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Mood, anxiety and personality disorders in patients with systemic lupus erythematosus
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Comprehensive Psychiatry 54 (2013) 341 – 345 www.elsevier.com/locate/comppsych
Mood, anxiety and personality disorders in patients with systemic lupus erythematosus Faruk Uguz a,⁎, Adem Kucuk b , Erdinc Cicek c , Fatih Kayhan d , Recep Tunc e a Department of Psychiatry, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey Department of Rheumatology, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey c Department of Psychiatry, Urfa State Hospital, Urfa, Turkey d Department of Psychiatry, Beysehir State Hospital, Konya, Turkey e Department of Rheumatology, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey
b
Abstract Objective: This study presents the current prevalence of mood, anxiety and personality disorders and factors associated with the existence of psychiatric disorders in patients with systemic lupus erythematosus (SLE). Methods: The study sample was comprised of 45 patients with SLE and 60 control subjects. Mood and anxiety disorders were ascertained by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition/Clinical Version. Personality disorders were diagnosed with the Structured Clinical Interview for DSM, Revised Third Edition Personality Disorders. The disease activity was assessed with SLE Disease Activity Index. Results: Of the 45 patients, 21 (46.7%) had at least one mood or anxiety disorder, and 16 (35.6%) had at least one personality disorder. The most common Axis I and Axis II diagnoses in the patient group were major depression (22.2%) and obsessive–compulsive personality disorder (20.0%), respectively. Specifically, major depression, generalized anxiety disorder and obsessive–compulsive personality disorder were more prevalent in the SLE group compared to the control group. The existence of Axis I disorders was associated with a more severe disease activity of SLE. Conclusion: Mood and anxiety disorders, particularly major depression and generalized anxiety disorder, are frequently observed in patients with SLE. © 2013 Elsevier Inc. All rights reserved.
1. Introductıon Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many organ systems (eg., neurological, hematological, cardiovascular, and kidney). Its clinical outcome is highly variable, ranging from permanent remission to death [1,2]. A prospective study in 7 European countries indicated that the 10-year mortality rate of SLE was 6.8% [2]. The prevalence rate of SLE in the general population is reported to be between 1 and 8 per 10,000 people. Although SLE can emerge at any age, the mean age at the
⁎ Corresponding author. Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Psikiyatri Anabilim Dalı, Akyokuş 42080, Konya, Turkey. Tel.: +90 332 223 6306. E-mail address: [email protected] (F. Uguz). 0010-440X/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.comppsych.2012.10.003
onset of symptoms is reported to be 29 years [2–4]. The disease is experienced more frequently by female subjects [2]. While the specific etiology of SLE still remains unclear, it seems to be a rheumatological disease resulting from interactions among various factors (e.g., genetic susceptibility, infections, hormonal, environmental and immunological factors) [2,5–7]. SLE not only exhibits a wide range of physical manifestations of the disease but can also be related to neuropsychiatric problems. These neuropsychiatric problems include anxiety or mood disorders in addition to many symptoms associated with central nervous system and peripheral nervous system [8,9]. Nery et al. [10] suggested that approximately 3/4 of female patients with SLE have at least one psychiatric disorder during their lifetime. Mood disorders appear to be more frequent compared to anxiety disorders [10–12]. However, the number of studies based on a structured clinical interview is inadequate. Moreover, most
342
F. Uguz et al. / Comprehensive Psychiatry 54 (2013) 341–345
of the available studies do not include a comparison of patients with SLE with healthy controls in terms of psychiatric diagnoses. Additionally, to our knowledge, there is no published study examining Axis II disorders in patients with SLE. The objectives of this study were to investigate the current prevalence of mood, anxiety and personality disorders in SLE patients and to examine the factors associated with the existence of a mood or anxiety disorder in this patient group.
2. Methods A total of 45 consecutive patients with SLE who were admitted to the Rheumatology Outpatient Clinic of Meram Faculty of Medicine of Necmettin Erbakan University were recruited to this study. All patients were admitted to the clinic for routine follow-up visits of SLE. Illiteracy, cognitive incompetence, which can make psychiatric interview difficult, a history of schizophrenia or related psychotic disorders, a history of neurological disease or severe neurological manifestations of SLE (e.g., cerebrovascular disease, movement disorder, seizure, polyneuropathy and cranial neuropathy), concomitant serious medical illnesses such as uncontrolled endocrine abnormalities, cardiovascular or pulmonary disease, and usage of psychotrophic medication within the last 4 weeks were the exclusion criteria. The study sample also included a control group which was composed of 60 hospital personnel and their relatives who were matched for the sociodemographic characteristics of the SLE patients. They had the same exclusion criteria as those of the patient group. The diagnosis of SLE was determined according to the American College of Rheumatology (ACR) revised criteria for SLE [13]. Mood and anxiety disorders were ascertained by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition/Clinical Version (SCID-I/CV) [14]. Personality disorders were diagnosed with the Structured Clinical Interview for DSM, Revised Third Edition Personality Disorders (SCID-II) [15]. To assess the disease activity of SLE, the SLE Disease Activity Index (SLEDAI) was used in which higher scores reflect more severity manifestation of SLE [16]. The onset time of psychiatric diagnoses was established from the patients' reports. Initially, the objectives and procedures of the present study were explained to all participants, and written informed consent was obtained from them. After rheumatological assessments and recording the sociodemographical features, the patients were referred to the psychiatry outpatient clinic of the same hospital. Psychiatric interviews were carried out by psychiatrists with at least 4 years of experience on psychiatric disorders and diagnostic instruments. The psychiatrists were also blinded to the rheumatological evaluations of the patients.
Statistical analyses were performed with SPSS 13.0 for Windows (Statistical Package for the Social Sciences, Chicago, IL). For comparisons between the study groups t test was used for continuous variables and χ 2 test or Fisher's exact test for categorical variables. All significant levels were 2-tailed and set at the level of 0.05.
3. Results The mean age of the study sample (n = 105) was 39.92 ± 8.59 years. The participants were mostly female (n = 96, 91.4%), married (n = 89, 84.8%), unemployed (n = 92, 87.6%) and primary school graduates (n = 76, 87.6%). The disease duration was 66.67 ± 43.26 months in the patient group. All of the patients were taking at least one medication for SLE. These medications were prednisone in 32 (71.1%) subjects, chloroquine in 28 (62.2%) subjects, cyclophosphamide in 3 (6.7%) subjects, and azathioprine in 2 (4.4%) subjects. There was no significant difference between the patients and control groups in terms of sociodemographic characteristics (Table 1). Table 2 shows the current prevlence rate of mood, anxiety and personality disorders in patients with SLE and the control subjects. Twenty-one (46.7%) subjects with SLE met the criteria of at least one mood or anxiety disorder according to SCID-I. Among the patients, the current prevalence of any mood disorder and any anxiety disorder was 24.6% and 28.9%, respectively. Specifically, the most common psychiatric disorders were major depression (n = 10, 22.2%) and generalized anxiety disorder (n = 7, 15.6%). These two diagnoses were also significantly more prevalent in the patient group compared to the control group. We found no significant difference between the groups with respect to prevalence of dysthymic disorder, panic disorder, obsessive–compulsive disorder, specific phobia, social phobia, and posttraumatic stress disorder. None of the participants
Table 1 Sociodemographic characteristics of the study sample. Patient group Control group P value n = 45 n = 60 Age, mean ± SD, years Gender, n (%) Female Education, n (%) Primary school Secondary school University Employment status, n (%) Unemployed Marital status, n (%) Single Married Widowed, divorced or seperated a b c
t test. Fisher Exact Test. χ 2 Test.
39.24 ± 9.91
38.68 ± 7.54
42 (93.3)
54 (96.0)
35 (77.8) 6 (13.3) 4 (8.9)
41 (68.3) 12 (20.0) 7 (11.7)
40 (88.9)
52 (86.7)
0.742 a 0.729 b 0.556 c
0.775 b 0.939 c 5 (11.1) 39 (86.7) 1 (2.2)
7 (11.7) 51 (85.0) 1 (3.3)
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Table 2 Current prevalence rate of mood, anxiety and personality disorders in the study groups. Psychiatric disorders, n (%)
Patient group n = 45
Control group n = 60
Odds ratio (95% Cl)
P value a
Any mood disorder Major depression Dysthymic disorder Bipolar disorder Any anxiety disorder Panic disorder Obsessive–compulsive disorder Social phobia Spesific phobia Posttraumatic stress disorder Generalized anxiety disorder Any mood or anxiety disorder Any axis II disorder Avoidant Dependent Obsessive–compulsive Passive–aggressive Paranoid Schizotypal Schizoid Histrionic Borderline Narcissistic Antisocial
11 (24.4) 10 (22.2) 2 (4.4) (0) 13 (28.9) 3 (6.7) 3 (6.7) 4 (8.9) 3 (6.7) 1 (2.2) 7 (15.6) 21 (46.7) 16 (35.6) 4 (8.9) 3 (6.7) 9 (20.0) 2 (4.4) 0 (0) 0 (0) 0 (0) 1 (2.2) 1 (2.2) 1 (2.2) 0 (0)
5 (8.3) 3 (5.0) 2 (3.3) 0 (0) 7 (11.7) 2 (3.3) 1 (1.7) 3 (5.0) 3 (5.0) 1 (1.7) 2 (3.3) 10 (16.7) 7 (11.7) 2 (3.3) 2 (3.3) 1 (1.7) 1 (1.7) 0 (0) 0 (0) 0 (0) 1 (1.7) 1 (1.7) 1 (1.7) 0 (0)
2.93 (1.09–7.83) 4.44 (1.29–15.22) 1.33 (0.19–9.11) – 2.47 (1.08–5.70) 2.00 (0.35–11.47) 4.02 (0.43–37.20) 1.78 (0.42–7.55) 1.53 (0.28–6.30) 1.33 (0.08–20.74) 4.67 (1.02–21.40) 2.80 (1.47–5.34) 3.05 (1.37–6.78) 2.66 (0.51–13.92) 2.00 (0.35–11.47) 12.00 (1.57–91.32) 2.66 (0.25–28.50) – – – 1.33 (0.08–20.74) 2.00 (0.35–11.47) 1.33 (0.08–20.74) –
0.029 0.014 1.000 – 0.043 0.649 0.311 0.458 1.000 1.000 0.036 0.001 0.004 0.398 0.649 0.002 0.575 – – – 1.000 1.000 1.000 –
a
Fisher's exact test.
had diagnosis of bipolar disorder (Table 2). According to reports of the participants, psychiatric disturbances emerged after the onset of the disease in 71.5% (n = 15) of the patients with a mood or anxiety disorder. Sixteen patients with SLE had any personality disorder. Specifically, obsessive–compulsive personality disorder (n = 9, 20.0%) and avoidant personality disorder (n = 4, 8.9%) were most frequently determined in this group. Compared to the control group, the prevalence rate of any Axis II diagnosis and obsessive–compulsive personality disorder was significantly higher in the SLE group. Schizoid, schizotipal, paranoid and antisocial personality disorders were not identified in the two study groups (Table 2). SLE patients with and without any Axis I psychiatric disorder had similar age (t = −1.18, P = 0.169), duration of illness (t = −1.06, P = 0.296), gender (Fisher's exact test, P = 0.592), educational level (χ 2 = 0.832, P = 0.660), employment status (Fisher's exact test, P = 0.652), marital status (χ 2 = 1.24, P = 0.539), and the existence of any Axis II diagnosis (Fisher's exact test, P = 0.765). The mean score of SLEDAI in SLE patients with and without any Axis I psychiatric disorder was 5.81 ± 2.20 and 3.50 ± 3.41, respectively. The difference was statistically significant (t = −2.265, P = 0.011).
4. Dıscussıon In our sample, while any mood or anxiety disorder was determined in nearly half of subjects with SLE, the rate was only 16.7% in the control subjects. The prevalence rate
established in the SLE patients was found to be higher than the estimated prevalence of the current Axis I psychiatric disorders in the general population [17–19]. Several studies including different interview methods suggest that 18.2%– 59.2% of subjects with SLE have concurrently at least one psychiatric disorder, which is consistent with our findings. In this study, the overall current prevalence of anxiety and mood disorders was significantly higher in patients with SLE than the control subjects. We have no studies comparing any mood disorder between patient and control groups in the published literature. Moreover, the number of noncomparative studies is very few. Nery et al. [10] using SCID found the prevalence rate of any mood disorder to be 26.8%, which is similar to our rate. However, they reported a higher prevalence rate (46.5%) of any anxiety disorder compared to those of the present study (28.9%). This discrepancy could be due to a significant difference of prevalence rate of specific phobia between these studies (25.4% vs 6.7%). Major depression was the most prevalent Axis I disorder with a rate of 22.2% in the SLE sample. Although Hugo et al. [20] reported a much lower rate of major depression at 1.1%, two recent studies show results consistent with those of the present study [10,11]. Bachen et al. [21] who compared the lifetime prevalence rate of psychiatric disorders in SLE subjects and the general population derived from a sample of the National Comorbidity Survey Replication, revealed a statistically higher prevalence rate in SLE patients. Nevertheless, they reported that generalized anxiety disorder was less common in SLE patients compared with the national estimates. They explained this unexpected finding as a possiblity that the
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high rate of major depression in their study made it difficult to assess the lifetime generalized anxiety disorder. In addition, the prevalence of generalized anxiety disorder in our sample seems to be relatively high compared with previous studies on SLE patients (15.6% vs 2.4%–9.9%) [10,11]. This may have resulted from underlying differences among communities in which the studies were conducted. Few studies have examined factors associated with psychiatric disturbances in patients with SLE. The consistent scientific data available suggest that the duration of SLE is unrelated to psychiatric disorders [11,21,22]. In contrast, a connection between the disease activity and psychiatric disorders is relatively conraversial in the literature. Nery et al. [22] reported that SLE patients with more active disease have a greater risk of the occurrence of major depression. However, they found in another study that SLE patients with or without a lifetime history of a psychiatric diagnosis had similar scores of SLEDAI [10]. Jarpa et al. [11] found that neither major depression nor a DSM-IV diagnosis was related to lupus activity. On the other hand, Bachen et al. [21] revealed that the disease activity was associated with a lifetime history of a mood or anxiety disorder. In addition, according to results of the study by Segui et al. [23], SLE patients with clinically inactive disease showed lower psychological distress. In our sample, the disease activity alone associated with the presence of current mood or anxiety disorder within the evaluated sociodemographic and clinical variables. The present study also suggested that personality disorders appear to be unrelated to mood anxiety disorders in SLE patients, which is to our knowledge, the first report in the literature on this topic. We found the prevalence rate of any Axis II disorder as 35.6% in patients with SLE and 11.7% in the control subjects. Epidemiological studies have reported 5.3%– 14.5% prevalence rates of any personality disorder in the general population [19,24,25]. The current results suggest that a considerable number of subjects with SLE attending a rheumatological outpatient clinic have Axis II psychiatric disorders. In our sample, obsessive–compulsive personality disorder was an Axis II diagnosis found to be higher in SLE patients compared to the control subjects. Further prospective studies should be carried out to confirm our results and examine whether these findings have any clinical importance in SLE. Being of a cross-sectional nature, the present study is limited by an insufficiency to indicate whether the evaluated Axis I or Axis II psychiatric disorders have causal relevance to SLE. It is unclear whether Axis I disorders are a contributing factor that may exacerbate of SLE, or is secondary to the development of a more active SLE [23,26]. When our results, including the onset time of mood or anxiety disorders are considered, these disorders seem to be secondary to the severity of lupus rather than play a primary role in the exacerbation of SLE. However, it is unclear whether there is a biological basis of this condition or psychological reaction to the severity of SLE. Moreover, the onset time method of mood
or anxiety disorder in this study is a restrictive factor in interpretation of our results. The relatively small sample size is another limitation of the current study. In addition, we did not examine any family history of mental disorders. In conclusion, results of the present study suggest that patients with SLE who were admitted to a rheumatology outpatient clinic have frequent psychiatric disturbances. Further controlled studies with larger sample sizes should be conducted to investigate long-term effects of psychiatric disorders and their treatments in the course of SLE. References [1] Cervera R, Kamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period. A comparison of early and late manifestations in a cohort of 1000 patients. Medicine 2003;82:299-308. [2] O'Neill S, Cervera R. Systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2010;24:841-55. [3] Cervera R, Khamashta MA, Hughes GRV. The Euro-lupus project: epidemiology of systemic lupus erythematosus in Europe. Lupus 2009; 18:869-74. [4] Osio-Salido E, Manapat-Reyes H. Epidemiology of systemic lupus erythematosus in Asia. Lupus 2010;19:1365-73. [5] Davis LS, Hutcheson J, Mohan C. The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus. J Interferon Cytokine Res 2011;31:781-9. [6] Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol 2003;56:481-90. [7] Chai HC, Phipps ME, Chua KH. Genetic risk factors of systemic lupus erythematosus in the Malaysian population: a minireview. Clin Dev Immunol 2012 (In press). [8] Bruns A, Meyer O. Neuropsychiatric manifestations of systemic lupus erythematosus. Joint Bone Spine 2006;73:639-45. [9] Ainiala H, Loukkola J, Peltola J, Korpela M, Hietaharju A. The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology 2001;57:496-500. [10] Nery FG, Borba EF, Viana VS, Hatch JP, Soares JC, Bonfa E, et al. Prevalence of depressive and anxiety disorders in systemic lupus erthematosus and their association with anti-ribosomal P antibodies. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:695-700. [11] Jarpa E, Babul M, Calderon J, Gonzalez M, Martinez ME, BravoZehnder M, et al. Common mental disorders and psychosocial distress in systemic lupus erythematosus are not associated with disease activity. Lupus 2011;20:58-66. [12] Hawro T, Krupinska-Kun M, Rabe-Jedrzejowska A, Robak E, Bogaczewicz J, Wozniacka A. Rheumatol Int 2011;10:1387-91. [13] Hochberg MC. Updating the American College of Rheumatology revised criteria for the calassification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725. [14] First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical ınterview for DSM-IV clinical version (SCID-I/CV). Washington, DC: American Psychiatric Press; 1997. [15] Spitzer RL, Williams JBW, Gibbon M, First M. Manual for the structured clinical ınterview for DSM-III-R personality disorders. Washington D.C.: American Psychiatric Press; 1990 [16] Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. Arthritis Rheum 1992;35:630-40. [17] Vicente B, Kohn R, Rioseco P, Saldivia S, Baker C, Torres S. Population prevalence of psychiatric disorders in Chile: 6-month and 1-month rates. Br J Psychiatry 2004;84:299-305. [18] Bijl RV, Ravelli A, van Zessen G. Prevalence of psychiatric disorder in the general population: results of the Netherlands Mental Health
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Survey and Incidence Study (NEMESIS). Soc Psychiatry Psychiatr Epidemiol 1998;33:587-95. Andrews G, Henderson S, Hall W. Prevalence, comorbidity, disability and service utilisation. Overview of the Australian National Mental Health Survey. Br J Psychiatry 2001;178:145-53. Hugo FJ, Halland AM, Spangenberg JJ, Whitelaw DA, Rickman RC, Hewlett RH, et al. DSM-III-R classification of psychiatric symptoms in systemic lupus erythematosus. Psychosomatics 1996;37:262-9. Bachen EA, Chesney MA, Criswell LA. Prevalence of mood and anxiety disorders in women with systemic lupus erythematosus. Arthritis Rheum 2009;61:822-9. Nery FG, Borba EF, Hatch JP, Soares JC, Bonfa E, Neto FL. Major depressive disorder and disease activity in systemic lupus erythematosus. Compr Psychiatry 2007;48:14-9.
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[23] Segui J, Ramos-Casals MR, Garcia-Carrasco M, de Flores T, Cervera R, Valdes M, et al. Psychiatric and psychosocial disorders in patients with systemic lupus erythematosus: a longitidunal study of active and inactive stages of the disease. Lupus 2000;9:584-8. [24] Grant BF, Hasin DS, Stinson FS, Dawson DA, Chou SP, Ruan WJ, et al. Prevalence, correlates, and disability of personality disorders in the United States: results from the National Epidemiologic Survey on alcohol and related conditions. J Clin Psychiatry 2004;65:948-58. [25] Lenzenweger MF, Lane MC, Loranger AW, Kessler RC. DSM-IV personality disorders in the National Comorbidity Survey Replication. Biol Psychiatry 2007;62:553-64. [26] Carr FN, Nicassio PM, Ishimori ML, Moldovan I, Katsaros E, Torralba K, et al. Depression predicts self-reported disease activity in systemic lupus erythematosus. Lupus 2011;20:80-4.
Comprehensive Psychiatry 54 (2013) 341 – 345 www.elsevier.com/locate/comppsych
Mood, anxiety and personality disorders in patients with systemic lupus erythematosus Faruk Uguz a,⁎, Adem Kucuk b , Erdinc Cicek c , Fatih Kayhan d , Recep Tunc e a Department of Psychiatry, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey Department of Rheumatology, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey c Department of Psychiatry, Urfa State Hospital, Urfa, Turkey d Department of Psychiatry, Beysehir State Hospital, Konya, Turkey e Department of Rheumatology, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey
b
Abstract Objective: This study presents the current prevalence of mood, anxiety and personality disorders and factors associated with the existence of psychiatric disorders in patients with systemic lupus erythematosus (SLE). Methods: The study sample was comprised of 45 patients with SLE and 60 control subjects. Mood and anxiety disorders were ascertained by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition/Clinical Version. Personality disorders were diagnosed with the Structured Clinical Interview for DSM, Revised Third Edition Personality Disorders. The disease activity was assessed with SLE Disease Activity Index. Results: Of the 45 patients, 21 (46.7%) had at least one mood or anxiety disorder, and 16 (35.6%) had at least one personality disorder. The most common Axis I and Axis II diagnoses in the patient group were major depression (22.2%) and obsessive–compulsive personality disorder (20.0%), respectively. Specifically, major depression, generalized anxiety disorder and obsessive–compulsive personality disorder were more prevalent in the SLE group compared to the control group. The existence of Axis I disorders was associated with a more severe disease activity of SLE. Conclusion: Mood and anxiety disorders, particularly major depression and generalized anxiety disorder, are frequently observed in patients with SLE. © 2013 Elsevier Inc. All rights reserved.
1. Introductıon Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many organ systems (eg., neurological, hematological, cardiovascular, and kidney). Its clinical outcome is highly variable, ranging from permanent remission to death [1,2]. A prospective study in 7 European countries indicated that the 10-year mortality rate of SLE was 6.8% [2]. The prevalence rate of SLE in the general population is reported to be between 1 and 8 per 10,000 people. Although SLE can emerge at any age, the mean age at the
⁎ Corresponding author. Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Psikiyatri Anabilim Dalı, Akyokuş 42080, Konya, Turkey. Tel.: +90 332 223 6306. E-mail address: [email protected] (F. Uguz). 0010-440X/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.comppsych.2012.10.003
onset of symptoms is reported to be 29 years [2–4]. The disease is experienced more frequently by female subjects [2]. While the specific etiology of SLE still remains unclear, it seems to be a rheumatological disease resulting from interactions among various factors (e.g., genetic susceptibility, infections, hormonal, environmental and immunological factors) [2,5–7]. SLE not only exhibits a wide range of physical manifestations of the disease but can also be related to neuropsychiatric problems. These neuropsychiatric problems include anxiety or mood disorders in addition to many symptoms associated with central nervous system and peripheral nervous system [8,9]. Nery et al. [10] suggested that approximately 3/4 of female patients with SLE have at least one psychiatric disorder during their lifetime. Mood disorders appear to be more frequent compared to anxiety disorders [10–12]. However, the number of studies based on a structured clinical interview is inadequate. Moreover, most
342
F. Uguz et al. / Comprehensive Psychiatry 54 (2013) 341–345
of the available studies do not include a comparison of patients with SLE with healthy controls in terms of psychiatric diagnoses. Additionally, to our knowledge, there is no published study examining Axis II disorders in patients with SLE. The objectives of this study were to investigate the current prevalence of mood, anxiety and personality disorders in SLE patients and to examine the factors associated with the existence of a mood or anxiety disorder in this patient group.
2. Methods A total of 45 consecutive patients with SLE who were admitted to the Rheumatology Outpatient Clinic of Meram Faculty of Medicine of Necmettin Erbakan University were recruited to this study. All patients were admitted to the clinic for routine follow-up visits of SLE. Illiteracy, cognitive incompetence, which can make psychiatric interview difficult, a history of schizophrenia or related psychotic disorders, a history of neurological disease or severe neurological manifestations of SLE (e.g., cerebrovascular disease, movement disorder, seizure, polyneuropathy and cranial neuropathy), concomitant serious medical illnesses such as uncontrolled endocrine abnormalities, cardiovascular or pulmonary disease, and usage of psychotrophic medication within the last 4 weeks were the exclusion criteria. The study sample also included a control group which was composed of 60 hospital personnel and their relatives who were matched for the sociodemographic characteristics of the SLE patients. They had the same exclusion criteria as those of the patient group. The diagnosis of SLE was determined according to the American College of Rheumatology (ACR) revised criteria for SLE [13]. Mood and anxiety disorders were ascertained by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition/Clinical Version (SCID-I/CV) [14]. Personality disorders were diagnosed with the Structured Clinical Interview for DSM, Revised Third Edition Personality Disorders (SCID-II) [15]. To assess the disease activity of SLE, the SLE Disease Activity Index (SLEDAI) was used in which higher scores reflect more severity manifestation of SLE [16]. The onset time of psychiatric diagnoses was established from the patients' reports. Initially, the objectives and procedures of the present study were explained to all participants, and written informed consent was obtained from them. After rheumatological assessments and recording the sociodemographical features, the patients were referred to the psychiatry outpatient clinic of the same hospital. Psychiatric interviews were carried out by psychiatrists with at least 4 years of experience on psychiatric disorders and diagnostic instruments. The psychiatrists were also blinded to the rheumatological evaluations of the patients.
Statistical analyses were performed with SPSS 13.0 for Windows (Statistical Package for the Social Sciences, Chicago, IL). For comparisons between the study groups t test was used for continuous variables and χ 2 test or Fisher's exact test for categorical variables. All significant levels were 2-tailed and set at the level of 0.05.
3. Results The mean age of the study sample (n = 105) was 39.92 ± 8.59 years. The participants were mostly female (n = 96, 91.4%), married (n = 89, 84.8%), unemployed (n = 92, 87.6%) and primary school graduates (n = 76, 87.6%). The disease duration was 66.67 ± 43.26 months in the patient group. All of the patients were taking at least one medication for SLE. These medications were prednisone in 32 (71.1%) subjects, chloroquine in 28 (62.2%) subjects, cyclophosphamide in 3 (6.7%) subjects, and azathioprine in 2 (4.4%) subjects. There was no significant difference between the patients and control groups in terms of sociodemographic characteristics (Table 1). Table 2 shows the current prevlence rate of mood, anxiety and personality disorders in patients with SLE and the control subjects. Twenty-one (46.7%) subjects with SLE met the criteria of at least one mood or anxiety disorder according to SCID-I. Among the patients, the current prevalence of any mood disorder and any anxiety disorder was 24.6% and 28.9%, respectively. Specifically, the most common psychiatric disorders were major depression (n = 10, 22.2%) and generalized anxiety disorder (n = 7, 15.6%). These two diagnoses were also significantly more prevalent in the patient group compared to the control group. We found no significant difference between the groups with respect to prevalence of dysthymic disorder, panic disorder, obsessive–compulsive disorder, specific phobia, social phobia, and posttraumatic stress disorder. None of the participants
Table 1 Sociodemographic characteristics of the study sample. Patient group Control group P value n = 45 n = 60 Age, mean ± SD, years Gender, n (%) Female Education, n (%) Primary school Secondary school University Employment status, n (%) Unemployed Marital status, n (%) Single Married Widowed, divorced or seperated a b c
t test. Fisher Exact Test. χ 2 Test.
39.24 ± 9.91
38.68 ± 7.54
42 (93.3)
54 (96.0)
35 (77.8) 6 (13.3) 4 (8.9)
41 (68.3) 12 (20.0) 7 (11.7)
40 (88.9)
52 (86.7)
0.742 a 0.729 b 0.556 c
0.775 b 0.939 c 5 (11.1) 39 (86.7) 1 (2.2)
7 (11.7) 51 (85.0) 1 (3.3)
F. Uguz et al. / Comprehensive Psychiatry 54 (2013) 341–345
343
Table 2 Current prevalence rate of mood, anxiety and personality disorders in the study groups. Psychiatric disorders, n (%)
Patient group n = 45
Control group n = 60
Odds ratio (95% Cl)
P value a
Any mood disorder Major depression Dysthymic disorder Bipolar disorder Any anxiety disorder Panic disorder Obsessive–compulsive disorder Social phobia Spesific phobia Posttraumatic stress disorder Generalized anxiety disorder Any mood or anxiety disorder Any axis II disorder Avoidant Dependent Obsessive–compulsive Passive–aggressive Paranoid Schizotypal Schizoid Histrionic Borderline Narcissistic Antisocial
11 (24.4) 10 (22.2) 2 (4.4) (0) 13 (28.9) 3 (6.7) 3 (6.7) 4 (8.9) 3 (6.7) 1 (2.2) 7 (15.6) 21 (46.7) 16 (35.6) 4 (8.9) 3 (6.7) 9 (20.0) 2 (4.4) 0 (0) 0 (0) 0 (0) 1 (2.2) 1 (2.2) 1 (2.2) 0 (0)
5 (8.3) 3 (5.0) 2 (3.3) 0 (0) 7 (11.7) 2 (3.3) 1 (1.7) 3 (5.0) 3 (5.0) 1 (1.7) 2 (3.3) 10 (16.7) 7 (11.7) 2 (3.3) 2 (3.3) 1 (1.7) 1 (1.7) 0 (0) 0 (0) 0 (0) 1 (1.7) 1 (1.7) 1 (1.7) 0 (0)
2.93 (1.09–7.83) 4.44 (1.29–15.22) 1.33 (0.19–9.11) – 2.47 (1.08–5.70) 2.00 (0.35–11.47) 4.02 (0.43–37.20) 1.78 (0.42–7.55) 1.53 (0.28–6.30) 1.33 (0.08–20.74) 4.67 (1.02–21.40) 2.80 (1.47–5.34) 3.05 (1.37–6.78) 2.66 (0.51–13.92) 2.00 (0.35–11.47) 12.00 (1.57–91.32) 2.66 (0.25–28.50) – – – 1.33 (0.08–20.74) 2.00 (0.35–11.47) 1.33 (0.08–20.74) –
0.029 0.014 1.000 – 0.043 0.649 0.311 0.458 1.000 1.000 0.036 0.001 0.004 0.398 0.649 0.002 0.575 – – – 1.000 1.000 1.000 –
a
Fisher's exact test.
had diagnosis of bipolar disorder (Table 2). According to reports of the participants, psychiatric disturbances emerged after the onset of the disease in 71.5% (n = 15) of the patients with a mood or anxiety disorder. Sixteen patients with SLE had any personality disorder. Specifically, obsessive–compulsive personality disorder (n = 9, 20.0%) and avoidant personality disorder (n = 4, 8.9%) were most frequently determined in this group. Compared to the control group, the prevalence rate of any Axis II diagnosis and obsessive–compulsive personality disorder was significantly higher in the SLE group. Schizoid, schizotipal, paranoid and antisocial personality disorders were not identified in the two study groups (Table 2). SLE patients with and without any Axis I psychiatric disorder had similar age (t = −1.18, P = 0.169), duration of illness (t = −1.06, P = 0.296), gender (Fisher's exact test, P = 0.592), educational level (χ 2 = 0.832, P = 0.660), employment status (Fisher's exact test, P = 0.652), marital status (χ 2 = 1.24, P = 0.539), and the existence of any Axis II diagnosis (Fisher's exact test, P = 0.765). The mean score of SLEDAI in SLE patients with and without any Axis I psychiatric disorder was 5.81 ± 2.20 and 3.50 ± 3.41, respectively. The difference was statistically significant (t = −2.265, P = 0.011).
4. Dıscussıon In our sample, while any mood or anxiety disorder was determined in nearly half of subjects with SLE, the rate was only 16.7% in the control subjects. The prevalence rate
established in the SLE patients was found to be higher than the estimated prevalence of the current Axis I psychiatric disorders in the general population [17–19]. Several studies including different interview methods suggest that 18.2%– 59.2% of subjects with SLE have concurrently at least one psychiatric disorder, which is consistent with our findings. In this study, the overall current prevalence of anxiety and mood disorders was significantly higher in patients with SLE than the control subjects. We have no studies comparing any mood disorder between patient and control groups in the published literature. Moreover, the number of noncomparative studies is very few. Nery et al. [10] using SCID found the prevalence rate of any mood disorder to be 26.8%, which is similar to our rate. However, they reported a higher prevalence rate (46.5%) of any anxiety disorder compared to those of the present study (28.9%). This discrepancy could be due to a significant difference of prevalence rate of specific phobia between these studies (25.4% vs 6.7%). Major depression was the most prevalent Axis I disorder with a rate of 22.2% in the SLE sample. Although Hugo et al. [20] reported a much lower rate of major depression at 1.1%, two recent studies show results consistent with those of the present study [10,11]. Bachen et al. [21] who compared the lifetime prevalence rate of psychiatric disorders in SLE subjects and the general population derived from a sample of the National Comorbidity Survey Replication, revealed a statistically higher prevalence rate in SLE patients. Nevertheless, they reported that generalized anxiety disorder was less common in SLE patients compared with the national estimates. They explained this unexpected finding as a possiblity that the
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high rate of major depression in their study made it difficult to assess the lifetime generalized anxiety disorder. In addition, the prevalence of generalized anxiety disorder in our sample seems to be relatively high compared with previous studies on SLE patients (15.6% vs 2.4%–9.9%) [10,11]. This may have resulted from underlying differences among communities in which the studies were conducted. Few studies have examined factors associated with psychiatric disturbances in patients with SLE. The consistent scientific data available suggest that the duration of SLE is unrelated to psychiatric disorders [11,21,22]. In contrast, a connection between the disease activity and psychiatric disorders is relatively conraversial in the literature. Nery et al. [22] reported that SLE patients with more active disease have a greater risk of the occurrence of major depression. However, they found in another study that SLE patients with or without a lifetime history of a psychiatric diagnosis had similar scores of SLEDAI [10]. Jarpa et al. [11] found that neither major depression nor a DSM-IV diagnosis was related to lupus activity. On the other hand, Bachen et al. [21] revealed that the disease activity was associated with a lifetime history of a mood or anxiety disorder. In addition, according to results of the study by Segui et al. [23], SLE patients with clinically inactive disease showed lower psychological distress. In our sample, the disease activity alone associated with the presence of current mood or anxiety disorder within the evaluated sociodemographic and clinical variables. The present study also suggested that personality disorders appear to be unrelated to mood anxiety disorders in SLE patients, which is to our knowledge, the first report in the literature on this topic. We found the prevalence rate of any Axis II disorder as 35.6% in patients with SLE and 11.7% in the control subjects. Epidemiological studies have reported 5.3%– 14.5% prevalence rates of any personality disorder in the general population [19,24,25]. The current results suggest that a considerable number of subjects with SLE attending a rheumatological outpatient clinic have Axis II psychiatric disorders. In our sample, obsessive–compulsive personality disorder was an Axis II diagnosis found to be higher in SLE patients compared to the control subjects. Further prospective studies should be carried out to confirm our results and examine whether these findings have any clinical importance in SLE. Being of a cross-sectional nature, the present study is limited by an insufficiency to indicate whether the evaluated Axis I or Axis II psychiatric disorders have causal relevance to SLE. It is unclear whether Axis I disorders are a contributing factor that may exacerbate of SLE, or is secondary to the development of a more active SLE [23,26]. When our results, including the onset time of mood or anxiety disorders are considered, these disorders seem to be secondary to the severity of lupus rather than play a primary role in the exacerbation of SLE. However, it is unclear whether there is a biological basis of this condition or psychological reaction to the severity of SLE. Moreover, the onset time method of mood
or anxiety disorder in this study is a restrictive factor in interpretation of our results. The relatively small sample size is another limitation of the current study. In addition, we did not examine any family history of mental disorders. In conclusion, results of the present study suggest that patients with SLE who were admitted to a rheumatology outpatient clinic have frequent psychiatric disturbances. Further controlled studies with larger sample sizes should be conducted to investigate long-term effects of psychiatric disorders and their treatments in the course of SLE. References [1] Cervera R, Kamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period. A comparison of early and late manifestations in a cohort of 1000 patients. Medicine 2003;82:299-308. [2] O'Neill S, Cervera R. Systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2010;24:841-55. [3] Cervera R, Khamashta MA, Hughes GRV. The Euro-lupus project: epidemiology of systemic lupus erythematosus in Europe. Lupus 2009; 18:869-74. [4] Osio-Salido E, Manapat-Reyes H. Epidemiology of systemic lupus erythematosus in Asia. Lupus 2010;19:1365-73. [5] Davis LS, Hutcheson J, Mohan C. The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus. J Interferon Cytokine Res 2011;31:781-9. [6] Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol 2003;56:481-90. [7] Chai HC, Phipps ME, Chua KH. Genetic risk factors of systemic lupus erythematosus in the Malaysian population: a minireview. Clin Dev Immunol 2012 (In press). [8] Bruns A, Meyer O. Neuropsychiatric manifestations of systemic lupus erythematosus. Joint Bone Spine 2006;73:639-45. [9] Ainiala H, Loukkola J, Peltola J, Korpela M, Hietaharju A. The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology 2001;57:496-500. [10] Nery FG, Borba EF, Viana VS, Hatch JP, Soares JC, Bonfa E, et al. Prevalence of depressive and anxiety disorders in systemic lupus erthematosus and their association with anti-ribosomal P antibodies. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:695-700. [11] Jarpa E, Babul M, Calderon J, Gonzalez M, Martinez ME, BravoZehnder M, et al. Common mental disorders and psychosocial distress in systemic lupus erythematosus are not associated with disease activity. Lupus 2011;20:58-66. [12] Hawro T, Krupinska-Kun M, Rabe-Jedrzejowska A, Robak E, Bogaczewicz J, Wozniacka A. Rheumatol Int 2011;10:1387-91. [13] Hochberg MC. Updating the American College of Rheumatology revised criteria for the calassification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725. [14] First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical ınterview for DSM-IV clinical version (SCID-I/CV). Washington, DC: American Psychiatric Press; 1997. [15] Spitzer RL, Williams JBW, Gibbon M, First M. Manual for the structured clinical ınterview for DSM-III-R personality disorders. Washington D.C.: American Psychiatric Press; 1990 [16] Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. Arthritis Rheum 1992;35:630-40. [17] Vicente B, Kohn R, Rioseco P, Saldivia S, Baker C, Torres S. Population prevalence of psychiatric disorders in Chile: 6-month and 1-month rates. Br J Psychiatry 2004;84:299-305. [18] Bijl RV, Ravelli A, van Zessen G. Prevalence of psychiatric disorder in the general population: results of the Netherlands Mental Health
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