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Summary: Purpose: This study examined affective disorders, anxiety disorders, and suicidality in children with epilepsy and their association with seizure-related, cognitive, linguistic, family history, social competence, and demographic variables.
Methods: A structured psychiatric interview, mood self-report scales, as well as cognitive and language testing were administered to 100 children with complex partial seizures (CPSs), 71 children with childhood absence epilepsy (CAE), and 93 normal children, aged 5 to 16 years. Parents provided behavioral information on each child through a structured psychiatric interview and behavior checklist.
Results: Significantly more patients had affective and anxiety disorder diagnoses (33%) as well as suicidal ideation (20%) than did the normal group, but none had made a suicide attempt. Anxiety disorder was the most frequent diagnosis among the patients with a diagnosis of affective or anxiety disorders, and combined affective/anxiety and disruptive disorder diagnoses, in those with suicidal ideation. Only 33% received some form of mental health service. Age, verbal IQ, school problems, and seizure type were related to the presence of a diagnosis of affective or anxiety disorder, and duration of illness, to suicidal ideation.
Conclusions: These findings together with the high rate of unmet mental health underscore the importance of early detection and treatment of anxiety disorders and suicidal ideation children with CPSs and CAE.
Depression and anxiety are the most prevalent psychiatric disorders in adults with epilepsy (1–4). They affect quality of life (5,6) and how patients respond to poor seizure control (7). Nevertheless, most cases of depression go undiagnosed and untreated in these patients [See review in Barry, 2000 (8)].
In terms of the underlying mechanisms, seizure-related variables, such as seizure frequency (9) and cognition (10), are unrelated to the mood disorders of adults with epilepsy, and findings are inconsistent regarding lateralization of EEG findings (11,12). However, the underlying pathology of the disorder involving the hippocampus (13), amygdala (14), and subcortical nuclei (15) might play a role in these disorders.
Studies in childhood epilepsy report mood disorders in 12–26% of these patients (1–22). This wide range reflects methodologic differences, such as differences in types of diagnostic instruments (e.g., structured psychiatric interviews, self-report scales), number and type of informants (e.g., child, parent, teacher), diagnostic end points [e.g., Diagnostic and Statistical Manual of Mental Disorders–IV (DSM-IV) diagnosis, borderline/clinical T scores], age range of subjects (e.g., children, adolescents), recruitment sources (e.g., community samples, university-affiliated clinics), chronicity of study samples (new-onset seizures, chronic epilepsy, postsurgical patients), and sample size.
Thus in their population survey of mental health problems in children with epilepsy, Davies et al. (17) found emotional disorders in 16.7% of 67 children with complicated epilepsy (e.g., with a learning disorder and/or neurologic abnormality) and in 16% of those with uncomplicated epilepsy compared with 6.4% in children with diabetes and 4.2% in the general population base by using a clinician-reviewed structured psychiatric interview conducted with the child, parent, and teacher. With children and parents as informants during a structured psychiatric interview, the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) (23), Ott et al. (22) reported mood disorders (e.g., depression and anxiety disorders) in 12% and 13%, respectively, of 48 children with complex partial seizure disorder (CPS) and 40 children with childhood absence epilepsy (CAE) recruited from both community and tertiary epilepsy pediatric neurology clinics.
Brent et al. (24,25) made a K-SADS diagnosis of depression in 23 children with epilepsy treated with phenobarbital (PB) but in none of the 17 treated with carbamazepine (CBZ). The depression resolved in the children whose PB was discontinued but persisted in those maintained on this medication. Kaminer et al. (26) found similar K-SADS depressive cluster scores in 26 adolescents with epilepsy and 26 with asthma, a diagnosis of affective disorder in one epilepsy patient, and higher depression symptom cluster scores in the epilepsy patients taking hydantoin (phenytoin; PHT) compared with CBZ. Although Alwash et al. (27) reported DSM-IV diagnoses of depression in 77.2% and of anxiety in 48.5% of 101 of 14- to 24-year-old epilepsy patients, they did not indicate what instruments were used to make these diagnoses.
In terms of self-report instruments, Dunn et al. (18) found a rate of 25% in a community sample of 115 adolescents based on the Children's Depression Inventory (CDI) (28). Brent et al. (24,25) also reported significantly higher CDI scores in the children with epilepsy treated with PB compared with CBZ.
Among 35 pediatric epilepsy outpatients aged 9 to 18 years, Oguz et al. (20) reported more depression in the 12- to 18-year-old patients based on the CDI, but increased anxiety by using the State Trait Anxiety Inventory (29) in both the 9- to 11-year-old and 12- to 18-year-old patients compared with normal healthy children. This anxiety instrument also revealed higher levels of trait anxiety in children with epilepsy than in healthy controls subjects, but similar levels compared with learning-disabled children (30).
Ettinger et al. (19) found depression in 26% and anxiety in 16% of 44 epilepsy patients, aged 7 to 18 years, on the CDI and Revised Child Manifest Anxiety Scale (RCMAS) (31), respectively. Williams et al. (21) reported a similar rate of anxiety, 23%, with the RCMAS in a large sample of 101 patients with epilepsy aged 6 to 16 years.
The previously reviewed studies of depression and anxiety disorders included mainly children with chronic epilepsy (16,19,32). Higher parent-based internalizing compared with externalizing scores in the children with new-onset seizures (33,34) imply that some of the behavior difficulties of these children might reflect mood disorders.
Adults with epilepsy have suicidal acts 3.5 times more than does the general population (35), particularly if they have a psychiatric diagnosis, earlier onset of epilepsy, and antipsychotic treatment. Jones et al. (36) described significantly more depression, anxiety disorder, as well as combined depression and anxiety disorder among 139 adult epilepsy patients, 12.2% of whom had suicide attempts, and 20.8%, suicidal ideation. Although seizure variables are unrelated to suicidal behavior in adults with epilepsy [See review in Jones et al. (36)], some studies report higher suicidal rates in adults with temporal lobe epilepsy (37,38).
Only a few studies, however, examined suicidality in children with epilepsy (19,22,24). Ott et al. (22) reported suicidal ideation in 17% of 48 CPS and 18% of 39 CAE and suicidal intent in 8% and 11% of the CPS and CAE groups, respectively, but these rates were not significantly higher than those in 59 normal children (9% ideation, 1% intent). Ettinger et al. (19) identified suicidal ideation with intent in 4.3% and without intent in 11% of children with epilepsy. Among 15 children with epilepsy treated with PB, Brent et al. (24) found suicidal ideation in 40% compared with only 4% of 24 children with epilepsy treated with CBZ.
Regarding predictors of mood disorder in children and adolescents, as found in the general population (39,40), a gender effect is found, with more depression in adolescent girls with epilepsy (18), and an age effect with higher depression rates in adolescents compared with children with epilepsy (20). Some studies report no association with seizure variables (16–18,22,32), and others report an association with seizure frequency (20), antiepileptic drug (AED) polytherapy (20,21), type of AED (24–26), and duration of illness (20). Other than the reported association with PB (24), no similar studies have evaluated the relation between suicidal ideation and seizure variables in children with epilepsy.
Cognitive variables are related to the presence of mood disorders with more severe mood disorders in children with epilepsy with mental retardation (17,41) and increased anxiety in children with comorbid learning and attentional difficulties (21). Similar studies have not been conducted regarding suicidal behavior in children and adolescents with epilepsy.
Depression in children with epilepsy is associated with family discord, number of stressful life events in those treated with PB (24), broken homes in adolescents treated with PHT (26), and a family history of depression (24,25). Suicidal ideation has been related to a mood-disorder diagnosis in these children (19,24).
Psychosocial variables that might contribute to learned helplessness (42), such as decreased satisfaction with family relationships, negative attitude toward illness, and unknown or external locus of control were associated with higher CDI scores in adolescents with depression (18). Although social difficulties can trigger depression in the general child and adolescent population (43), their role has not been studied in mood disorders comorbid with pediatric epilepsy.
The study presented here examined the rate of affective disorders, anxiety disorders, and suicidal ideation in children with epilepsy compared with normal children based on structured psychiatric interviews with both the children and their parents as separate informants. By using a K-SADS based DSM-IV diagnosis of a major affective or anxiety disorder as the gold standard, it then compared the sensitivity and specificity of two self-report instruments, the CDI, and the Manifest Anxiety Scale for Children (44), as well as parent Child Behavior Checklist internalizing and anxiety/depression scores (CBCL) (45). The study also examined the role played by seizure-related, cognitive, linguistic, family history, social competence, and demographic variables on the mood measures.
We hypothesized that children with epilepsy would have significantly higher rates of depression and anxiety disorder than do normal children after controlling for differences in demographic, cognitive, and linguistic variables. With a DSM-IV diagnosis as the gold standard, we hypothesized that the CDI would have better sensitivity and specificity for depression, and the MASC, for anxiety among the patients than the internalizing or anxiety/depressions factor scores of the CBCL. Finally, we posited that cognitive and linguistic deficits, a family history of a mood disorder in first-degree relatives, and impaired social competence, but not seizure variables would be associated with the presence of affective disorder, anxiety disorder, suicidal ideation, and high mood scores in the children with epilepsy.
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This is the first study to demonstrate a high rate of affective and anxiety disorder diagnoses (33%) as well as suicidal ideation/plan (20%), but no suicidal acts in children with CPS and CAE of average intelligence compared with normal children, controlling for between-group demographic, cognitive, and linguistic differences. More patients with affective and anxiety disorders had anxiety than depression, whereas the most frequent diagnosis among those with suicidal ideation was comorbid affective/anxiety and disruptive disorders. In a subsample of subjects, the MASC had the highest sensitivity, and the CBCL attention/depression factor score, the highest specificity. The presence of affective and anxiety disorders was related to age and verbal IQ, and the presence of suicidal ideation, to increased duration of illness. Depression was more frequent in the CPS patients, and anxiety disorders, in the CAE patients.
These findings differ from those of prior studies (16–22) in the higher rate of affective and anxiety disorders as well as the increased frequency of anxiety disorders compared with major affective disorders (e.g., depression). Methodologic differences, such as study sample (e.g., clinical vs. epidemiologic), types of instruments, diagnostic end point, and informants might account for these differences.
As in other studies on clinical samples (16,18–22), we also found higher rates of affective and anxiety disorders than in Davies et al. (17) epidemiologic study. In terms of diagnostic instruments, to obtain a diagnosis with the K-SADS, a child must meet specified diagnostic criteria defined by the DMS-IV. Psychopathology instruments, such as the CBCL, CDI, and MASC, however, provide psychometrically determined cut-off scores of depression or anxiety symptoms based on normative data rather than on a psychiatric diagnosis.
Given the internalizing nature of the symptoms of affective and anxiety disorders, informants, such as parents, are frequently unaware of mood and anxiety symptoms their children experience. In addition, parents' psychiatric status might influence what and how they communicate information [See review in Grills and Ollendick (54)]. Thus depressed and anxious parents might be aware of their children's symptoms, but underestimate or downplay the severity of these symptoms [See reviews in Gould (55) and Ryan (56)]. Parents might also unwittingly perceive epilepsy-related phenomena as abnormal behaviors (57–59). Therefore administration of a structured psychiatric interview separately to both the child and parent, as in our study, probably increased the likelihood of obtaining information on internalizing symptoms and might account for our higher rate of affective and anxiety disorders in this study.
Regarding control groups, some studies have used normative data (18–20,60) rather than a control group. Several researchers suggested that norms based on psychiatrically referred and normal children, as found in the CBCL, CDI, and MASC, might not be adequate in studies of children with chronic illness (61,62). Because we did not include a control group of children with chronic illness, we were unable to examine the possible role of having a chronic illness on the affective and anxiety disorder rate in the CPS and CAE children. Davies et al. (17), however, reported a significantly higher rate of emotional disorders in children with epilepsy compared with children with diabetes.
Regarding differences across studies in the type of mood disorders, more depression, particularly in female patients (18) and lower rates of anxiety (19) in previous studies on children with epilepsy might stem from the older age range of the subjects in these studies compared with our study. Similar to what has been described in the general population of children (63) and by Oguz et al. (20) in children with epilepsy, we found a trend for depression in the older children and for anxiety in the younger children. Given the lack of a relation with seizure frequency in our study, the high rate of anxiety disorders does not appear to reflect specific features of epilepsy, such as the unpredictability of ictal events and the loss of control the child experiences during a seizure.
Furthermore, our findings suggest that children with epilepsy also have high rates of comorbid anxiety and disruptive disorders, but not comorbid depression and anxiety disorders, as found in adults with epilepsy (64). In the general population of children and adolescents, anxiety disorders are also comorbid with disruptive disorders (56,65).
The sensitivity and specificity data suggesting that the MASC and K-SADS were highly correlated might reflect the high rate of anxiety disorders and the relatively small sample size included in the sensitivity–specificity study. Further studies are needed to determine if more anxiety disorders and comorbid disruptive disorders, as well as high sensitivity of the MASC, are an age-related finding in children with epilepsy and change with age through adolescence.
In examining which children with epilepsy might be at risk for affective and anxiety disorders, we found an association of subtle verbal IQ deficits and school difficulties with these diagnoses, similar to findings in other studies of children with epilepsy (21,41), children with anxiety disorders (66), and children with reading disorders (67). Scholastic achievement might make children with epilepsy vulnerable to mood disorders by affecting self-esteem (67) and cognitive flexibility (66), variables related to mood disorders in children,
Like adults (9,11) and adolescents (18) with epilepsy, other than type of seizure disorder, seizure variables were unrelated to affective and anxiety disorders. Although more depression in the CPS and more anxiety disorders in the CAE groups probably reflected the significantly older age of the CPS patients with depression compared with the CAE with anxiety, the possible role of amygdala (14), hippocampal (13), and frontal involvement [See review in Kanner (68)] on these findings should be further explored.
As in Jones et al. (36) and Nilsson et al. (35) in adult epilepsy patients, one fifth of the patients in our study had suicidal ideation, and most of these children had a psychiatric diagnosis. In contrast to the findings in the adult studies, none of these children had made suicide attempts. In addition, comorbid disruptive and affective/anxiety disorders rather than depression, as well as increased duration of illness, were associated with the presence of suicidal ideation in the children in the study.
Because most of the children in the study were prepubertal, the absence of suicidal attempts might reflect the low suicide rate in the general population of 10- to 14-year-old youth, 1.5 per 100,000, compared with 8.2 per 100,000 in 15- to 19-year-old individuals [See review in Gould et al. (55)]. Nevertheless, suicidal ideation in 20% of the children is 3.85 times higher than the 5.2% found in 1,285 children randomly chosen from the general population between the ages of 9 and 17 years (69).
Given the low rate of depression in our study, it is not surprising that depression was not the psychiatric diagnosis most commonly associated with suicidal behavior. In addition, the increased frequency of comorbid disruptive and affective/anxiety disorders imply that impulsivity, which plays a role in adolescent suicide, particularly in boys (55,70,71), might be implicated in the suicidal ideation of children with epilepsy.
Finally, it is important to note that even though half of the children in the study were recruited from tertiary, and half, from community sources, the high rate of both affective and anxiety disorders and suicidal ideation in the sample studied might not be generalizable to the community at large of children with epilepsy. Generalizability of the study's conclusions are further limited because we computed multiple statistical comparisons to examine the association of seizure, cognitive, linguistic, and psychopathology variables with affective and anxiety disorder diagnoses and suicidal ideation in a relatively small sample of children. Additionally, use of different IQ (i.e., WISC-R, WISC-II) and language instruments (i.e., TOLD-Primary, TOLD-Intermediary, TOAL), as well as availability of MASC and CDI data for only a small sample of the children in the study, highlights the need to replicate the findings on affective and anxiety-related variables and diagnostic sensitivity/specificity.
Notwithstanding these limitations, only 33% of the children with affective and anxiety disorders and suicidal ideation received some form of mental health services. This high rate of unmet mental health needs, together with the high rate of depression, anxiety, and suicide in adults with epilepsy (1–4), and the age-related increase of suicidal acts and deaths in adolescence (35) emphasize the importance of early detection and treatment of affective and anxiety disorders in children with epilepsy.