SEARCH

SEARCH BY CITATION

Keywords:

  • Depression;
  • Anxiety;
  • Suicide;
  • Complex partial seizure disorder;
  • Absence epilepsy;
  • Child

Abstract

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgments
  7. REFERENCES

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.

METHODS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgments
  7. REFERENCES

Subjects

The study included 171 epilepsy patients, 100 children with CPS, 71 children with CAE, and 93 children without epilepsy, aged 5 to 16 years. Table 1 describes the demographic, cognitive, linguistic, and family history features of the children in the study. The CAE group was younger than the CPS group, and both patient groups had significantly lower mean IQ and language scores compared with the normal group. No significant differences were found in the Hollingshead 2 factor index (46), derived from parent occupational and educational status, and in the ethnic distribution of the subject groups. We tested 181children in 1994 through 1998 and 83 in 1999 through 2004. Other than lower socioeconomic status and older age in the CPS, as well as lower IQ scores in the CAE subjects tested in 1994 through 1998, no significant demographic, seizure, cognitive, and linguistic differences were noted between the children tested earlier and later.

Table 1. Demographic, cognitive, and linguistic features of study groups
 All patientsCPSCAENormal
  1. Other than age, no significant differences were noted between CPS and CAE groups. Therefore t tests on IQ were computed between combined CPS/CAE and normal groups.

  2. at (169) = 2.13; p < 0.03.

  3. bt (245) = 9.02; p < 0.0001.

  4. ct (225) = 8.43; p < 0.0001.

  5. dt (253) = 7.06; p < 0.0001.

  6. et (213) = 6.25; p < 0.0001.

No.1711007193
Age (yr)10.3 (2.74)   10.7 (2.47)   9.8 (2.18)a 10.6 (2.55)   
Male/Female47%/53%49%/51%44%/56%48%/52%
SES High (i–iii)/Low (iv–v)55%/45%60%/40%48%/52%63%/37%
Ethnicity
 White52%58%44%54%
 Non-white48%42%56%46%
Full Scale IQ94 (17.83)92 (18.38)97 (16.92)111 (12. 60)b
Verbal IQ94 (18.60)93 (18.90)95 (18.21)112 (15.05)c
Performance IQ96 (17.27)94 (18.10)98 (16.92)109 (11.62)d
SLQ90 (18.22)90 (18.45)91 (18.04)104 (14.76)e
First-degree relative
 Psychiatric diagnosis30.8%36.4%21.0%28.6%
 Mood disorder34.6%39.3%26.3%39.2%
 Epilepsy21.8%25.0%15.8%0

To be included in the study, the patients had to have a diagnosis of CPS or CAE, as defined by the International Classification of Epilepsy (47), and at least one seizure during the year before the child's participation in the study. As described in this classification, children with a clinical history of CPS, but no EEG evidence for focal epileptic activity, were included in the study sample. All CAE patients had EEG evidence of three-per-second spike and wave. We excluded patients with a mixed seizure disorder, an underlying neurologic disorder, a metabolic disorder, a hearing disorder, and past epilepsy surgery.

The primary pediatric neurologist at each site reviewed the clinical history, EEG records, and diagnosis of potential CPS and CAE subjects and referred them for the study irrespective of their psychiatric history. Table 2 presents recruitment and information on seizure frequency during the past year, current AEDs, age at onset of seizures, duration of illness, as well as the number of febrile convulsions and number of prolonged seizures (i.e., >5 min) from the parents and the child's medical records.

Table 2. Seizure-related variables in CPS and CAE groups
 AllCPSCAE
  1. aχ2 (1) = 7.89; p < 0.01.

  2. bχ2 (1) = 11.42; p < 0.003.

  3. ct162= 2.61; p < 0.01.

  4. dχ2 (1) = 7.90; p < 0.02.

  5. eχ2 (1) = 35.19; p < 0.0001.

  6. fχ2 (1) = 4.96; p < 0.02.

Recruitment source
 Tertiary50%61%37%a
 Community50%39%63% 
Seizure frequency
 ≤1/yr34%33%36%b
 2–10/yr21%30% 9% 
 >10/yr45%37%55% 
Age at onset5.7 (3.21)5.4 (3.12)5.8 (2.37) 
Duration4.7 (3.21)5.2 (2.94)3.9 (2.46)c
AEDs
 None 8% 5%13%d
 Monotherapy68%65%73% 
 Polytherapy24%30%14% 
Prolonged seizures28%46% 4%e
Febrile seizures21%27%13%f

We recruited significantly more CPS patients from tertiary centers (e.g., UCLA Pediatric Neurology services, Children's Hospital of Los Angeles) and more CAE from the community (e.g., Kaiser Sunset, Kaiser-Orange County, private pediatric neurologists, Los Angeles and San Diego branches of the Epilepsy Foundation of America) (Table 2). As predicted from the illness course, significantly more CPS patients had two to 10 seizures per year, AED polytherapy, prolonged seizures, and febrile convulsions, but significantly more CAE had >10 seizures per year (Table 2).

We recruited the nonepilepsy control subjects from four public and two private schools in the Los Angeles community after screening for neurologic, psychiatric, language, and hearing disorders through a telephone conversation with a parent. We excluded from the study nonepilepsy children manifesting symptoms of these disorders in the past.

Procedures

This study was conducted in accordance with the policies of the Human Subjects Protection Committees of the University of California, Los Angeles. Informed assents and consents were obtained from all subjects and their parents, respectively.

The Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS)

The Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children, Epidemiologic Version (K-SADS-E) (48) and Present and Lifetime Version (K-SADS-PL) (23) during 1994 to 1998 and 1999 to 2003, respectively, was administered to each child and parent by R.C. or a trained research assistant. We found no significant differences in the number of children who met criteria for a psychiatric diagnosis and the type of psychiatric diagnosis in the children tested in 1994 to 1998 and 1999 to 2003.

Because the child or parent often talks about the child's seizures during the interview, these interviewers were not blinded with regard to the child's seizure disorder (i.e., presence or absence type). A consensus DSM-IV (49) diagnosis was reached after reviewing videotapes of the child interviews and audiotapes of the parent interviews. A child was excluded from the study if a diagnostic consensus was not reached.

Although the K-SADS provides current and past psychiatric diagnoses, we describe only current diagnoses. The presence or absence of suicidal acts and ideation, both current and past, was abstracted from responses to questions on suicidal acts and thoughts about death and dying (e.g., active and passive thoughts) in the depression section of the K-SADS interview.

Given the large number of diagnoses relative to the number of subjects in each diagnostic group, we grouped the diagnoses as follows: “disruptive” disorders included attention-deficit disorder, oppositional defiant disorder, and conduct disorder; and “affective/anxiety” disorders included any mood or anxiety disorder. Children with a “comorbid” diagnosis had both “disruptive” and “affective/anxiety” disorders.

We obtained information on mental health treatment (i.e., any contact with a mental health professional, including therapy and psychotropic medication treatment) from the parent and/or child K-SADS interview. In this article, mental health treatment refers to both past and current mental health treatment.

The Child Behavior Checklist (CBCL)

Parents completed the 118 behavior problem and 20 social competency items, which are scored on a 3-point scale ranging from not true to often true of the child (45). The CBCL generates a total T score, broad-band (i.e., externalizing, internalizing) and narrow-band behavioral scales (i.e., anxiety/depression, hyperactivity, social). The cut point for borderline/clinically significant pathology in this study was 60 for the broad-band and 67 for the narrow-band scales (45).

The three social competence subscales measure competencies in the following domains: activities (e.g., sports, hobbies); social (e.g., friendships, interpersonal skills); and school (e.g., performance, ability, school problems). The selected cut points for clinically significant pathology in the total social competence score was 37 for the school and 30 for the social and activities scores.

Individual item intraclass correlations (ICC) are >0.90. Stability of ICCs over a 3-month period is 0.84 for behavior problems and 0.97 for social competencies. Test/retest reliability is 0.89. Tests of criterion-related validity for referred/nonreferred children support the validity of the instrument, and normative data are extensive.

The Children's Depression Inventory (CDI)

This 27-item self-report instrument (28) for 7- to 17-year-old children and adolescents has a 3-point scale and produces a total score and five factor scores: dysphoric mood, acting out, loss of personal and social interest, self-deprecation, and vegetative symptoms. It has a solid internal consistency reliability (0.59–0.88), variable test/retest reliability (0.38–0.87), and poor discriminant validity (e.g., high false-negative rate). Nevertheless, it is sensitive to change, has good normative data, and has been extensively used in children with chronic illness and developmental disorders. CDI data were available only for subjects recruited in 1999–2004 who were 7 years or older (n = 67). CDI T scores of ≥50 were considered clinically relevant.

The Multideminsional Anxiety Scale for Children

This 39-item self-report instrument (44) uses a 4-point scoring scale and generates a total score and four factor scores (e.g., physical symptoms, social anxiety, harm avoidance, separation anxiety). Used in children and adolescents, aged 8–19 years, psychometric properties are generally strong with internal consistency reliabilities ranging from 0.60 to 0.90 and test/retest reliabilities ranging from 0.65 to 0.93. In addition, it discriminates with an accuracy of 0.74 between children with and without anxiety disorder. A total T-score >70 matches a generalized anxiety disorder diagnosis. This instrument was available only for subjects tested in 1999–2004 who were 8 years or older (n = 81), and T scores of ≥50 were considered clinically relevant.

Cognition

The Wechsler Intelligence Scale for Children-Revised (WISC-R) (50), given to children tested from 1994 to 1998, and the Wechsler Intelligence Scale for Children–3rd edition (WISC-III) (51), administered to children tested from 1999 to 2003, generated Full Scale, Verbal, and Performance IQ scores. Although the Full Scale, Verbal, and Performance IQ scores of both instruments are highly correlated (52), children score lower on the WISC-III compared with the WISC-R. Although the CAE children tested with the WISC-R (mean, 98; SD, 14.10) had significantly higher Performance IQ scores (t83 = 1.94; p < 0.05) than did those tested with the WISC-III (mean, 94; SD, 20.81), no other significant differences in Full Scale and Verbal IQ scores were seen in the children tested in 1994–1998 and 1999–2003.

The Test of Language Development (TOLD)

The TOLD has three forms: the TOLD-2 Primary, normed for children aged 4–8 years; the TOLD-2 Intermediate, normed for children aged 8–12 years; and the TOAL, normed for adolescents aged 12–18 years (53). Each form of the TOLD-2 consists of a series of subtests through which it assesses both vocabulary and grammar. We administered the TOLD Primary to 29%, the TOLD Intermediate to 47%, and the TOAL to 23% of the children in the study. Spoken language quotient (SLQ) derived from each of these tests was used as an independent variable. Language data were missing in 15 CPS, seven CAE, and two normal subjects because of problems ascertaining ceiling (n = 3) and basal levels (n = 16), as well as test-administration errors (n = 5).

Data analysis

Epilepsy patients and normal subjects were compared on the rate of affective and anxiety disorders, types of disorders, suicidal acts/ideation/plan, as well as T-scores and mean scores for CBCL, MASC, and CDI with logistic regression for categorical variables and analyses of variance (ANOVAs) for continuous variables. Age, gender, socioeconomic status, ethnicity, and Full Scale IQ scores were used as covariates in these analyses. We then divided the patient group into three groups: patients with affective and anxiety disorders, patients with a psychiatric disorder other than affective and anxiety disorders, and patients without a psychiatric diagnosis. We then compared CBCL, CDI, and MASC measures in these three groups of patients and normal subjects by using ANOVA procedures and logistic regression. We also examined the relation of these measures to seizure, cognitive, linguistic, perinatal, and demographic variables in these groups. Further, we investigated suicidality in the patient group by comparing patients with and without suicidality on demographic, seizure, cognitive, linguistic, CBCL, CDI, and MASC measures.

Finally, we computed sensitivity and specificity of the CDI, MASC, and the CBCL internalizing anxiety/depression factor scores to predict affective and anxiety disorders in the patient group by using logistic regression. All tests were two-tailed, and an α level of 0.05 was adopted for all inferences. Because this was a hypothesis-driven study, we did not correct for multiple comparisons.

RESULTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgments
  7. REFERENCES

Mood disorders and suicidal ideation: rate

After controlling for differences in age, demographic, cognitive, and linguistic variables, the rate of affective and anxiety disorders, 33% (n = 57), was significantly higher (χ2 (2) 11.18; p < 0.0008) in the patients than in the normal group, 6% (n = 6). Children with CPS and CAE were 5 times more likely to have an affective or anxiety disorder than were the normal subjects (OR, 5.1; 95% CI, 1.95–13.29). Although none of the children had made a suicide attempt, significantly more patients (20%) had suicidal ideation compared with the normal subjects (9%) (χ2= 5.1; p < 0.02), and 37% of these patients also had suicidal plans.

Regarding type of disorder (Table 4), most of the children with an affective or anxiety disorder diagnosis had anxiety disorders (63%) or comorbid affective/anxiety and disruptive disorders (26.1%). Whereas only few (5.2%) had depression as a sole diagnosis, most cases of depression were comorbid with anxiety disorders (3.5%) or disruptive disorders (28%). Among the 26.1% patients with comorbid affective/anxiety and disruptive disorders, half had anxiety disorders; one fourth, major affective disorder; and one fourth, combined anxiety and major affective disorder diagnoses. A trend for depression occurred more in patients with comorbid affective/anxiety and disruptive disorders than in those with only mood disorders (χ2 (2), 5.54; p < 0.06).

Table 4. Distribution of affective and anxiety disorders in CPS and CAE
DiagnosisAllCPSCAE
  1. aχ2 (2) = 8. 03; p < 0.02 comparing the CPS and CAE groups on the presence of anxiety, depression, and combined anxiety and depression diagnoses.

No.573720
Anxiety36 (63%)19 (51%)17 (85%)a
Anxiety20 (35%)10 (27%)10 (50%)
Anxiety + Disruptive16 (28%) 9 (24%) 7 (35%)
Depression11 (19%) 8 (21.6%) 3 (15%)
Depression 3 (5%) 2 (5.4%) 1 (5%)
Depression + Disruptive 8 (14%) 6 (16.2%) 2 (10%)
Anxiety + Depression10 (17.5%)10 (27%) 0
Anxiety + Depression 2 (3.5%) 2 (5.4%) 0
Anxiety+Depression+Disruptive 8 (14%) 8 (21.6%) 0

After controlling for age, gender, socioeconomic status, ethnicity, and IQ, significantly more patients with suicidal ideation had a DSM-IV diagnosis than did those without suicidal ideation (Table 3). Children with epilepsy who had a combined disruptive and affective/anxiety disorder were 12 times more likely to have suicidal ideation than were those without a psychiatric diagnosis (OR, 12.64; 95% CI, 4.05–39.38). The rate of anxiety and depression, however, was similar in the children with and without suicidal ideation.

Table 3. Psychopathology in patients with/without suicidal ideation/plan (SI/P)
 With SI/P(n = 34)No SI/P(n = 127)F2dfp Value
  1. Age, gender, socioeconomic status, ethnicity, perinatal, IQ, and language in model.

DMS-IV diagnosis 27 (79%)69 (52%)7.9710.004
Mood 3 (9%)21 (16%)21.371<0.0001
Disruptive  7 (20%)31 (24%) 
Mood + Disruptive 17 (50%)13 (10%) 
None  7 (21%)64 (50%) 
CBCL Total T>60 24 (75%)42 (33%)15.201<.0001
Mean 65 (9.52)55.4 (10.84) 19.421,152.0001
CBCL Int. T>60 21 (66%)44 (35%)9.1710.002
Mean65.4 (9.99) 55.24 (10.50)  21.121,1520.0001
CBCL Ext. T>60 13 (41%)27 (21%)4.5710.03
Mean57.5 (11.19)50.17 (11.12)  10.211,1520.001
CBCL A/D T>67 13 (41%)14 (11%)12.641<0.0004
Mean63.1 (8.73) 55.6 (7.60)  20.771,1510.0001
CDI T>50  5 (83%)10 (28%)5.9910.01
Mean59.8 (13.30)44.9 (6.65)  21.131,35 0.0001
MASC T>50  9 (82%)15 (35%)5.4010.02
Mean59.5 (12.92)40.3 (17.64) 7.631,47 0.008

Of note, only one third of the children with an affective and anxiety disorder diagnosis had prior psychiatric assessment and/or care. Similarly, only one third of those with suicidal ideation received some kind of mental health service.

Mood disorders and suicidal ideation: other psychopathology measures

The epilepsy subjects with affective and anxiety disorders had significantly higher mean CBCL internalizing and anxiety/depression factor scores, CDI, and MASC scores, and significantly more children had T-scores in the borderline/clinical range compared with those without a psychiatric diagnosis, with a psychiatric diagnosis other than affective and anxiety disorders, and the normal children (Table 5). These scores were also significantly higher in the patients with suicidal ideation compared with those without suicidality (Table 3).

Table 5. CBCL, MASC, and CDI by psychiatric diagnosis
 EPI + Affect/AnxietyEPI + Psych DgEPI − Psych DgNormal-Psych Dg
  1. Age, gender, socioeconomic status, ethnicity, perinatal, IQ, and language in model.

  2. EPI + Psych Diagnosis, psychiatric diagnosis other than affective and anxiety disorder.

  3. aF3, 234= 13.12, p < 0.0001.

  4. bχ2(3) = 35.86; p < 0.0001.

  5. cF3, 234= 13.92; p < 0.0001.

  6. dχ2(3) = 20.64; p < 0.0001.

  7. eF3, 234= 3.62; p < 0.01.

  8. fχ2(3) = 11.10; p < 0.01;

  9. gF3, 233= 12.10; p < 0.0001.

  10. hχ2(3) = 24.59; p < 0.0001.

  11. iF3, 73= 3. 62; p < 0.02.

  12. jχ2 (3) = 12.82; p < 0.005.

  13. kF3, 59= 5.89; p < 0.001

  14. lThe model did not converge.

No.57427280
CBCL Total Mean 62 (10.07)59.3 (11.91)52.7 (10.01)46.9 (12.02)a
T>6066.7%52.5%16.9%13.9%b
CBCL Int. Mean62.8 (9.40) 56.4 (12.24)53.4 (10.01)48.5 (11.60)c
T>6063%40%25.3%19%d
CBCl Ext. Mean54.2 (12.42)54.4 (11.80)48.1 (9.99) 46.6 (10.18)e
T>6033.3%37.5%12.7%10.1%f
CBCL A/D Mean61.8 (9.87) 56.8 (7.86) 53.9 54.6 (6.55)g
T>6738%17.5% 2.8% 7.6%h
MASCN = 15N = 13N = 26N = 27
Mean54.5 (15.54)42.1 (17.95)39.3 (18.39)40.8 (14.33)i
T>5086.7%30.8%26.9%22.2%j
CDIN = 12N = 8N = 22N = 25
Mean52.9 (12.63)43.6 (5.47) 45.0 (6.97) 40.1 (3.00)k
T>5058.3%12.5%31.8%0l   

Sensitivity and specificity of instruments

Table 6 indicates that the MASC provided the best sensitivity, and the CBCL Anxiety/Depression factor score, the best specificity to predict an affective and anxiety disorder diagnosis in the patients compared with the CDI, CBCL anxiety/depression factor score, the CBCL internalizing scores, and use of these instruments together.

Table 6. Sensitivity and specificity of mood instruments
InstrumentSensitivitySpecificity
MASC86.7%71.8%
CDI58.3%73.3%
CBCL
 Anxiety/Depression38%  91.9%
 Internalizing62.7%69.4%
MASC+CDI+Anxiety/Depression60%  92.9%

Mood disorders and suicidal ideation: demographic, pregnancy, familial, seizure, cognitive, and linguistic variables

There was a trend for the epilepsy patients with an affective and anxiety disorder diagnosis to be girls (62% vs. 43%; χ2 (1) = 3.3; p < 0.06) and to have significantly fewer delivery problems (16% vs. 36%; χ2 (1) = 4.47; p < 0.03) than the subgroup of epilepsy patients with psychiatric diagnoses other than affective and anxiety disorders. Among the epilepsy patients with affective and anxiety disorders, those with depression tended (t (45) = 1.8; p < 0.08) to be older (mean, 11.2; SD, 1.98) than those with anxiety disorder (mean, 9.7; SD, 2.62), but there was no significant gender effect. Age and gender were unrelated to the presence of suicidal ideation and associated psychiatric diagnoses. A history of affective and anxiety disorders or epilepsy in first-degree relatives was unrelated to the presence of affective and anxiety disorders and to suicidal ideation among the patients.

In terms of seizure variables, the distribution of affective and anxiety disorders (Table 4) differed in the CPS and CAE groups, with a significantly higher rate of depression and comorbid depression and anxiety disorders in the CPS group, but higher rate of anxiety disorders in the CAE group (χ2 (2) = 8. 03; p < 0.02). The CPS with depression were significantly older (mean age, 11.2; SD, 2.1) than the CAE (mean age, 9.2; SD, 2.7) with anxiety disorders [t (33) = 2.48; p = 0.02].

None of the other seizure variables differentiated the affective and anxiety disorder patients from those with a psychiatric diagnosis other than affective and anxiety disorders and those without a psychiatric diagnosis. In the patients with suicidal ideation, other than a significantly longer duration of illness compared with those without suicidal ideation (meanSI, 6.0 years; SD, 3.38, vs. meanNo SI, 4.3 years; SD, 3.10; t162= 2.81; p < 0.005), no significant differences were found in the seizure variables of these two patient subgroups. Significantly more CPS patients with missing SLQ scores had a history of status epilepticus than did the remaining CPS patients (χ2= 4.64; p < 0.03).

Controlling for socioeconomic status and ethnicity, the children with epilepsy with affective and anxiety disorders had significantly lower IQ and SLQ scores, as well as parent report of school difficulties, compared with the normal children without a psychiatric diagnosis (p < 0.0001) and the epilepsy patients without a psychiatric diagnosis (p < 0.05), but scores similar to those of the patients with a psychiatric diagnosis (Table 6). In contrast, no significant differences were noted in the IQ, SLQ, and parent report of school difficulties in the CPS and CAE patients with and without suicidal ideation. Although the CPS patients with missing SLQ scores had significantly lower IQ scores than the remaining patients (t105= 3.09; p < 0.002), they had similar rates of affective disorders, anxiety disorders, and suicidal ideation to the remaining patients.

Within the group of patients with affective and anxiety disorder, those with combined anxiety disorders and depression had significantly lower Full Scale (F2, 54= 3.73; p < 0.03) and Verbal IQ scores (F2, 54= 3.86; p < 0.02) compared with those with only depression (p < 0.01) or anxiety diagnoses (p < 0.02). Similarly, the children with comorbid disruptive and affective/anxiety disorders had significantly lower Verbal IQ compared with those with mood/anxiety disorders alone (F1, 51= 6.64; p < 0.01).

The epilepsy patients with affective and anxiety disorders had significantly more school problems (F3, 202= 6.05; p < 0.0006) based on CBCL parent report than the normal children (p < 0.001) and the patients with no psychiatric diagnosis (p < 0.02), but similar to those with other psychiatric diagnoses. No significant differences, however, were noted in the CBCL social activities and interaction scores of the children with affective and anxiety disorder diagnoses compared with the normal, no psychiatric diagnosis, and other psychiatric diagnosis groups.

DISCUSSION

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgments
  7. REFERENCES

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.

Acknowledgments

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgments
  7. REFERENCES

Acknowledgment:  This study was supported by grant NS32070 (R.C.). We appreciate the technical assistance of Erin Lanphier, Ph.D., Amy Mo, Alexander Kaminski, Kimberley Smith, Narod Simciyan, Lorrie Shiota, Shawn Zink, R.N., Natasha Wheeler, D. Psy, and Jennifer Philips.

REFERENCES

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgments
  7. REFERENCES