Original Article
Anxiety and Depression in Adolescents With Epilepsy
Journal of Child Neurology 1-8 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073815587942 jcn.sagepub.com
Karen Ling Kwong, MD1, David Lam, MD1, Sarah Tsui, MD1, Mary Ngan, MD1, Brian Tsang, MD1, Tai Sum Lai2, and Siu Man Lam2
Abstract The present study examined anxiety and depression in adolescents with epilepsy and the association of these disorders with seizure-related and sociodemographic variables. The Hospital Anxiety and Depression Scale was administered to 140 children with epilepsy and 50 children with asthma aged 10 to 18 years attending mainstream schools. Adolescents with epilepsy had significantly higher scores on the depression subscale than those with asthma (5.2 + 3.3 vs 4.2 + 3.2, P ¼ .032). Anxiety subscale scores and the frequency of anxiety and depression in both the epilepsy and asthma groups were not statistically significant. In the epilepsy group, 32.8% had anxiety and 22.1% had depression. Factors associated with anxiety were older age at the time of the study and polytherapy (2 or more antiepileptic drugs). Adolescents who had been seizure-free for 12 months or more at time of the study were less likely to experience anxiety. Factors associated with depression were medical comorbidities, female gender, frequent seizures, and younger age of seizure onset. A common risk factor for both anxiety and depression was the duration of epilepsy. Anxiety and depression were also highly associated with each other. Affective disorders are common in epilepsy and screening for psychiatric symptoms is required. Keywords epilepsy, adolescents, anxiety, depression Received June 11, 2014. Received revised March 17, 2015. Accepted for publication April 28, 2015.
Epilepsy is a chronic neurologic disorder complicated by recurrent seizures and neurobehavioral comorbidities, including mood disorders, which adversely affect quality of life.1,2 The increased prevalence of affective disorders in children with epilepsy compared with the general population and children with nonneurologic disorders has been documented.3 Two population-based studies, 30 years apart, demonstrated that a psychiatric burden is an important complication of chronic childhood epilepsy, particularly for those with complicated epilepsy.4,5 A recent national health survey involving 91 605 children reported that children with a seizure disorder were significantly more likely to experience depression and anxiety than those who had not been diagnosed with a seizure disorder.6 However, the need for mental health care often remains unmet.7 This may be partly explained by underrecognition of mental health problems. Adolescence is a particularly vulnerable period marked by profound developmental changes in the biological, social, and psychological domains. Coping with these changes may be especially challenging for adolescents with epilepsy.8 Conflicts between life expectations and the limitations of a chronic disease could also reduce quality of life and result in increased emotional problems. In addition, one study reported suicide ideation in 20.3% of 177 children with epilepsy aged 5 to 16 years.9 Early identification
of affective disorders is therefore a crucial component of the management of children and adolescents with epilepsy. For children with epilepsy, estimates of the prevalence of mood disorders range from 12% to 33%.3,5,6,10-12 The breadth of this range could be due to geographic, demographic, and methodological variables. The pervasive effects of epilepsy, its unpredictability, the physical manifestations of seizures, and a potential common pathogenic mechanism give rise to the hypothesis that adolescents with epilepsy have significantly higher rates of affective disorders than adolescents with other chronic nonneurologic diseases. There is also evidence indicating that affective disorders in the general child population are multifactorial, and the present authors hypothesize that adolescents with epilepsy are vulnerable to multietiologic risk factors for affective disorders, including biological, social, seizure-
1
Department of Paediatrics and Adolescent Medicine, Tuen Mun Hospital, Hong Kong 2 Department of Child Psychiatry, Castle Peak Hospital, Hong Kong Corresponding Author: Karen Ling Kwong, MD, Department of Paediatrics and Adolescent Medicine, Tuen Mun Hospital, Tsing Chung Koon Road, Hong Kong SAR, China. Email: [email protected]
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related, and iatrogenic risk factors. In the present study, the rates of anxiety and depression in adolescents with epilepsy were assessed and compared with those of adolescents with asthma, one of the most common chronic childhood illnesses. The relationships between affective symptoms and seizurerelated and sociodemographic variables in the adolescents with epilepsy were also evaluated.
Methods The present study used a cross-sectional approach with participants recruited between January and June 2010. A total of 140 adolescents (71 boys and 69 girls) aged 10 to 18 years were recruited from patients who attended the neurology outpatient clinic at Tuen Mun Hospital in Hong Kong. Inclusion criteria were a diagnosis of epilepsy (whether treated with antiepileptic drugs or not), attendance at a mainstream school, and literacy in Chinese. Those who had experienced a seizure within the previous 24 hours, attended a special needs school, with progressive structural brain abnormalities such as malignancy or neurodegenerative disorders, had surgery in the previous 4 weeks, or who had pseudo-seizures were excluded. Children were referred to a Child Assessment Center for cognitive assessment and school placement when required. In Hong Kong, schools with special needs are provided for children with physical handicaps, visual impairment, hearing impairment, and mental handicaps (Chapter 7, Government of Hong Kong SAR, General revenue account, Education Department, Service for students with special educational needs). In addition, 50 adolescents aged 10 to 18 years with asthma and who attended mainstream schools were recruited from a respiratory clinic for comparison; those who had a history of seizure disorder were excluded. Ethics approval was obtained from the Regional Hospital Ethics Committee, and written informed consent was obtained from all participants. Tuen Mun Hospital is the only hospital that serves the northwest section of Hong Kong. Participants had been referred to the neurology outpatient clinic from various sources, including maternal and child centers, student health services, general practitioners, and accident and emergency departments. There is no private pediatric neurologist in the study district. Therefore, it was assumed that the study population represented an unbiased pediatric population with epilepsy. Data were collected using the Hospital Anxiety and Depression Scale, which has subscales for anxiety and depression. The Hospital Anxiety and Depression Scale is a self-reported scale that has been validated and applied locally: psychometric evaluation of a large local sample of adolescents in Hong Kong reported the Hospital Anxiety and Depression Scale possessed adequate internal consistency, with alpha coefficient values of 0.8 for the anxiety subscale and 0.63 for the depression subscale.13 Medical records of participants were reviewed to collect information such as details of seizures, age of seizure onset, epilepsy etiology, current antiepileptic drugs, electroencephalogram (EEG) results, neuroimaging findings, and seizure outcomes. A number of potential sociodemographic and health confounders were identified, including age, gender, parental education qualification, parental employment status, tenure of accommodation, need for Comprehensive Social Security Assistance (CSSA), psychiatric illness in first-degree relatives, and other medical comorbidities. The present study used revised terminology and concepts for organization of seizures and epilepsies based on the Report of the ILAE
Commission on Classification and Terminology, 2005-2009.14 Epilepsy classification was based on seizure descriptions, physical examination, and relevant investigations. Epilepsy was defined as 2 or more unprovoked seizures more than 24 hours apart in a child over 1 month of age. Seizure-free status was defined as no seizure for at least 12 months at the time the Hospital Anxiety and Depression Scale was administered in the present study. To evaluate sociodemographic and seizure-related variables, children with anxiety or depression were included as cases; children without anxiety or depression were included as controls. A Hospital Anxiety and Depression Scale score cut-off of 8 was used.15 Data were analyzed using SPSS (version 11). Parametric and nonparametric tests were used to evaluate the effects of a variety of demographic and disease-related factors. The Hospital Anxiety and Depression Scale scores of children with epilepsy and asthma were compared using a Mann-Whitney test, and chi-square and Fisher tests were used to compare categorical variables. Odds ratios at a 95% confidence interval were calculated. Forward logistic regression was used for multivariate analysis, and P values .05 were considered significant.
Results The social and demographic characteristics of the group of children with epilepsy and the group of children with asthma are described in Table 1. The Hospital Anxiety and Depression Scale depression score was higher for adolescents with epilepsy (5.2 + 3.3) than for those with asthma (4.2 + 3.2) (P ¼ .032). For the anxiety subscale, the score for the epilepsy group was 6.1 + 3.8 and 5 + 3.5 for the group of children with asthma (P ¼ .084). Thirty-one (22.1%) adolescents with epilepsy reported a score of 8 on the Hospital Anxiety and Depression Scale depression subscale compared with 7 (14.3%) in the group of children with asthma (P ¼ nonsignificant). In the epilepsy group, 46 (32.8%) adolescents scored 8 on the Hospital Anxiety and Depression Scale anxiety subscale compared with 10 (20.4%) in the group of children with asthma (P ¼ nonsignificant). For the epilepsy group, the mean anxiety score for females was 6.5 + 4.1 and for males 5.7 + 5.5 (P ¼ nonsignificant). The mean depression score for females was 5.3 + 3.3, and 5.1 + 3.2 for males (P ¼ nonsignificant). In the epilepsy group, 15 (10.7%) adolescents had a score of 8 for both the anxiety and depression subscales; 15 (10.7%) reported profound anxiety symptoms, with a Hospital Anxiety and Depression Scale anxiety score of 11, and 12 (8.6%) had a score of 11 on the depression subscale. Psychiatric services had been provided for 15% of those in the epilepsy group at the time of the study. A majority (65.7%) of those with epilepsy had focal seizures, and structural/metabolic causes accounted for 26.4% of epilepsy etiology. Ninety-three (66.4%) adolescents had been seizure-free for more than 12 months, 27 (19.3%) had 1 or more seizures during the past year but not more than once per month, 14 (10%) had 1 or more seizures per month, 6 (4.3%) had more than 1 seizure per week and antiepileptic drugs were discontinued in 35 (25%). Fifteen (10.7%) had medically refractory epilepsy.
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Table 1. Social and Demographic Features of Children With Epilepsy and Children With Asthma. Epilepsy (n ¼ 140) Age at examination, y Gender, female (%) Father education qualification: college/university or above (%) Mother education qualification: college/university or above (%) Father employment status: economically inactive (%) Mother employment status: economically inactive (%) Rented accommodation (%) Comprehensive Social Security Assistance Scheme (%) Psychiatric illness in first degree relative (%) Concomitant medical illness (%) Duration of disease, y (M + SD)
Asthma (n ¼ 50)
14.5 + 2.8 13.6 + 2.36 48.9 38 3.5 2.1
P value NS NS NS
4.2
6
NS
15
10
NS
42.2
36
NS
42.8 20.9
60 16
NS NS
5.2
12
NS
18.5 5.6 + 3.9
16 5.8 + 4.2
NS NS
Abbreviations: NS, nonsignificant; SD, standard deviation.
Analysis of Factors Related to a Hospital Anxiety and Depression Scale Anxiety Subscale Score of 8 in Adolescents With Epilepsy In the univariate analysis, 5 demographic or clinical factors were significantly associated with a HAD anxiety subscale score of 8 (Table 2). In order of strength of association, these were: A higher mean depression score (study group: 6.5 + 3.1, control group: 4.6 + 3.2; odds ratio ¼ 1.21, 95% confidence interval ¼ 1.08, 1.36, P ¼ .001); higher rates of polytherapy (study group: 26.1%, control group: 11.7%; odds ratio ¼ 2.15, 95% confidence interval ¼ 1.26, 3.69, P ¼ .005); longer duration of epilepsy (study group: 6.8 + 4.8 years, control group: 5 + 3.4 years; odds ratio ¼ 1.12, 95% confidence interval ¼ 1.02, 1.23, P ¼ .013); older age at time of study (study group: 15.2 + 2.7 years, control group: 14.1 + 2.8 years; odds ratio ¼ 1.16, 95% confidence interval ¼ 1.02, 1.33, P ¼ .028). Being seizure free for at least 12 months was found to be a favorable factor (odds ratio ¼ 0.4, 95% confidence interval ¼ 0.19, 0.83, P ¼ .014). The presence of a psychiatric illness in a first-degree relative was observed in 8.3% of the study group and 3.8% of the control group (P ¼ nonsignificant). Other sociodemographic factors (gender, parental education qualification, parental employment status, tenure of accommodation, need for Comprehensive Social Security Assistance), medical comorbidities, and epilepsy-related variables (epilepsy types, electroclinical syndromes, magnetic resonance imaging [MRI] abnormalities, EEG abnormalities, status epilepticus) were not statistically significant. Frequent seizures (weekly or daily) at onset were observed in 41.9% of the study group and 25.8% of the control group (odds ratio ¼ 2.07, 95% confidence interval ¼ 0.96, 4.44, P ¼ .06). Medically refractory epilepsy was not a significant risk factor (study group: 13%, control group: 9.6%).
After multivariate analysis, the depression score was the only independent factor retained (odds ratio ¼ 1.22, 95% confidence interval ¼ 1.05, 1.4, P ¼ .008). Duration of epilepsy (odds ratio ¼ 1.12, 95% confidence interval ¼ 0.99, 1.26, P ¼ .065) and frequent seizures (odds ratio ¼ 2.36, 95% confidence interval ¼ 0.87, 6.45), P ¼ .092) tended to be associated with anxiety in adolescents with epilepsy. There was a tendency for being seizure-free for at least 12 months (odds ratio ¼ 0.36, 95% confidence interval ¼ 0.12, 1.07, P ¼ .066) and not being on antiepileptic drugs at the time of study (odds ratio ¼ 0.29, 95% confidence interval ¼ 0.07, 1.17, P ¼.082) to be favorable factors (Table 3). Excluding 15 adolescents with coexisting Hospital Anxiety and Depression Scale depression subscales score of 8, univariate analysis identified older age at time of study as a significant risk factor (study group: 15.2 + 2.7 years, control group: 14.1 + 2.8 years) (odds ratio ¼ 1.17, 95% confidence interval ¼ 1, 1.36, P ¼ .047) and not being on antiepileptic drug at time of study (odds ratio ¼ 0.34, 95% confidence interval ¼ 0.11, 1.08, P ¼.067) was a favorable factor. These 2 factors were retained after multivariate analysis: older age at time of study (odds ratio ¼ 1.5, 95% confidence interval ¼ 1.03, 2.17, P ¼ .032) and not being on antiepileptic drug at time of study (odds ratio ¼ 0.11, 95% confidence interval ¼ 0.01, 0.87, P ¼ .036).
Analysis of Factors Related to a Hospital Anxiety and Depression Scale Depression Subscale Score of 8 in Adolescents With Epilepsy Results of a univariate analysis of the relationship between potential risk factors and a Hospital Anxiety and Depression Scale depression subscale score of 8 are depicted in Table 3. Five significant factors were identified (in order of strength of association): medical comorbidities, 38.7% of the study group compared with 11.9% of the control group (odds ratio ¼ 4.57, 95% confidence interval ¼ 1.81, 11.53, P ¼ .001); more frequent seizures (weekly or daily seizures) at onset (odds ratio ¼ 3.52, 95% confidence interval ¼ 1.51, 8.17, P ¼ .003); a Hospital Anxiety and Depression Scale anxiety subscale score of 7.94 + 4.47 in the study group and 5.57 + 3.4 in the control group (odds ratio ¼ 1.17, 95% confidence interval ¼ 1.05, 1.31, P ¼ .003); longer duration of epilepsy, 7.5 + 4.3 years for the study group and 5.1 + 3.7 years for the control group (odds ratio ¼ 1.15, 95% confidence interval ¼ 1.05, 1.27, P ¼ .005); and a younger age at seizure onset (odds ratio ¼ 0.88, 95% confidence interval ¼ 0.79, 0.98, P ¼ .016). Other sociodemographic and epilepsy-related variables were not of statistical significance. Medically refractory epilepsy was not a significant risk factor (study group: 12.9%, control group: 10.1%). Multivariate analysis was performed to assess independent risk factors (Table 3). The factors retained were an anxiety score (odds ratio ¼ 1.62, 95% confidence interval ¼ 1.2, 2.2, P ¼ .002) and female gender (odds ratio ¼ 8.86, 95%
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Odds ratio (95% CI)
P value
25.8 74.4 12.7 8.5 4.3 29.8 57.4 11.7 4.6 þ 3.2
13 60.9 26.1 6.5 þ 3.1
1.1
0 41.9 54.3 30 10.8 4.4
4.3
1.21 (1.08, 1.36) .001
2.07 (0.96, 4.44) .06 0.4 (0.19, 0.83) .014 NS NS NS 2.15 (1.26, 3.69) .005
46.8 NS 14.1 + 2.8 1.16 (1.02, 1.33) .028 (10-18.9) 17.2 NS 3.8 NS 8.8 + 3.8 NS (1.5-17) 5 + 3.4 1.12 (1.02, 1.23) .013 (0.4-16) NS 14.9 3.2 0 16 3.2 5.3 1.1 24.4 1.1 25.5
Controls (n ¼ 94)
4.3
13 2.2 4.3 13 2.2 6.5 4.3 23.9 0 26.1
54.3 15.2 + 2.7 (10-18.4) 20 8.3 8.3 + 4.9 (0.3-16) 6.8 + 4.8 (0.5-17)
Cases (n ¼ 46)
Abbreviations: CI, confidence interval; HADS, Hospital Anxiety and Depression Scale; NS, nonsignificant.
Frequent Seizures (weekly or daily seizures) at onset, % Seizure free for 12 months, % 1 seizure for 12 months but < 1 seizure per month, % 1 seizure per month, % 1 seizure per week, % Antiepileptic drugs at time of study, % None (n ¼ 35) Monotherapy (n ¼ 82) Polytherapy (n ¼ 23) Mean depression score Mean anxiety score
Electroclinical syndromes and other epilepsy (%) Benign epilepsy with centrotemporal spikes (n ¼ 20) Panayiotopoulos syndrome (n ¼ 4) Juvenile absence epilepsy (n ¼ 2) Epilepsy with generalized tonic-clonic seizures alone (n ¼ 21) Febrile seizures plus (n ¼ 4) Childhood absence epilepsy (n ¼ 8) Juvenile myoclonic epilepsy (n ¼ 3) Epilepsies attributable to structural-metabolic causes (n ¼ 34) Hypothalamic hamartoma (n ¼ 1) Epilepsies that do not fit into any of these diagnostic categories on the basis of presence or absence of presumed cause, focal (n ¼ 36) Epilepsies that do not fit into any of these diagnostic categories on the basis of presence or absence of presumed cause, generalized (n ¼ 6) Unknown (n ¼ 1)
Mean duration of epilepsy, y
Medical comorbidities, % Psychiatric illness in first-degree relatives, % Mean age at seizure onset, y
Gender, female, % Mean age at time of study, y
Factors
Anxiety score 8 Controls (n ¼ 109)
Odds ratio (95% CI)
P value
7.9 + 4.5
12.9 64.5 22.6
53.3 64.3 16.1 9.7 9.7
0
6.5
5.6 + 3.4
29.1 57.4 14.8
24.5 68.8 19.3 9.2 2.8
0.9
3.7
1.17 (1.05, 1.31)
3.52 (1.51, 8.17)
.003
.003 NS NS NS NS NS
51.6 48.6 NS 14.4 + 3 14.5 + 2.7 NS (10-18.9) (10-18.8) 38.7 11.9 4.57 (1.81, 11.53) .001 8 4.5 NS 7.1 + 4.1 9.1 + 3.9 0.88 (0.79, 0.98) .016 (0.6-16.5) (0.3-17) 7.5 + 4.3 5.1 + 3.7 1.15 (1.05, 1.27) .005 (0.5-16) (0.4-17) NS 6.5 16.5 3.2 2.8 3.2 0.9 16.1 14.8 0 3.7 3.2 6.5 0 2.8 19.4 25.6 3.2 0 38.7 22
Cases (n ¼ 31)
Depression score 8
Table 2. Univariate Analysis of Sociodemographic and Clinical Factors Related to Hospital Anxiety and Depression Scale Anxiety Score 8 and Depression Score 8.
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Table 3. Multivariate Analysis of Factors Related to HADS Anxiety Score 8 and Depression Score 8.a Anxiety score 8 Factors Sex (female) Duration of epilepsy Age at seizure onset Seizure free for 12 mo No antiepileptic drug at time of study Depression score Anxiety score
Odds ratio (95% CI)
Depression score 8 P value
NS 1.12 (0.99, 1.26) .065
Odds ratio (95% CI)
P value
8.86 (1.22, 64.06) .024 NS
NS
0.7 (0.49, 1.01)
.058
0.36 (0.12, 1.07) .066
0.08 (0.06, 1.19)
.067
0.29 (0.07, 1.17) .082
1.22 (1.05, 1.4)
NS
.008 1.62 (1.2, 2.2)
.002
Abbreviations: CI, confidence interval; HADS, Hospital Anxiety and Depression Scale; NS, nonsignificant. a Variables: gender, age at time of study, medical comorbidities, housing, Comprehensive Social Security Scheme, age at seizure onset, duration of epilepsy, seizure type, frequent seizures at onset, not on antiepileptic drugs, etiologies, seizure free for 12 months and anxiety score, depression score.
confidence interval ¼ 1.22, 64.06, P ¼ .024). Age at seizure onset (odds ratio ¼ 0.7, 95% confidence interval ¼ 0.49, 1.01, P ¼ .058) and being seizure free for at least 12 months (odds ratio ¼ 0.08, 95% confidence interval ¼ 0.06, 1.19, P ¼ .067) were associated with a Hospital Anxiety and Depression Scale depression subscale score of 8. Excluding 15 adolescents with coexisting Hospital Anxiety and Depression Scale anxiety subscales score of 8, univariate analysis identified medical comorbidities as a significant risk factor, 43.8% of the study group compared with 12% of the control group (odds ratio ¼ 5.62, 95% confidence interval ¼ 1.79, 17.54, P ¼ .003), and this was retained after multivariate analysis (odds ratio ¼ 5.38, 95% confidence interval ¼ 1.25, 23.25, P ¼ .024).
Discussion The findings of the present study add to the growing literature that demonstrates psychiatric comorbidity is a common burden for adolescents with epilepsy. Affective disorders are not only pertinent to treatment-refractory patients but are also relevant in less severe epilepsy. One-third of our patients had anxiety and one-quarter had depression, a frequency that is comparable to the rates found in population-based studies. Anxiety and depression were highly correlated with one another and the significance was retained after multivariate analysis, although disease-related variables were not entirely identical for anxiety and depression. This indicates that it is important for clinicians evaluating adolescents with epilepsy to include discussion about the patient’s mood as part of the basic epilepsy evaluation.
Adolescents with epilepsy were found to have higher depression scores than those with asthma. Scores on the anxiety subscale and the frequency of both affective disorders were also higher in the epilepsy group, although the differences between epilepsy and asthma groups were not statistically significant. However, this may be explained by the relatively small number of adolescents with asthma recruited for the study. Adolescents for both the epilepsy and the asthma groups were recruited from mainstream schools, meaning that the study sample may have included adolescents with limited intellectual functioning, Asperger syndrome, or learning disorders. The disability was not directly based on academic performance. Seven (0.5%) participants in the epilepsy group were found to have borderline intellectual functioning or Asperger syndrome (P ¼ nonsignificant), although these were not found in the asthma group. The risk of anxiety and depression in children with asthma differed considerably between studies, and there have also been studies showing no increased risk of anxiety and depression in asthma.16,17 It is noteworthy that there has been no previous research comparing affective disorders in adolescents with epilepsy and asthma. However, children with epilepsy have been found to experience significantly poorer psychosocial adaptation than those with asthma.18 A community-based study of adults with epilepsy reported higher depression scores in adults with epilepsy than in adults with asthma.19 It has been suggested that even if rates of depression in epilepsy are comparable with the rates of depression in asthma, the nature of depression in the 2 disorders may be different. For example, epilepsy-related depression has been argued to have high rates of irritability and a tendency toward occasional euphoric periods.20 Potential etiologies for depression in epilepsy such as ictal effects, underlying central nervous system abnormalities, and antiepileptic drug effects are unique and therefore would not pertain to other chronic illnesses.21 The present study had a number of strengths. For example, the clinical characteristics were broadly representative, with two-thirds of participants in the epilepsy group being seizure free for at least 1 year, the majority receiving monotherapy, and one-quarter were not on any antiepileptic drug. The present study also had a response rate of 99.3% for the epilepsy group. Seizure types and epilepsy syndromes classification were carefully evaluated, with 71.4% of participants in the epilepsy group having undergone an MRI brain scan to detect underlying pathology, and EEG results were available for all participants in this group. However, the study also had limitations. Cognitive assessments were not performed for all patients, meaning the relationship between psychiatric symptoms and cognitive status could not be evaluated. The Hospital Anxiety and Depression Scale was used to determine anxiety and depression status rather than a structured clinical interview. The Hospital Anxiety and Depression Scale had been previously validated and shown to correlate well with clinical diagnosis and there is research evidence to support the ability of self-report scales to adequately detect internalizing disorders. However, the scale is a screening instrument with a false positive rate of 20%,22-26 meaning that the prevalence of affective
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disorders may be overstated. The present study was a crosssectional survey that highlights association but gives little information on causation. Children with epilepsy from the age of 10 years were included in the study sample as this age is considered to mark the beginning of adolescence according to the World Health Organization (WHO) age criteria for adolescence. Epilepsy can cause stress in addition to the other challenges that are characteristic of adolescence. Further stressors, such as stigma, have also been demonstrated in association with epilepsy. In addition, frequent school absences may limit school attendance and result in poorer academic achievement, whereas excessive restrictions on activities and parental overprotection may limit the acquisition of independence.27,28 Female gender was an independent risk factor associated with depression in the present study cohort. This is consistent with the higher rates of depression that are well-recognized among women in the general population. However, gender has not been shown to be a consistent factor in the investigations of affective disorders in epilepsy. Alfstad et al29 reported that epilepsy was a much stronger risk factor for developing emotional problems in girls than in boys. A community-based study observed that being female was an independent predictor of depression in children with epilepsy,30 and female gender has been associated with higher mean depression scores in other studies of children with epilepsy.30,31 However, in a study of psychiatric comorbidity in children with new-onset epilepsy, Jones et al32 found no significant association between mood disorders and gender. Baki et al33 also reported no association between age and affective disorders in 35 children with epilepsy aged 7 to 19 years. The present study highlights the association between anxiety and depression. Coexistence of anxiety and depression has been widely reported in people with or without epilepsy.1,34,35 In internalizing disorders, current depression has been reported to be associated with a 28-fold increase in current anxiety, according to a study of childhood psychiatric disorders.36 Our findings showed that medical comorbidities had a greater impact on depression than on anxiety, although the association between medical comorbidities and depression was not specifically reported in the children with epilepsy. Using the Strengths and Difficulties Questionnaire–Parent report, a study by Alfstad et al29 reported that the presence of other chronic diseases along with epilepsy was an independent factor for developing overall psychiatric symptoms. Comorbid conditions have also been identified as a significant predictor of higher levels of anxiety in children and adolescents with epilepsy.37 The present study analyzed epilepsy- and treatment-related variables. Chronicity of illness was found to be a common risk factor for both affective disorders. Seizure variables that were associated with affective disturbances were not retained after multivariate analysis. In addition, different epilepsy types and syndromes were compared and no specific subtypes of epilepsy were found to be differentially associated with psychiatric disorders. This suggests a more general impact of epilepsy on mental health. However, the small number of subjects in the
different epilepsy subtypes limits this interpretation. There is also a lack of compelling evidence regarding an association between subtypes of epilepsy and affective disorders in recent literature.35,37,38 The literature also reports disparate findings regarding polytherapy, whereas our study found that polytherapy was associated with anxiety but less so with depression. Antiepileptic drugs can cause symptoms of anxiety and depression, but their mood-stabilizing properties mean that they are also used in the management of psychiatric disorders.39,40 Pharmacoresistance has been reported to be associated with affective disorders in children with epilepsy,37,41 although Ettinger et al34 observed that neither monotherapy nor polytherapy affected measures of depression or anxiety in children with epilepsy. Literature on the impact of seizure control on affective disorders is equally inconclusive. Our findings demonstrated that adolescents who were seizure-free for at least 12 months at the time of the study were less likely to experience anxiety on univariate analysis, but that the association between being seizurefree and depression was not statistically significant. It may be that anxiety decreases when seizures are controlled because patients are not under the constant heightened state of caution associated with the unpredictability of seizures. Epilepsy is a stigmatizing disease even though seizure is controlled; hence, the association between seizure freedom and depression cannot be clearly demonstrated. The lack of 5-year seizure remission has been reported to be associated with internalizing disorders in children with uncomplicated epilepsy,35 and poorly controlled seizures have been shown to be a predictor of depression.30 However, the absence of a clear association between mood disorders and seizure control reflects the complexity of the matter. A population-based study of adolescents with juvenile myoclonic epilepsy 25 years after seizure onset demonstrated that two-thirds of study participants were on moodaltering medication even though seizures were controlled.42 The present study supports the hypothesis that adolescents with epilepsy have significantly higher rates of affective disorders than adolescents with asthma. However, the hypothesis that adolescents with epilepsy are vulnerable to multietiologic risk factors for developing affective disorders was incompletely demonstrated, as many factors were not retained after multivariate analysis. Demographic and seizure-related variables tended to make different contributions to mood disorders. Less than one-sixth of the adolescents with epilepsy in our study received psychiatric services at the time of the study. This unmet need for psychiatric services may reflect underrecognition of psychiatric comorbidities. A comprehensive assessment including an assessment of mood disorders is required to improve the quality of life for children and adolescents with epilepsy. Acknowledgments This work was completed with help of Miss Eliza Yip, neurology nurse, and Miss Leung Sui Ping, respiratory nurse.
Author Contributions KLK made substantial contribution in design, data interpretation, and preparation of manuscript. DL was responsible for design and for
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acquisition of data in patients having asthma. ST collected and analyzed data in patients with asthma. MN and BT collected and review data in patients with epilepsy. TML and SML provided important support in assessment tool administration and its relevance in psychiatric disorder.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval The study was approved by Ethic Committee in Tuen Mun Hospital.
References 1. Johnson EK, Jana EJ, Seidenberg M, Hermann BP. The relative impact of anxiety, depression, and clinical seizure features on health-related quality of life in epilepsy. Epilepsia. 2004;45: 544-550. 2. Kwan P, Yu E, Leung H, et al. Association of subjective anxiety, depression, and sleep disturbance with quality-of-life ratings in adults with epilepsy. Epilepsia. 2009;50:1059-1066. 3. McDermott S, Mani S, Krishnaswami S. A population-based analysis of specific behavior problems associated with childhood seizures. J Epilepsy. 1995;8:110. 4. Rutter M, Graham P, Yule W. A Neuropsychiatric Study in Childhood. London: S.I.M.P./William Heinemann Medical Books; 1970. 5. Davies S, Heyman I, Goodman R. A population survey of mental health problems in children with epilepsy. Dev Med Child Neurol. 2003;45:292-295. 6. Russ SA, Larson K, Halfon N. A national profile of childhood epilepsy and seizure disorder. Pediatrics. 2012;129:256-264. 7. Ott D, Siddarth P, Gurbani A, et al. Behavioral disorders in pediatric epilepsy. Epilepsia. 2003;44:591-597. 8. MacLeod JS, Autstin JK. Stigma in the lives of adolescents with epilepsy: a review of the literature. Epilepsy Behav. 2003;4: 112-117. 9. Jones JE, Siddarth P, Gurbani S, et al. Screening for suicidal ideation in children with epilepsy. Epilepsy Behav. 2013;29:521-526. 10. Plioplys S, Dunn DW, Caplan R. 10-year research update review: psychiatric problems in children with epilepsy. J Am Acad Child Adolesc Psychiatry. 2007;46:1389-1402. 11. Reilly C, Agnew R, Neville BGR. Depression and anxiety in childhood epilepsy: a review. Seizure. 2011;20:589-597. 12. Dunn D, Austin J, Huster G. Symptoms of depression in adolescents with epilepsy. J Am Acad Child Adolesc Psychiatry. 1999; 38:1132-1138. 13. Chan YF, Leung YP, Fong DYT, et al. Psychiatric evaluation of the Hospital Anxiety and Depression Scale in a large community sample of adolescents in Hong Kong. Qual life Res. 2010;19: 865-873.
14. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005. Epilepsia. 2010;51:676-685. 15. White D, Leach C, Sims R, Atkinson M. Validation of the Hospital Anxiety and Depression Scale for use with adolescents. Br J Psychiatry. 1999;175:452-454. 16. Letitre SL, de Groot EP, Draaisma E, Brand PL. Anxiety, depression and self-esteem in children with well-controlled asthma: a case-controlled study. Arch Dis Child. 2014;99:744-748. 17. Villa G, Nollet-Clemencon. de Blic. Prevalence of DSM-IV anxiety and affective disorders in a paediatric population of asthmatic children and adolescents. J Affect Disord. 2000;58:223-231. 18. Austin JK. Comparison of child adaptation to epilepsy and asthma. J Child Adolesc Psychiatr Ment Health Nurs. 1989;2: 139-144. 19. Ettinger A, Reed M, Cramer J. Depression and comorbidity in community-based patients with epilepsy or asthma. Neurology. 2004;63:1008-1014. 20. Blumer D. Antidepressant ad double antidepressant treatment for the affective disorder of epilepsy. J Clin Psychiatry. 1997; 58:3-11. 21. Hermann BP, Whitman S. Psychopathology in epilepsy: a multietiologic model. In: Hermann BP, Whitman S, eds. Psychopathology in Epilepsy: Social Dimensions. New York: Oxford University Press; 1986:5-37. 22. Aben I, Verhey R, Lousberg R, et al. Validity of Beck Depression Inventory, Hospital Anxiety and Depression Scale, SCL-90, and Hamilton depression Rating Scale as screening instruments for depression in stroke patients. Psychosomatics. 2002;43:386-393. 23. Lewis G, Wessely S. Comparison of the General Health Questionnaire and the Hospital Anxiety and Depression Scale. Br J Psychiatry. 1990;157:860-864. 24. Bowling A. Measuring Disease. Buckingham: Open University Press; 1995. 25. Herrero MJ, Blanch J, Peri JM, et al. A validation study of the Hospital Anxiety and Depression Scale (HADS) in a Spanish population. Gen Hosp Psychiatry. 2003;25:277-283. 26. Brennan C, Worrall-Davies A, McMillan D, et al. The Hospital Anxiety and Depression Scale: a diagnostic meta-analysis of case-finding ability. J Psychosom Res. 2010;69:371-378. 27. Austin JK, Osborne-Shafer P, Beach-Deering J. Epilepsy familiarity knowledge, and perceptions of stigma: report from a survey of adolescents in the general population. Epilepsy Behav. 2002; 3:368-375. 28. Meador KJ. Research use of the new qualify of life of epilepsy inventory. Epilepsia. 1993;34:34-38. 29. Alfstad KA, Clench-Aas J, Van Roy B, et al. Psychiatric symptoms in Norwegian children with epilepsy aged 8-13 years: effects of age and gender? Epilepsia. 2011;52:1231-1238. 30. Turky A, Beavis JM, Thapa AK, Kerr MP. Psychopathology in children and adolescents with epilepsy: an investigation of predictive variables. Epilepsy Behav. 2008;12:136-144. 31. Austin JK, Risingerr MW, Beckett LA. Correlates of behavior problems in children with epilepsy. Epilepsia. 1992;33:1115-1122.
Downloaded from jcn.sagepub.com at CALIFORNIA STATE UNIV FRESNO on July 6, 2015
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32. Jones JE, Watson R, Sheth R, et al. Psychiatric comorbidity in children with new onset epilepsy. Dev Med Child Neurol. 2007;49:493-497. 33. Baki O, Erdogan A, Kantarci O, et al. Anxiety and depression in children with epilepsy and their mothers. Epilepsy Behav. 2004;5: 958-964. 34. Ettinger AB, Weisbrot DM, Nolan EE, et al. Symptoms of depression and anxiety in pediatric epilepsy patients Epilepsia. 1998;39: 595-599. 35. Berg AT, Caplan R, Hesdorffer DC. Psychiatric and neurodevelopmental disorders in childhood-onset epilepsy. Epilepsy Behav. 2011;20:550-555. 36. Costello EJ, Mustillo S, Erkanli A, et al. Prevalence and development of psychiatric disorders in childhood and adolescence. Arch Gen Psychiatry. 2003;60:837-844. 37. Williams J, Steel C, Sharp GB, et al. Anxiety in children with epilepsy. Epilepsy Behav. 2003;4:729-732.
38. Og˘uz A, Kurul S, Dirik E. Relationship of epilepsy-related factors to anxiety and depression scores in epileptic children. J Child Neurol. 2002;17:39-40. 39. Brent DA, Crumine PK, Varma RR, et al. Phenobarbital treatment and major depressive disorder in children with epilepsy. Pediatrics. 1987;80:909-917. 40. Sadock BJ, Sadock VA. Mood disorders and suicide. In: Pataki CS, Ahmad S, eds. Concise Textbook of Child and Adolescent Psychiatry. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:145-146. 41. Adewuya AO, Ola BA. Prevalence of and risk factors for anxiety and depressive disorders in Nigerian adolescents with epilepsy. Epilepsy Behav. 2005;6:342-347. 42. Camfield CS, Camfield PR. Juvenile myoclonic epilepsy 25 years after seizure onset: a population based study. Neurology. 2009;73: 1041-1045.
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Anxiety and Depression in Adolescents With Epilepsy
Journal of Child Neurology 1-8 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073815587942 jcn.sagepub.com
Karen Ling Kwong, MD1, David Lam, MD1, Sarah Tsui, MD1, Mary Ngan, MD1, Brian Tsang, MD1, Tai Sum Lai2, and Siu Man Lam2
Abstract The present study examined anxiety and depression in adolescents with epilepsy and the association of these disorders with seizure-related and sociodemographic variables. The Hospital Anxiety and Depression Scale was administered to 140 children with epilepsy and 50 children with asthma aged 10 to 18 years attending mainstream schools. Adolescents with epilepsy had significantly higher scores on the depression subscale than those with asthma (5.2 + 3.3 vs 4.2 + 3.2, P ¼ .032). Anxiety subscale scores and the frequency of anxiety and depression in both the epilepsy and asthma groups were not statistically significant. In the epilepsy group, 32.8% had anxiety and 22.1% had depression. Factors associated with anxiety were older age at the time of the study and polytherapy (2 or more antiepileptic drugs). Adolescents who had been seizure-free for 12 months or more at time of the study were less likely to experience anxiety. Factors associated with depression were medical comorbidities, female gender, frequent seizures, and younger age of seizure onset. A common risk factor for both anxiety and depression was the duration of epilepsy. Anxiety and depression were also highly associated with each other. Affective disorders are common in epilepsy and screening for psychiatric symptoms is required. Keywords epilepsy, adolescents, anxiety, depression Received June 11, 2014. Received revised March 17, 2015. Accepted for publication April 28, 2015.
Epilepsy is a chronic neurologic disorder complicated by recurrent seizures and neurobehavioral comorbidities, including mood disorders, which adversely affect quality of life.1,2 The increased prevalence of affective disorders in children with epilepsy compared with the general population and children with nonneurologic disorders has been documented.3 Two population-based studies, 30 years apart, demonstrated that a psychiatric burden is an important complication of chronic childhood epilepsy, particularly for those with complicated epilepsy.4,5 A recent national health survey involving 91 605 children reported that children with a seizure disorder were significantly more likely to experience depression and anxiety than those who had not been diagnosed with a seizure disorder.6 However, the need for mental health care often remains unmet.7 This may be partly explained by underrecognition of mental health problems. Adolescence is a particularly vulnerable period marked by profound developmental changes in the biological, social, and psychological domains. Coping with these changes may be especially challenging for adolescents with epilepsy.8 Conflicts between life expectations and the limitations of a chronic disease could also reduce quality of life and result in increased emotional problems. In addition, one study reported suicide ideation in 20.3% of 177 children with epilepsy aged 5 to 16 years.9 Early identification
of affective disorders is therefore a crucial component of the management of children and adolescents with epilepsy. For children with epilepsy, estimates of the prevalence of mood disorders range from 12% to 33%.3,5,6,10-12 The breadth of this range could be due to geographic, demographic, and methodological variables. The pervasive effects of epilepsy, its unpredictability, the physical manifestations of seizures, and a potential common pathogenic mechanism give rise to the hypothesis that adolescents with epilepsy have significantly higher rates of affective disorders than adolescents with other chronic nonneurologic diseases. There is also evidence indicating that affective disorders in the general child population are multifactorial, and the present authors hypothesize that adolescents with epilepsy are vulnerable to multietiologic risk factors for affective disorders, including biological, social, seizure-
1
Department of Paediatrics and Adolescent Medicine, Tuen Mun Hospital, Hong Kong 2 Department of Child Psychiatry, Castle Peak Hospital, Hong Kong Corresponding Author: Karen Ling Kwong, MD, Department of Paediatrics and Adolescent Medicine, Tuen Mun Hospital, Tsing Chung Koon Road, Hong Kong SAR, China. Email: [email protected]
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Journal of Child Neurology
related, and iatrogenic risk factors. In the present study, the rates of anxiety and depression in adolescents with epilepsy were assessed and compared with those of adolescents with asthma, one of the most common chronic childhood illnesses. The relationships between affective symptoms and seizurerelated and sociodemographic variables in the adolescents with epilepsy were also evaluated.
Methods The present study used a cross-sectional approach with participants recruited between January and June 2010. A total of 140 adolescents (71 boys and 69 girls) aged 10 to 18 years were recruited from patients who attended the neurology outpatient clinic at Tuen Mun Hospital in Hong Kong. Inclusion criteria were a diagnosis of epilepsy (whether treated with antiepileptic drugs or not), attendance at a mainstream school, and literacy in Chinese. Those who had experienced a seizure within the previous 24 hours, attended a special needs school, with progressive structural brain abnormalities such as malignancy or neurodegenerative disorders, had surgery in the previous 4 weeks, or who had pseudo-seizures were excluded. Children were referred to a Child Assessment Center for cognitive assessment and school placement when required. In Hong Kong, schools with special needs are provided for children with physical handicaps, visual impairment, hearing impairment, and mental handicaps (Chapter 7, Government of Hong Kong SAR, General revenue account, Education Department, Service for students with special educational needs). In addition, 50 adolescents aged 10 to 18 years with asthma and who attended mainstream schools were recruited from a respiratory clinic for comparison; those who had a history of seizure disorder were excluded. Ethics approval was obtained from the Regional Hospital Ethics Committee, and written informed consent was obtained from all participants. Tuen Mun Hospital is the only hospital that serves the northwest section of Hong Kong. Participants had been referred to the neurology outpatient clinic from various sources, including maternal and child centers, student health services, general practitioners, and accident and emergency departments. There is no private pediatric neurologist in the study district. Therefore, it was assumed that the study population represented an unbiased pediatric population with epilepsy. Data were collected using the Hospital Anxiety and Depression Scale, which has subscales for anxiety and depression. The Hospital Anxiety and Depression Scale is a self-reported scale that has been validated and applied locally: psychometric evaluation of a large local sample of adolescents in Hong Kong reported the Hospital Anxiety and Depression Scale possessed adequate internal consistency, with alpha coefficient values of 0.8 for the anxiety subscale and 0.63 for the depression subscale.13 Medical records of participants were reviewed to collect information such as details of seizures, age of seizure onset, epilepsy etiology, current antiepileptic drugs, electroencephalogram (EEG) results, neuroimaging findings, and seizure outcomes. A number of potential sociodemographic and health confounders were identified, including age, gender, parental education qualification, parental employment status, tenure of accommodation, need for Comprehensive Social Security Assistance (CSSA), psychiatric illness in first-degree relatives, and other medical comorbidities. The present study used revised terminology and concepts for organization of seizures and epilepsies based on the Report of the ILAE
Commission on Classification and Terminology, 2005-2009.14 Epilepsy classification was based on seizure descriptions, physical examination, and relevant investigations. Epilepsy was defined as 2 or more unprovoked seizures more than 24 hours apart in a child over 1 month of age. Seizure-free status was defined as no seizure for at least 12 months at the time the Hospital Anxiety and Depression Scale was administered in the present study. To evaluate sociodemographic and seizure-related variables, children with anxiety or depression were included as cases; children without anxiety or depression were included as controls. A Hospital Anxiety and Depression Scale score cut-off of 8 was used.15 Data were analyzed using SPSS (version 11). Parametric and nonparametric tests were used to evaluate the effects of a variety of demographic and disease-related factors. The Hospital Anxiety and Depression Scale scores of children with epilepsy and asthma were compared using a Mann-Whitney test, and chi-square and Fisher tests were used to compare categorical variables. Odds ratios at a 95% confidence interval were calculated. Forward logistic regression was used for multivariate analysis, and P values .05 were considered significant.
Results The social and demographic characteristics of the group of children with epilepsy and the group of children with asthma are described in Table 1. The Hospital Anxiety and Depression Scale depression score was higher for adolescents with epilepsy (5.2 + 3.3) than for those with asthma (4.2 + 3.2) (P ¼ .032). For the anxiety subscale, the score for the epilepsy group was 6.1 + 3.8 and 5 + 3.5 for the group of children with asthma (P ¼ .084). Thirty-one (22.1%) adolescents with epilepsy reported a score of 8 on the Hospital Anxiety and Depression Scale depression subscale compared with 7 (14.3%) in the group of children with asthma (P ¼ nonsignificant). In the epilepsy group, 46 (32.8%) adolescents scored 8 on the Hospital Anxiety and Depression Scale anxiety subscale compared with 10 (20.4%) in the group of children with asthma (P ¼ nonsignificant). For the epilepsy group, the mean anxiety score for females was 6.5 + 4.1 and for males 5.7 + 5.5 (P ¼ nonsignificant). The mean depression score for females was 5.3 + 3.3, and 5.1 + 3.2 for males (P ¼ nonsignificant). In the epilepsy group, 15 (10.7%) adolescents had a score of 8 for both the anxiety and depression subscales; 15 (10.7%) reported profound anxiety symptoms, with a Hospital Anxiety and Depression Scale anxiety score of 11, and 12 (8.6%) had a score of 11 on the depression subscale. Psychiatric services had been provided for 15% of those in the epilepsy group at the time of the study. A majority (65.7%) of those with epilepsy had focal seizures, and structural/metabolic causes accounted for 26.4% of epilepsy etiology. Ninety-three (66.4%) adolescents had been seizure-free for more than 12 months, 27 (19.3%) had 1 or more seizures during the past year but not more than once per month, 14 (10%) had 1 or more seizures per month, 6 (4.3%) had more than 1 seizure per week and antiepileptic drugs were discontinued in 35 (25%). Fifteen (10.7%) had medically refractory epilepsy.
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Table 1. Social and Demographic Features of Children With Epilepsy and Children With Asthma. Epilepsy (n ¼ 140) Age at examination, y Gender, female (%) Father education qualification: college/university or above (%) Mother education qualification: college/university or above (%) Father employment status: economically inactive (%) Mother employment status: economically inactive (%) Rented accommodation (%) Comprehensive Social Security Assistance Scheme (%) Psychiatric illness in first degree relative (%) Concomitant medical illness (%) Duration of disease, y (M + SD)
Asthma (n ¼ 50)
14.5 + 2.8 13.6 + 2.36 48.9 38 3.5 2.1
P value NS NS NS
4.2
6
NS
15
10
NS
42.2
36
NS
42.8 20.9
60 16
NS NS
5.2
12
NS
18.5 5.6 + 3.9
16 5.8 + 4.2
NS NS
Abbreviations: NS, nonsignificant; SD, standard deviation.
Analysis of Factors Related to a Hospital Anxiety and Depression Scale Anxiety Subscale Score of 8 in Adolescents With Epilepsy In the univariate analysis, 5 demographic or clinical factors were significantly associated with a HAD anxiety subscale score of 8 (Table 2). In order of strength of association, these were: A higher mean depression score (study group: 6.5 + 3.1, control group: 4.6 + 3.2; odds ratio ¼ 1.21, 95% confidence interval ¼ 1.08, 1.36, P ¼ .001); higher rates of polytherapy (study group: 26.1%, control group: 11.7%; odds ratio ¼ 2.15, 95% confidence interval ¼ 1.26, 3.69, P ¼ .005); longer duration of epilepsy (study group: 6.8 + 4.8 years, control group: 5 + 3.4 years; odds ratio ¼ 1.12, 95% confidence interval ¼ 1.02, 1.23, P ¼ .013); older age at time of study (study group: 15.2 + 2.7 years, control group: 14.1 + 2.8 years; odds ratio ¼ 1.16, 95% confidence interval ¼ 1.02, 1.33, P ¼ .028). Being seizure free for at least 12 months was found to be a favorable factor (odds ratio ¼ 0.4, 95% confidence interval ¼ 0.19, 0.83, P ¼ .014). The presence of a psychiatric illness in a first-degree relative was observed in 8.3% of the study group and 3.8% of the control group (P ¼ nonsignificant). Other sociodemographic factors (gender, parental education qualification, parental employment status, tenure of accommodation, need for Comprehensive Social Security Assistance), medical comorbidities, and epilepsy-related variables (epilepsy types, electroclinical syndromes, magnetic resonance imaging [MRI] abnormalities, EEG abnormalities, status epilepticus) were not statistically significant. Frequent seizures (weekly or daily) at onset were observed in 41.9% of the study group and 25.8% of the control group (odds ratio ¼ 2.07, 95% confidence interval ¼ 0.96, 4.44, P ¼ .06). Medically refractory epilepsy was not a significant risk factor (study group: 13%, control group: 9.6%).
After multivariate analysis, the depression score was the only independent factor retained (odds ratio ¼ 1.22, 95% confidence interval ¼ 1.05, 1.4, P ¼ .008). Duration of epilepsy (odds ratio ¼ 1.12, 95% confidence interval ¼ 0.99, 1.26, P ¼ .065) and frequent seizures (odds ratio ¼ 2.36, 95% confidence interval ¼ 0.87, 6.45), P ¼ .092) tended to be associated with anxiety in adolescents with epilepsy. There was a tendency for being seizure-free for at least 12 months (odds ratio ¼ 0.36, 95% confidence interval ¼ 0.12, 1.07, P ¼ .066) and not being on antiepileptic drugs at the time of study (odds ratio ¼ 0.29, 95% confidence interval ¼ 0.07, 1.17, P ¼.082) to be favorable factors (Table 3). Excluding 15 adolescents with coexisting Hospital Anxiety and Depression Scale depression subscales score of 8, univariate analysis identified older age at time of study as a significant risk factor (study group: 15.2 + 2.7 years, control group: 14.1 + 2.8 years) (odds ratio ¼ 1.17, 95% confidence interval ¼ 1, 1.36, P ¼ .047) and not being on antiepileptic drug at time of study (odds ratio ¼ 0.34, 95% confidence interval ¼ 0.11, 1.08, P ¼.067) was a favorable factor. These 2 factors were retained after multivariate analysis: older age at time of study (odds ratio ¼ 1.5, 95% confidence interval ¼ 1.03, 2.17, P ¼ .032) and not being on antiepileptic drug at time of study (odds ratio ¼ 0.11, 95% confidence interval ¼ 0.01, 0.87, P ¼ .036).
Analysis of Factors Related to a Hospital Anxiety and Depression Scale Depression Subscale Score of 8 in Adolescents With Epilepsy Results of a univariate analysis of the relationship between potential risk factors and a Hospital Anxiety and Depression Scale depression subscale score of 8 are depicted in Table 3. Five significant factors were identified (in order of strength of association): medical comorbidities, 38.7% of the study group compared with 11.9% of the control group (odds ratio ¼ 4.57, 95% confidence interval ¼ 1.81, 11.53, P ¼ .001); more frequent seizures (weekly or daily seizures) at onset (odds ratio ¼ 3.52, 95% confidence interval ¼ 1.51, 8.17, P ¼ .003); a Hospital Anxiety and Depression Scale anxiety subscale score of 7.94 + 4.47 in the study group and 5.57 + 3.4 in the control group (odds ratio ¼ 1.17, 95% confidence interval ¼ 1.05, 1.31, P ¼ .003); longer duration of epilepsy, 7.5 + 4.3 years for the study group and 5.1 + 3.7 years for the control group (odds ratio ¼ 1.15, 95% confidence interval ¼ 1.05, 1.27, P ¼ .005); and a younger age at seizure onset (odds ratio ¼ 0.88, 95% confidence interval ¼ 0.79, 0.98, P ¼ .016). Other sociodemographic and epilepsy-related variables were not of statistical significance. Medically refractory epilepsy was not a significant risk factor (study group: 12.9%, control group: 10.1%). Multivariate analysis was performed to assess independent risk factors (Table 3). The factors retained were an anxiety score (odds ratio ¼ 1.62, 95% confidence interval ¼ 1.2, 2.2, P ¼ .002) and female gender (odds ratio ¼ 8.86, 95%
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Odds ratio (95% CI)
P value
25.8 74.4 12.7 8.5 4.3 29.8 57.4 11.7 4.6 þ 3.2
13 60.9 26.1 6.5 þ 3.1
1.1
0 41.9 54.3 30 10.8 4.4
4.3
1.21 (1.08, 1.36) .001
2.07 (0.96, 4.44) .06 0.4 (0.19, 0.83) .014 NS NS NS 2.15 (1.26, 3.69) .005
46.8 NS 14.1 + 2.8 1.16 (1.02, 1.33) .028 (10-18.9) 17.2 NS 3.8 NS 8.8 + 3.8 NS (1.5-17) 5 + 3.4 1.12 (1.02, 1.23) .013 (0.4-16) NS 14.9 3.2 0 16 3.2 5.3 1.1 24.4 1.1 25.5
Controls (n ¼ 94)
4.3
13 2.2 4.3 13 2.2 6.5 4.3 23.9 0 26.1
54.3 15.2 + 2.7 (10-18.4) 20 8.3 8.3 + 4.9 (0.3-16) 6.8 + 4.8 (0.5-17)
Cases (n ¼ 46)
Abbreviations: CI, confidence interval; HADS, Hospital Anxiety and Depression Scale; NS, nonsignificant.
Frequent Seizures (weekly or daily seizures) at onset, % Seizure free for 12 months, % 1 seizure for 12 months but < 1 seizure per month, % 1 seizure per month, % 1 seizure per week, % Antiepileptic drugs at time of study, % None (n ¼ 35) Monotherapy (n ¼ 82) Polytherapy (n ¼ 23) Mean depression score Mean anxiety score
Electroclinical syndromes and other epilepsy (%) Benign epilepsy with centrotemporal spikes (n ¼ 20) Panayiotopoulos syndrome (n ¼ 4) Juvenile absence epilepsy (n ¼ 2) Epilepsy with generalized tonic-clonic seizures alone (n ¼ 21) Febrile seizures plus (n ¼ 4) Childhood absence epilepsy (n ¼ 8) Juvenile myoclonic epilepsy (n ¼ 3) Epilepsies attributable to structural-metabolic causes (n ¼ 34) Hypothalamic hamartoma (n ¼ 1) Epilepsies that do not fit into any of these diagnostic categories on the basis of presence or absence of presumed cause, focal (n ¼ 36) Epilepsies that do not fit into any of these diagnostic categories on the basis of presence or absence of presumed cause, generalized (n ¼ 6) Unknown (n ¼ 1)
Mean duration of epilepsy, y
Medical comorbidities, % Psychiatric illness in first-degree relatives, % Mean age at seizure onset, y
Gender, female, % Mean age at time of study, y
Factors
Anxiety score 8 Controls (n ¼ 109)
Odds ratio (95% CI)
P value
7.9 + 4.5
12.9 64.5 22.6
53.3 64.3 16.1 9.7 9.7
0
6.5
5.6 + 3.4
29.1 57.4 14.8
24.5 68.8 19.3 9.2 2.8
0.9
3.7
1.17 (1.05, 1.31)
3.52 (1.51, 8.17)
.003
.003 NS NS NS NS NS
51.6 48.6 NS 14.4 + 3 14.5 + 2.7 NS (10-18.9) (10-18.8) 38.7 11.9 4.57 (1.81, 11.53) .001 8 4.5 NS 7.1 + 4.1 9.1 + 3.9 0.88 (0.79, 0.98) .016 (0.6-16.5) (0.3-17) 7.5 + 4.3 5.1 + 3.7 1.15 (1.05, 1.27) .005 (0.5-16) (0.4-17) NS 6.5 16.5 3.2 2.8 3.2 0.9 16.1 14.8 0 3.7 3.2 6.5 0 2.8 19.4 25.6 3.2 0 38.7 22
Cases (n ¼ 31)
Depression score 8
Table 2. Univariate Analysis of Sociodemographic and Clinical Factors Related to Hospital Anxiety and Depression Scale Anxiety Score 8 and Depression Score 8.
Kwong et al
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Table 3. Multivariate Analysis of Factors Related to HADS Anxiety Score 8 and Depression Score 8.a Anxiety score 8 Factors Sex (female) Duration of epilepsy Age at seizure onset Seizure free for 12 mo No antiepileptic drug at time of study Depression score Anxiety score
Odds ratio (95% CI)
Depression score 8 P value
NS 1.12 (0.99, 1.26) .065
Odds ratio (95% CI)
P value
8.86 (1.22, 64.06) .024 NS
NS
0.7 (0.49, 1.01)
.058
0.36 (0.12, 1.07) .066
0.08 (0.06, 1.19)
.067
0.29 (0.07, 1.17) .082
1.22 (1.05, 1.4)
NS
.008 1.62 (1.2, 2.2)
.002
Abbreviations: CI, confidence interval; HADS, Hospital Anxiety and Depression Scale; NS, nonsignificant. a Variables: gender, age at time of study, medical comorbidities, housing, Comprehensive Social Security Scheme, age at seizure onset, duration of epilepsy, seizure type, frequent seizures at onset, not on antiepileptic drugs, etiologies, seizure free for 12 months and anxiety score, depression score.
confidence interval ¼ 1.22, 64.06, P ¼ .024). Age at seizure onset (odds ratio ¼ 0.7, 95% confidence interval ¼ 0.49, 1.01, P ¼ .058) and being seizure free for at least 12 months (odds ratio ¼ 0.08, 95% confidence interval ¼ 0.06, 1.19, P ¼ .067) were associated with a Hospital Anxiety and Depression Scale depression subscale score of 8. Excluding 15 adolescents with coexisting Hospital Anxiety and Depression Scale anxiety subscales score of 8, univariate analysis identified medical comorbidities as a significant risk factor, 43.8% of the study group compared with 12% of the control group (odds ratio ¼ 5.62, 95% confidence interval ¼ 1.79, 17.54, P ¼ .003), and this was retained after multivariate analysis (odds ratio ¼ 5.38, 95% confidence interval ¼ 1.25, 23.25, P ¼ .024).
Discussion The findings of the present study add to the growing literature that demonstrates psychiatric comorbidity is a common burden for adolescents with epilepsy. Affective disorders are not only pertinent to treatment-refractory patients but are also relevant in less severe epilepsy. One-third of our patients had anxiety and one-quarter had depression, a frequency that is comparable to the rates found in population-based studies. Anxiety and depression were highly correlated with one another and the significance was retained after multivariate analysis, although disease-related variables were not entirely identical for anxiety and depression. This indicates that it is important for clinicians evaluating adolescents with epilepsy to include discussion about the patient’s mood as part of the basic epilepsy evaluation.
Adolescents with epilepsy were found to have higher depression scores than those with asthma. Scores on the anxiety subscale and the frequency of both affective disorders were also higher in the epilepsy group, although the differences between epilepsy and asthma groups were not statistically significant. However, this may be explained by the relatively small number of adolescents with asthma recruited for the study. Adolescents for both the epilepsy and the asthma groups were recruited from mainstream schools, meaning that the study sample may have included adolescents with limited intellectual functioning, Asperger syndrome, or learning disorders. The disability was not directly based on academic performance. Seven (0.5%) participants in the epilepsy group were found to have borderline intellectual functioning or Asperger syndrome (P ¼ nonsignificant), although these were not found in the asthma group. The risk of anxiety and depression in children with asthma differed considerably between studies, and there have also been studies showing no increased risk of anxiety and depression in asthma.16,17 It is noteworthy that there has been no previous research comparing affective disorders in adolescents with epilepsy and asthma. However, children with epilepsy have been found to experience significantly poorer psychosocial adaptation than those with asthma.18 A community-based study of adults with epilepsy reported higher depression scores in adults with epilepsy than in adults with asthma.19 It has been suggested that even if rates of depression in epilepsy are comparable with the rates of depression in asthma, the nature of depression in the 2 disorders may be different. For example, epilepsy-related depression has been argued to have high rates of irritability and a tendency toward occasional euphoric periods.20 Potential etiologies for depression in epilepsy such as ictal effects, underlying central nervous system abnormalities, and antiepileptic drug effects are unique and therefore would not pertain to other chronic illnesses.21 The present study had a number of strengths. For example, the clinical characteristics were broadly representative, with two-thirds of participants in the epilepsy group being seizure free for at least 1 year, the majority receiving monotherapy, and one-quarter were not on any antiepileptic drug. The present study also had a response rate of 99.3% for the epilepsy group. Seizure types and epilepsy syndromes classification were carefully evaluated, with 71.4% of participants in the epilepsy group having undergone an MRI brain scan to detect underlying pathology, and EEG results were available for all participants in this group. However, the study also had limitations. Cognitive assessments were not performed for all patients, meaning the relationship between psychiatric symptoms and cognitive status could not be evaluated. The Hospital Anxiety and Depression Scale was used to determine anxiety and depression status rather than a structured clinical interview. The Hospital Anxiety and Depression Scale had been previously validated and shown to correlate well with clinical diagnosis and there is research evidence to support the ability of self-report scales to adequately detect internalizing disorders. However, the scale is a screening instrument with a false positive rate of 20%,22-26 meaning that the prevalence of affective
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Journal of Child Neurology
disorders may be overstated. The present study was a crosssectional survey that highlights association but gives little information on causation. Children with epilepsy from the age of 10 years were included in the study sample as this age is considered to mark the beginning of adolescence according to the World Health Organization (WHO) age criteria for adolescence. Epilepsy can cause stress in addition to the other challenges that are characteristic of adolescence. Further stressors, such as stigma, have also been demonstrated in association with epilepsy. In addition, frequent school absences may limit school attendance and result in poorer academic achievement, whereas excessive restrictions on activities and parental overprotection may limit the acquisition of independence.27,28 Female gender was an independent risk factor associated with depression in the present study cohort. This is consistent with the higher rates of depression that are well-recognized among women in the general population. However, gender has not been shown to be a consistent factor in the investigations of affective disorders in epilepsy. Alfstad et al29 reported that epilepsy was a much stronger risk factor for developing emotional problems in girls than in boys. A community-based study observed that being female was an independent predictor of depression in children with epilepsy,30 and female gender has been associated with higher mean depression scores in other studies of children with epilepsy.30,31 However, in a study of psychiatric comorbidity in children with new-onset epilepsy, Jones et al32 found no significant association between mood disorders and gender. Baki et al33 also reported no association between age and affective disorders in 35 children with epilepsy aged 7 to 19 years. The present study highlights the association between anxiety and depression. Coexistence of anxiety and depression has been widely reported in people with or without epilepsy.1,34,35 In internalizing disorders, current depression has been reported to be associated with a 28-fold increase in current anxiety, according to a study of childhood psychiatric disorders.36 Our findings showed that medical comorbidities had a greater impact on depression than on anxiety, although the association between medical comorbidities and depression was not specifically reported in the children with epilepsy. Using the Strengths and Difficulties Questionnaire–Parent report, a study by Alfstad et al29 reported that the presence of other chronic diseases along with epilepsy was an independent factor for developing overall psychiatric symptoms. Comorbid conditions have also been identified as a significant predictor of higher levels of anxiety in children and adolescents with epilepsy.37 The present study analyzed epilepsy- and treatment-related variables. Chronicity of illness was found to be a common risk factor for both affective disorders. Seizure variables that were associated with affective disturbances were not retained after multivariate analysis. In addition, different epilepsy types and syndromes were compared and no specific subtypes of epilepsy were found to be differentially associated with psychiatric disorders. This suggests a more general impact of epilepsy on mental health. However, the small number of subjects in the
different epilepsy subtypes limits this interpretation. There is also a lack of compelling evidence regarding an association between subtypes of epilepsy and affective disorders in recent literature.35,37,38 The literature also reports disparate findings regarding polytherapy, whereas our study found that polytherapy was associated with anxiety but less so with depression. Antiepileptic drugs can cause symptoms of anxiety and depression, but their mood-stabilizing properties mean that they are also used in the management of psychiatric disorders.39,40 Pharmacoresistance has been reported to be associated with affective disorders in children with epilepsy,37,41 although Ettinger et al34 observed that neither monotherapy nor polytherapy affected measures of depression or anxiety in children with epilepsy. Literature on the impact of seizure control on affective disorders is equally inconclusive. Our findings demonstrated that adolescents who were seizure-free for at least 12 months at the time of the study were less likely to experience anxiety on univariate analysis, but that the association between being seizurefree and depression was not statistically significant. It may be that anxiety decreases when seizures are controlled because patients are not under the constant heightened state of caution associated with the unpredictability of seizures. Epilepsy is a stigmatizing disease even though seizure is controlled; hence, the association between seizure freedom and depression cannot be clearly demonstrated. The lack of 5-year seizure remission has been reported to be associated with internalizing disorders in children with uncomplicated epilepsy,35 and poorly controlled seizures have been shown to be a predictor of depression.30 However, the absence of a clear association between mood disorders and seizure control reflects the complexity of the matter. A population-based study of adolescents with juvenile myoclonic epilepsy 25 years after seizure onset demonstrated that two-thirds of study participants were on moodaltering medication even though seizures were controlled.42 The present study supports the hypothesis that adolescents with epilepsy have significantly higher rates of affective disorders than adolescents with asthma. However, the hypothesis that adolescents with epilepsy are vulnerable to multietiologic risk factors for developing affective disorders was incompletely demonstrated, as many factors were not retained after multivariate analysis. Demographic and seizure-related variables tended to make different contributions to mood disorders. Less than one-sixth of the adolescents with epilepsy in our study received psychiatric services at the time of the study. This unmet need for psychiatric services may reflect underrecognition of psychiatric comorbidities. A comprehensive assessment including an assessment of mood disorders is required to improve the quality of life for children and adolescents with epilepsy. Acknowledgments This work was completed with help of Miss Eliza Yip, neurology nurse, and Miss Leung Sui Ping, respiratory nurse.
Author Contributions KLK made substantial contribution in design, data interpretation, and preparation of manuscript. DL was responsible for design and for
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Kwong et al
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acquisition of data in patients having asthma. ST collected and analyzed data in patients with asthma. MN and BT collected and review data in patients with epilepsy. TML and SML provided important support in assessment tool administration and its relevance in psychiatric disorder.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval The study was approved by Ethic Committee in Tuen Mun Hospital.
References 1. Johnson EK, Jana EJ, Seidenberg M, Hermann BP. The relative impact of anxiety, depression, and clinical seizure features on health-related quality of life in epilepsy. Epilepsia. 2004;45: 544-550. 2. Kwan P, Yu E, Leung H, et al. Association of subjective anxiety, depression, and sleep disturbance with quality-of-life ratings in adults with epilepsy. Epilepsia. 2009;50:1059-1066. 3. McDermott S, Mani S, Krishnaswami S. A population-based analysis of specific behavior problems associated with childhood seizures. J Epilepsy. 1995;8:110. 4. Rutter M, Graham P, Yule W. A Neuropsychiatric Study in Childhood. London: S.I.M.P./William Heinemann Medical Books; 1970. 5. Davies S, Heyman I, Goodman R. A population survey of mental health problems in children with epilepsy. Dev Med Child Neurol. 2003;45:292-295. 6. Russ SA, Larson K, Halfon N. A national profile of childhood epilepsy and seizure disorder. Pediatrics. 2012;129:256-264. 7. Ott D, Siddarth P, Gurbani A, et al. Behavioral disorders in pediatric epilepsy. Epilepsia. 2003;44:591-597. 8. MacLeod JS, Autstin JK. Stigma in the lives of adolescents with epilepsy: a review of the literature. Epilepsy Behav. 2003;4: 112-117. 9. Jones JE, Siddarth P, Gurbani S, et al. Screening for suicidal ideation in children with epilepsy. Epilepsy Behav. 2013;29:521-526. 10. Plioplys S, Dunn DW, Caplan R. 10-year research update review: psychiatric problems in children with epilepsy. J Am Acad Child Adolesc Psychiatry. 2007;46:1389-1402. 11. Reilly C, Agnew R, Neville BGR. Depression and anxiety in childhood epilepsy: a review. Seizure. 2011;20:589-597. 12. Dunn D, Austin J, Huster G. Symptoms of depression in adolescents with epilepsy. J Am Acad Child Adolesc Psychiatry. 1999; 38:1132-1138. 13. Chan YF, Leung YP, Fong DYT, et al. Psychiatric evaluation of the Hospital Anxiety and Depression Scale in a large community sample of adolescents in Hong Kong. Qual life Res. 2010;19: 865-873.
14. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005. Epilepsia. 2010;51:676-685. 15. White D, Leach C, Sims R, Atkinson M. Validation of the Hospital Anxiety and Depression Scale for use with adolescents. Br J Psychiatry. 1999;175:452-454. 16. Letitre SL, de Groot EP, Draaisma E, Brand PL. Anxiety, depression and self-esteem in children with well-controlled asthma: a case-controlled study. Arch Dis Child. 2014;99:744-748. 17. Villa G, Nollet-Clemencon. de Blic. Prevalence of DSM-IV anxiety and affective disorders in a paediatric population of asthmatic children and adolescents. J Affect Disord. 2000;58:223-231. 18. Austin JK. Comparison of child adaptation to epilepsy and asthma. J Child Adolesc Psychiatr Ment Health Nurs. 1989;2: 139-144. 19. Ettinger A, Reed M, Cramer J. Depression and comorbidity in community-based patients with epilepsy or asthma. Neurology. 2004;63:1008-1014. 20. Blumer D. Antidepressant ad double antidepressant treatment for the affective disorder of epilepsy. J Clin Psychiatry. 1997; 58:3-11. 21. Hermann BP, Whitman S. Psychopathology in epilepsy: a multietiologic model. In: Hermann BP, Whitman S, eds. Psychopathology in Epilepsy: Social Dimensions. New York: Oxford University Press; 1986:5-37. 22. Aben I, Verhey R, Lousberg R, et al. Validity of Beck Depression Inventory, Hospital Anxiety and Depression Scale, SCL-90, and Hamilton depression Rating Scale as screening instruments for depression in stroke patients. Psychosomatics. 2002;43:386-393. 23. Lewis G, Wessely S. Comparison of the General Health Questionnaire and the Hospital Anxiety and Depression Scale. Br J Psychiatry. 1990;157:860-864. 24. Bowling A. Measuring Disease. Buckingham: Open University Press; 1995. 25. Herrero MJ, Blanch J, Peri JM, et al. A validation study of the Hospital Anxiety and Depression Scale (HADS) in a Spanish population. Gen Hosp Psychiatry. 2003;25:277-283. 26. Brennan C, Worrall-Davies A, McMillan D, et al. The Hospital Anxiety and Depression Scale: a diagnostic meta-analysis of case-finding ability. J Psychosom Res. 2010;69:371-378. 27. Austin JK, Osborne-Shafer P, Beach-Deering J. Epilepsy familiarity knowledge, and perceptions of stigma: report from a survey of adolescents in the general population. Epilepsy Behav. 2002; 3:368-375. 28. Meador KJ. Research use of the new qualify of life of epilepsy inventory. Epilepsia. 1993;34:34-38. 29. Alfstad KA, Clench-Aas J, Van Roy B, et al. Psychiatric symptoms in Norwegian children with epilepsy aged 8-13 years: effects of age and gender? Epilepsia. 2011;52:1231-1238. 30. Turky A, Beavis JM, Thapa AK, Kerr MP. Psychopathology in children and adolescents with epilepsy: an investigation of predictive variables. Epilepsy Behav. 2008;12:136-144. 31. Austin JK, Risingerr MW, Beckett LA. Correlates of behavior problems in children with epilepsy. Epilepsia. 1992;33:1115-1122.
Downloaded from jcn.sagepub.com at CALIFORNIA STATE UNIV FRESNO on July 6, 2015
8
Journal of Child Neurology
32. Jones JE, Watson R, Sheth R, et al. Psychiatric comorbidity in children with new onset epilepsy. Dev Med Child Neurol. 2007;49:493-497. 33. Baki O, Erdogan A, Kantarci O, et al. Anxiety and depression in children with epilepsy and their mothers. Epilepsy Behav. 2004;5: 958-964. 34. Ettinger AB, Weisbrot DM, Nolan EE, et al. Symptoms of depression and anxiety in pediatric epilepsy patients Epilepsia. 1998;39: 595-599. 35. Berg AT, Caplan R, Hesdorffer DC. Psychiatric and neurodevelopmental disorders in childhood-onset epilepsy. Epilepsy Behav. 2011;20:550-555. 36. Costello EJ, Mustillo S, Erkanli A, et al. Prevalence and development of psychiatric disorders in childhood and adolescence. Arch Gen Psychiatry. 2003;60:837-844. 37. Williams J, Steel C, Sharp GB, et al. Anxiety in children with epilepsy. Epilepsy Behav. 2003;4:729-732.
38. Og˘uz A, Kurul S, Dirik E. Relationship of epilepsy-related factors to anxiety and depression scores in epileptic children. J Child Neurol. 2002;17:39-40. 39. Brent DA, Crumine PK, Varma RR, et al. Phenobarbital treatment and major depressive disorder in children with epilepsy. Pediatrics. 1987;80:909-917. 40. Sadock BJ, Sadock VA. Mood disorders and suicide. In: Pataki CS, Ahmad S, eds. Concise Textbook of Child and Adolescent Psychiatry. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:145-146. 41. Adewuya AO, Ola BA. Prevalence of and risk factors for anxiety and depressive disorders in Nigerian adolescents with epilepsy. Epilepsy Behav. 2005;6:342-347. 42. Camfield CS, Camfield PR. Juvenile myoclonic epilepsy 25 years after seizure onset: a population based study. Neurology. 2009;73: 1041-1045.
Downloaded from jcn.sagepub.com at CALIFORNIA STATE UNIV FRESNO on July 6, 2015
