety disorders are amongst the commonest CNS manifestations in patients
Correspondence to: Anselm Mak, National University of Singapore Division of Rheumatology, Department of Medicine, University Medicine Cluster, Level 10, #10-086, NUHS Tower Block, 1 E Kent Ridge Road, 119228 Singapore. Email: [email protected] Received 23 November 2014; accepted 21 May 2015
with SLE.2–5 In addition to the higher prevalence of depression and anxiety in lupus patients than in the general population,6,7 depression and anxiety entail substantial physical and psychosocial burden amongst patients with SLE.8,9 The negative physical and psychosocial impact of depression on lupus patients which has been commonly described included poor sleep quality10 and health-related quality of life (HRQoL),11–13 fatigue,14 fibromyalgia,15,16 sexual dysfunction,17 lupus-related organ damage18 and suicidal ideation.19 Lupusrelated organ damage, high cumulative glucocorticoids,20 bodily pain,21 fibromyalgia,22 fatigue21 and poor HRQoL20 have been shown to be associated with more severe anxiety symptoms amongst adult patients with SLE.
! The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at FLORIDA ATLANTIC UNIV on September 2, 2015
10.1177/0961203315591026
Anxiety, depression and disease activity in SLE SH Tay et al.
2
As a psychological reaction to the disease or a potential biological effect of proinflammatory cytokines and lupus-related autoantibodies on the CNS, it is logical to hypothesize that patients with active SLE are vulnerable to more severe depressive and anxiety symptoms. Although a number of studies supported the presence of a psychobiological relationship between lupus disease activity and depression,2,23,24 several studies have refuted such a relationship.25–29 While different characteristics amongst study populations, divergent assessment methods and tools for depression adopted in different studies may partly contribute to the inconsistency,30 one of the major caveats which has been overlooked in previous studies attempting to address disease activity and depression is the intrinsic inter-correlation between and the co-existence of depression and anxiety.20,31 Since depression and anxiety symptoms are closely related, anxiety symptoms should be considered as a potential confounder in the relationship between disease activity of SLE and depression. In this study, we aimed at (1) identifying the prevalence of symptoms of depression and anxiety in patients with SLE and confirming whether lupus patients had more severe depressive and anxiety symptoms than a group of age- and gendermatched healthy controls (HCs) and (2), exploring whether disease activity of SLE is an independent predictor for depression and anxiety after adjusting for confounders, including anxiety and depression, respectively, in multiple regression models. A point of note is, in order to enhance a more clear-cut assessment of the relationship between lupusrelated depression and/or anxiety and SLE Disease Activity Index (SLEDAI), patients with anxiety and/or depressive disorders prior to the diagnosis of SLE would be excluded. Such exclusion would help minimize the prevalence of anxiety and depression which was much less likely to be related to SLE.
Materials and methods Participants Patients who attended the lupus clinic of the National University Hospital (NUH), Singapore, and fulfilled the American College of Rheumatology (ACR) 1997 revised classification criteria for SLE32 were recruited for two ongoing projects aiming at studying cardiovascular disease and the relationship between vitamin D and cognitive function in patients with SLE (The vitamin
D/SLE study). HCs matched for age (4 years) and gender who were mainly nursing staff of the NUH medical clinic and their relatives without acute and/ or chronic medical conditions, and past or current psychiatric conditions, were recruited for comparison. Lupus patients with existing or past history of idiopathic or iatrogenic endocrinopathy, and cerebrovascular and cardiovascular diseases were excluded. Patients with history of anxiety and/or depression, as well as other major psychiatric conditions including schizophrenia, bipolar disorder, psychosis, dementia and autism prior to the diagnosis of SLE, and those who were or had been on psychotropic agents were also excluded. In order to test our hypothesis that SLE disease activity is related to psychiatric symptoms, we did not exclude lupus patients with any neuropsychiatric manifestations because their psychiatric symptoms were likely related to the inflammatory effect of SLE. Assessment of depression, anxiety and lupus disease activity and damage For all participants, the severity of anxiety and depressive symptoms was assessed by the Hospital Anxiety and Depression Scale (HADS).20,33 HADS is a formally validated, reliable and widely utilized psychological measure of medical patients with chronic illnesses in hospital and clinic settings.33 This is a 14-item questionnaire which comprises two seven-item subscales for measuring the severity of anxiety (HADS-Anxiety) and that of depression (HADS-Depression) and scores between 0 and 21 for each subscales. A score of 8 on either subscale is conventionally considered to define clinical anxiety and depression, with sensitivity and specificity above 80% and 90%, respectively.34 In patients with SLE, disease activity and damage were assessed by the SLEDAI and the Systemic Lupus International Collaborating clinics/ACR damage index (SLICC), respectively.35,36 All the demographics, clinical and laboratory data were collected via clinical interview and electronic medical record review. Written informed consent was obtained from all the participants prior to recruitment. Statistical analyses Values were expressed as meanstandard deviation (SD) unless otherwise specified. Normality of data was checked by the Kolmogorov-Smirnov test. Continuous variables between the SLE and HC groups were compared by using Student’s t-test or Mann-Whitney U test where appropriate while
Lupus Downloaded from lup.sagepub.com at FLORIDA ATLANTIC UNIV on September 2, 2015
Anxiety, depression and disease activity in SLE SH Tay et al.
3
comparisons between discrete variables were made by the 2 test. Univariate linear regression analysis was used to determine the relationships between the severity of depression (and severity of anxiety) and demographic as well as clinical variables. Multiple regression models were constructed to identify potential demographic and clinical variables which were independently associated with the severity of depression (and severity of anxiety). Only variables with p < 0.2 in the univariate analysis were entered into the multiple regression models by using the forced entry approach. To ascertain the validity of the regression equations, only independent variables of tolerance >0.4, which indicates minimal multi-collinearity, were accepted into the final regression model.37 All statistical analyses were performed with SPSS (SPSS version 22.0, Chicago, IL, USA). A twotailed p value of
