Epilepsy & Behavior 42 (2015) 22–28

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Parent-rated emotional–behavioral and executive functioning in childhood epilepsy Brian C. Kavanaugh a,b, Vanessa Ramos Scarborough a, Cynthia F. Salorio a,b,c,⁎ a b c

Department of Neuropsychology, Kennedy Krieger Institute, USA Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, USA

a r t i c l e

i n f o

Article history: Received 23 July 2014 Revised 3 November 2014 Accepted 8 November 2014 Available online xxxx Keywords: Epilepsy Children Neuropsychological Executive functioning Emotional–behavioral functioning Comorbidities

a b s t r a c t The present study examined clinical and demographic risk factors associated with parent-rated emotional– behavioral and executive functioning in children and adolescents with epilepsy. The medical records of 152 children and adolescents with epilepsy referred for neuropsychological evaluation were reviewed. Results indicated that the sample displayed significantly elevated symptoms across the emotional–behavioral and executive domains assessed. Executive functioning and behavioral symptoms had the highest rates of clinically elevated scores, with lowest rates of elevated scores in internalizing and externalizing emotional problems. Only 34% of those participants with clinically significant emotional–behavioral or executive functioning difficulties had a history of psychological or counseling services, highlighting the underserved mental health needs of this population. In regard to clinical factors, the majority of seizure-related variables were not associated with emotional– behavioral or executive functioning. However, the frequency of seizures (i.e., seizure status) was associated with behavioral regulation aspects of executive functioning, and the age at evaluation was associated with externalizing problems and behavioral symptoms. Family psychiatric history (with the exception of ADHD) was associated with all domains of executive and emotional–behavioral functioning. In summary, emotional–behavioral and executive functioning difficulties frequently co-occur with seizures in childhood epilepsy, with both seizure-related and demographic factors contributing to the presentation of such neurobehavioral comorbidities. The present findings provide treatment providers of childhood epilepsy with important information to assist in better identifying children and adolescents who may be at risk for neurobehavioral comorbidities and may benefit from intervention. © 2014 Elsevier Inc. All rights reserved.

1. Introduction Childhood epilepsy is often associated with psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), depressive disorders, and anxiety disorders [1]. Based on diagnostic interviews in clinically referred samples, studies have identified comorbidity rates of 26–40% for ADHD, 27–36% for anxiety disorders, 13–23% for depressive disorders, and 13% for oppositional defiant disorder [2–4]. Within a community sample of children and adolescents with epilepsy [5], the comorbidity rate was 21% for ADHD, 13% for depressive disorders, 5% for anxiety disorders, and 5% for oppositional defiant disorder/conduct disorder (ODD/CD). Initial research hypothesized that such neurobehavioral comorbidities of epilepsy were primarily due to consequences of stigmatization, life obstacles, and other psychosocial stressors. However, the more recent theory in the field is that the shared underlying neurobiologic pathogenic mechanisms responsible for the ⁎ Corresponding author at: Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205, USA. Tel.: +1 443 923 2728. E-mail address: [email protected] (C.F. Salorio).

http://dx.doi.org/10.1016/j.yebeh.2014.11.006 1525-5050/© 2014 Elsevier Inc. All rights reserved.

manifestations of seizures play a large role in neurobehavioral comorbidities [6–9]. Neurobehavioral comorbidities appear to be the rule rather than the exception in epilepsy, with challenges frequently identified in emotional, cognitive, and social functioning [7,10]. Given the identified shared genetic pathways with other neurodevelopmental disorders as well as the frequency of these neurobehavioral comorbidities, epilepsy has more recently been classified as a neurodevelopmental disorder, as have autism spectrum disorders, intellectual disability, and schizophrenia [6,11]. Neuropsychological evaluation can be an effective clinical tool in the delineation of difficulties in emotional–behavioral and executive functioning, two neuropsychological domains frequently involved in a range of psychiatric conditions [12–14]. One method of assessing emotional–behavioral and executive functioning is parent-rating forms, which have proven effective in the assessment of childhood conditions such as ADHD, depressive disorders, and anxiety disorders [12]. Because of their clinical effectiveness, as well as brevity and costefficiency, rating forms have been frequently used in children with epilepsy to identify psychiatric comorbidities [15]. While a complete review of studies using rating forms in childhood epilepsy is beyond the

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scope of this article, Rodenburg and colleagues [16] conducted a metaanalysis on the use of rating forms (parent, teacher, and self) to assess emotional–behavioral functioning in childhood epilepsy. Results indicated medium to large effect sizes across symptoms of psychopathology, most notably in attention problems, thought problems, and social problems. A few studies to date have used the Behavior Assessment System for Children—Second Edition—Parent Report Scales (BASC-2-PRS) [17] to assess emotional–behavioral functioning in childhood epilepsy [15, 18–20]. While each research group uniquely studied emotional– behavioral functioning in their respective samples, the studies generally identified elevated symptoms across the domains of internalizing problems, externalizing problems, and behavioral symptoms. For example, within a mixed clinical sample, Clary and colleagues [20] identified the most frequently occurring clinical elevations in the subdomains of atypicality (45%), withdrawal (37%), and depressive symptoms (29%). In another study, Bender and colleagues [15] identified clinical elevations in the domains of externalizing problems in 7%, behavioral symptoms in 10%, and internalizing symptoms in 19% of their mixed clinical sample. Within a sample of childhood absence epilepsy, Vega and colleagues [18] identified clinical elevations in the subdomains of anxiety (11%) and depression (24%). Additionally, at least three studies have used the Behavioral Rating Inventory of Executive Function (BRIEF) [21] parent-report form to assess the everyday or behavioral components of executive functioning in a mixed clinical sample of children with epilepsy, in a sample of children with intractable epilepsy, and in a group with idiopathic epilepsy (generalized and location-related) [22–24]. Broadly, these studies identified significantly elevated symptoms in their samples with epilepsy across BRIEF domains and subdomains, reflecting significant executive functioning difficulties in the everyday behaviors of these children and adolescents. The majority of research studies have not found epilepsy-related variables to be significantly associated with emotional–behavioral functioning in children and adolescents with epilepsy [1,4,25–28]. However, while the sum of the research is inconclusive, a few studies have identified some specific relationships between epilepsy variables and select outcomes. For example, younger age at seizure onset and longer duration of epilepsy have been associated with the presence of anxiety disorders as well as anxiety and depressive symptoms [4,19,27]. Seizure frequency/severity and medication status (polytherapy versus monotherapy) have been associated with the presence of internalizing disorders as well as anxiety and depressive symptoms [5,27,29]. Further, temporal lobe seizure foci have been associated with increased behavioral problems and diagnosis of depression [2], localization-related seizures have been associated with tic disorders and depressive disorders, generalized seizures have been associated with conduct disorder, and childhood absence epilepsy has been associated with anxiety disorders [3,4]. Associations have also been examined between epilepsyrelated variables and executive functioning using both performancebased and parent-report measures [23]. MacAllister and colleagues identified significant associations between epilepsy-related variables (seizure frequency, number of antiepileptic drugs [AEDs], and age at epilepsy onset) and performance-based executive functions (impulsivity and total time of problem solving). In contrast, they found no associations between epilepsy-related variables and parent-rated executive functioning (i.e., BRIEF) [23]. In sum, more information is needed regarding the variables or factors that are responsible for such neurobehavioral comorbidities [4] in order to provide clinicians with appropriate information on how to accurately identify and treat those patients who are at increased risk for such comorbidities. This study aimed to provide clarity to prior inconsistent research findings by examining clinical and demographic risk factors associated with parent-rated emotional–behavioral and executive functioning in children and adolescents with epilepsy within a large clinically referred mixed sample. The present study sought to examine the potential influence of demographic, family history, and epilepsy-related variables on

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emotional–behavioral functioning (internalizing and externalizing problems and behavioral symptoms) and executive functioning (metacognition and behavior regulation) as measured by parent-rating scales. While the BASC-2 and BRIEF have previously been studied in childhood epilepsy, the current study simultaneously assessed the factors associated with both scales within a large mixed clinical sample to provide a more cohesive understanding of emotional–behavioral and executive functioning in childhood epilepsy. 2. Methods 2.1. Participants Institutional Review Board approval was obtained through the Johns Hopkins University School of Medicine. Three hundred forty-one children, adolescents, and young adults with epilepsy consecutively referred for neuropsychological evaluation at the Kennedy Krieger Institute (KKI) between 2009 and 2014 were considered for inclusion in the present study. Participants were generally referred for neuropsychological evaluation to characterize cognitive functioning and guide treatment planning. The inclusion criteria for the present study were 6–18 years of age at the time of neuropsychological evaluation, English identified as the primary spoken language, diagnosis of epilepsy made by the treating neurologist based on the International League Against Epilepsy (ILAE) criteria, billing diagnosis of epilepsy, sufficient information available in hospital electronic medical records to extract key variables, and completion of parent-report measures of emotional–behavioral and/or executive functioning as part of the evaluation. Additional exclusion criteria were implemented to remove conditions and variables known to independently influence cognitive functioning including the following: diagnosis of an autism spectrum disorder or fetal alcohol syndrome disorder, prior central nervous system (CNS)-involved surgery or CNSdirected cancer treatment, prior cardiac surgery, prenatal exposure to nonprescribed drugs, premature birth (b 35 weeks gestation), identified or suspected child maltreatment or prolonged foster care placement, history of psychotic features, prior traumatic brain injury (TBI, excluding concussions), and formally diagnosed hearing or visual impairment. The final sample included 152 children and adolescents with a diagnosis of epilepsy. The earliest completed neuropsychological evaluation available in KKI electronic medical records was used for the present study, and as such, a small percentage of initial evaluations used for the present study were conducted from 2005 to 2009 (as opposed to the participants' reevaluation data from 2009 to 2014). A small sample of participants received neuropsychological evaluations at KKI prior to seizure onset due to earlier emergence of neurocognitive difficulties (e.g., inattention); in these cases, the earliest completed neuropsychological evaluation after the onset of seizures was used for the present study. All participants were administered standard tests of intelligence, and exclusion criteria were not implemented based on intellectual functioning. Full Scale Intelligence Quotient data were available for 135 of the participants, with a mean of FSIQ = 85.50 (standard deviation = 11.68; range = 41–126). 2.2. Variables Demographic, psychiatric, neuropsychological, and seizure-related variables were taken directly from each participant's electronic medical record for research purposes. Information at the time of the clinical neuropsychological evaluation was gathered from a combination of prior medical records (e.g., neurology appointment notes) and parent interview. With regard to seizure-related variables, the present study included age at seizure onset, number of epilepsy-related medications (antiepileptic drugs [AEDs]), seizure frequency, duration of epilepsy (i.e., time since the first seizure), prior prolonged seizure (N5 min), and seizure type (absence, generalized, focal, mixed/other). Seizure

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frequency was characterized as daily seizures (1), not daily, but at least once per week (2), not weekly, but at least once per month (3), not monthly, but at least once every six months (4), and no current seizures (5). Family seizure, psychiatric, and ADHD history was coded as 1 (positive identification) or 0 (no history identified). Family psychiatric history included mood disorders, anxiety disorders, and psychotic disorders. Information on the specific family member or position in the family (e.g., mother and cousin) was not available. Data are shown in Table 1. 2.3. Materials 2.3.1. Behavioral Rating Inventory of Executive Function (BRIEF) Parents or caregivers of the participants completed the ageappropriate parent-report version of the BRIEF as part of the neuropsychological evaluation. The BRIEF is a standardized questionnaire designed to assess domains and subdomains of executive functioning via parent ratings of observable everyday behaviors. Superordinate indices include the Behavioral Regulation Index (BRI) and Metacognition Index (MI) as well as the overall Global Executive Composite (GEC) score. The BRI consists of multiple subscales, including Inhibition, Shifting, and Emotional Control, while the MRI consists of Working Memory, Initiation, Plan/Organize, Organization of Materials, and Monitoring subscales. A t-score ≥65 is considered the BRIEF cutoff score for clinically significant elevations [21]. The BRIEF has demonstrated excellent psychometric properties [21]. Table 1 Demographic and epilepsy-related variables (n = 152). Age Sex Female Male Race Black Hispanic White Multiracial Asian Other Not reported Mother's education bHS High school Some college College Graduate degree Not available Family history Psychiatric disorders ADHD Seizures Seizure type Absence Location-related Generalized convulsive/unspecified/mixed Prolonged seizures (N5 min) Yes No Duration of epilepsy Age at onset Current status Daily seizures Weekly seizures Monthly seizures Seizures in past 6 months No seizures in past 6 months Not available AEDs 3+ 2 1 0 Specifics not available

10.69 (3.40) 53.9% (n = 82) 46.1% (n = 70) 17.8% (n = 27) 3.3% (n = 5) 63.2% (n = 96) 5.9% (n = 9) .7% (n = 1) 2.0% (n = 3) 7.2% (n = 11) .8% (n = 1) 13.2% (n = 17) 20.2% (n = 26) 38.8% (n = 50) 27.1% (n = 35) n = 23 47.3% (n = 70) 29.7% (n = 44) 38.5% (n = 57) 21.7% (n = 33) 42.1% (n = 64) 36.2% (n = 55) 25% (n = 38) 75% (n = 114) 5.63 (3.93) 5.06 (3.96) 11.1% (n 12.5% (n 12.5% (n 23.6% (n 40.3% (n n=8

= = = = =

16) 18) 18) 34) 58)

5.4% (n = 8) 27.5% (n = 41) 50.3% (n = 75) 16.8% (n = 25) n=3

2.3.2. Behavior Assessment System for Children—Second Edition (BASC-2) Parents or caregivers of the participants completed the ageappropriate parent-report version of the BASC-2 as part of the neuropsychological evaluation. The BASC-2 is a standardized questionnaire designed to assess multiple aspects of behavioral, emotional, and social functioning. Overall domains include Externalizing Problems, Internalizing Problems, Behavior Symptoms Index (BSI), and Adaptive Skills Composite. Subscales include symptoms of hyperactivity, aggression, conduct problems, anxiety, depression, somatization, atypicality, withdrawal, attention problems, adaptability, social skills, leadership, activities of daily living, and functional communication. A t-score between 60 and 69 is considered to be in the “at risk” range, while t-scores ≥70 are considered clinically significant elevations [17]. The BASC-2 has demonstrated appropriate psychometric properties [17]. The Adaptive Skills Composite and its associated subscales were not examined for the present study. 2.4. Statistical analyses In order to characterize emotional–behavioral and executive functioning in the present sample, single sample t-tests were conducted on BASC-2 and BRIEF domain scores against published normative data (BRIEF GEC, BRI, and MI and BASC-2 Externalizing Problems, Internalizing Problems, and BSI). The percentage of clinically elevated domain scores in the sample was calculated (BASC-2 ≥ 70; BRIEF ≥ 65). To identify any history of psychological or counseling services in those at risk for psychiatric conditions, frequency analyses examined the rate of prior or present psychological or counseling services within the clinical elevation groups. Next, correlational analyses were conducted to assess for associations between BASC-2/BRIEF domain scores and demographic and epilepsy-related variables. Pearson correlation analyses were used for linear variables (age at testing, age at onset, duration of epilepsy), point biserial correlation analyses were conducted for dichotomous variables (sex, prolonged seizure, family history [seizure, psychiatric, ADHD]), and Spearman's Rho correlation analyses were used for ordinal variables (current status, current AEDs, seizure type, and mother's education). Of note, only one individual had mother's education identified as less than high-school completion. This individual was removed from those analyses involving mother's education to reduce the potential influence of this outlier. Statistical significance was set at p b .05. 3. Results All domain scores on the BASC-2 and BRIEF were significantly higher in the group with epilepsy than published normative data, including BRIEF GEC (p b .001), BRIEF MCI (p b .001), BRIEF BRI (p b .001), BASC-2 Externalizing Problems (p b .01), BASC-2 Internalizing Problems (p b .001), and BASC-2 BSI (p b .001). Percentages of participants scoring in the clinical range extended from 8.9% (BASC-2 Externalizing Problems) to 46.9% (BRIEF MCI). Almost a quarter of the sample had at least one clinical elevation on one of the BASC-2 domains, roughly half of the sample had at least one clinical elevation on one of the BRIEF domains, and over half of the sample had at least one clinical elevation across both scales. With regard to a history of psychological or counseling services in participants with clinically elevated BASC-2/ BRIEF domain scores, rates ranged from 25% of those participants with an elevation on any of the BRIEF domains (GEC, BRI, and MCI) to 54% of those participants with an elevation on the BASC-2 Externalizing Problems. Results are provided in Table 2. With regard to demographic variables, family psychiatric history was significantly correlated with all domains assessed: BRIEF GEC (r = .213), BRIEF MCI (r = .182), BRIEF BRI (r = .215), BASC-2 Externalizing Problems (r = .171), BASC-2 Internalizing Problems (r = .251), and BASC-2 BSI (r = .216). Age at testing was correlated with BASC-2 Externalizing Problems (r = − .170) and BASC-2 BSI (r = − .163).

B.C. Kavanaugh et al. / Epilepsy & Behavior 42 (2015) 22–28

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Table 2 BASC-2 and BRIEF mean scores, rates of elevations, and history of services. BASC-2/BRIEF elevations

n

Mean (SD)

% clinically elevated

% with a history of psychological services

BASC-2 Internalizing Problems BASC-2 Externalizing Problems BASC-2 Behavioral Symptoms Index Any BASC-2 index elevation BRIEF Behavior Regulation Index BRIEF Metacognition Index BRIEF Global Executive Composite Any BRIEF index elevations Any BASC-2/BRIEF index elevations

146 146 146 146 144 143 144 143 152

54.75 (11.65)⁎⁎⁎ 53.12 (12.41)⁎⁎ 58.09 (12.15)⁎⁎⁎ – 57.92 (12.03)⁎⁎⁎ 62.20 (11.88)⁎⁎⁎ 61.58 (11.86)⁎⁎⁎

9.6% 8.9% 18.5% 24.7% 29.9% 46.9% 45.5% 54.5% 57%

50% 54% 37% 39% 37% 34% 35% 25% 34%

– –

⁎ p b .05. ⁎⁎ p b .01. ⁎⁎⁎ p b .001.

With regard to epilepsy-related variables, current status was correlated with BRIEF BRI (r = −.173). Results are provided in Table 3. Secondary correlation analyses were conducted to examine the association between subscale scores and relevant demographic or epilepsy-related variables. The negative correlation between BRIEF BRI and current seizure status appears to stem predominantly from the “Shift” subscale, as this was the only subscale of BRI correlated with current seizure status (r = −.188). With regard to the association between age and BASC-2 Externalizing Problems and BSI, age was most highly correlated with the subscales of aggression (r = − .167), attention (r = − .198), and atypicality (r = − .228). The majority of subscales on both measures correlated with family psychiatric history, suggesting that family psychiatric history is associated with significant symptoms across multiple categories.

• This sample displayed elevated symptoms of emotional–behavioral and executive functioning based on parent-rating scales, compared to a nonclinical normative sample, with the majority of the sample displaying clinically significant elevations in at least one aspect of executive or emotional–behavioral functioning. The most prevalent areas of concern involved executive functions and behavioral symptoms and, to a lesser degree, internalizing and externalizing emotional symptoms. • Only a small proportion of those with clinically significant symptoms had a prior history of psychological or counseling services, highlighting the fact that such difficulties in this population may be underserved. • Family psychiatric history, age at evaluation, and epilepsy status were the only factors associated with emotional–behavioral and executive functioning, with family psychiatric history strongly associated with multiple symptom domains.

4. Discussion Given prior inconsistent research findings, the present study examined clinical and demographic risk factors associated with parent-rated emotional–behavioral and executive functioning in children and adolescents with epilepsy. This is the first study to our knowledge that has examined and successfully identified such risk factors for emotional–behavioral and executive functioning dysfunction within a large outpatient sample of patients with childhood epilepsy. The following can summarize the results

The present sample displayed significant emotional–behavioral and executive functioning difficulties across all assessed domains, consistent with prior research [15,18,20,22–24]. Specifically, 57% of the present sample displayed clinically significant symptoms in at least one domain of executive or emotional–behavioral functioning. Approximately one-quarter of the sample displayed clinically significant symptoms in emotional–behavioral functioning, most notably in behavioral difficulties. Additionally, the majority of the sample also displayed clinically significant symptoms in executive functioning,

Table 3 Correlations between BASC-2/BRIEF domains and demographic/epilepsy-related variables.

Demographic Age Sex Mother's education Family seizure hx Family psychiatric hx Family ADHD hx Epilepsy-related Prolonged seizure Age at onset Duration of epilepsy Current status AEDs Seizure type

GEC

MCI

BRI

Externalizing

Internalizing

BSI

– – – – .213⁎ –

– – – – .182⁎ –

– – – – .215⁎ –

−.170⁎ – – – .171⁎ –

– – – – .251⁎⁎ –

−.163⁎ – – – .216⁎⁎ –

– – – – – –

– – – – – –

– – – −.173⁎ – –

– – – – – –

– – – – – –

– – – – – –

Note. GEC = BRIEF Global Executive Composite; MCI = BRIEF Metacognition Index; BRI = BRIEF Behavior Regulation Index; Externalizing = BASC-2 Externalizing Problems; Internalizing = BASC-2 Internalizing Problems; BSI = BASC-2 Behavioral Symptoms Index. ⁎ p b .05. ⁎⁎ p b .01.

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most notably in metacognitive difficulties. Of note, a large percentage of such comorbidities (metacognitive and internalizing problems) may not involve overt behavioral challenges (which are naturally more easy to detect by providers, parents, and teachers) and, therefore, may continue to negatively influence the day-to-day functioning of these children in the absence of appropriate neurobehavioral screening. The current findings highlight the prominence of neurobehavioral comorbidities in the presentation of childhood epilepsy and the effectiveness of parent-report measures in identifying such comorbidities. While it is hypothesized that both seizures and neurobehavioral comorbidities manifest in epilepsy due to shared underlying neurobiologic pathogenic mechanisms [6–9], we sought to identify demographic and epilepsy-related variables that may contribute to emotional–behavioral and behavioral functioning. From a clinical perspective, the present study identified easily obtainable variables, notably patient age, family psychiatric history, and epilepsy status, which were significantly associated with each domain of emotional– behavioral and executive functioning in our sample. Family history of psychiatric disorders was associated with all domains assessed (internalizing and externalizing problems, behavioral symptoms, metacognition, and behavior regulation) but was the only variable significantly associated with internalizing symptoms and metacognitive aspects of executive functioning. Age at evaluation was associated with externalizing problems and behavioral symptoms, in which younger age was associated with more elevated problems. Additionally, current epilepsy status was significantly correlated with behavioral regulatory aspects of executive functioning, in which greater frequency of seizures was associated with more reported symptoms. The identification of such associations will likely help clinicians identify those in need of psychological services and target appropriate supports. Only 34% of those participants with clinically elevated symptoms of emotional–behavioral or executive functioning difficulties had a history of receiving outpatient psychological or counseling services. Unfortunately, this rate is very similar to the 33% of a similar sample reported by Caplan and colleagues [3] almost a decade ago, suggesting that the neurobehavioral comorbidities experienced by children and adolescents with epilepsy continue to go undertreated. Consistent with prior research on barriers and patterns of mental health service utilization in childhood epilepsy [30,31], we hypothesize that this underutilization is primarily due to underidentification of neurobehavioral comorbidities in combination with other factors such as an insufficient number of psychologists with epilepsy expertise available for referral, lack of focus on comorbidities by parents and providers given the severity of neurological symptoms (e.g., seizures), additional burden of families with additional appointments, insurance coverage limitations, and the general mental health stigma of our society. Interestingly, it appeared that children with externalizing behaviors were not necessarily more likely to receive these services than those with more internalizing issues. Ideally, treatment of neurobehavioral comorbidities would be conducted by a mental health professional (e.g., psychologist, clinical social worker, and psychiatrist) with a combined expertise in childhood epilepsy and cognitive–behavioral therapy (CBT). Individual CBT sessions with parent consultation may be appropriate for older children and adolescents, while treatment with younger children may primarily emphasize parent involvement and behavioral interventions. However, the research on CBT in childhood epilepsy is still limited, and future research will clarify the effectiveness and utility of specific approaches and protocols. Additionally, psychiatric intervention should be sought when the comorbidities would benefit from pharmacological intervention. Again, it is likely that the lack of providers who are comfortable with adding medications in children already taking medication for epilepsy (particularly regarding stimulant medication) hinders this process. The identification of seizure-related and demographic variables, specifically younger age, presence of family history of psychiatric disorders, and more frequently occurring seizures, which can be easily

obtained during clinic appointments, may provide neurologists with much needed information on those patients who may be experiencing emotional–behavioral or executive functioning problems and, thus, warranting a referral for pediatric neuropsychology and/or pediatric psychology services. As future research identifies clear risk factors for comorbidities, those at risk can be identified earlier and be monitored more closely, allowing intervention to be initiated at the first signs of problems. Consistent with prior research, the majority of domains were not associated with epilepsy-related variables [1,4,25–28]. In our study, the only significant epilepsy-related finding was that greater seizure frequency at the time of the evaluation was associated with higher BRIEF Behavior Regulation Index, a domain assessing shifting, emotional control, and inhibition. While the BRIEF was not associated with epilepsyrelated variables in a recent study [23], seizure frequency/severity has been associated with the presence of internalizing disorders as well as anxiety and depressive symptoms in other studies [5,27,29]. Future studies will need to elucidate the mixed findings on the association between the BRIEF and epilepsy-related variables. The most significant finding in the present study was the strong association of nonspecific family history of psychiatric disorders with aspects of parent-rated emotional–behavioral and executive functioning. While it is possible that parent psychiatric history influences their ratings of the child's status, prior research suggests that this is not the case. Previous studies have consistently identified that parents with a history of depression can accurately assess their child's emotional– behavioral functioning, the level of parent depressive symptoms does not influence ratings of child functioning, and those ratings reliably predict future psychiatric diagnoses [32,33]. Additionally, research has found that individuals with a family psychiatric history (e.g., depression) are more likely to utilize psychiatric treatments, potentially reflecting a “family mental health literacy” phenomenon [34]. This suggests that families with a psychiatric history may more accurately identify symptoms and the need for appropriate treatment. Thus, parent report is considered a valid assessment tool in a multitude of populations including populations with childhood psychiatric disorders and childhood epilepsy [15,16,32,33]. Alternatively, these findings may reflect the significant heritability of psychiatric disorders (and their associated symptoms) in epilepsy. Outside the context of epilepsy, it is well known that psychiatric disorders are highly heritable disorders. Family history of psychiatric disorders is a significant and nonspecific predictor of the presence of psychiatric disorder in offspring in the general population [35,36]. The nonspecific nature of the transmission may help explain why general psychiatric disorder history in the present study was associated with aspects of both executive and emotional–behavioral functioning (and yet, family ADHD history was not associated with ratings). The influence of family history is multifactorial in nature and suggests a combination of genetic and environmental variables. While this is a well-established notion in the psychiatric literature, there is very little literature examining the influence of family psychiatric history on psychiatric disorders and symptoms in childhood epilepsy. As such, our findings have a limited context. Given recent research identifying molecular evidence for shared genetic etiology in five major psychiatric disorders, including schizophrenia, bipolar disorder, autism spectrum disorders, ADHD, and major depressive disorder [37], it is hypothesized that the present findings reflect the genetic and environmental influence on emotional–behavioral and executive functioning in childhood epilepsy. This suggests that those children with a family history of psychiatric disorders are at the greatest risk for psychiatric comorbidities. In our study, age at evaluation was negatively correlated with externalizing problems and behavioral symptoms, suggesting that younger age is associated with amplified symptoms that may decrease in severity with age. This is an interesting finding, given that from a developmental psychopathological perspective, externalizing symptoms and related behavioral disorders typically increase in prevalence from

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childhood into adolescence [12]. These findings may suggest a similar phenomenon to what is seen in ADHD in that symptoms of hyperactivity tend to decline through childhood into adolescence, while inattentive symptoms remain stable and potentially increase in severity during this developmental period [12]. There are several limitations to the present study that warrant discussion. First, this was a clinical study, relying on retrospective chart review of neuropsychological evaluations conducted at an outpatient neuropsychology program within a university medical center. As such, data extraction was limited to available variables, and some children were excluded due to incomplete data. In addition, the use of a clinically referred sample may limit generalizability to a less symptomatic cohort who were not referred for neuropsychological evaluation. The lack of a control group also limits the generalizability of the current findings. In addition, specific information regarding family history was not available, and we were therefore unable to differentiate between family members with a positive psychiatric history (e.g., primary versus secondary relatives and mother versus father). Future research will need to utilize more detailed family history information in examining the influence of familial–genetic risk factors on functioning in childhood epilepsy. Parent report, which certainly has its utility in clinical practice, may potentially limit the accuracy obtained in reporting the child's developmental and medical history, family history of psychiatric conditions, and current functioning on parent forms. Future studies will need to continue to research this topic using more controlled and prospective studies of a more unbiased sample of children with epilepsy to better characterize the emotional–behavioral and executive functioning of this population. Additionally, incorporating self- and teacher-report measures, as well as performance-based measures, will be critical in future studies as such information may provide greater detail of such functioning across settings and from differing perspectives. Finally, any statistical approach has inherent strengths and weaknesses. This was an exploratory study, assessing the potential importance of multiple demographic and clinical variables. We chose not to correct for multiple comparisons for several reasons. It is well known that every analysis has risk of type I error, and the more analyses performed (within a paper or even across a career), the more likely a statistical result will occur by chance that leads to rejection of the null hypothesis. That said, Bonferroni type corrections (i.e., setting an alpha level for the whole study, as opposed to for each analysis) are really only crucial when testing the hypothesis that all associations are false simultaneously (i.e., an omnibus test), not whether an individual association is false [38,39]. In addition, setting a family-wise alpha level raises the risk of type II error and makes it more likely that the null hypothesis will be accepted when it is in fact not true. The fundamental question is not whether the statistical results from this study are spurious (result of type I error) but whether the associations suggested by the statistics are “real” and “meaningful”. The fact that the results from the current study are generally consistent with findings from other groups is encouraging; however, future research is needed to replicate these associations and further clarify the significance of these variables and the interactions among variables. 5. Conclusions In conclusion, childhood epilepsy is often characterized by emotional–behavioral and executive functioning difficulties, yet the mental health needs of these young people continue to go underserved. The present study identified seizure-related and demographic variables associated with parent ratings of emotional–behavioral and executive functioning, specifically seizure status, age at evaluation, and family psychiatric history. Assessing these variables in the clinical treatment of childhood epilepsy and identifying those individuals at risk for emotional–behavioral or executive functioning difficulties could provide children and adolescents with epilepsy with improved overall treatment.

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Conflict of interest We wish to confirm that there are no known conflicts of interest associated with this publication.

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