Psychiatric symptoms in patients with systemic lupus erythematosus: frequency and association with disease activity using the Adult Psychiatric Morbidity Questionnaire

Beltrão, Sônia Maria da Rosa; Gigante, Luciana Beltrão; Zimmer, Débora Beltrão; Zimmermann, Paulo Roberto; Schmoeller, Deonilson; Batistella, Fábio; Staub, Henrique Luiz

Abstracts

INTRODUCTION: While the neurolupus criteria are well-established, global psychiatric manifestations are of variable frequency in patients with systemic lupus erythematosus (SLE); their relation with disease activity is unknown. OBJECTIVE: To evaluate the frequency of psychiatric symptoms in SLE using the Adult Psychiatric Morbidity Questionnaire (APMQ); to correlate APMQ changes with disease activity and socio-economic variables. MATERIALS AND METHODS: This cross-sectional study evaluated patients with active or inactive SLE as to the prevalence of psychiatric symptoms utilizing, for the first time, the APMQ. Eight or more affirmative replies out of 45 questions defined the APMQ as abnormal. Patients were classified according to the American Collge of Rheumatology 1997 criteria, and disease activity was measured by the SLEDAI. RESULTS: Seventy-two SLE patients entered the study, being 68 females (94.4%). Mean age was 46.1 years (± 12 SD). The frequency of abnormal APMQ was of 89%. Out of the 64 SLE patients with altered APMQ, 60 (93.7%) had common mental disorders, mostly anxiety and somatization. There was no correlation of psychiatric symptoms with active disease (rs = 0.09; P = 0.46), or with history of psychosis and/or seizures attributable to SLE (P = 1.00). Psychiatric symptoms also did not correlate with age at disease onset (rs = -0.16) or disease duration (rs = -0.11). There was an association of abnormal APMQ with low education level (P = 0.02), but not with family income allotted to the patient (P = 0.24). CONCLUSION: The frequency of psychiatric symptoms measured by the APMQ was high in our SLE population. An abnormal APMQ was disconnected from SLE activity, but it did associate with low education level.

Systemic lupus erythematosus; Psychiatric symptoms; Adult Psychiatric Morbidity; Questionnaire; SLEDAI

INTRODUÇÃO: Enquanto os critérios de neurolúpus estão bem-estabelecidos, manifestações psiquiátricas globais são de frequência variável em pacientes com lúpus eritematoso sistêmico (LES); suas relações com atividade da doença e prognóstico são desconhecidas. OBJETIVO: Avaliar a frequência de sintomas psiquiátricos no LES utilizando o Questionário de Morbidade Psiquiátrica em Adultos (QMPA); correlacionar alterações no QMPA com atividade da doença e variáveis socioeconômicas. MATERIAIS E MÉTODOS: Este estudo transversal avaliou pacientes com LES ativo ou inativo quanto à prevalência de sintomas psiquiátricos utilizando, pela primeira vez, o QMPA. Oito ou mais respostas afirmativas entre 45 perguntas definiram um QMPA como anormal. Os pacientes foram classificados de acordo com os critérios do American College of Rheumatology de 1997, e o grau de atividade da doença foi mensurado pelo SLEDAI. RESULTADOS: Participaram do estudo 72 pacientes com LES, dos quais 68 eram do sexo feminino (94,4%). A média de idade foi de 46,1 anos (± 12 DP). A frequência de QMPA anormal foi de 89%. Entre os 64 pacientes lúpicos com QMPA alterado, 60 (93,7%) apresentavam distúrbios mentais comuns, a maioria ansiedade e somatização. Não houve correlação de sintomas psiquiátricos com atividade da doença (P = 0,46; rs = 0,09) ou com história de psicose e/ou convulsões atribuíveis ao LES (P = 1,00). Sintomas psiquiátricos também não se correlacionaram com idade de início da doença (rs = -0,16) ou duração da doença (rs = -0,11). Houve associação de QMPA anormal com baixo nível educacional (P=0,02), mas não com renda familiar destinada ao paciente (P = 0,24). CONCLUSÃO: A frequência de sintomas psiquiátricos medidos pelo QMPA foi alta em nossa população com LES. Um QMPA anormal esteve dissociado da atividade do LES, mas se associou com baixo nível educacional.

Lúpus eritematoso sistêmico; Sintomas psiquiátricos; Questionário de Morbidade; Psiquiátrica em Adultos; SLEDAI

ORIGINAL ARTICLE

^IClínica Sensorial - Tratamentos Complementares, Porto Alegre, RS, Brazil

^IIFaculty of Medicine, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

ABSTRACT

INTRODUCTION: While the neurolupus criteria are well-established, global psychiatric manifestations are of variable frequency in patients with systemic lupus erythematosus (SLE); their relation with disease activity is unknown.

OBJECTIVE: To evaluate the frequency of psychiatric symptoms in SLE using the Adult Psychiatric Morbidity Questionnaire (APMQ); to correlate APMQ changes with disease activity and socio-economic variables.

MATERIALS AND METHODS: This cross-sectional study evaluated patients with active or inactive SLE as to the prevalence of psychiatric symptoms utilizing, for the first time, the APMQ. Eight or more affirmative replies out of 45 questions defined the APMQ as abnormal. Patients were classified according to the American College of Rheumatology 1997 criteria, and disease activity was measured by the SLEDAI.

RESULTS: Seventy-two SLE patients entered the study, being 68 females (94.4%). Mean age was 46.1 years (± 12 SD).The frequency of abnormal APMQ was of 89%. Out of the 64 SLE patients with altered APMQ, 60 (93.7%) had common mental disorders, mostly anxiety and somatization. There was no correlation of psychiatric symptoms with active disease (rs = 0.09; P = 0.46), or with history of psychosis and/or seizures attributable to SLE (P = 1.00). Psychiatric symptoms also did not correlate with age at disease onset (rs = -0.16) or disease duration (rs = -0.11).There was an association of abnormal APMQ with low education level (P = 0.02), but not with family income allotted to the patient (P = 0.24).

CONCLUSION: The frequency of psychiatric symptoms measured by the APMQ was high in our SLE population. An abnormal APMQ was disconnected from SLE activity, but it did associate with low education level.

Keywords: Systemic lupus erythematosus; Psychiatric symptoms; Adult Psychiatric Morbidity; Questionnaire; SLEDAI

Introduction

Systemic lupus erythematosus (SLE) is a chronic multisystemic disorder of unpredictable outcome. Genetic, hormonal, and environmental factors are involved in its etiology. The influence of psychological factors on activity and outcome of disease is a matter to be considered.¹

Seizures and psychosis are classical criteria for neuropsychiatric SLE, occurring in up to 20% of cases.² Overall, neuropsychiatric manifestations of SLE are seen in 9 to 80% of cases.³ Headache is the most frequent neurological manifestation, and stroke the most severe.⁴ Anti-neuronal antibodies,⁵ as well as antibodies to receptors NR2,⁶ have been recently associated to brain involvement in SLE patients. Apart from vasculitis, complex neuropsychiatric syndromes in SLE may also be the result of ischemia, early atherosclerosis or associated morbidities.⁷

While the organic neuropsychiatric syndromes are well known in SLE patients, the global frequency of psychiatric symptoms in these patients has been a polemic issue. Fatigue, fibromyalgia, cognitive dysfunction and depression are all contributors to poor quality of life in SLE patients. These disturbs comprise notorious bias for psychological assessment of these patients.⁷A variety of instruments have been developed to measure health-related quality of life in SLE; among them, the Medical Outcomes Survey Short Form 36 has been the most common method utilized in these group of patients.⁸

The psychometric assessment of SLE patients can be obtained by using the Wechsler scale⁷and the cognitive symptoms inventory.^9,10 Common mental disorders (CMD, here comprising depressive, anxiety and somatoforms disturbs) can, in turn, be evaluated by the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition),¹¹ but also by depression, anxiety and/or stress scales,¹² socioeconomic scales¹³ and personality scales.¹⁴There is no consensual method to evaluate psychiatric symptoms in SLE, and such multiplicity of approaches turn problematic the comprehension of the psychiatric morbidity of such patients.

The Adult Psychiatric Morbidity Questionnaire (APMQ), described in 1982,¹⁵ is an instrument structured in factors, aiming to characterize symptoms of CMD or psychosis. Even though each APMQ factor is not diagnostic on its own, it might represent a psychopatological dimension potentially useful in the screening of psychiatric disorders.

To date, the APMQ has not been utilized in the screening of psychiatric morbidity in patients with chronic autoimmune disease. In the current study, we aimed to utilize the APMQ in the evaluation of psychiatric symptoms of patients with SLE. In parallel, we sought to investigate the correlation of APMQ scores with disease activity, history of psychosis and/or seizures attributable to SLE, age at disease onset, disease duration, education level, and family income allotted to the patient.

Materials and methods

Subjects

This cross-sectional study included SLE patients followed in the Outpatient Unit (Lupus Clinic) of our Rheumatology Department, Hospital São Lucas, of Pontífica Universidade Católica do Rio Grande do Sul (PUCRS). We recruited consecutive subjects during the last two years. The inclusion criteria were: a) patients 15 years of age or older, of both sexes, who agreed to enter the study; b) patients with at least 4 of the 11 ACR 1997 criteria for classification of SLE.¹⁶Patients with clinical or laboratory data insufficient to allow evaluation of disease activity were excluded.

SLE patients answered the psychiatric questionnaire and responded to a structured interview concerning their demographic background. All patients authorized the use of their medical chart to determine de grade of disease activity (systemic lupus erythematosus disease activity index, SLEDAI). All participants signed an informed consent form. The study was approved by the Ethics Committee of the Hospital São Lucas of PUCRS (CEP/PUCRS 08/04469).

Measures

Demographic and clinical data of the SLE patients were obtained by interview and searching of their medical records. The demographic variables included age, sex, race, socioeconomic status, and education level.

The psychiatric symptoms were evaluated using the 45item APMQ.¹⁷The scale groups symptoms in factors to distinguish individuals with features of anxiety/somatization or irritability/ depression (CMD) from those with psychosis, the latter characterized by delirium, paranoid features and auditive hallucination. The alternatives for answers were "yes" or "no", to which were attributed values of 1 or 0, respectively. The first 43 questions regarded to symptoms proper of the individual being interviewed, whereas the last 2 questions (44 and 45) related to symptoms which might be present in any member of the family.

The 45 questions included in the APMQ were carried out as follows:

Since last year...

1. Have you suffered from lack of appetite?

2. Have you had difficulty to sleep?

3. Have you suffered from buzzing in your ears or mental agony?

4. Have you experimented stabbing pain in your head or headaches?

5. Have you noticed weakness in your legs, or nerve pain?

6. Have you become aggressive, "exploding" easily?

7. Have you felt depressed, or demotivated?

8. Have you felt a lump in the throat, burning or fullness in the stomach?

9. Have you experienced trembling or coldness in your hands?

10. Have you often had bouts of irritability?

11. Have you been having difficulties on understanding, learning or remembering?

12. Have you been consuming alcoholic beverages?

13. Have you ever got stuck crying a lot?

14. Have you considered committing suicide?

15. Have you noticed you were out of control, affected by mental illness?

16. Have you been unable to work due to nervousness or mental illness?

17. Have you ever felt that you could not speak or see properly?

18. Have you ever locked yourself in your room to avoid seeing anyone?

19. Have you got drunk at least once a week?

20. Do you drink every day?

21. Have you experimented heart palpitation or tightness?

22. Have you suffered from anxiety?

23. Have you been concerned about being ill?

24. Have you had an attack after being scared or upset?

25. Have you been afraid of things, animals, darkness or closed places?

6. Have you ever had to ensure that the doors were closed after you had closed them?

27. Have you been hearing voices or seeing things others do not see?

28. Have you ever been told that you say things which do not make sense?

29. Have you been speaking or laughing alone?

30. Have you ever felt that you have been followed? Have you ever noticed that people wish you bad luck?

31. Have you ever felt telepathically controlled by radio or by spirit?

32. Have you ever stayed a long time in an awkward position?

33. Have you had moments when you feel very happy without any reason?

34. Have you been moving, singing or talking non-stop?

35. Have you taken medicines to sleep or to get calm?

36. Have you ever felt that you could not attend school?

37. Have you suffered from bouts of madness?

38. Have you suffered from mental retardation?

39. Have you been concerned about cleaning in an exaggerated way?

40. Have you been treated for anxiety or mental illness?

41. Have you presented seizures falling to the floor with muscular contractions?

42. Have you been using drugs? Which one?

43. Have you consumed alcohol excessively? Someone in your family...

44. Does not know how to get dressed? Urinates or defecates in their own clothes?

45. Does not speak, does not walk or does not recognize people?

In the screening for psychopaties, APMQ questions as those of numbers 3, 4, 5, 7, 8, 9 and 21 group symptoms more properly related to the anxiety/somatization factor; in turn, the questions 6, 7, 10, 13, 14 and 18 congregate symptoms more linked to the irritability/depression factor. The questions 27, 30 and 31 assemble symptoms pertinent to psychotic disturbs.

The APMQ was considered positive for the presence of psychiatric symptoms if the patient scored 8 or more affirmative answers.¹⁷The questionnaire was applied by the first author and by two trained psychologists.

Disease activity was evaluated by the SLEDAI; 24 clinical variables were studied. The "weighted" index of 9 organ systems for disease activity were utilized as follows: 8 for central nervous system and vascular system, 4 for renal and musculoskeletal, 2 for serosal, dermal and immunological, and 1 for constitutional and hematological features. An SLEDAI above 4 was compatible with active disease.¹⁸The clinical and laboratorial data to calculate the SLEDAI score were obtained within 10 days, at the most, from the APMQ evaluation.

The following variables were also correlated with the APMQ scores: previous history of psychosis and/or seizures attributable to SLE according to medical records; age at disease onset; disease duration; education level (being low education level up to elementary school, and high education level the high school or college); and family income allotted to the patient (in Brazilian minimum salaries).

Data analysis

Quantitative statistical analysis was performed using a SPSS 13.0 software, considering a 5% level of significance. The variables were described by means and standard deviation or by absolute and relative frequencies. The statistical analysis included Student's t test and the Mann-Whitney test for the continuous variables, and chi-square or Fisher's exact test for categorical variables. Spearman's test was utilized to calculate the correlation coefficient.

Results

The final sample consisted of 72 SLE patients, 68 (94.4%) females and 60 (83.3%) of the white ethnicity.The mean age was 46.1 years (SD ± 12). The mean age at disease onset was 35 years, and the mean duration of disease was 13 years. Approximately half of the patients had the disease for 10 years or less; one-third had less than 5 years of disease duration. Regarding the educational level, 47 patients (65.2%) did not reach the high school level. In 80.5% of the cases, the family income allotted to the patient was 1.5 times or less the Brazilian minimum salary. Nearly all (96%) patients were utilizing corticosteroids. Table 1 presents the demographic and clinical characteristics of our patients with SLE.

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The overall prevalence of abnormal APMQ scores was 89% in our SLE population (64 patients). Sixty of the 64 SLE patients (93.7%) with psychiatric symptoms could be classified as having CMD and 4 (6.3%) as having psychosis. Among the 60 patients with CMD, 50 (83.3%) had anxiety/somatization symptoms, while 10 patients (16.7%) showed irritability/depression.

Out of the total number of patients with SLE, 27 (37.5%) showed active disease (SLEDAI > 4). Table 2 shows the relationship of APMQ scores with SLE activity measured by the SLEDAI. Psychiatric symptoms did not associate with elevated scores of SLEDAI.

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Fig. 1 presents the graphical distribution of patients according to the scores reached in the APMQ and SLEDAI, considering quantitative variables and the Spearman coefficient of correlation (rs). There was no significant correlation of APMQ scores with the SLEDAI. A straight line could not be estimated, once the rs was lower than 0.5.

Among the 72 SLE patients, 12 (16.6%) had past history of psychosis and/or seizures attributable to disease. There was no association of elevated APMQ scores with this variable (P = 1.00, Fisher's test). Psychiatric symptoms also did not correlate with age at disease onset (rs = -0.16; P = 0.2) or disease duration (rs = -0.11; P = 0.3).

The association of psychiatric symptoms with educational level and family income allotted to the patient is presented in Table 3. There was a significant association of elevated APMQ scores with low educational level, but not with family income allotted to the patient.

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Discussion

The APMQ is a screening instrument for psychiatric morbidity described nearly three decades behind.^15,19 The interdependency of variables and the psychometric properties of APMQ, determined by multivariate analysis, indicated that the questionnaire factors were consonant with the respective psychopathies (CMD, psychosis) defined in clinical practice.^15,17,19In populational inquiries using a cut-point of 6/7, the method showed good sensitivity (75% to 93%), variable specificity (between 53% and 94%) and a kappa of 0.88.^15,17,19

Over the last years, the scale was utilized in a quite large context: to study the relationship of the parents' mental health with the mental health of children;¹⁹ to assess the effect of socioeconomic variables and family milieu on child mental health;²⁰to evaluate the epidemiology of psychotropic use in the city of São Paulo;²¹ to assess mental health of the mothers of malnourished children;²²to evaluate the impact of informal jobs in the mental health of women;²³to verify the effect of housework and paid work on psychiatric symptoms;²⁴ to evaluate depressive and anxiety symptoms among housemaids;²⁵ to assess the effects of social inequality in the prevalence of depressive disorders in Bahia, Brazil;²⁶ and to screen psychiatric morbidity in pregnant women on alcohol use.²⁷The present study utilizes for the first time the APMQ in the verification of psychiatric symptoms in SLE patients.

Our SLE patients were predominantly females (94.4%) and of the white ethnicity (83.3%), with a mean age of 46.1 years. The literature points to a higher SLE incidence in non-white women aged 20 to 30 years.²⁸Our demographic data showed similarity with the literature regarding sex predominance, but differed regarding to race.²⁸ In accordance with our findings, Chahade et al. documented a high incidence of SLE in Caucasians of the Brazilian Southeast.²⁹

Approximately two-thirds of our SLE survey had a disease onset at 20 to 40 years of age, findings suportted by the American literature.³⁰About one-third had less than 5 years of disease duration. Our SLE sample, largely dependent on public health services, had, in general terms, a low educational level: 65.2% of the patients did not attend high school. In 80.5% of cases, the family income allotted to the patient was 1.5 times the minimum salary or less. For short, this survey is representative of a public tertiary center of a big Southern city (mostly white, low income, low education level).

The frequency of psychiatric symptoms evaluated by the APMQ was very high in our SLE population (89%). Of interest, the prevalence of psychiatric disturbs as screened by the APMQ was previously assessed in 6746 individuals of three metropolitans areas of Brazil (Brasília, São Paulo and Porto Alegre). The frequency of psychopathology (mostly anxiety disorders) ranged from 19% (São Paulo) to 34% (Brasília and Porto Alegre). That report³¹comprised the first Brazilian investigation of mental ilness in an urban population, and brought about our interest for screening psychiatric illness in SLE using the APMQ. As seen, the prevalence of an abnormal APMQ largely differed when a sample of general population³¹ is compared, even indirectly, to a specific group of SLE patients.

The 89% prevalence of abnormal APMQ in our SLE patients may well be an overestimate. The test might be hypersensitive by detecting symptoms of functional syndromes (questions 2, 4, 9 and 21, for instance) or organic complaints of SLE (questions 1, 41). In a hospital-based study including thirty patients, the prevalence of psychiatric disorders using another method (the Presumptive Stressful Life Event Scale) was of 50%, according to a study from 1999.³² In a Brazilian survey of SLE patients evaluated by traditional scales, cognitive disorders, anxiety and/or depression were seen in 75% of the cases, a frequency close to ours regarding CMD.³³

Among our 64 SLE patients with psychiatric symptoms, there was a strong predominance of CMD (93.7%) in comparison to psychosis (6.3%). Inside the CMD picture, most of the patients (83.3%) fit in the anxiety/somatization group, and the remaining in the irritability/depression category. In the large group of patients with the anxiety/somatization factor, symptoms attributable to SLE such fatigue and "leg weakness"³⁴were also computed in our study (question 5 of APMQ); this overlapping of psychiatric and organic symptoms may have generated a confounding bias in our analysis.

Our data did not point to a significant correlation of APMQ scores with disease activity measured by the SLEDAI. Out of 83 Chilean patients with SLE evaluated for psychiatric morbidity by the DSM-IV and a psychological suffering scale, 44.6% presented psychiatric diagnoses, particularly major depressive episodes. In accordance with our study, there was no correlation of psychiatric distress with disease activity.³⁵

Three studies, also using other methods but not the QMPA, corroborated a lack of association between psychiatric illness and disease activity.^32,33,36 This finding suggests that the psychological suffering of these patients, manifested mainly by CMD, could have a multifactorial etiology, including disease chronicity, treatment and socioeconomic variables.^32,33,36 Some Brazilian studies, in fact, accounted for worsening of SLE symptoms due to psychological factors.^37-39According to Toloza et al, the current measures to appraise disease activity and organic damage in SLE do not seem "to capture" the health-related quality of life of such patients.⁴⁰

Of major interest, we also did not observe an association of altered APMQ with previous history of psychosis and/or seizures, classical psychiatric SLE criteria.^2,41We could then infer that the psychiatric symptoms currently extracted by the APMQ are not in a direct way linked to history of neurolupus.

The literature indicates that the earlier the onset of SLE, the more serious the clinical features can be.⁴² Although elevated APMQ scores would be expected to be more frequent in patients early disease, this correlation was not confirmed in our study. Considering previous reports claiming cumulative brain damage in patients with SLE,⁴³ an association of psychiatric symptoms with longer disease duration would be plausible, but this correlation was also not evident in our survey.

A correlation of psychiatric symptoms with low educational level (below high school) was noticed in our SLE survey. In another words, SLE patients with higher educational level could be less susceptible to affirmative answers in the APMQ. It is possible, also, that individuals with lower education level have had more difficulty in leading with the extension and complexity of the questionnaire, resulting in a bias of positive answers.

Eleven Brazilian patients with SLE were recently evaluated for neuropsychological function using the "mini-mental", neuropsychiatric inventory and other tests. A defined impairment of cognitive functions was documented, and these alterations also related to a low education level. Worthy of note, symptoms of anxiety/irritability and hallucinations were particularly frequent in these individuals.⁴⁴

Our data did not confirm a correlation of abnormal APMQ with family income allotted to the patient. According to a recent report, chronic disease, low educational level and low acquisitive power predisposed to depressive, anxiety and somatoform disturbances in SLE.⁴⁵These discrepancies on the role of acquisitive power on psychiatric disturbs of SLE patients shall be clarified in forecoming studies.

Although deprived from diagnostic properties, the APMQ, with its wide structure in factors, seemed useful in the screening of CMD (which largely predominated in our SLE sample), as well as in the differentiation of CMD with psychosis. In patients with altered APMQ, more specific psychiatric diagnoses can potentially be obtained in a future longitudinal study.

Our study shows limitations which must be mentioned, the uncontrolled cross-sectional design being the first of them. The absence of a control group without SLE restricted the statistical analysis. The low number of individuals with psychosis did not allow analysis of subgroups of patients with abnormal APMQ. Also, a majority of our patients (96%) were using corticosteroids, so that it was not statistically feasible to associate psychiatric symptoms with the intake of these drugs.

Knowingly, corticosteroid intake is linked to disturbances of sleep, cognition and behaviour.⁴⁶Stratification for corticosteroid dosage could have been performed in our study, once dose is related to incidence of psychiatric symptoms; nevertheless, dosage does not appear to associate to severity or duration of psychiatric features.⁴⁶ Our SLE patients were not subdivided as to use of psychotropics, also due to the high frequency of intake of such drugs; besides, a large variety of psychotropics were utilized by different patients, turning difficult the stratification.The fact that we have evaluated a specific SLE population of tertiary center (as a whole with low education level and low income) also restrict our results. As a limitation of APMQ per si, the method evaluated symptoms present only in the last year.

In summary, an abnormal APMQ was highly frequent in SLE patients. The test might be hypersensitive; anyhow, these data bring into discussion the need for more aggressive screening programs of psychological disturbs in SLE populations. An abnormal APMQ did not correlate with active disease, and the association of an altered test with low education level requires elucidation. Further studies are warranted to confirm the usefulness of the APMQ as screening instrument for psychiatric morbidity in SLE patients.

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