International Journal of Psychiatry in Clinical Practice, 2008; 12(1): 1924
ORIGINAL ARTICLE
Mood and anxıety dısorders ın patıents wıth multıple sclerosıs
FARUK UGUZ1, ZEHRA AKPINAR2, ISHAK OZKAN3 & SERHAT TOKGOZ1
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1
Department of Psychiatry, Meram Faculty of Medicine, Selc¸uk University, Konya, Turkey 2Department of Neurology, Meram Faculty of Medicine, Selc¸uk University, Konya, Turkey, and 3Department of Psychiatry, Health Center of Has Vak, Ankara, Turkey
Abstract Objective. This study aims to investigate the current prevalences of mood and anxiety disorders, as well as the sociodemographic and clinical features associated with these disorders in multiple sclerosis (MS). Method. A total of 74 patients with relapsingremitting MS (42 patients in exacerbation phase, 32 patients in remission phase) were included in the study. Mood and anxiety disorders were diagnosed by means of the Structured Clinical Interview for DSM-IV (SCID-I). The Expanded Disability Status Scale (EDSS) was used to determine degree of disability due to MS. Results. Forty-five (60.8%) patients met the criterion of at least one mood or anxiety disorder. Major depression (33.8%) was the most common psychiatric diagnosis. Generalized anxiety disorder (18.9%), specific phobia (18.9%) and obsessive-compulsive disorder (OCD) (14.9%) were other frequent psychiatric disorders. Major depression, panic disorder and OCD were significantly more common among patients in the exacerbation phase compared to patients in the remission phase. The predictors of any depressive disorder were presence of exacerbation phase of MS and higher disability level, and the predictors of any anxiety disorder were presence of exacerbation phase of MS and shorter disease duration. Conclusions. Our results suggest that the patients with relapsingremitting MS, particularly during exacerbation phase have high prevalence of mood and anxiety disorders.
Key Words: Multiple sclerosis, anxiety, depression, psychiatric disorders, prevalence
Introduction Multiple sclerosis (MS) is a chronic neurological disease with an onset age primarily between 20 and 45 years, and which may lead to different degrees of disability [1]. In addition to neurological disabilities (e.g., visual loss, bowel and bladder incontinence), subjects with MS have significantly poorer quality of life [2,3] and high prevalence of neuropsychiatric symptoms (e.g., depression, irritability) [4]. In the last two decades, psychiatric aspects of MS have been better understood. Figved et al. [4] reported at least one psychiatric symptom in 80% of the patients with MS. The studies suggested that patients with MS had higher levels of depressive symptoms than the controls [57]. Major depression is the most common psychiatric disorder with lifetime (current past) prevalence rates of 4050% in MS. In addition, when compared to other chronic diseases and the general population, depression is observed more frequently in MS [6,811]. This aspect is also a strong factor affecting the quality of life in MS patients [1,12,13].
There is no agreement regarding the relationship between depression and disability status, duration of illness and fatigue in the literature. Whereas some authors found no association between these variables and depression [10,14], others reported that shorter duration of illness [15,16], higher degree of disability [4,6,15,17] and severity of fatigue [15] were associated with depression. In conrast, the data regarding relation of depression with gender and age is more consistent. In most studies, depression was found unrelated with age [6,10,14,17] and gender [10,14,15,17,19]. Several studies have reported high levels of anxiety in subjects with MS [8]. Recently, Galeazzi et al. [6] found 36% lifetime prevalence of any anxiety disorder in MS. Nevertheless, the data regarding frequencies of anxiety disorders in patients with MS during clinical evaluation are inadeqate. Moreover, the prevalences of depressive and anxiety disorders in exacerbation and remission phases of MS have not been detailed. This study had three aims: first, to investigate the current prevalence of mood and anxiety disorders in
¨ niversitesi, Meram Tıp Faku¨ltesi, Psikiyatri Anabilim Dalı, Meram, 42080 Konya, Turkey. Tel: 90-332-223-6837. Correspondence: Faruk Uguz, Selc¸uk U E-mail: [email protected]
(Received 14 November 2006; accepted 8 February 2007) ISSN 1365-1501 print/ISSN 1471-1788 online # 2008 Taylor & Francis DOI: 10.1080/13651500701330825
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MS. Second, to investigate whether there is any difference between the exacerbation and remission phases of MS in terms of the prevalence of these disorders. Third, to investigate sociodemographic and clinical features associated with any depressive and anxiety disorder.
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Methods The study was conducted among the patients with a diagnosis of relapsingremitting MS according to criteria of Poser and colleagues [20]. The subjects were between 18 and 65 years of age, and were regularly followed at the MS Outpatient Clinic of the Neurology Department of Meram Faculty of Medicine, Selc¸uk University. Initially, a total of 134 consecutive patients were recruited from the MS Outpatient Clinic between February 2005 and October 2005. Of these, 80 patients were admitted to the clinic for routine follow-up visits, while 54 patients had new onset neurological symptoms before proceeding on to routine follow-up visits. According to the criteria of Poser and colleagues [20], frequencies of the patients in exacerbation and remission phases of MS were 51 and 83, respectively. The objectives and procedures of the study were explained to the patients. Thirteen patients refused to participate in the study because of lack of time (n 7) and without any reason (n 6). Subjects receiving corticosteroids (n 10), interferon therapies (n 11), psychotrophic drugs (n 14) and two or more combination of these medications (n 7) within the last 6 months, and subjects with a history of neurological disease except MS (n 1) and severe head trauma (n 1), and with a significant concomitant general medical illness such as endocrine abnormalities (n 1), cardiovascular (n 1) and respiratory (n 1) system diseases were excluded from the study. The remaining 74 patients (42 patients in exacerbation phase, 32 patients in remission phase) comprised the sample of the study. Written informed consent to participate in the study was obtained from the pariticipants. Mood and anxiety disorders were ascertained by means of the Structured Clinical Interview for DSM-IV (SCID-I) [21]. SCID-I is a standardized diagnostic instrument performed by an interviewer experienced in psychiatric disturbances to determine Axis I psychiatric diagnoses according to DSM-IV criteria. Sociodemographic features can be collected by using this instrument as a part of the clinical interview. The Expanded Disability Status Scale (EDSS) [22] was used to determine degree of disability due to MS. This scale consists of eight items (pyramidal functions, cerebellar functions, brain-stem functions, sensory functions, bowel/bladder functions, visual functions, mental functions and other functions). Each patient have a score range of 010 on
this scale. The higher points reflect more degree of disability. All statistical analyses were conducted using Statistical Package for the Social Sciences (SPSS), version 12.0 for Windows. Student t-test was used for comparisons involving quantitative variables, and chi-square test for categorical data. Fisher’s exact test was performed when necessary. The predictors of any depressive and any anxiety disorder were examined with logistic regression analysis. Statistically significance level was accepted as P B0.05). Results Of the 74 patients who participanted in the study, 50 (67.6%) were women, 55 (74.3%) were married, and 48 (64.9%) were primary school graduates. The mean age at assessment, age at onset and disease duration of sample 34.57911.93 (range: 1863), 29.01910.48 (range: 1452), and 5.4794.81 (range: 125) years, respectively. Their EDSS scores ranged from 0 to 6, with a mean 1.4491.24. No significant difference was found between the patients in exacerbation and remission phases of MS with respect to these variables (Table I). Overall, 45 (60.8%) patients met the criteria for at least one current mood or anxiety disorder. The prevalence rates of any mood disorder and any anxiety disorder were 40.5 and 45.9%, respectively. Major depression (33.8%) was the most common psychiatric disorder followed by generalized anxiety disorder (GAD) (18.9%), specific phobia (18.9%), obsessive-compulsive disorder (OCD) (14.9%), dysthymic disorder (13.5%) and social phobia (13.5%). When compared with patients in remission phase, the patients in exacerbation phase were more likely to meet the criteria for at least one mood and anxiety disorder. Specifically, these patients had significantly higher frequencies of major depression, panic disorder and OCD (Table II). Existence of any depressive disorder (major depression or dysthymic disorder) was unrelated with gender (x2 3.528, P 0.475), marital status (x2 1.728, P 0.182), educational level (x2 3.142, P 0.208), age at asssessment (t 1.397, P 0.453), age at onset (t 1.622, P 0.109), and duration of illness (t 0.754, P 0.453). The mean EDSS score was significantly greater in the patients with a depressive disorder than the patients without any depressive disorder (2.0991.44 vs 1.0290.87, t 3.567, P 0.001). No significant relationship was found between any anxiety disorder and gender (x2 1.020, P 0.312), marital status (x2 0.152, P 0.697), educational level (x2 4.061, P 0.131), age at assessment (t 1.606, P 0.113), age at onset (t 0.320, P 0.750), and EDSS scores (t 0.550, P 0.584). The mean duration of illness was significantly shorter in the patients with any anxiety disorder than the patients
Mood and anxıety dısorders ın patıents wıth multıple sclerosıs
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Table I. Sociodemographic and clinical features of the sample. Total (n 74)
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Gender, n (%) Female Male
Exacerbation phase (n 42)
Remission phase (n 32)
Significance x2 0.097, NS
50 (67.6) 24 (32.4)
29 (69.0) 13 (31.0)
21 (65.6) 11 (34.4) x2 0.142, NS
Education, n (%) Primary school Secondary school University
48 (68.9) 15 (20.3) 11 (14.9)
28 (66.7) 8 (19.0) 6 (14.3)
20 (62.5) 7 (21.9) 5 (15.6)
Marital status, n (%) Single Married Age at assessment, mean9SD, years Age at onset, mean9SD, years Duration of illness, mean9SD, years EDSS, mean9SD
19 (25.7) 55 (74.3) 34.57911.93 29.01910.48 5.4794.81 1.4491.24
8 (19.0) 34 (81.0) 33.86911.19 29.2699.72 4.9094.88 1.4591.30
11 (34.4) 21 (65.6) 35.50912.96 28.69911.55 6.2294.69 1.4291.18
x2 2.24, NS
t 0.584, NS t 0.232, NS t 1.167, NS t 0.104, NS
NS, not significant.
without any anxiety disorder (3.9793.49 vs 6.759 5.42, t 2.658, P 0.010). As a result of logistic regression analysis, we found that the predictors of any depressive disorder were the presence of exacerbation phase of MS (B 1.365, Wald x2 5.300, df 1, P 0.021) and higher disability level (B 0.931, Wald x2 10.352, df 1, P 0.001), while the predictors of any anxiety disorder were presence of the exacerbation phase of MS (B 1.233, Wald x2 5.603, df 1, P 0.018) and shorter disease duration (B 0.137, Wald x2 4.376, df 1, P 0.036). Discussion This study indicated that a considerable number of the patients with relapsingremitting MS attending an MS clinic had current mood (40.5%) and anxiety (45.9%) disorders. These rates are higher than estimated in the general population. According to epidemiological data, current and lifetime prevalence of any mood disorder are 5.16.5 and 7.9 20.8%, and of any anxiety disorder are 6.87.3 and 10.428.8% in the community, respectively
[2328]. Anxiety disorders may be common in people with MS, because there is a high rate of comorbidity among anxiety and mood disorders. However, the data on patients with MS, particularly regarding the prevalence of anxiety disorders, is very limited [8]. Moreover, the studies have been focused on the prevalence of major depression rather than other mood disorders. Several studies based on anxiety rating scales suggested that roughly onethird of subjects with MS had a level of clinically significant anxiety [2,29]. Ron and Logsdail [7] reported that 20 (17.2%) of 116 patients with MS had mood disorder, and none of these patients had anxiety disorder during interview. Recently, Galeazzi et al. [6] reported that the lifetime prevalence of any anxiety disorder was 36% in 50 patients with MS. Our current prevalence rate of any anxiety disorder is higher than this report. This discrepancy could be due to a difference between the clinical features of the samples. For example, while approximately half of our patients were in the exacerbation phase, their sample was clinically stable in terms of MS. In the present study, the prevalence of any anxiety disorder was higher than any mood disorder in patients with
Table II. Current prevalences of mood and anxiety disorders of sample, n (%).
Disorder Major depression Dysthymic disorder Bipolar disorder Panic disorder Obsessive-compulsive disorder Agoraphobia Social phobia Spesific phobia Posttraumatic stress disorder Generalized anxiety disorder Any mood disorder Any anxiety disorder Any mood or anxiety disorder
Total (n 74) 25 10 1 6 11 3 10 14 1 14 30 34 45
(33.8) (13.5) (1.4) (8.1) (14.9) (4.1) (13.5) (18.9) (1.4) (18.9) (40.5) (45.9) (60.8)
Exacerbation phase (n 42) 19 8 1 6 10 2 6 11 1 9 22 25 32
(45.2) (19.0) (2.4) (14.3) (23.8) (4.8) (14.3) (26.2) (2.4) (21.4) (52.4) (59.5) (76.2)
Remission phase (n 32) 6 (18.8) 2 (6.3) ( ) ( ) 1 (3.1) 1 (3.1) 4 (12.5) 3 (9.4) ( ) 5 (15.6) 8 (25.0) 9 (28.1) 13 (40.6)
Fisher exact test P 0.025 0.172 1.000 0.033 0.019 1.000 1.000 0.080 1.000 0.566 0.031 0.010 0.004
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MS, which is compatible with the results of the community-based studies [23,2628]. Therefore, anxiety disorders should be evaluated in patients with MS, although the previous studies have mainly focused on depression. We found that the most common specific psychiatric disorder was major depression, which is in agreement with results of study conducted by Galeazzi et al. [6]. In this study, the current prevalence of major depression (33.8%) was higher than reported in the general community (2.24.9%) [23,24,3032] and subjects with MS (1222%) [6,7,19,33,34]. However, when this prevalence is considered only for the patients in the remission phase, our finding is similar to those of other studies in patients with MS. In the current study, one patient met the criteria for bipolar disorder with hypomanic episode. In accordance with our results, previous studies [7,33,34] reported 02% current prevalence of bipolar disorder in patients with MS. However, we did not record subclinical psychiatric symptoms such as emotional lability, irritability and euphoria in our patient group. These symptoms do not meet the criteria for a mood episode. Therefore, it is possible that hypomanic symptoms were more frequently observed compared to bipolar disorder in our sample. The frequencies of dysthymic disorder, OCD, panic disorder, social and specific phobia, and GAD were greater in our sample than observed in the general population [23,24,31,35]. There is limited data regarding the relation of current prevalence of dysthymic disorder and specific anxiety disorders in patients with MS. Mo¨ller et al. [14] reported dysthymic disorder in 8% and panic disorder with agoraphobia in 4% of 25 patients with MS. Joffe et al. [34] found that current prevalence rates of panic disorder and GAD were 1 and 2%, respectively. In this study, we observed that patients in exacerbation phase of MS had higher prevalence of major depression, panic disorder, OCD, and any mood or anxiety disorder. We found no adequately detailed information regarding differences in frequencies of psychiatric disorders, particularly anxiety disorders between phases of MS from studies that explored the psychiatric aspects of MS. Dalos et al. [36] reported that the prevalence of emotional disturbance was higher in exacerbating or progressing patients than stable patients. McCabe [37] reported higher levels of anxiety in MS exacerbation group compared to no-exacerbation group. In contrast, Minden et al. [10] noted no association between depression and clinical status (exacerbation versus remission). We are considering as a notable finding of our study that OCD and panic disorder were established more frequent in exacerbation phase than remission phase of MS. This finding suggests that OCD and panic
disorder symptoms are new begin in at least some subjects during exacerbation phase of MS, although the present study has a cross-sectional design. Further neuroimaging studies investigating the association between new onset OCD or panic disorder symptoms and localization of MS lesions in the exacerbation phase of MS may contribute to greater understanding of the pathogenesis of these two disorders. Similar to our results, a number of studies found no association between depression and age at assessment [6,10,14,17], age at onset [6], gender [10,14,15,17,19] and duration of illness [6,10,14, 17,19]. Conversely, some investigators reported the association of depression with female gender [6], shorter duration of illness [15,16], and younger age [15,19]. In addition, some authors [15,17] observed elevated frequencies of divorced, widowed or seperated subjects, and lower educational level in depressed patients, which are inconsistent with our findings. The present study showed that a greater degree of disability was a predictor for any depressive disorder, and this finding is consistent with most reports that have noted correlations with disability status of depression [4,6,15,17], although there are some studies [5,10,14] that have not found a relationship between these variables. The psychosocial factors due to disability (e.g., dependence on other persons for daily activities, economical problems resulting from unemployment) may contribute to depression in MS [4]. However, the impact of disability may be modified by various factors such as personality properties, meaning and place of the illness in an individual’s life, predisposition to depression, and availability of social support [10]. There is a need to study systematically evaluated influences of these potential factors on depression and the localizations of nervous system lesions which may have caused greater disability. To date and to our knowledge, factors associated with any anxiety disorder have not been explored. Earlier studies based on anxiety rating scales reported controversial consequences about the relation of anxiety with the degree of disability [2,5]. We observed that shorter disease duration was related to any anxiety disorder within the examined sociodemographic and clinical characteristics except the status of illness. This finding should be replicated by other studies. Indeed, the present study has methodological restrictions regarding the duration of disease. We accepted the time after diagnosis of MS as the duration of illness. On the other hand, the disease may have onset well before diagnosis in at least some patients. Finally, anxiety disorders include a variety of specific subtypes. The sample size of our study was not sufficiently large to determine the factors associated with each specific anxiety disorder.
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Mood and anxıety dısorders ın patıents wıth multıple sclerosıs The presence of the exacerbation phase of MS was a predictor for both any depressive and any anxiety disorder. As a consequence, a biological connection between psychiatric disorders and MS is likely. Zorzon et al. [38] found a significant correlation between depression and right temporal atrophy, and proposed that temporal lobes may play a role in the etiology of depression in MS. Feinstein et al. [39] reported more hyperintense lesions in the left anterior medial frontal regions and greater atrophy of the left anterior temporal regions in depressed patients with MS compared to nondepressed patients with MS. Recently, some authors found an increased (inferior parietal cortex and left inferior frontal cortex) and a reduced metabolism (right talamus, bilateral cerebellum, and left inferior parietal cortex) in some brain regions in patients with MS compared to controls [40]. Alterations in metabolism and neurotransmitter function in brain regions affected by MS lesions may be a possible pathogenetic mechanism to delineate any correlation between psychiatric disorders and MS. In addition, investigators have shown significantly higher cerebrospinal fluid (CSF) and serum levels of tumor necrosis factor-a (TNF-a) in relapsing phase, as compared with both those in remission or the controls [41,42], and during relapse phase, a significant increase of some serum pro-inflammatory cytokines such as TNF-a [43]. Mikova et al. [42] also noted that increased serum TNF-alpha was more pronounced in patients diagnosed with depression than in MS patients. Pro-inflammatory cytokines such as TNF-a may play a role in the development of mood and anxiety disorders by impacting central monoamine turnover [44] in susceptible subjects during exacerbation of MS. However, because there may be a reciprocal relationship between mood or anxiety disorders and phases of MS, we cannot conclude from our study (a cross-sectional research) that the exacerbation phase of MS leads to these mental disorders. Future prospective controlled studies may ensure more correct information in this respect. Our study had several limitations. First, the sample size was relatively small. Second, it was conducted in a clinical sample which might be underpresented all patients with MS. This condition is a factor restricting the generalization of our results. Third, this study was conducted as a cross-sectional research. The results of this study suggest an association between psychiatric disorders and phases of MS. However, large scale prospective studies should be performed to elucidate exact clinical relationship between psychiatric disorders and MS. In conclusion, despite some limitations, this study suggests that current prevalences of mood and anxiety disorders in patients with a diagnosis of relapsingremitting MS attending a MS clinic are higher than estimated in the general population, and patients in exacerbation phase are more likely to
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meet the diagnostic criteria for these disorders. For this reason, these disorders should be carefully screened in all patients with MS, especially during exacerbation phase. In addition, the patients in exacerbation phase may apply to a psychiatry clinic to seek help regarding the symptoms of depressive or anxiety disorders prior to diagnosis of MS. Finally, further prospective controlled studies are needed to investigate the influence of psychiatric disorders on the prognosis and course of MS. Key points . A considerable number of outpatients with a diagnosis of multiple sclerosis have mood or anxiety disorders . Among outpatients with multiple sclerosis, the most common mood disorder is major depression, and the predictors of any depressive disorder are presence of exacerbation phase of multiple sclerosis and higher disability level . The most common anxiety disorders are generalized anxiety disorder and specific phobia in outpatients with multiple sclerosis. Shorter disease duration and the presence of exacerbation phase predict any anxiety disorder in this patient group . The diagnoses of major depression, panic disorder and obsessive-compulsive disorder are more frequent among patients in exacerbation phase compared to patients in the remission phase in multiple sclerosis Statement of interest The authors have no conflict of interest with any commerical or other associations in connection with submitted paper.
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ORIGINAL ARTICLE
Mood and anxıety dısorders ın patıents wıth multıple sclerosıs
FARUK UGUZ1, ZEHRA AKPINAR2, ISHAK OZKAN3 & SERHAT TOKGOZ1
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1
Department of Psychiatry, Meram Faculty of Medicine, Selc¸uk University, Konya, Turkey 2Department of Neurology, Meram Faculty of Medicine, Selc¸uk University, Konya, Turkey, and 3Department of Psychiatry, Health Center of Has Vak, Ankara, Turkey
Abstract Objective. This study aims to investigate the current prevalences of mood and anxiety disorders, as well as the sociodemographic and clinical features associated with these disorders in multiple sclerosis (MS). Method. A total of 74 patients with relapsingremitting MS (42 patients in exacerbation phase, 32 patients in remission phase) were included in the study. Mood and anxiety disorders were diagnosed by means of the Structured Clinical Interview for DSM-IV (SCID-I). The Expanded Disability Status Scale (EDSS) was used to determine degree of disability due to MS. Results. Forty-five (60.8%) patients met the criterion of at least one mood or anxiety disorder. Major depression (33.8%) was the most common psychiatric diagnosis. Generalized anxiety disorder (18.9%), specific phobia (18.9%) and obsessive-compulsive disorder (OCD) (14.9%) were other frequent psychiatric disorders. Major depression, panic disorder and OCD were significantly more common among patients in the exacerbation phase compared to patients in the remission phase. The predictors of any depressive disorder were presence of exacerbation phase of MS and higher disability level, and the predictors of any anxiety disorder were presence of exacerbation phase of MS and shorter disease duration. Conclusions. Our results suggest that the patients with relapsingremitting MS, particularly during exacerbation phase have high prevalence of mood and anxiety disorders.
Key Words: Multiple sclerosis, anxiety, depression, psychiatric disorders, prevalence
Introduction Multiple sclerosis (MS) is a chronic neurological disease with an onset age primarily between 20 and 45 years, and which may lead to different degrees of disability [1]. In addition to neurological disabilities (e.g., visual loss, bowel and bladder incontinence), subjects with MS have significantly poorer quality of life [2,3] and high prevalence of neuropsychiatric symptoms (e.g., depression, irritability) [4]. In the last two decades, psychiatric aspects of MS have been better understood. Figved et al. [4] reported at least one psychiatric symptom in 80% of the patients with MS. The studies suggested that patients with MS had higher levels of depressive symptoms than the controls [57]. Major depression is the most common psychiatric disorder with lifetime (current past) prevalence rates of 4050% in MS. In addition, when compared to other chronic diseases and the general population, depression is observed more frequently in MS [6,811]. This aspect is also a strong factor affecting the quality of life in MS patients [1,12,13].
There is no agreement regarding the relationship between depression and disability status, duration of illness and fatigue in the literature. Whereas some authors found no association between these variables and depression [10,14], others reported that shorter duration of illness [15,16], higher degree of disability [4,6,15,17] and severity of fatigue [15] were associated with depression. In conrast, the data regarding relation of depression with gender and age is more consistent. In most studies, depression was found unrelated with age [6,10,14,17] and gender [10,14,15,17,19]. Several studies have reported high levels of anxiety in subjects with MS [8]. Recently, Galeazzi et al. [6] found 36% lifetime prevalence of any anxiety disorder in MS. Nevertheless, the data regarding frequencies of anxiety disorders in patients with MS during clinical evaluation are inadeqate. Moreover, the prevalences of depressive and anxiety disorders in exacerbation and remission phases of MS have not been detailed. This study had three aims: first, to investigate the current prevalence of mood and anxiety disorders in
¨ niversitesi, Meram Tıp Faku¨ltesi, Psikiyatri Anabilim Dalı, Meram, 42080 Konya, Turkey. Tel: 90-332-223-6837. Correspondence: Faruk Uguz, Selc¸uk U E-mail: [email protected]
(Received 14 November 2006; accepted 8 February 2007) ISSN 1365-1501 print/ISSN 1471-1788 online # 2008 Taylor & Francis DOI: 10.1080/13651500701330825
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MS. Second, to investigate whether there is any difference between the exacerbation and remission phases of MS in terms of the prevalence of these disorders. Third, to investigate sociodemographic and clinical features associated with any depressive and anxiety disorder.
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Methods The study was conducted among the patients with a diagnosis of relapsingremitting MS according to criteria of Poser and colleagues [20]. The subjects were between 18 and 65 years of age, and were regularly followed at the MS Outpatient Clinic of the Neurology Department of Meram Faculty of Medicine, Selc¸uk University. Initially, a total of 134 consecutive patients were recruited from the MS Outpatient Clinic between February 2005 and October 2005. Of these, 80 patients were admitted to the clinic for routine follow-up visits, while 54 patients had new onset neurological symptoms before proceeding on to routine follow-up visits. According to the criteria of Poser and colleagues [20], frequencies of the patients in exacerbation and remission phases of MS were 51 and 83, respectively. The objectives and procedures of the study were explained to the patients. Thirteen patients refused to participate in the study because of lack of time (n 7) and without any reason (n 6). Subjects receiving corticosteroids (n 10), interferon therapies (n 11), psychotrophic drugs (n 14) and two or more combination of these medications (n 7) within the last 6 months, and subjects with a history of neurological disease except MS (n 1) and severe head trauma (n 1), and with a significant concomitant general medical illness such as endocrine abnormalities (n 1), cardiovascular (n 1) and respiratory (n 1) system diseases were excluded from the study. The remaining 74 patients (42 patients in exacerbation phase, 32 patients in remission phase) comprised the sample of the study. Written informed consent to participate in the study was obtained from the pariticipants. Mood and anxiety disorders were ascertained by means of the Structured Clinical Interview for DSM-IV (SCID-I) [21]. SCID-I is a standardized diagnostic instrument performed by an interviewer experienced in psychiatric disturbances to determine Axis I psychiatric diagnoses according to DSM-IV criteria. Sociodemographic features can be collected by using this instrument as a part of the clinical interview. The Expanded Disability Status Scale (EDSS) [22] was used to determine degree of disability due to MS. This scale consists of eight items (pyramidal functions, cerebellar functions, brain-stem functions, sensory functions, bowel/bladder functions, visual functions, mental functions and other functions). Each patient have a score range of 010 on
this scale. The higher points reflect more degree of disability. All statistical analyses were conducted using Statistical Package for the Social Sciences (SPSS), version 12.0 for Windows. Student t-test was used for comparisons involving quantitative variables, and chi-square test for categorical data. Fisher’s exact test was performed when necessary. The predictors of any depressive and any anxiety disorder were examined with logistic regression analysis. Statistically significance level was accepted as P B0.05). Results Of the 74 patients who participanted in the study, 50 (67.6%) were women, 55 (74.3%) were married, and 48 (64.9%) were primary school graduates. The mean age at assessment, age at onset and disease duration of sample 34.57911.93 (range: 1863), 29.01910.48 (range: 1452), and 5.4794.81 (range: 125) years, respectively. Their EDSS scores ranged from 0 to 6, with a mean 1.4491.24. No significant difference was found between the patients in exacerbation and remission phases of MS with respect to these variables (Table I). Overall, 45 (60.8%) patients met the criteria for at least one current mood or anxiety disorder. The prevalence rates of any mood disorder and any anxiety disorder were 40.5 and 45.9%, respectively. Major depression (33.8%) was the most common psychiatric disorder followed by generalized anxiety disorder (GAD) (18.9%), specific phobia (18.9%), obsessive-compulsive disorder (OCD) (14.9%), dysthymic disorder (13.5%) and social phobia (13.5%). When compared with patients in remission phase, the patients in exacerbation phase were more likely to meet the criteria for at least one mood and anxiety disorder. Specifically, these patients had significantly higher frequencies of major depression, panic disorder and OCD (Table II). Existence of any depressive disorder (major depression or dysthymic disorder) was unrelated with gender (x2 3.528, P 0.475), marital status (x2 1.728, P 0.182), educational level (x2 3.142, P 0.208), age at asssessment (t 1.397, P 0.453), age at onset (t 1.622, P 0.109), and duration of illness (t 0.754, P 0.453). The mean EDSS score was significantly greater in the patients with a depressive disorder than the patients without any depressive disorder (2.0991.44 vs 1.0290.87, t 3.567, P 0.001). No significant relationship was found between any anxiety disorder and gender (x2 1.020, P 0.312), marital status (x2 0.152, P 0.697), educational level (x2 4.061, P 0.131), age at assessment (t 1.606, P 0.113), age at onset (t 0.320, P 0.750), and EDSS scores (t 0.550, P 0.584). The mean duration of illness was significantly shorter in the patients with any anxiety disorder than the patients
Mood and anxıety dısorders ın patıents wıth multıple sclerosıs
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Table I. Sociodemographic and clinical features of the sample. Total (n 74)
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Gender, n (%) Female Male
Exacerbation phase (n 42)
Remission phase (n 32)
Significance x2 0.097, NS
50 (67.6) 24 (32.4)
29 (69.0) 13 (31.0)
21 (65.6) 11 (34.4) x2 0.142, NS
Education, n (%) Primary school Secondary school University
48 (68.9) 15 (20.3) 11 (14.9)
28 (66.7) 8 (19.0) 6 (14.3)
20 (62.5) 7 (21.9) 5 (15.6)
Marital status, n (%) Single Married Age at assessment, mean9SD, years Age at onset, mean9SD, years Duration of illness, mean9SD, years EDSS, mean9SD
19 (25.7) 55 (74.3) 34.57911.93 29.01910.48 5.4794.81 1.4491.24
8 (19.0) 34 (81.0) 33.86911.19 29.2699.72 4.9094.88 1.4591.30
11 (34.4) 21 (65.6) 35.50912.96 28.69911.55 6.2294.69 1.4291.18
x2 2.24, NS
t 0.584, NS t 0.232, NS t 1.167, NS t 0.104, NS
NS, not significant.
without any anxiety disorder (3.9793.49 vs 6.759 5.42, t 2.658, P 0.010). As a result of logistic regression analysis, we found that the predictors of any depressive disorder were the presence of exacerbation phase of MS (B 1.365, Wald x2 5.300, df 1, P 0.021) and higher disability level (B 0.931, Wald x2 10.352, df 1, P 0.001), while the predictors of any anxiety disorder were presence of the exacerbation phase of MS (B 1.233, Wald x2 5.603, df 1, P 0.018) and shorter disease duration (B 0.137, Wald x2 4.376, df 1, P 0.036). Discussion This study indicated that a considerable number of the patients with relapsingremitting MS attending an MS clinic had current mood (40.5%) and anxiety (45.9%) disorders. These rates are higher than estimated in the general population. According to epidemiological data, current and lifetime prevalence of any mood disorder are 5.16.5 and 7.9 20.8%, and of any anxiety disorder are 6.87.3 and 10.428.8% in the community, respectively
[2328]. Anxiety disorders may be common in people with MS, because there is a high rate of comorbidity among anxiety and mood disorders. However, the data on patients with MS, particularly regarding the prevalence of anxiety disorders, is very limited [8]. Moreover, the studies have been focused on the prevalence of major depression rather than other mood disorders. Several studies based on anxiety rating scales suggested that roughly onethird of subjects with MS had a level of clinically significant anxiety [2,29]. Ron and Logsdail [7] reported that 20 (17.2%) of 116 patients with MS had mood disorder, and none of these patients had anxiety disorder during interview. Recently, Galeazzi et al. [6] reported that the lifetime prevalence of any anxiety disorder was 36% in 50 patients with MS. Our current prevalence rate of any anxiety disorder is higher than this report. This discrepancy could be due to a difference between the clinical features of the samples. For example, while approximately half of our patients were in the exacerbation phase, their sample was clinically stable in terms of MS. In the present study, the prevalence of any anxiety disorder was higher than any mood disorder in patients with
Table II. Current prevalences of mood and anxiety disorders of sample, n (%).
Disorder Major depression Dysthymic disorder Bipolar disorder Panic disorder Obsessive-compulsive disorder Agoraphobia Social phobia Spesific phobia Posttraumatic stress disorder Generalized anxiety disorder Any mood disorder Any anxiety disorder Any mood or anxiety disorder
Total (n 74) 25 10 1 6 11 3 10 14 1 14 30 34 45
(33.8) (13.5) (1.4) (8.1) (14.9) (4.1) (13.5) (18.9) (1.4) (18.9) (40.5) (45.9) (60.8)
Exacerbation phase (n 42) 19 8 1 6 10 2 6 11 1 9 22 25 32
(45.2) (19.0) (2.4) (14.3) (23.8) (4.8) (14.3) (26.2) (2.4) (21.4) (52.4) (59.5) (76.2)
Remission phase (n 32) 6 (18.8) 2 (6.3) ( ) ( ) 1 (3.1) 1 (3.1) 4 (12.5) 3 (9.4) ( ) 5 (15.6) 8 (25.0) 9 (28.1) 13 (40.6)
Fisher exact test P 0.025 0.172 1.000 0.033 0.019 1.000 1.000 0.080 1.000 0.566 0.031 0.010 0.004
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MS, which is compatible with the results of the community-based studies [23,2628]. Therefore, anxiety disorders should be evaluated in patients with MS, although the previous studies have mainly focused on depression. We found that the most common specific psychiatric disorder was major depression, which is in agreement with results of study conducted by Galeazzi et al. [6]. In this study, the current prevalence of major depression (33.8%) was higher than reported in the general community (2.24.9%) [23,24,3032] and subjects with MS (1222%) [6,7,19,33,34]. However, when this prevalence is considered only for the patients in the remission phase, our finding is similar to those of other studies in patients with MS. In the current study, one patient met the criteria for bipolar disorder with hypomanic episode. In accordance with our results, previous studies [7,33,34] reported 02% current prevalence of bipolar disorder in patients with MS. However, we did not record subclinical psychiatric symptoms such as emotional lability, irritability and euphoria in our patient group. These symptoms do not meet the criteria for a mood episode. Therefore, it is possible that hypomanic symptoms were more frequently observed compared to bipolar disorder in our sample. The frequencies of dysthymic disorder, OCD, panic disorder, social and specific phobia, and GAD were greater in our sample than observed in the general population [23,24,31,35]. There is limited data regarding the relation of current prevalence of dysthymic disorder and specific anxiety disorders in patients with MS. Mo¨ller et al. [14] reported dysthymic disorder in 8% and panic disorder with agoraphobia in 4% of 25 patients with MS. Joffe et al. [34] found that current prevalence rates of panic disorder and GAD were 1 and 2%, respectively. In this study, we observed that patients in exacerbation phase of MS had higher prevalence of major depression, panic disorder, OCD, and any mood or anxiety disorder. We found no adequately detailed information regarding differences in frequencies of psychiatric disorders, particularly anxiety disorders between phases of MS from studies that explored the psychiatric aspects of MS. Dalos et al. [36] reported that the prevalence of emotional disturbance was higher in exacerbating or progressing patients than stable patients. McCabe [37] reported higher levels of anxiety in MS exacerbation group compared to no-exacerbation group. In contrast, Minden et al. [10] noted no association between depression and clinical status (exacerbation versus remission). We are considering as a notable finding of our study that OCD and panic disorder were established more frequent in exacerbation phase than remission phase of MS. This finding suggests that OCD and panic
disorder symptoms are new begin in at least some subjects during exacerbation phase of MS, although the present study has a cross-sectional design. Further neuroimaging studies investigating the association between new onset OCD or panic disorder symptoms and localization of MS lesions in the exacerbation phase of MS may contribute to greater understanding of the pathogenesis of these two disorders. Similar to our results, a number of studies found no association between depression and age at assessment [6,10,14,17], age at onset [6], gender [10,14,15,17,19] and duration of illness [6,10,14, 17,19]. Conversely, some investigators reported the association of depression with female gender [6], shorter duration of illness [15,16], and younger age [15,19]. In addition, some authors [15,17] observed elevated frequencies of divorced, widowed or seperated subjects, and lower educational level in depressed patients, which are inconsistent with our findings. The present study showed that a greater degree of disability was a predictor for any depressive disorder, and this finding is consistent with most reports that have noted correlations with disability status of depression [4,6,15,17], although there are some studies [5,10,14] that have not found a relationship between these variables. The psychosocial factors due to disability (e.g., dependence on other persons for daily activities, economical problems resulting from unemployment) may contribute to depression in MS [4]. However, the impact of disability may be modified by various factors such as personality properties, meaning and place of the illness in an individual’s life, predisposition to depression, and availability of social support [10]. There is a need to study systematically evaluated influences of these potential factors on depression and the localizations of nervous system lesions which may have caused greater disability. To date and to our knowledge, factors associated with any anxiety disorder have not been explored. Earlier studies based on anxiety rating scales reported controversial consequences about the relation of anxiety with the degree of disability [2,5]. We observed that shorter disease duration was related to any anxiety disorder within the examined sociodemographic and clinical characteristics except the status of illness. This finding should be replicated by other studies. Indeed, the present study has methodological restrictions regarding the duration of disease. We accepted the time after diagnosis of MS as the duration of illness. On the other hand, the disease may have onset well before diagnosis in at least some patients. Finally, anxiety disorders include a variety of specific subtypes. The sample size of our study was not sufficiently large to determine the factors associated with each specific anxiety disorder.
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Mood and anxıety dısorders ın patıents wıth multıple sclerosıs The presence of the exacerbation phase of MS was a predictor for both any depressive and any anxiety disorder. As a consequence, a biological connection between psychiatric disorders and MS is likely. Zorzon et al. [38] found a significant correlation between depression and right temporal atrophy, and proposed that temporal lobes may play a role in the etiology of depression in MS. Feinstein et al. [39] reported more hyperintense lesions in the left anterior medial frontal regions and greater atrophy of the left anterior temporal regions in depressed patients with MS compared to nondepressed patients with MS. Recently, some authors found an increased (inferior parietal cortex and left inferior frontal cortex) and a reduced metabolism (right talamus, bilateral cerebellum, and left inferior parietal cortex) in some brain regions in patients with MS compared to controls [40]. Alterations in metabolism and neurotransmitter function in brain regions affected by MS lesions may be a possible pathogenetic mechanism to delineate any correlation between psychiatric disorders and MS. In addition, investigators have shown significantly higher cerebrospinal fluid (CSF) and serum levels of tumor necrosis factor-a (TNF-a) in relapsing phase, as compared with both those in remission or the controls [41,42], and during relapse phase, a significant increase of some serum pro-inflammatory cytokines such as TNF-a [43]. Mikova et al. [42] also noted that increased serum TNF-alpha was more pronounced in patients diagnosed with depression than in MS patients. Pro-inflammatory cytokines such as TNF-a may play a role in the development of mood and anxiety disorders by impacting central monoamine turnover [44] in susceptible subjects during exacerbation of MS. However, because there may be a reciprocal relationship between mood or anxiety disorders and phases of MS, we cannot conclude from our study (a cross-sectional research) that the exacerbation phase of MS leads to these mental disorders. Future prospective controlled studies may ensure more correct information in this respect. Our study had several limitations. First, the sample size was relatively small. Second, it was conducted in a clinical sample which might be underpresented all patients with MS. This condition is a factor restricting the generalization of our results. Third, this study was conducted as a cross-sectional research. The results of this study suggest an association between psychiatric disorders and phases of MS. However, large scale prospective studies should be performed to elucidate exact clinical relationship between psychiatric disorders and MS. In conclusion, despite some limitations, this study suggests that current prevalences of mood and anxiety disorders in patients with a diagnosis of relapsingremitting MS attending a MS clinic are higher than estimated in the general population, and patients in exacerbation phase are more likely to
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meet the diagnostic criteria for these disorders. For this reason, these disorders should be carefully screened in all patients with MS, especially during exacerbation phase. In addition, the patients in exacerbation phase may apply to a psychiatry clinic to seek help regarding the symptoms of depressive or anxiety disorders prior to diagnosis of MS. Finally, further prospective controlled studies are needed to investigate the influence of psychiatric disorders on the prognosis and course of MS. Key points . A considerable number of outpatients with a diagnosis of multiple sclerosis have mood or anxiety disorders . Among outpatients with multiple sclerosis, the most common mood disorder is major depression, and the predictors of any depressive disorder are presence of exacerbation phase of multiple sclerosis and higher disability level . The most common anxiety disorders are generalized anxiety disorder and specific phobia in outpatients with multiple sclerosis. Shorter disease duration and the presence of exacerbation phase predict any anxiety disorder in this patient group . The diagnoses of major depression, panic disorder and obsessive-compulsive disorder are more frequent among patients in exacerbation phase compared to patients in the remission phase in multiple sclerosis Statement of interest The authors have no conflict of interest with any commerical or other associations in connection with submitted paper.
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