Gender difference in relation to depression and quality of life among patients with a primary brain tumor

European Psychiatry 21 (2006) 194–199 http://france.elsevier.com/direct/EURPSY/

Original article

Gender difference in relation to depression and quality of life among patients with a primary brain tumor Arja Mainio a,b,*, Helinä Hakko a,b, Asko Niemelä a,b, John Koivukangas c, Pirkko Räsänen a,b a

Department of Psychiatry, University of Oulu, Box 5000, 90014 Oulu, Finland Department of Psychiatry, Oulu University Hospital, Box 26, 90029 Oys, Finland c Department of Neurosurgery, Oulu University Hospital, Box 26, 90029 Oys, Finland b

Received 11 October 2004; accepted 26 May 2005 Available online 02 September 2005

Abstract Objective. – We studied the relationship between depressive symptoms and quality of life (QOL) as well as functional status in primary brain tumor patients at recurrent measurements. Differences in QOL between depressive and non-depressive samples by gender were controlled for tumor characteristics and patients’ psychosocial factors. Materials and methods. – The data consisted of 77 patients with a primary brain tumor, 30 males and 47 females. Depression of the patients was assessed by Beck Depression Inventory (BDI) and Crown-Crisp Experiential Index (CCEI), functional status by Karnofsky Performance scale (KPS) and QOL by Sintonen’s 15D before tumor operation as well as at 3 months and at 1 year from surgical operation of the tumor. Results. – The level of QOL in females was lower compared to that of males. Depression was the main predictor for worse QOL in the patients at all measurements. Depressive patients with a benign brain tumor had significantly worse QOL versus non-depressive ones. Discussion and conclusion. – Decreased QOL was strongly related to depression, especially among patients with a benign brain tumor. Further studies are needed to find whether sufficient depression therapy improves the QOL of patients. © 2005 Elsevier SAS. All rights reserved. Keywords: Brain tumor; Depression; Functional status; Gender; Quality of life

1. Introduction Mourning and sadness are normal reactions in patients facing any serious disease. Prolonged grief can, however, turn into clinical depressive disorder, which is known to be associated with decreased quality of life (QOL) in cancer patients [29]. Among brain tumor patients, the association of depression with lowered QOL has gained a great deal of interest in studies during this decade [8,11,14,19,24,29]. Unfortunately, in spite of many patients’ long survival the focus of the studies on QOL among brain tumor patients has been mainly cross-sectional [8,14,24,28,33]. Besides, only a few studies have investigated the contemporary assessment of depressive disorder and QOL by clinically valid tools [8,24].

* Corresponding author. Tel.: +358 8 315 4509; fax: +358 8 315 4648. E-mail address: [email protected] (A. Mainio). 0924-9338/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.eurpsy.2005.05.008

Pelletier and colleagues (2002) reported that in the patients, depression, fatigue, emotional distress and existential tension were all significantly interrelated with each other. In particular the presence of depression was shown to be the most notable single predictor of overall worse QOL among the patients [24]. The studies on the gender difference in QOL among brain tumor patients are mainly lacking [33] although it is known that QOL in female patients with many somatic diseases such as chronic lymphocytic leukemia [10], inflammatory bowel disease [5], chronic arterial disease [23,34], and a myocardial infarct [1,30] had shown to be significantly worse than in males. Further, absence of depression or anxiety and living with partner has suggested to play an important role to protect the strain caused by an acute myocardial infarction [17]. In addition, Emery and colleagues (2004) showed that impaired emotional QOL in female cardiac disease patients was associated with the lack of perceived social support; in

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particular the sense of belonging or companionship was associated with [7]. The aim of the present study was to study the relationship between the level of depression and QOL as well as functional status in primary brain tumor patients, among males and females, separately. Secondly, we examined the difference in QOL and functional status between depressive and non-depressive male and female patients after controlling for tumor characteristics and patients’ psychosocial factors. Preand postoperative measurements enabled us to study the change of these issues over a 1 year follow-up. 2. Material and methods The study population consisted of 77 patients with a solitary primary brain tumor treated surgically at the Oulu Clinic of Neurosurgery, Oulu University Hospital in Northern Finland. The patients’ sociodemographic and clinical characteristics were collected during the admission to hospital for the tumor surgery, and a trained physician interviewed the patients. Written informed consent was obtained from all the participants and the Ethics Committee of Oulu University Hospital approved the study protocol. The variables used in this study are described and summarized in Table 1. The radiological diagnosis of the brain tumor was carried out by computer tomography (CT) or magnetic resonance imaging (MRI). The tumors were divided into two size classes according to the volume of the tumor, i.e. tumors with volume of 25 ml or less and those with volume exceeding 25 ml, determined manually from the CT or MRI. The histology of the tumor was defined according to the WHO classification [15]. The detailed description of the original database has been documented earlier [22].

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Table 1 The sociodemographic and clinical characteristics of the patients with a primary brain tumor Variables

Mean age in years (S.D.) Psychosocial factors Marital status Married/cohabiting Not married Education Elementary school or less Middle school High school graduate Employment status Employed On sickness leave Not employed History of previous depression Yes No Tumor characteristics Histology of the tumor Grade I–II glioma Grade III–IV glioma Benign brain tumors a Location of the tumor In left hemisphere In right hemisphere Bilateral/other Tumor volume Less than 25 ml 25 ml or more

Males % (n) Females % (n) Gender N = 30 N = 47 difference, P-value b 48.5 (11.2) 45.9 (11.7) 0.149

80.0 (24) 20.0 (6)

80.9 (38) 19.1 (9)

0.474

60.0 (18) 23.3 (7) 16.7 (5)

59.6 (28) 29.8 (14) 10.6 (5)

0.533

36.7 (11) 26.6 (8) 36.7 (11)

40.4 (19) 31.9 (15) 27.7 (13)

0.757

50.0 (15) 50.0 (15)

59.6 (28) 40.4 (19)

0.483

23.3 (7) 36.7 (11) 40.0 (12)

19.1 (9) 8.5 (4) 72.3 (34)

0.005 c

50.0 (15) 30.0 (9) 20.0 (6)

44.7 (21) 34.0 (16) 21.3 (10)

0.653

46.7 (14) 53.3 (16)

44.7 (21) 55.3 (26)

0.825

a

Meningioma, acoustic neurinoma, pituitary adenoma. Mann–Whitney U-test. c Fischer exact test.

b

2.1. Assessment of depression

2.2. Assessment of QOL

Depressive symptoms were evaluated by the Beck depression inventory (BDI). BDI is widely used and accepted as a valid screening instrument for depressive symptoms corresponding to diagnostic criteria for depressive disorders followed by DSM-IV diagnostic classification [4]. BDI has been used in earlier studies evaluating depressive symptoms among patients with a primary brain tumor [12,24]. As defined in BDI, at least mild depression is indicated to be present if the sum of the depression scores is 10 or higher, and this was also used as a cut-off point for depression in the present study. The patients were also asked if they have formerly had depressive periods in their history. This previous depression was evaluated by using the depression scale of Crown-Crisp Experiential Index (CCEI) [2]. The patients completed both questionnaires during the admission for the surgical operation of the brain tumor, within 1–5 days before operation, and they also completed the BDI at two postoperative follow-ups 3 months and 1 year after the operation. Both questionnaires were administered by a trained psychologist.

The patients’ QOL was assessed by Sintonen’s 15D scale before tumor operation as well as at 3 months and at 1 year after the operation by a trained physician. Sintonen’s 15D scale is a generic, comprehensive, 15-dimensional, standardized, self-administered measure of health-related QOL [31]. It is possible to obtain a sumscore of different dimensions ranging from 0 to 1. The value “0” means that the person has died, and “1” means good QOL of a completely healthy person. The 15D instrument has also been used in previous studies assessing QOL among cancer patients [25] and depressive patients [20]. 2.3. Assessment of functional outcome Karnofsky Performance Scale (KPS) is the scale indicating a person’s overall functional outcome [13]. The main purpose of the scale is to assess a person’s ability to work, his physical activity, and self-care. The KPS scores of three measurements were rated at 10-unit intervals by a trained physician, varying from 0 (dead) to 100 (healthy). A trained phy-

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sician also assessed the functional status of the patients at three time points: before tumor operation, at 3 months, and at 1 year after the operation. 2.4. Statistical analyses One preoperative and two postoperative measurements in depression, QOL and functional state were available for all the study subjects. The gender differences in categorical variables were assessed with Pearson’s Chi-square test or Fisher’s Exact test, and in continuous variables with Student’s t-test or Mann–Whitney U-test, whichever was appropriate. The change over time in depression (BDI), QOL (Sintonen’s 15D) and functional state (KPS) was examined with Wilcoxon signed ranks test. Logistic regression analysis was used to assess the group difference (depressed vs. non-depressed patients) in QOL and functional state after adjusting for age and tumor histology (type, volume and location of the tumor) and psychosocial variables (a history of previous depression, marital and employment status, educational state). All statistical analyses were performed, by using the SPSS statistical software, version 11, and the results in this study were considered statistically significant when the appropriately calculated two-tailed P-value was ≤ 0.05.

3. Results Fig. 1 visualizes the change over time in the mean level of QOL, functional state, and depression of the patients. Females had lower QOL in all measurements compared to males (P = 0.054). In functional state by KPS, no difference was found (P = 0.522). Further, 1 year after the operation females were more depressive than males, but the difference did not reach statistical significance (P = 0.159). In males, a statistically significant increase in QOL was observed between pre- operative measurements and those made 1 year after the operation (Wilcoxon signed ranks test, P = 0.046) as well as between postoperative measurements 3 months and 1 year after the operation (Wilcoxon signed ranks test, P = 0.001). In addition, among males depression scores decreased significantly between pre- operative measurements and those made 1 year after the operation (Wilcoxon signed ranks test, P = 0.047). In female patients, as seen in Fig. 1, QOL showed a statistically significant increase in postoperative measurements from 3 months to 1 year (Wilcoxon signed ranks test, P = 0.008), while the change in functional status was significant between preoperative measurements and those made 1 year after the operation (Wilcoxon signed ranks test, P = 0.047). A significant decrease was found in depression level between preoperative measurements and those made 3 months postoperatively (P = 0.046). After controlling for age and gender of the patients, the increased level of depressive symptoms was statistically significantly associated with decreased QOL of the patients

Fig. 1. The change over time in the level of depression, functional outcome and QOL among male and female patients with a primary brain tumor. QOL: quality of life; KPS: karnofsky Scale; BDI: Beck Depession Inventory

before operation (OR 13.28, 95%CI 3.70–47.70, < 0.001) and also at 3 months (OR 11.29, 95%CI 3.12–40.90, < 0.001) and at 1 year (OR 20.82, 95%CI 3.92–110.61, < 0.001) after operation. The adjustment for functional status, psychosocial factors (marital, employment, and educational status as well

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Table 2 QOL and functional state among depressed and non-depressed patients with a brain tumor at three measurements separately according to histological subgroups Patients with

Before surgery Sintonen 15D KPS 3 months after surgery Sintonen 15D KPS 1 year after surgery Sintonen 15D KPS

Grade I–II gliomas N = 18 Depressed Non-depressed Mean (S.D.) Mean (S.D.) P value

Grade II–IV gliomas N = 12 Depressed Non-depressed Mean (S.D.) Mean (S.D.) P value

Benign brain tumors N = 47 Depressed Non-depressed Mean (S.D.) Mean (S.D.) P value

0.83 (0.11) 83.3 (8.2)

0.91 (0.06) 82.0 (14.0)

0.065 0.754

0.78 (0.12) 60.0 (16.3)

0.89 (0.08) 85.0 (12.0)

0.105 0.010

0.77 (0.09) 75.0 (11.6)

0.91 (0.06) 86.3 (11.0)

0.000 0.004

0.79 (0.03) 90.0 (0.0)

0.88 (0.08) 83.1 (13.0)

0.067 0.380

0.81 (0.14) 80.0 (10.0)

0.89 (0.07) 93.3 (8.2)

0.465 0.047

0.79 (0.12) 80.0 (10.7)

0.89 (0.08) 88.9 (9.4)

0.007 0.005

0.79 (0.07) 83.3 (11.6)

0.95 (0.05) 90.0 (11.6)

0.012 0.291

0.83 (0.0) 80.0 (0.0)

0.93 (0.06) 90.0 (7.1)

0.206 0.143

0.79 (0.12) 81.5 (11.4)

0.93 (0.07) 92.3 (7.2)

0.000 0.001

as previous history of depression) and clinical characteristics of the tumor (tumor histology, location and volume of tumor) did not change the results. Table 2 shows the mean scores of QOL (Sintonen’s 15D) and the functional state (KPS) assessed in one pre- and two postoperative measurements for depressed and non-depressed subjects by histology. A decreased QOL and functional state of the patients was associated with increased level of depressive symptoms at all measurement points only in the patients with a benign brain tumor. The corresponding association was not seen in the patients with gliomas.

4. Discussion We found in the study of the patients with a primary brain tumor that the level of QOL in females was lower compared to that of males before tumor operation and up to 1 year of follow-up after surgical operation of the tumor. Recently, a corresponding gender difference in the level of QOL has been found in other follow-up studies among patients with different somatic diseases as well [1,5,10,23,30,34]. In the study among brain tumor patients findings had the same tendency as in our study; Weitzner and colleagues (1986) found in their cross-sectional study that female patients with a primary brain tumor had higher levels of psychological distress compared to males, and at the same time their overall QOL was lower than among males [33]. Our study is the first study so far in which a gender difference has been found in the level of QOL among brain tumor patients using a 1-year follow-up and both pre- and postoperative measurements. The reasons for the lower QOL in female patients have remained obscure [1]. It has been suggested that the gender difference in QOL among patients with cardiac diseases is caused by elevated levels of anxiety and depression in females [34] or due to overall worse psychosocial profiles in females [30]. In our study, an increased level of depression was significantly associated with worse QOL at 3-months and at 1 year after tumor surgery. Also, when the mean scores of QOL were controlled for psychosocial factors and the tumor character-

istics, the only significant factor for worse QOL both in males and females was depression. It is known that female cancer patients are in general likely to use many of their friends/relatives and their partner to provide social support during their cancer crisis, while male cancer patients are more likely to have only one confidante [9]. Since one main symptom of depressive disorder is withdrawal from social connections, it is probable that depressive females with primary brain tumor cannot utilize their social network, and thus cannot gain mastery over their lives in spite of the prognosis of their disease. Furthermore, brain tumor patients are known to exhibit increased emotional reactivity and lowered tolerance for stressful situations [32]. It can be suggested that depressive females with these problems can experience their normal daily events as being highly distressing reflecting on QOL. Depressive patients with a benign brain tumor had a significantly decreased functional status measured by KPS compared to that of non-depressive benign tumor patients. A corresponding difference was not found among depressive versus non-depressive low-grade glioma patients. In the patients with high-grade gliomas depression was associated with decreased functional status at the first two measurements. Our finding is in line with the earlier studies showing that patients reported good QOL when their KPS scores were above 80 [18,27,32]. Formerly, no correlation had been found between KPS and depression, but the results had not been reported separately for patients with different histological subgroups [21]. Further research is needed to evaluate the possible delaying effect of depression on the whole rehabilitation process among brain tumor patients. In our study, a decreased QOL was not directly linked with the malignancy of tumor. Reversely, a lowered QOL was significantly associated with the level of depressive symptoms in the patients with benign tumors. In our database, a great proportion of high-grade gliomas were found in males, while females had the majority of the benign tumors. Thus, depressive female patients with a benign brain tumor may have a high risk for decreased QOL during the postoperative time up to 1 year after tumor surgery. Formerly, loss of life-quality has been found in meningioma patients after successful opera-

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tion compared to normal population, leading to problems in the family and in the workplace [26]. We emphasize the importance of our finding of the gender difference in QOL, since, although the treatment of a histologically benign brain tumor can be curative, limitations in life satisfaction and in functional capacity might remain, especially in depressive females. The importance of depression treatment as soon as depression has been diagnosed has been emphasized [24]. Psychosocial interventions for brain tumor patients should include therapy with antidepressants and psychotherapy [33]. Studies focusing on evidence of effective psychotherapy for depression among brain tumor patients are limited [24]. The knowledge of efficient psychotherapy is based on studies among patients with traumatic brain injury and post-stroke depression, and according to these studies cognitive therapy can be the therapy of choice in these neuropsychiatric disorders [3,16]. The limitations of our study were the heterogenic histology of tumors and the small number of subjects in different histological subgroups. However, our study samples consisted of unselected population in the large area of Northern Finland. In addition, the study protocol did not unfortunately include an assessment of the exact psychiatric diagnosis according to any structured criteria-based diagnostic interview. Neither do we have any information on the treatment of the patients’ depression. Although significant differences were found between depressive and non-depressive patients with benign brain tumors, the clinical importance of the findings remains open due to the quite low mean BDI scores of the patients at different measurement points. Further investigations using a larger database of brain tumor patients are needed to confirm the findings.

[2]

5. Conclusion

[14]

Our study indicates that decreased QOL was strongly related to depression, especially among patients with a benign brain tumor. All treatment efforts that relieve patients’ symptoms caused by the disease have inevitably a positive impact on their daily resilience. It is known that patients themselves may be reluctant to initiate discussion on emotional symptoms, but are willing to discuss psychosocial aspects of their disease if the physician takes the initiative [6]. Further studies are needed to evaluate which are the most efficient treatment modalities for depression among brain tumor patients, and whether sufficient therapy improves the QOL of patients. The causality of the gender difference in the level of QOL among brain tumor patients also deserves special attention in future research.

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