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Parents of childhood X-linked adrenoleukodystrophy: High risk for depression and neurosis
Brain & Development 30 (2008) 477–482 www.elsevier.com/locate/braindev
Original article
Parents of childhood X-linked adrenoleukodystrophy: High risk for depression and neurosis Izumi Kuratsubo a,*, Yasuyuki Suzuki b, Nobuyuki Shimozawa c, Naomi Kondo a b
a Department of Pediatrics, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan Medical Education Development Center, Gifu University Graduate School of Medicine, Gifu University, Gifu, Japan c Life Science Research Center, Gifu University, Gifu, Japan
Received 5 September 2007; received in revised form 21 December 2007; accepted 27 December 2007
Abstract The purpose of this study was to assess mental health in parents of patients with the childhood cerebral form of X-linked adrenoleukodystrophy (CCALD) and to investigate factors relating to psychological problems in order to improve clinical management and quality of life. Sixteen fathers and 21 mothers of patients with CCALD completed a battery of psychological examinations including the Beck Depression Inventory second edition (BDI-II), the General Health Questionnaire 60 (GHQ60), and the State–Trait Anxiety Inventory (STAI). Three fathers and 11 mothers showed high scores on the BDI-II, suggesting that they were in a depressive state. Depression in the mothers was serious as compared with previous reports. Six fathers and 11 mothers were considered to be in a state of neurosis, according to the results of the GHQ60. Four fathers and 8 mothers showed high levels of anxiety on the STAI. Health and social status of the mothers correlated with their mental health, and younger mothers with young patients tended to be more depressed. Thus, parents of patients with CCALD have a high risk of depression and neurosis. Understanding the mental state of these parents and improvements in the social support system including mental counseling, home nursing care, supports in workplace and community are necessary to prevent and treat psychological problems. Especially, early intervention for mental health problems should be provided for younger mothers with few years since the child’s diagnosis. Ó 2008 Published by Elsevier B.V. Keywords: Childhood cerebral form of X-linked adrenoleukodystrophy; Depression; Neurosis; Mental health; General Health Questionnaire 60; State–Trait Anxiety Inventory; Beck Depression Inventory second edition
1. Introduction X-linked adrenoleukodystrophy (ALD) is a severe neurodegenerative disease with demyelination of the central nervous system and adrenal insufficiency [1]. Accumulation of very-long chain fatty acids (VLCFA) in tissues and body fluids is the hallmark of this disease [2]. The pathogenic gene for X-linked ALD is found on chromosome Xq28 [3], and the gene product, ALD protein, is located in the membrane of peroxisomes and has *
Corresponding author. Tel.: +81 58 230 6386; fax: +81 58 230 6387. E-mail address: [email protected] (I. Kuratsubo). 0387-7604/$ - see front matter Ó 2008 Published by Elsevier B.V. doi:10.1016/j.braindev.2007.12.012
been suggested to act as a transporter of VLCFA into peroxisomes [4]. The incidence of X-linked ALD has been estimated to be one in 20,000–200,000 males [1]. There are several clinical phenotypes: the childhood cerebral form (CCALD), the adolescent form, adrenomyeloneuropathy (AMN) with spinal cord disturbance, the adult cerebral form with disturbed intellectual ability, the olivo-ponto-cerebellar form with cerebellar ataxia, and Addison’s disease with adrenal insufficiency [1]. CCALD is the most common phenotype and is characterized by the rapid progression of intellectual, visual, auditory, and gait disturbances between the age of 3 and 11 with an average onset age of 7 years. The prognosis
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of CCALD is generally poor and patients usually progress to a vegetative state within a few years [5]. Several therapeutic trials, including hematopoietic stem cell transplantation (HSCT) [6,7], Lorenzo’s oil [8–10], and lovastatin [11], have been carried out in patients with CCALD. HSCT is considered to be the therapy of choice for CCALD patients with minimum neurological progression. However, not all patients can receive HSCT due to the difficulty in finding donors. Coordination with unrelated bone marrow donors is often time-consuming in Japan, and cord blood transplantation is still limited. In addition, complications and deterioration may occur during or after HSCT [7]. Supplementation of Lorenzo’s oil, consisting of oleic acid (C18:1) and erucic acid (C22:1), decreases blood VLCFA levels in patients [8], however, improvement of neurological symptoms has not been reported [10]. Long-term prophylactic use of Lorenzo’s oil for pre-symptomatic boys may protect against disease onset [9]. Gene therapy is a promising future therapeutic strategy for ALD and a clinical trial is beginning (Nature News, 30 October 2007). Psychological problems in relatives of patients with CCALD have been overlooked. Many patients with CCALD show deterioration of neurological symptoms, and progress to a vegetative state within a few years [5]. In the early stage of the disease, parents consult specialists for a correct diagnosis, parents also have to choose difficult treatments, and come to terms with serious genetic problems. In later years, parents are responsible for a significant amount of the patient’s home care including nutrition, rehabilitation, respiratory care, and educational support over a long period of time, which may lead to both physical and psychological stress. In this study we determined the psychological status of parents of CCALD patients using a questionnaire and mental health examinations and discuss issues relating to support for these problems.
Table 1 Background of subjects
Mean age Health status after disease onset No problems Physical tiredness (score 1) Mental tiredness (score 1) Illness (score 1) Mean health status score (±SD) (max score 3) Social status after disease onset No change Difficulties in family relations (score 1) Change or loss of job (score 1) Financial problems (score 1) Moving house (score 1) Mean social status score (±SD) (max score 4) Psychological counseling Not received Received Seeking
Father (n = 16)
Mother (n = 21)
48.2 years (34–60)
45.1 years (32–57)
7 3 9 2 0.88 ± 0.34
5 9 15 7 1.48 ± 0.51
7 4
3 13
5
9
6 0 0.94 ± 0.25
9 3 1.70 ± 0.47
12 2 0
12 4 5
Patients (n = 21) Age at this investigation (range) Years from disease onset (range) Bone-marrow transplantation Activities of daily life (ADL) Independent Half dependent Totally dependent Education and care Vocational aid center School for disabled Home care Hospitalization/welfare facility Social support (multiple choice) Home nursing Daycare Public financial support
16.8 years (8–24) 8.7 years (2–16) 1 0 1 20 1 6 8 2 2 3 20
2. Subjects and methods Mental health examinations and a questionnaire were sent to 40 ALD families who were members of the Japanese Association of ALD families. Thirty-seven parents (16 fathers and 21 mothers) of CCALD patients replied after gaining permission from the patient. Mean age of fathers and mothers were 48.2 years (34–60), and 45.1 years (32–57), respectively. Mean age of their 21 children at disease onset, at diagnosis, and at the time of this investigation were, 8.3 years, 8.8 years, and 16.8 years, respectively. A boy was received bone marrow transplantation. The questionnaire included queries on the health status of parents after disease onset, social status, experience of psychological counseling, activities of daily living (ADL) of the patients, education, patient care, and social support. Health and social status of the parents were scored and compared (Table 1).
Mental health of the parents of CCALD patients was assessed using the Beck Depression Inventory second edition (BDI-II, The Psychological Corporation, Tokyo, Japan) [12], the General Health Questionnaire 60 (GHQ60, Nihon Bunka Kagakusha Co., Ltd., Tokyo, Japan) [13], and the State and Trait Anxiety Inventory (STAI, Sankyobo, Kyoto, Japan) [14]. Inadequate answers were omitted from the analysis. Briefly, the BDI-II is a 21-item self-rated scale which evaluates depression severity. The BDI-II measures attitudes and symptoms which are characteristic of depression such as mood, pessimism, sense of failure, lack of satisfaction, guilt, sense of punishment, self-hate, selfaccusations, etc. Each item consists of 4 statements and a client selects one appropriate statement, scores
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range from 0 to 63. A score below 13 is considered to be normal and the subject non-depressed, a score of 14–19 suggests the subject is mildly depressed, 20–28 moderately depressed, and 29–63 highly depressed. The GHQ60 is a 60-item self-rated scale which evaluates mental and physical distress and the risk for psychiatric disorders, scores range from 0 to 60. A score of 17 or above indicates a high risk for neurosis. The STAI is composed of two separate 20-item subscales constructed to measure ‘‘state” and ‘‘trait” anxiety, using 4-point scales. On the State Scale, respondents are asked to indicate ‘‘how [he/she] feels right now”, whereas on the Trait Scale, respondents are asked to indicate ‘‘how [he/she] generally feels”. State or trait anxiety scores range from 20 to 80, with higher scores reflecting a greater degree of anxiety. Data of subjects in these psychological tests were compared with normative data in Japanese population. Statistical analyses of the GHQ60, STAI and BDI-II were performed using Spearman’s correlation coefficient. Correlations between descriptions in the questionnaire and results of the GHQ60, STAI and BDI-II were evaluated with Spearman’s correlation. Statistical differences between fathers and mothers in the GHQ60, STAI and BDI-II were evaluated using the Student’s T test or Welch’s T test. Comparison of the mothers with low and high scores on the BDI-II, (age of the mothers, age of the patients, years from onset, GHQ60 score, State Anxiety score, health status score, and social status score) was analyzed using the Mann–Whitney’s U test.
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or schools for the disabled, but many stayed home or were hospitalized. Many families utilized public financial support, however, utilization of human resources for welfare, such as home nursing and daycare was very limited. 3.2. BDI-II The average scores on the BDI-II in 14 fathers and 19 mothers were 8.9 (range 0–23) and 18.7 (range 0–44), respectively (Fig. 1). These scores were higher than those of healthy adult Japanese (male 8.21 ± 6.46, female 9.61 ± 6.31) [15]. Three fathers (21.4%) and 11 mothers (57.8%) scored over 14 points, suggesting that these parents were in a depressed state [16]. One father (7.1%) was mildly depressed, and 2 (14.3%) were moderately depressed. Two mothers (10.5%) were mildly depressed, 3 (15.8%) were moderately depressed and 6 (31.6%) were severely depressed. These findings, particularly in the mothers, were significantly different from those of healthy adult Japanese (81.7% normal, 12.0% mild, 5.0% moderate, 1.4% severe) [15]. The scores of the mothers were significantly higher than those of the fathers (p = 0.01). 3.3. GHQ60 The average scores on the GHQ60 in 15 fathers and 21 mothers were 12.9 (range 0–35) and 19.7 (range 2– 58), respectively (Fig. 2). These scores were higher than p = 0.01
3. Results 50
3.1. Questionnaire
40
30 (Point)
The backgrounds of the parents and the patients are summarized in Table 1. Many of the parents felt physical or mental tiredness, and some developed illnesses such as depressive disorder, irritable colon, facial palsy, autonomic imbalance, duodenal ulcer, lumbar disc hernia and lumbar strain. Social problems, including difficulties in family relations within their families and other relatives, change or loss of job, decreased income or increased expense, and moving house due to care of the patient or change of job, were also frequently reported. When each problem was scored as 1 point (max 3 points for health status and 4 points for social status), the mean score for mothers was slightly higher than that for fathers, although no statistically significant differences were observed (p = 0.07). Four mothers and 2 fathers had already received psychological counseling, and 5 mothers were seeking to receive counseling. The mean number of years after disease onset was 8.7 years, and ADL of the patients in this study showed that all but 1 were totally dependent on their parents. Some patients were able to attend vocational training centers
20
10
0 Father
Mother
Fig. 1. Scores on the BDI-II in parents of patients with CCALD. Three fathers and 11 mothers were considered to be depressed. The scores of the mothers were significantly higher than those of the fathers (p = 0.01).
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Fig. 2. Scores on the GHQ60 in parents of patients with CCALD. Six fathers and 11 mothers scored over 17 points, suggesting that these parents were in a state of neurosis.
those of healthy adult Japanese (8.08 ± 5.3) [17]. Scores of the mothers were slightly higher than those of the fathers (p = 0.14). Six fathers (40.0%) and 11 (52.4%) mothers scored over 17 points, suggesting that these parents were in a state of neurosis [17,18]. 3.4. STAI The mean value of the State Anxiety scores in 15 fathers and 20 mothers was 45 (range 19–62) and 53.0 (range 19–77), respectively (Fig. 3). The mean value of the Trait Anxiety scores in 14 fathers and 19 mothers was 43.7 (range 24–65) and 51.6 (range 30–73), respectively. These mean values were higher than those in healthy adult Japanese (State Anxiety 36.6 ± 8.98, Trait Anxiety 38.8 ± 9.68) [19]. Scores of the mothers were slightly higher than those of the fathers (State Anxiety: p = 0.11, Trait Anxiety: p = 0.09). Four fathers and 8 mothers showed high scores in both State Anxiety (>50 for males, >51 for females) and Trait Anxiety (>53 for males, >55 for females). 3.5. Correlations between psychological examinations and the questionnaire The results of the BDI-II, GHQ60 and STAI were positively correlated with each other both in the fathers
Fig. 3. Scores on the STAI in parents of patients with CCALD. Six fathers and 12 mothers showed high levels of State Anxiety and 5 fathers and 8 mothers showed high levels of Trait Anxiety.
and in the mothers (rs = 0.60–0.91). Correlations between the psychological examinations and the scores of health or social status of the parents are shown in Table 2. Health status such as tiredness and illness correlated positively with the results of psychological examinations both in the fathers and in the mothers. On the other hand, correlations between social status such as difficulties in family relations and financial problems and the results of psychological examinations were weak, especially in the fathers. A weak negative correlation (rs = 0.51) between the scores on the BDI-II in the
Table 2 Correlations between psychological examinations and questionnaire
Father BDI-II GHQ60 State Anxiety Trait Anxiety Mother BDI-II GHQ60 State Anxiety Trait Anxiety *
P < 0.05.
Health status
Social status
rs = 0.69* 0.65* 0.63* 0.62*
rs = 0.20 0.36 0.09 0.17
0.49* 0.42* 0.60* 0.63*
0.49* 0.49* 0.40 0.49*
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Table 3 Comparison of mothers with low and high scores on the BDI-II
Mean age of the mothers Mean age of the patients Years from onset GHQ60 score State Anxiety score Health status scorea Social status scoreb a b
BDI-II score <19 (n = 10)
BDI-II score >20 (n = 9)
P value
48.0 years 19.8 years 11.6 15.3 43.8 1.3 1.67
41.9 13.3 5.1 26 63 1.89 1.89
0.06 0.004 0.005 0.18 0.005 0.26 0.89
Physical tiredness (score 1) + mental tiredness (score 1) + illness (score 1). Difficulties in family relations (score 1) + change or loss of job (score 1) + financial problems (score 1) + moving house (score 1).
mothers and the number of years from disease onset was found. When we compared 2 groups of mothers with low and high scores on the BDI-II, the mean age of the patients was lower and the number of years from disease onset was shorter in mothers with a high score (moderately to severely depressed group) (Table 3). State Anxiety scores were also higher in the moderately to severely depressed group. Health status or social status scores were not significantly different. 4. Discussion In the present study, we clarified the objective evidence for psychological status in the parents of patients with CCALD, using psychological examinations and a questionnaire. The questionnaire revealed that many of the parents had health problems such as physical and mental tiredness, and various illnesses probably related to their physical and mental distress. Social difficulties in human relations, employment, finance, and housing were also identified. These problems and difficulties are likely to be more serious in mothers as, for the most part, mothers are the main caregivers of children with CCALD, however, no objective evidence for this speculation was provided. We have found that parents of CCALD patients are at high risk of depression. In particular, 57.8% of mothers showed high scores on the BDI-II, and 47.4% were moderately to severely depressed. As the distribution of BDI-II scores in healthy populations has been found to be similar in different countries [15,20], we can compare the severity of depression in mothers. In Turkey, 48.5% of mothers with epileptic children were shown to be depressed as assessed by the BDI, and 33.3% were moderately to severely depressed [21]. In the UK, 57% of mothers of adolescent cancer patients showed depression at the time of diagnosis, and 27% were moderately to severely depressed [22]. Similar results in mothers of children with hematopoietic malignancies have been reported from Iran [23]. These reports suggest that the mental health of Japanese mothers of CCALD patients is more impaired than that of mothers of patients with other diseases. As subjects with a moderate to severe
depression score on the BDI-II have a higher risk of developing true depression [15], parents of patients with CCALD should be carefully followed. Several factors that may affect the mental status of parents of CCALD patients are considered. Firstly, the X-linked recessive inheritance of ALD may greatly affect parents. In X-linked diseases, mothers often feel guilty about having passed on the faulty gene which may lead to conflict between parents and other relatives. Mothers of sons with fragile X syndrome reported more pessimism about their son’s future and more conflict within the family than mothers of sons with Down syndrome [24]. Many of the mothers in this study also stated feelings of guilt and sadness in the questionnaire (data not shown). These emotional problems might greatly affect the risk of depression. Secondly, mothers of ALD patients are often carriers and 15–25% of female carriers have a risk of developing neurological symptoms that are similar to AMN [25,26]. Among women with AMN symptoms, not only do they have a child who will die, but they themselves will develop physical disabilities as they age. In our study, none of the mothers developed neurological symptoms, and the questionnaire did not include queries relating to anxiety about their own future. However, this may be another important factor which requires further investigation. Thirdly, external support would be of great help to parents and would improve their mental status. Mothers have a considerable burden in the care of their child, which requires time and patience. In addition to external support such as nursing help, daycare, and public financial support, social support in the family, workplace and community would be of significant help. Without such support, parents would be under more stress. Our study showed that only a few parents utilized home nursing and daycare (Table 1). We also identified a correlation between low social status and psychological problems (Table 2). Fourthly, adequate psychological support for parents might have an influence on their mental status. Our study showed that many of the parents were seeking psychological counseling. Younger mothers with young patients tended to be more depressed (Table 3). During the first few years after disease onset, parents encounter
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various medical, social, and psychological problems, and seem to become nervous, frustrated, and depressed. We should establish a mental care system to include parents and their care. Intervention for mental health problems should be early in the course of the disease, because younger mothers with few years since the child’s diagnosis appear to have the most severe depression. Thus we should not only consider the biomedical issues of patients with CCALD, but the psychological aspects of parents should also be taken into account. Recognition of the mental status of each parent is essential for adequate medical advice regarding their social life and psychological support, and to maintain appropriate family relationships. The BDI-II, GHQ60 and STAI may be useful in genetic counseling or in the out-patient clinic.
[8]
[9] [10]
[11] [12] [13] [14] [15]
Acknowledgement This study was supported by Grant-in-Aid for ‘‘the Research Committee for Ataxic Disease” of the Research on Measures for Intractable Disease from the Ministry of Health, Welfare and Labour, Japan. References [1] Moser HW, Smith KD, Watkins PA, Powers J, Moser AB. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. X-linked adrenoleukodystrophy. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill; 2001. p. 3257–301. [2] Igarashi M, Schaumburg HH, Powers J, Kishimoto Y, Colodney E, Suzuki K. Fatty acid abnormality in adrenocerebroleukodystrophy. J Neurochem 1976;26:851–60. [3] Mosser J, Douar AM, Sarde CO, Kioschis P, Feil R, Moser H, et al. Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature 1993;361:726–30. [4] Singh I, Moser AE, Goldfischer S, Moser HW. Lignoceric acid is oxidized in the peroxisome: implications for the Zellweger cerebro-hepato-renal syndrome and adrenoleukodystrophy. Proc Natl Acad Sci USA 1984;81:4203–7. [5] Suzuki Y, Takemoto Y, Shimozawa N, Imanaka T, Kato S, Furuya H, et al. Natural history of X-linked adrenoleukodystrophy in Japan. Brain Dev 2005;27:353–7. [6] Aubourg P, Blanche S, Jambaque I, Rocchiccioli F, Kalifa G, Naud-Saudreau C, et al. Reversal of early neurologic and neuroradiologic manifestations of X-linked adrenoleukodystrophy by bone marrow transplantation. N Engl J Med 1990;322:1860–6. [7] Suzuki Y, Isogai K, Teramoto T, Tashita H, Shimozawa N, Nishimura M, et al. Bone marrow transplantation for the
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Original article
Parents of childhood X-linked adrenoleukodystrophy: High risk for depression and neurosis Izumi Kuratsubo a,*, Yasuyuki Suzuki b, Nobuyuki Shimozawa c, Naomi Kondo a b
a Department of Pediatrics, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan Medical Education Development Center, Gifu University Graduate School of Medicine, Gifu University, Gifu, Japan c Life Science Research Center, Gifu University, Gifu, Japan
Received 5 September 2007; received in revised form 21 December 2007; accepted 27 December 2007
Abstract The purpose of this study was to assess mental health in parents of patients with the childhood cerebral form of X-linked adrenoleukodystrophy (CCALD) and to investigate factors relating to psychological problems in order to improve clinical management and quality of life. Sixteen fathers and 21 mothers of patients with CCALD completed a battery of psychological examinations including the Beck Depression Inventory second edition (BDI-II), the General Health Questionnaire 60 (GHQ60), and the State–Trait Anxiety Inventory (STAI). Three fathers and 11 mothers showed high scores on the BDI-II, suggesting that they were in a depressive state. Depression in the mothers was serious as compared with previous reports. Six fathers and 11 mothers were considered to be in a state of neurosis, according to the results of the GHQ60. Four fathers and 8 mothers showed high levels of anxiety on the STAI. Health and social status of the mothers correlated with their mental health, and younger mothers with young patients tended to be more depressed. Thus, parents of patients with CCALD have a high risk of depression and neurosis. Understanding the mental state of these parents and improvements in the social support system including mental counseling, home nursing care, supports in workplace and community are necessary to prevent and treat psychological problems. Especially, early intervention for mental health problems should be provided for younger mothers with few years since the child’s diagnosis. Ó 2008 Published by Elsevier B.V. Keywords: Childhood cerebral form of X-linked adrenoleukodystrophy; Depression; Neurosis; Mental health; General Health Questionnaire 60; State–Trait Anxiety Inventory; Beck Depression Inventory second edition
1. Introduction X-linked adrenoleukodystrophy (ALD) is a severe neurodegenerative disease with demyelination of the central nervous system and adrenal insufficiency [1]. Accumulation of very-long chain fatty acids (VLCFA) in tissues and body fluids is the hallmark of this disease [2]. The pathogenic gene for X-linked ALD is found on chromosome Xq28 [3], and the gene product, ALD protein, is located in the membrane of peroxisomes and has *
Corresponding author. Tel.: +81 58 230 6386; fax: +81 58 230 6387. E-mail address: [email protected] (I. Kuratsubo). 0387-7604/$ - see front matter Ó 2008 Published by Elsevier B.V. doi:10.1016/j.braindev.2007.12.012
been suggested to act as a transporter of VLCFA into peroxisomes [4]. The incidence of X-linked ALD has been estimated to be one in 20,000–200,000 males [1]. There are several clinical phenotypes: the childhood cerebral form (CCALD), the adolescent form, adrenomyeloneuropathy (AMN) with spinal cord disturbance, the adult cerebral form with disturbed intellectual ability, the olivo-ponto-cerebellar form with cerebellar ataxia, and Addison’s disease with adrenal insufficiency [1]. CCALD is the most common phenotype and is characterized by the rapid progression of intellectual, visual, auditory, and gait disturbances between the age of 3 and 11 with an average onset age of 7 years. The prognosis
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of CCALD is generally poor and patients usually progress to a vegetative state within a few years [5]. Several therapeutic trials, including hematopoietic stem cell transplantation (HSCT) [6,7], Lorenzo’s oil [8–10], and lovastatin [11], have been carried out in patients with CCALD. HSCT is considered to be the therapy of choice for CCALD patients with minimum neurological progression. However, not all patients can receive HSCT due to the difficulty in finding donors. Coordination with unrelated bone marrow donors is often time-consuming in Japan, and cord blood transplantation is still limited. In addition, complications and deterioration may occur during or after HSCT [7]. Supplementation of Lorenzo’s oil, consisting of oleic acid (C18:1) and erucic acid (C22:1), decreases blood VLCFA levels in patients [8], however, improvement of neurological symptoms has not been reported [10]. Long-term prophylactic use of Lorenzo’s oil for pre-symptomatic boys may protect against disease onset [9]. Gene therapy is a promising future therapeutic strategy for ALD and a clinical trial is beginning (Nature News, 30 October 2007). Psychological problems in relatives of patients with CCALD have been overlooked. Many patients with CCALD show deterioration of neurological symptoms, and progress to a vegetative state within a few years [5]. In the early stage of the disease, parents consult specialists for a correct diagnosis, parents also have to choose difficult treatments, and come to terms with serious genetic problems. In later years, parents are responsible for a significant amount of the patient’s home care including nutrition, rehabilitation, respiratory care, and educational support over a long period of time, which may lead to both physical and psychological stress. In this study we determined the psychological status of parents of CCALD patients using a questionnaire and mental health examinations and discuss issues relating to support for these problems.
Table 1 Background of subjects
Mean age Health status after disease onset No problems Physical tiredness (score 1) Mental tiredness (score 1) Illness (score 1) Mean health status score (±SD) (max score 3) Social status after disease onset No change Difficulties in family relations (score 1) Change or loss of job (score 1) Financial problems (score 1) Moving house (score 1) Mean social status score (±SD) (max score 4) Psychological counseling Not received Received Seeking
Father (n = 16)
Mother (n = 21)
48.2 years (34–60)
45.1 years (32–57)
7 3 9 2 0.88 ± 0.34
5 9 15 7 1.48 ± 0.51
7 4
3 13
5
9
6 0 0.94 ± 0.25
9 3 1.70 ± 0.47
12 2 0
12 4 5
Patients (n = 21) Age at this investigation (range) Years from disease onset (range) Bone-marrow transplantation Activities of daily life (ADL) Independent Half dependent Totally dependent Education and care Vocational aid center School for disabled Home care Hospitalization/welfare facility Social support (multiple choice) Home nursing Daycare Public financial support
16.8 years (8–24) 8.7 years (2–16) 1 0 1 20 1 6 8 2 2 3 20
2. Subjects and methods Mental health examinations and a questionnaire were sent to 40 ALD families who were members of the Japanese Association of ALD families. Thirty-seven parents (16 fathers and 21 mothers) of CCALD patients replied after gaining permission from the patient. Mean age of fathers and mothers were 48.2 years (34–60), and 45.1 years (32–57), respectively. Mean age of their 21 children at disease onset, at diagnosis, and at the time of this investigation were, 8.3 years, 8.8 years, and 16.8 years, respectively. A boy was received bone marrow transplantation. The questionnaire included queries on the health status of parents after disease onset, social status, experience of psychological counseling, activities of daily living (ADL) of the patients, education, patient care, and social support. Health and social status of the parents were scored and compared (Table 1).
Mental health of the parents of CCALD patients was assessed using the Beck Depression Inventory second edition (BDI-II, The Psychological Corporation, Tokyo, Japan) [12], the General Health Questionnaire 60 (GHQ60, Nihon Bunka Kagakusha Co., Ltd., Tokyo, Japan) [13], and the State and Trait Anxiety Inventory (STAI, Sankyobo, Kyoto, Japan) [14]. Inadequate answers were omitted from the analysis. Briefly, the BDI-II is a 21-item self-rated scale which evaluates depression severity. The BDI-II measures attitudes and symptoms which are characteristic of depression such as mood, pessimism, sense of failure, lack of satisfaction, guilt, sense of punishment, self-hate, selfaccusations, etc. Each item consists of 4 statements and a client selects one appropriate statement, scores
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range from 0 to 63. A score below 13 is considered to be normal and the subject non-depressed, a score of 14–19 suggests the subject is mildly depressed, 20–28 moderately depressed, and 29–63 highly depressed. The GHQ60 is a 60-item self-rated scale which evaluates mental and physical distress and the risk for psychiatric disorders, scores range from 0 to 60. A score of 17 or above indicates a high risk for neurosis. The STAI is composed of two separate 20-item subscales constructed to measure ‘‘state” and ‘‘trait” anxiety, using 4-point scales. On the State Scale, respondents are asked to indicate ‘‘how [he/she] feels right now”, whereas on the Trait Scale, respondents are asked to indicate ‘‘how [he/she] generally feels”. State or trait anxiety scores range from 20 to 80, with higher scores reflecting a greater degree of anxiety. Data of subjects in these psychological tests were compared with normative data in Japanese population. Statistical analyses of the GHQ60, STAI and BDI-II were performed using Spearman’s correlation coefficient. Correlations between descriptions in the questionnaire and results of the GHQ60, STAI and BDI-II were evaluated with Spearman’s correlation. Statistical differences between fathers and mothers in the GHQ60, STAI and BDI-II were evaluated using the Student’s T test or Welch’s T test. Comparison of the mothers with low and high scores on the BDI-II, (age of the mothers, age of the patients, years from onset, GHQ60 score, State Anxiety score, health status score, and social status score) was analyzed using the Mann–Whitney’s U test.
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or schools for the disabled, but many stayed home or were hospitalized. Many families utilized public financial support, however, utilization of human resources for welfare, such as home nursing and daycare was very limited. 3.2. BDI-II The average scores on the BDI-II in 14 fathers and 19 mothers were 8.9 (range 0–23) and 18.7 (range 0–44), respectively (Fig. 1). These scores were higher than those of healthy adult Japanese (male 8.21 ± 6.46, female 9.61 ± 6.31) [15]. Three fathers (21.4%) and 11 mothers (57.8%) scored over 14 points, suggesting that these parents were in a depressed state [16]. One father (7.1%) was mildly depressed, and 2 (14.3%) were moderately depressed. Two mothers (10.5%) were mildly depressed, 3 (15.8%) were moderately depressed and 6 (31.6%) were severely depressed. These findings, particularly in the mothers, were significantly different from those of healthy adult Japanese (81.7% normal, 12.0% mild, 5.0% moderate, 1.4% severe) [15]. The scores of the mothers were significantly higher than those of the fathers (p = 0.01). 3.3. GHQ60 The average scores on the GHQ60 in 15 fathers and 21 mothers were 12.9 (range 0–35) and 19.7 (range 2– 58), respectively (Fig. 2). These scores were higher than p = 0.01
3. Results 50
3.1. Questionnaire
40
30 (Point)
The backgrounds of the parents and the patients are summarized in Table 1. Many of the parents felt physical or mental tiredness, and some developed illnesses such as depressive disorder, irritable colon, facial palsy, autonomic imbalance, duodenal ulcer, lumbar disc hernia and lumbar strain. Social problems, including difficulties in family relations within their families and other relatives, change or loss of job, decreased income or increased expense, and moving house due to care of the patient or change of job, were also frequently reported. When each problem was scored as 1 point (max 3 points for health status and 4 points for social status), the mean score for mothers was slightly higher than that for fathers, although no statistically significant differences were observed (p = 0.07). Four mothers and 2 fathers had already received psychological counseling, and 5 mothers were seeking to receive counseling. The mean number of years after disease onset was 8.7 years, and ADL of the patients in this study showed that all but 1 were totally dependent on their parents. Some patients were able to attend vocational training centers
20
10
0 Father
Mother
Fig. 1. Scores on the BDI-II in parents of patients with CCALD. Three fathers and 11 mothers were considered to be depressed. The scores of the mothers were significantly higher than those of the fathers (p = 0.01).
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Fig. 2. Scores on the GHQ60 in parents of patients with CCALD. Six fathers and 11 mothers scored over 17 points, suggesting that these parents were in a state of neurosis.
those of healthy adult Japanese (8.08 ± 5.3) [17]. Scores of the mothers were slightly higher than those of the fathers (p = 0.14). Six fathers (40.0%) and 11 (52.4%) mothers scored over 17 points, suggesting that these parents were in a state of neurosis [17,18]. 3.4. STAI The mean value of the State Anxiety scores in 15 fathers and 20 mothers was 45 (range 19–62) and 53.0 (range 19–77), respectively (Fig. 3). The mean value of the Trait Anxiety scores in 14 fathers and 19 mothers was 43.7 (range 24–65) and 51.6 (range 30–73), respectively. These mean values were higher than those in healthy adult Japanese (State Anxiety 36.6 ± 8.98, Trait Anxiety 38.8 ± 9.68) [19]. Scores of the mothers were slightly higher than those of the fathers (State Anxiety: p = 0.11, Trait Anxiety: p = 0.09). Four fathers and 8 mothers showed high scores in both State Anxiety (>50 for males, >51 for females) and Trait Anxiety (>53 for males, >55 for females). 3.5. Correlations between psychological examinations and the questionnaire The results of the BDI-II, GHQ60 and STAI were positively correlated with each other both in the fathers
Fig. 3. Scores on the STAI in parents of patients with CCALD. Six fathers and 12 mothers showed high levels of State Anxiety and 5 fathers and 8 mothers showed high levels of Trait Anxiety.
and in the mothers (rs = 0.60–0.91). Correlations between the psychological examinations and the scores of health or social status of the parents are shown in Table 2. Health status such as tiredness and illness correlated positively with the results of psychological examinations both in the fathers and in the mothers. On the other hand, correlations between social status such as difficulties in family relations and financial problems and the results of psychological examinations were weak, especially in the fathers. A weak negative correlation (rs = 0.51) between the scores on the BDI-II in the
Table 2 Correlations between psychological examinations and questionnaire
Father BDI-II GHQ60 State Anxiety Trait Anxiety Mother BDI-II GHQ60 State Anxiety Trait Anxiety *
P < 0.05.
Health status
Social status
rs = 0.69* 0.65* 0.63* 0.62*
rs = 0.20 0.36 0.09 0.17
0.49* 0.42* 0.60* 0.63*
0.49* 0.49* 0.40 0.49*
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Table 3 Comparison of mothers with low and high scores on the BDI-II
Mean age of the mothers Mean age of the patients Years from onset GHQ60 score State Anxiety score Health status scorea Social status scoreb a b
BDI-II score <19 (n = 10)
BDI-II score >20 (n = 9)
P value
48.0 years 19.8 years 11.6 15.3 43.8 1.3 1.67
41.9 13.3 5.1 26 63 1.89 1.89
0.06 0.004 0.005 0.18 0.005 0.26 0.89
Physical tiredness (score 1) + mental tiredness (score 1) + illness (score 1). Difficulties in family relations (score 1) + change or loss of job (score 1) + financial problems (score 1) + moving house (score 1).
mothers and the number of years from disease onset was found. When we compared 2 groups of mothers with low and high scores on the BDI-II, the mean age of the patients was lower and the number of years from disease onset was shorter in mothers with a high score (moderately to severely depressed group) (Table 3). State Anxiety scores were also higher in the moderately to severely depressed group. Health status or social status scores were not significantly different. 4. Discussion In the present study, we clarified the objective evidence for psychological status in the parents of patients with CCALD, using psychological examinations and a questionnaire. The questionnaire revealed that many of the parents had health problems such as physical and mental tiredness, and various illnesses probably related to their physical and mental distress. Social difficulties in human relations, employment, finance, and housing were also identified. These problems and difficulties are likely to be more serious in mothers as, for the most part, mothers are the main caregivers of children with CCALD, however, no objective evidence for this speculation was provided. We have found that parents of CCALD patients are at high risk of depression. In particular, 57.8% of mothers showed high scores on the BDI-II, and 47.4% were moderately to severely depressed. As the distribution of BDI-II scores in healthy populations has been found to be similar in different countries [15,20], we can compare the severity of depression in mothers. In Turkey, 48.5% of mothers with epileptic children were shown to be depressed as assessed by the BDI, and 33.3% were moderately to severely depressed [21]. In the UK, 57% of mothers of adolescent cancer patients showed depression at the time of diagnosis, and 27% were moderately to severely depressed [22]. Similar results in mothers of children with hematopoietic malignancies have been reported from Iran [23]. These reports suggest that the mental health of Japanese mothers of CCALD patients is more impaired than that of mothers of patients with other diseases. As subjects with a moderate to severe
depression score on the BDI-II have a higher risk of developing true depression [15], parents of patients with CCALD should be carefully followed. Several factors that may affect the mental status of parents of CCALD patients are considered. Firstly, the X-linked recessive inheritance of ALD may greatly affect parents. In X-linked diseases, mothers often feel guilty about having passed on the faulty gene which may lead to conflict between parents and other relatives. Mothers of sons with fragile X syndrome reported more pessimism about their son’s future and more conflict within the family than mothers of sons with Down syndrome [24]. Many of the mothers in this study also stated feelings of guilt and sadness in the questionnaire (data not shown). These emotional problems might greatly affect the risk of depression. Secondly, mothers of ALD patients are often carriers and 15–25% of female carriers have a risk of developing neurological symptoms that are similar to AMN [25,26]. Among women with AMN symptoms, not only do they have a child who will die, but they themselves will develop physical disabilities as they age. In our study, none of the mothers developed neurological symptoms, and the questionnaire did not include queries relating to anxiety about their own future. However, this may be another important factor which requires further investigation. Thirdly, external support would be of great help to parents and would improve their mental status. Mothers have a considerable burden in the care of their child, which requires time and patience. In addition to external support such as nursing help, daycare, and public financial support, social support in the family, workplace and community would be of significant help. Without such support, parents would be under more stress. Our study showed that only a few parents utilized home nursing and daycare (Table 1). We also identified a correlation between low social status and psychological problems (Table 2). Fourthly, adequate psychological support for parents might have an influence on their mental status. Our study showed that many of the parents were seeking psychological counseling. Younger mothers with young patients tended to be more depressed (Table 3). During the first few years after disease onset, parents encounter
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various medical, social, and psychological problems, and seem to become nervous, frustrated, and depressed. We should establish a mental care system to include parents and their care. Intervention for mental health problems should be early in the course of the disease, because younger mothers with few years since the child’s diagnosis appear to have the most severe depression. Thus we should not only consider the biomedical issues of patients with CCALD, but the psychological aspects of parents should also be taken into account. Recognition of the mental status of each parent is essential for adequate medical advice regarding their social life and psychological support, and to maintain appropriate family relationships. The BDI-II, GHQ60 and STAI may be useful in genetic counseling or in the out-patient clinic.
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