Epilepsy & Behavior 22 (2011) 3846

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Epilepsy & Behavior

j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h

Review

Child psychiatry
Lorie Hamiwka a, Jana E. Jones b, Jay Salpekar c, Rochelle Caplan d,
a
Division of Child Neurology, Ohio State University College of Medicine, Columbus, OH, USA
b
Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
c
Department of Psychiatry and Behavioral Sciences, Children's National Medical Center, George Washington University School of Medicine, Washington, DC, USA
d
Semel Institute for Neuroscience and Human Behavior, UCLA David Geffen School of Medicine, Los Angeles, CA, USA

a r t i c l e i n f o a b s t r a c t

Article history: This paper rst summarizes the main ndings of clinical studies conducted over the past two and a half
Received 8 February 2011 decades on psychopathology (i.e., psychiatric diagnoses, behavior and emotional problems) in children with
Accepted 10 February 2011 new onset and chronic epilepsy both with and without intellectual disability who are treated medically and
Available online 26 March 2011
surgically. Although impaired social relationships are core features of the psychiatric disorders found in
pediatric epilepsy, few studies have examined social competence (i.e., social behavior, social adjustment, and
Keywords:
Pediatric epilepsy
social cognition) in these children. There also is a dearth of treatment studies on the frequent psychiatric
Psychopathology comorbidities of pediatric epilepsy, attention decit hyperactivity disorder, anxiety disorders, and depression.
Comorbidities Drs. Hamiwka and Jones then describe their current and planned studies on social competence and cognitive
Social competence behavioral treatment of anxiety disorders, respectively, in these children and how they might mitigate the
Cognitive behavior therapy (CBT) poor long-term psychiatric and social outcome of pediatric epilepsy.
Treatment 2011 Elsevier Inc. All rights reserved.

1. State of the eld: Current trends
1.1. Prevalence of psychopathology
Since Hermann et al. [1] rst studied the multiple variables
associated with behavior problems in pediatric epilepsy, epidemiolog-
ical and community studies conducted over the past 26 years have
conrmed high rates of psychopathology (i.e., psychiatric diagnoses,
behavior and emotional problems) in children with new-onset and
chronic epilepsy, both with and without intellectual disability, who are
treated medically (see reviews in [24]) or by epilepsy surgery [5].
Psychiatric diagnoses, based on structured psychiatric interviews
(administered to children and their parents) [68], parent question-
naires [9], and self-report questionnaires [10], as well as broad-
spectrum behavior and emotional symptoms ascertained through
parent, teacher, and child self-report (see review in [4]) and
symptom-focused instruments [1113], have identied a wide range
of psychiatric diagnoses and symptoms in these children.
Among children with average intelligence, these diagnoses include
attention-decit/hyperactivity disorder (ADHD), particularly the inat-
tentive type, anxiety disorders, depression/dysthymia, bipolar disorder,
and psychosis. ADHD and mood/anxiety disorders appear to be the most
prevalent disorders in both epidemiological [14,15] and community [6
8,16] studies. The most frequent symptoms are thought problems,
inattention, and social problems based on parent reports (see review in
[4]), as well as depression and anxiety using child self-reports [10
13,1719]. In addition, 20% of children with chronic epilepsy have
suicidal ideation compared with 8% of the general child population [11],
and epilepsy is associated with increased suicide attempts in youth with
epilepsy who also have a past psychiatric history [20].
Similar to the high rate of autism [21] and ADHD [22] among children
with intellectual disability, autism [23,24] and ADHD, mainly the
combined or hyperactive type [25], are the most frequent psychiatric
diagnoses in children with epilepsy and intellectual disability. Similarly,
both epidemiological and community studies demonstrate an increased
prevalence of epilepsy in individuals with autism [2628] and risk for
seizures in individuals with ADHD [14].
Nonepileptic seizures (NES) are observed in youth with [29] and
without intellectual disability [30]. In children and youth with normal
intelligence, NES are associated primarily with conversion disorder, as
well as with comorbid depression, anxiety, and ADHD diagnoses (see
reviews in [31,32]).

From a special issue of Epilepsy & Behavior: "The Future of Clinical Epilepsy 1.2. Associated factors
Research" in which articles synthesize reviews from senior investigators with the
contributions and research directions of promising young investigators.
Corresponding author at: Semel Institute for Neuroscience and Human Behavior,
1.2.1. Biological variables
760 Westwood Plaza, Los Angeles, CA 900951759, USA. Fax: +1 310 206 4446. Evidence for the relationship of seizure variables with psychopa-
E-mail address: rcaplan@ucla.edu (R. Caplan). thology has been inconsistent in children with average intelligence (see

1525-5050/$ see front matter 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.yebeh.2011.02.013
 L. Hamiwka et al. / Epilepsy & Behavior 22 (2011) 3846
review in [2]). In fact, the ndings of cross-sectional [8,14,33] and
prospective [34,35] studies of children with new-onset epilepsy and
longitudinal studies of children with chronic epilepsy [36] and those
undergoing surgery [37,38] do not support a role for seizure variables in
the psychopathology of these children. However, the presence of
premorbid behavior problems in children with new-onset seizures and
their relationship with seizure recurrence [14,39] highlight the
bidirectional relationship between having epilepsy and psychopathol-
ogy in childhood.
Moreover, multimodal imaging studies have demonstrated struc-
tural and functional brain abnormalities associated with the presence
of psychiatric diagnoses [40], type of psychiatric diagnosis [4143],
suicidal ideation [44], as well as cognitive [40,45,46] and linguistic/
social communication [47,48] decits in children with new-onset and
chronic epilepsy. Together with evidence for continued psychopa-
thology as well as poor social, educational, and vocational adult
outcome of pediatric epilepsy [4951], these imaging ndings suggest
that psychopathology is a core illness component that reects the
underlying neuropathology of pediatric epilepsy.
In contrast, in children with epilepsy and intellectual disability,
interrelated seizure variables, such as epilepsy syndrome, seizure
control, age at onset, and antiepileptic drugs (number, type, dose)
[5254], as well as clinical neuroradiological abnormalities [55], are
related to behavior problems. The heterogeneity of epilepsy, psycho-
pathology, and associated variables (e.g., IQ, language, and demo-
graphic variables) emphasizes the methodological and theoretical
importance of conducting separate studies on psychopathology in
children with epilepsy with and without intellectual disability. From
the methodological perspective, identication of psychiatric disorders
and symptoms in children with and without intellectual disability
involves different diagnostic and behavioral instruments as well as
constructs (see review in [56]). From the theoretical perspective,
intellectual disability and structural brain abnormalities are each
associated with increased rates of psychopathology and seizures in
children (see review in [3]). Therefore, different neuropathological
mechanisms might underlie the psychopathology found in children
with epilepsy with average and below-average intelligence.
1.2.2. Other variables
The prevalence of psychiatric disorders and symptoms in pediatric
epilepsy is signicantly higher than in children with chronic medical
illness without central nervous system involvement, who, in turn,
have signicantly higher rates than children in the general population
[5759]. These ndings, together with the lack of association with
seizure variables in children with average intelligence, suggest a
central role for family and other psychosocial variables in addition to
biological variables in the psychopathology of children with epilepsy.
The extensive research conducted in this area is reviewed and
discussed in this special issue by Austin, Dunn, and colleagues.
In children who do not have epilepsy, additional factors associated
with psychopathology include impaired language skill [60,61]. Similar
to intelligence, language skill plays an important role in the behavior
and social skills of children [6264]. Decits in basic linguistic skills
and in higher-level discourse, social communication, and pragmatic
skills are observed in children with ADHD [6567], autism spectrum
disorders [68], conduct disorder [61], and psychosis [69]. Impaired
higher-level discourse, social communication, and pragmatic skills are
also evident in pediatric mood disorder symptoms [70].
Both children with new-onset [71] and those with chronic epilepsy
[72] with average intelligence have signicant basic linguistic decits,
and those with chronic epilepsy have discourse decits [73]. Impaired
basic linguistic skills are associated with anxiety disorder diagnoses
[72] in younger children with epilepsy and with depression symptoms
and poor self-esteem in subjects with new-onset epilepsy who
experience a decline in language processing speed, as well as in
verbal memory and learning, over a 3-year period [74]. Higher-level
39
discourse decits are associated with a comorbid ADHD diagnosis,
academic underachievement, and poor social competence [73]. Given
the importance of language in children's literacy [75] and its role in
the academic achievement of children with new-onset epilepsy [76],
these ndings have important implications for the poor long-term
educational and vocational outcome of pediatric epilepsy [4951].
Understanding the implications of psychopathology in children is
incomplete without addressing related social behaviors. Poor social
competence is observed in children without epilepsy who have
psychiatric disorders, including ADHD [77], autism spectrum diagnoses
[see review in [78]), psychosis (see review in [79]), depression [80],
and anxiety disorders [81], particularly social anxiety disorder [82]. The
social difculties of children with these diagnoses reect core symptoms
of these disorders [83], such as poor impulse control, inattention, and
linguistic pragmatic skills in ADHD; withdrawal and decits in social
communication and cognition in autism spectrum disorders; lack of
motivation, initiative, and engagement of affect in others together with
feelings of social rejection in depression; and poor reality testing,
delusions of persecution, abnormal social communication, and with-
drawn behavior in psychosis. Other than social anxiety disorder, the
social difculties of children with anxiety disorders are secondary to
the core symptoms of the disorder [84]. Thus, children with anxiety
disorder might refrain from social activities related to excessive
worries about social competence, difculties separating from parents,
or repetitive and time-consuming obsessions and compulsions.
Pediatric chronic illness, such as head trauma, brain tumor,
neurobromatosis, as well as treatment for primary cancer involving
the brain (e.g., cranial radiotherapy, intrathecal treatment), unlike
chronic medical illness, is associated with social skill impairments (see
review in [85]). Children with chronic epilepsy are also described as less
socially accepted, isolated, with poor social competence, social initiative,
and peer difculties compared with normative samples, healthy
children, siblings, and children with chronic medical illness based on
parent-, teacher-, and self-report instruments (see review in [86]). Most
studies have used parent-based Child Behavior Checklist (CBCL) [87]
social competence scores that appear to be driven by school problem
scores [88]. The CBCL social competence scores are related to IQ [88],
learning disability or academic achievement [54,89,90], and seizure
variables, such as lack of remission over 5 years [91], antiepileptic drug
treatment [91,92], multiple seizure types [92], longer duration of the
disorder [93], and seizure frequency [90,94]. In contrast, using specic
social skill instruments, Tse et al. [89] found that reduced social initiative
signicantly correlated with externalizing and internalizing CBCL
problem scores (e.g., rule breaking, anxious, withdrawn, attention,
and social problems) rather than seizure variables in children with
epilepsy.
In addition to the relationship with behavioral and emotional
problems, teasing, bullying, and social stigma also impact the social
functioning of children with [95] and without [96] cognitive and
linguistic decits. Interestingly, high rates of bullying do not appear to
be related to epilepsy variables, poor social skills, behavior problems,
anxiety, depression, or poor self-concept in small samples of children
and adolescents with epilepsy [97]. However qualitative methods, such
as focus groups [98] and semistructured open-ended interviews
[99,100] focused on social skills, provide information suggesting that
special education plays an important role in the teasing and social
stigma that surgically and medically treated youth with intractable
epilepsy experience even when seizure control facilitates their social
independence [99,100].
Therefore, the possible association among comorbid psychopa-
thology, cognitive and linguistic decits, stigma of both epilepsy and
psychiatric diagnoses, and poor social competence requires further
exploration in larger sample sizes. As discussed below under Gaps in
Knowledge, studies have just begun using state-of-the-art social skill
measures involving multiple informants including perceptions of
peers, self, and teachers of the social functioning of children with
40 L. Hamiwka et al. / Epilepsy & Behavior 22 (2011) 3846
epilepsy together with the relationship of these evaluations to seizure
variables, psychopathology, social cognition, and stigma.
1.3. Treatment of psychopathology
Despite prevalent psychiatric comorbidities in pediatric epilepsy,
only one-third of children with average intelligence [101,102] have
had a psychiatric, psychological, neuropsychological, speech, and
language evaluation, or treatment of these comorbidities. Yet, studies
on depression in mothers of children with epilepsy (see review in
[103]) and on quality of life [104106] attest to the signicant burden
both mothers and children experience related to the children's
behavior and emotional problems.
In addition to underdiagnosis, several additional factors might
contribute to the lack of treatment for these comorbidities. Regarding
psychopharmacological intervention, the optimal and safe treatment
dose of stimulants is yet to be determined for ADHD in pediatric
epilepsy [107]. Only three short-term double-blind randomized
controlled studies [107109], two open studies [110,111], one
involving a 12-month follow-up [111], and several case studies have
been conducted on methylphenidate treatment of ADHD in children
with epilepsy. Although there appears to be a treatment effect, the
possibility of increased seizure frequency needs to be ruled out in both
children with good and those with poor seizure control.
In terms of mood disorders, recent data in the child psychiatry
literature clearly demonstrate the superiority of combined treatment
with selective serotonin reuptake inhibitors (SSRI) and cognitive-
behavioral therapy (CBT) compared with each one of these modalities
alone in short-term double-blind randomized controlled studies and
long-term open studies of depression [112,113] and anxiety disorders
[112,114]. Although 9-month follow-up data suggest similar efcacy
for SSRI treatment and CBT in children with depression [113], data are
not yet available on more long-term effects of these treatment
approaches. Furthermore, high rates of recurrence of depression in
adolescents (46%), who also have anxiety, are unrelated to initial
treatment response or most effective treatment approach [115].
Similar studies have not been conducted in children with epilepsy.
Studies to date include one randomized CBT versus treatment-as-usual
study of adolescents, some of whom were depressed [116]; an open
sertraline/uoxetine study of mainly adolescents with chronic epilepsy
[117]; an ongoing open CBT study in children with recent-onset epilepsy
with anxiety disorder (described below by Jana Jones, Ph.D.); and a
retrospective diagnostic study of bipolar disorder and treatment effects
of antiepileptic drugs [118]. From the clinical perspective, because of the
complex presentation of children with epilepsy who have comorbid
depression and anxiety disorders and the black-box warnings regarding
suicidality and SSRI treatment in children [119], child psychiatrists and
pediatric neurologists/epileptologists may be apprehensive about
diagnosing and treating these comorbidities in children with epilepsy.
1.4. Conclusions
The long-term follow-up data of children with epilepsy suggest
that the problems of these children do not dissipate with age, are
unrelated to seizures or types of seizures, and might contribute to the
poor vocational and social outcome of these patients, as well as the
high rate of psychopathology and poor quality of life in adults with
epilepsy [4951]. Therefore, early identication of children at risk for
psychiatric diagnoses, together with treatment of their psychopathol-
ogy and related poor social skills, has both clinical and theoretical
importance. It will decrease the marked clinical morbidity of epilepsy,
and help further delineate mechanisms underlying these disorders.
The next section describes research topics that would advance the
eld toward this goal.
2. Important unanswered questions and unmet clinical needs
Among the many unanswered questions, we focus here on two:
early identication of children with epilepsy at risk for psychopa-
thology through studies on social skills and treatment of comorbid
depression and anxiety disorders using CBT.
2.1. Social skills in children with epilepsy
As previously described, social skills are impaired in children with
psychiatric disorders, cognitive decits, and poor language skills, and
these comorbidities are observed in children with epilepsy with and
without intellectual disabilities. Future studies need to determine if
social difculties are an epiphenomenon of the comorbid psychiatric
diagnoses or a primary comorbidity of pediatric epilepsy as in children
with other central nervous system disorders (see review in [85]). The
ndings of these studies would inform the design of subsequent
treatment studies regarding whether social skills training is indicated
in children with epilepsy with or without a psychiatric diagnosis. Such
studies could also determine if early identication and treatment of
impaired social skills would change the course of the behavior and
emotional problems associated with the illness. As such, they could
act as potential markers of children with epilepsy at risk for poor long-
term outcome. They would also provide information needed to begin
to conduct studies on the structural and functional abnormalities
involved in the poor social competence of these children. Further-
more, application of state-of-the-art research methods to studies of
children with epilepsy is essential for examining the development of
social cognition and social processing and the relationship with the
short-term and long-term behavioral/emotional and social outcomes
of pediatric epilepsy. Lorie Hamiwka, M.D., describes the rationale and
details of her ongoing social skill research program in children with
epilepsy later in this article.
2.2. Treatment
Evidence-based treatment for pediatric psychiatry has improved
over the past decade, but the knowledge base has been uncommonly
applied to the psychiatric comorbidities of pediatric epilepsy. Given
the high frequency of depression and anxiety disorders in children
and adolescents with epilepsy, a clear need exists for short-term
clinical trials to rst examine the efcacy and safety of CBT and of SSRI
treatment separately in these patients. Subsequent controlled trials
could examine their combined use as well as the long-term efcacy
and safety of these treatment modalities for these comorbidities.
Data demonstrating the superiority of combined CBT and SSRI
treatment for children without epilepsy who have depression [113]
and anxiety disorder diagnoses [114]; the high rate of suicidal
ideation in youth with epilepsy [11]; the possible increase in
suicidality following treatment with SSRIs [119] and antiepileptic
drugs [120]; and no increase in suicidal events in depressed youth
without epilepsy treated with CBT [113] argue for CBT studies in
children with epilepsy with depression and anxiety disorders. By
focusing on the cognitive distortions associated with depression [121]
and anxiety disorders [122] in children, this treatment approach
improves the problem-solving and coping skills of these children and
might promote long-term lifestyle changes.
Furthermore, administration of CBT using a computer with child-
friendly software, as described below by Jana Jones, Ph.D., is an added
motivator for children and allows use of the software and technique at
a distance from the clinic. Moreover, application of this treatment
modality to children with new-onset epilepsy has the potential of also
mitigating short-term difculties adapting to the stress of having a
chronic illness. Subsequent controlled clinical trials of this treatment
approach in children with new-onset and chronic epilepsy with
depression and anxiety disorders could provide important
 L. Hamiwka et al. / Epilepsy & Behavior 22 (2011) 3846
information on optimal timing for CBT intervention in children with
epilepsy with these comorbidities. Long-term studies are also needed
to ascertain if the treatment effect is maintained and the indications
and optimal timing for subsequent booster treatments. Jana Jones, Ph.
D., describes the rationale and details of her ongoing CBT research
program in children with epilepsy later in this article.
In addition to studies on SSRIs in youth with epilepsy with
depression and anxiety disorders, the eld is also clearly in need of
evidence-based treatment guidelines, preferably practice parameters,
on the psychopharmacological treatment of children with epilepsy
with ADHD with and without intellectual disability. This would
require short-term and long-term studies on large samples of children
with epilepsy to determine the efcacy and safety of stimulants.
Similar studies would also be needed on neuroleptics, as these drugs
are frequently used for impulse control and aggression in children
with intellectual disability and behavior problems despite limited
evidence-based guidelines for this population [123]. Finally, pediatric
pharmacokinetic data on the use of antiepileptic drugs together with
SSRIs, stimulants, and neuroleptics are essential for the safe treatment
of the psychiatric comorbidities of children with epilepsy.
3. Promising Areas of Research and Young Investigators
3.1. Lori Hamiwka
Social functioning in children with epilepsy
3.1.1. Rationale for studying social functioning in children with epilepsy.
Long-term follow-up studies of young adults with a history of epilepsy
in childhood indicate a high prevalence of poor psychosocial
functioning, including lower marriage rates, social isolation, and
lower rates of living independently [51,124127]. In individuals
without epilepsy, various aspects of childhood social development
(e.g., social information processing, social behavior and social
adjustment) are predictive of psychosocial functioning into adoles-
cence and adulthood [128130]. The extent to which these social
outcomes in adults with epilepsy reect difculties that begin in
childhood is not well understood. However, problems with social
functioning are reported in children with epilepsy from preschool to
adolescence [89,92,131] and include greater social isolation [132
134] and more difculties with peers compared with healthy controls
and with children with nonneurological disease [57,135].
The developmental literature suggests that social difculties
with peers in normally developing children can be a result of:
(1) maladaptive social behaviors, such as social ineptness, aggression,
inattentive/immature behavior, and social anxious/avoidant behav-
ior; (2) peer stigmatization, and (3) nonbehavior problems including
academic and cognitive difculties, limited athleticism, and physical
unattractiveness [137,138]. Children with epilepsy may be at
increased risk for social difculties as compared with their healthy
peers as it is well recognized that they have specic comorbidities
including psychopathology, cognitive problems, and academic dif-
culties [138]. Associations have been made with greater inattentive
and anxious behaviors, more externalizing behaviors, lower academic
achievement, poorer neuropsychological functioning, and lower IQ
[88]. They are also vulnerable to stigma [95,139,140] and bullying [97]
and show decreased participation in physical activities [141]. In
addition, illness variables, such as earlier age at epilepsy onset and
active seizure status, are also reported in relation to their social
difculties [90].
Although prior research has set the groundwork for recognizing that
children with epilepsy have social difculties [86,88,89,93,142,143],
there are limitations to the previous work that need to be addressed to
advance this area of investigation. Currently, there are no data on social
functioning in children with newly diagnosed epilepsy. Previous
research involves only children with established or chronic epilepsy.
41
Thus, the prevalence of difculties in social functioning early in the
course of epilepsy is not known. The lack of this type of knowledge
makes it difcult to clearly understand the natural history of social
difculty, determine risk factors for poor social functioning (preexisting
social difculties, psychopathology, cognitive-executive function de-
cits, impaired language skill, poor seizure control), and develop
appropriate and timely interventions.
The extant literature is also limited in quantity and suffers from
both conceptual and methodological shortcomings. Conceptually, the
existing research has not incorporated contemporary models of social
functioning. Models for both normally developing children and those
at neurological risk have emphasized distinctions between social
information processing, social behavior, and social adjustment
[144,145]. However, research conducted to date has been hampered
by the use of measures that provide a restricted view of social
functioning. These studies have focused largely on parental and/or
teacher reports using questionnaires, such as the CBCL, that are not
expressly designed to assess social functioning [87]. Previous research
has not incorporated methods from developmental neurosciences,
developmental psychology including the assessment of social infor-
mation processing, self-report of friendship quality, or peer report of
social interactions or relationships. Yet, developmental scientists have
long recognized the value of obtaining data about social development
from multiple sources, and place particular value on ratings and
nominations obtained from peer groups regarding social behavior,
peer acceptance, and friendships [129]. The ratings of numerous
children who interact daily at school can be combined to yield scores
that are reliable, stable, and predictive of concurrent and future
academic, emotional, and behavioral outcomes [129].
An additional methodological limitation of previous research on
the social functioning of children with epilepsy is that it has not used a
conceptual model. Conceptual models that build on and integrate
information about social functioning from the elds of developmental
neuroscience and developmental psychology may prove particularly
relevant for understanding specic social decits in children with
epilepsy and for developing effective intervention programs.
3.1.2. Current studies of social functioning in children with epilepsy. The
previously described rationale underlies my current research pro-
gram, which uses an innovative model and methodology to study
social function in children with epilepsy. The conceptual model I
proposed is based on the current epilepsy literature as well as
established models for understanding normative social development
in children [146,147] who are medically challenged (e.g., traumatic
brain injury or cancer) [145,148].
The basis for the model is social competence, which involves the
ability to attain personal goals in social interactions and also maintain
satisfactory relationships [149]. Distinctions between individual
characteristics or skills (social information processing), social perfor-
mance (social behavior), and social adjustment have been recognized
by theorists interested in typical social development [150] as well as
the social competence in children with chronic health conditions
affecting the central nervous system [144]. More specically, social
performance refers to children's actual behavior in social interactions
and to whether their responses are effective both in achieving their
own goals and in maintaining positive social relationships. Social
adjustment reects the extent to which children attain socially
desirable and developmentally appropriate goals. It encompasses the
quality of children's relationships with others, as well as other aspects
of social functioning, such as self-perceptions of loneliness or social
self-esteem. Thus, social competence depends on appropriate social
information processing (that allow interactions between people),
social behavior, and social adjustment. It is reected jointly in both
self-perceptions and the perceptions of others, that is, social
adjustment. As such, social competence is typically viewed as a
developmental process that is both time and context dependent.
42 L. Hamiwka et al. / Epilepsy & Behavior 22 (2011) 3846
Recent models of social competence include a variety of factors
that can hamper or promote social development [151153]. My
research incorporates both epilepsy-specic (epilepsy severity) and
more general family (family function) and child (stigma, uncertainty
of illness) factors that moderate social decits relative to children
without epilepsy.
Methodologically, my social functioning research involves two
types of data collection: individual assessments and classroom data
collection. This allows self- and parent assessments as well as reports
from peers and teachers who observe these children in their social
interactions on a daily basis over time. Children are compared with
age- and gender-matched healthy controls free of chronic disease.
Pilot data using the above methodology involved 35 children with
established epilepsy, aged 911 years, and 35 classmate controls
studied over a 1-year period (unpublished data). An analysis of
classroom data revealed that children with epilepsy were signicantly
less likely to be identied as a best friend by their classmates
compared with their classroom controls (P = 0.04). They were also
less likely to be chosen as reciprocal best friends compared with their
classroom controls (P = 0.03). Teachers of children with epilepsy
reported signicantly poorer total social skills (P = 0.017) compared
with normative published data. Specically, they noted lower levels of
assertion (P = 0.056) and less engagement (P = 0.002). Teachers
documented increased autism spectrum symptoms (P = 0.058) and
lower academic competence (P = 0.001).
Studying social functioning in children with epilepsy has both
clinical and theoretical importance. Clinically, children's relationships
with their peers are associated with multiple aspects of development
and adjustment and, therefore, play an important role in long-term
psychosocial functioning [128130]. Children who experience peer
relationship difculties are at risk for later problems such as school
dropout, criminality, and psychopathology [129]. Therefore, early
identication of difculties with social functioning may lead to
interventions that allow for improved long-term social outcomes.
Theoretically, by identifying underlying mechanisms of social com-
petence (social information processing, social behavior, and social
adjustment) and their relationship with epilepsy-specic risk factors,
as well as family and child risk factors, targeted intervention programs
can be developed.
3.1.3. Future directions. Clinically, this research program using the
model and methodology outlined above will allow for early detection
of children with epilepsy at risk for social difculties. It will also
identify risk factors (epilepsy risk factors, family risk factors,
comorbidities associated with epilepsy) for poor long-term social
outcomes. Furthermore, it will examine specic deciencies in social
information processing in children with epilepsy that could be the
target of future clinical trials to improve social outcomes in children
who are at risk or who already have difculties with peer
relationships. Theoretically, studies to determine the integrity of
brain structures known to be vulnerable in individuals with epilepsy
and implicated in social information processing will provide an
understanding of potential neurobiological mechanisms underlying
the social decits of children with epilepsy.
3.2. Jana E. Jones
Cognitive-behavioral therapy in children with epilepsy with
comorbid depression and/or anxiety disorders
3.2.1. Rationale for cognitive-behavioral therapy in youth depression
and anxiety disorders. For several decades, youth with epilepsy have
been known to be at increased risk for mental health problems
[57,58]; however, there have been no clinical trials assessing the
efcacy of psychotherapy in epilepsy. A recent Cochrane systematic
review of psychological treatment for epilepsy concluded that there is
no reliable evidence to support psychological treatments for people
with epilepsy [154]. Although, Martinovic et al. [116] recently
conducted a CBT study with 30 adolescents with epilepsy with mild
depression, there are no reports of nonpharmacological intervention
studies aimed at treating anxiety disorders in children with epilepsy
[154]. The limitations of this literature can be brought into better
focus by examining current trends in the general pediatric psychiatric
literature.
The existing general psychiatric literature suggests that depression
and anxiety disorders are prevalent, often with onset in youth, and that
delayed recognition and treatment contribute to disease progression
and treatment resistance. Based on the National Comorbidity Survey
(NCS), childhood depression lifetime prevalence estimates are
reported to be 12.4% for school-aged children and 15.3% for
adolescents [155]. Additionally, the National Comorbidity Survey
Replication (NCS-R) study reported that anxiety disorders constitute
the most prevalent class of disorders (28.8%) in the general population
and have a median age at onset of 11 years [156]. Kessler and
colleagues [156] specically recommend that interventions begin
early to prevent the progression of the disorder and the occurrence of
future comorbid disorders. Unfortunately, Wang and co-workers
review [157] of the NCS-R study revealed delayed access to treatment,
ranging from 9 to 23 years for anxiety disorders and from 6 to 8 years
for mood disorders. As a result, depression and anxiety disorders
remain untreated during childhood, with signicant consequences in
adulthood. Untreated depression and anxiety disorders have been
linked to academic difculties, low self-esteem, and peer relationship
problems [158].
To summarize, given evidence regarding the consequences of
depression and anxiety in the general population, and clear evidence
that these problems are quite common in children with epilepsy [6
8,1113,18,36,159167], it is essential to identify mental health
problems early, comprehensively characterize their associated com-
plications (family, self, and behavior), and make every effort to
develop and evaluate efcacious interventions.
3.3. Cognitive-behavioral therapy in childhood and adolescent
depression and anxiety disorders
Cognitive-behavioral therapy helps children and adolescents
reduce or eliminate counterproductive emotions, behaviors, and
thoughts using systematic and goal-oriented therapeutic techniques.
CBT intervention studies in the general population have increased
over the past 15 years, with a growing body of evidence indicating
their utility and efcacy in children and adolescents for the
management of depression [168,169] and anxiety disorders [170].
Kendall and his colleagues [171,172], in particular, have demonstrated
the efcacy of CBT in reducing symptoms of anxiety in children and
adolescents in randomized controlled trials, with treatment gains
maintained at 1- and 3-year follow-up visits [170172]. Therefore,
this treatment technique appears to be a particularly appropriate and
promising intervention to test in the treatment of anxiety disorders in
youth with epilepsy.
Manualized CBT interventions are used in clinical trials to ensure
that each child is receiving similar treatment protocols for standard-
ization purposes [170,173]. Additionally, the manualized approach
allows for the identication of essential elements required to improve
the efcacy of the intervention. Finally, the manualized approach
provides a way in which to easily disseminate the intervention,
allowing for application of the therapeutic approach beyond the
clinical trial. In pediatric epilepsy, manualized CBT intervention
provides an opportunity to use an effective treatment protocol and
design modications as needed to address the unique needs of these
children.
I am conducting a pilot intervention study using computer-
assisted CBT on 30 children, aged 813 years, with a diagnosis of
 L. Hamiwka et al. / Epilepsy & Behavior 22 (2011) 3846
epilepsy and an anxiety disorder. This effort represents the rst CBT
treatment study for anxiety disorders in children with epilepsy. The
intervention is based on a manualized treatment intervention that has
been demonstrated to be efcacious in children with anxiety in the
general population [174]. The study has several aims including the
following: (1) to examine the feasibility and acceptability of CBT in
children with epilepsy who have an anxiety disorder, (2) to determine
if computer-assisted administration of the treatment protocol can be
an effective tool, and (3) to assess the impact of the intervention on
symptoms of anxiety, family function, self-concept, and behavioral
problems. All participants undergo a semistructured, clinician-
administered psychiatric interview using the Kiddie Schedule for
Affective Disorders and Schizophrenia [175] and complete well-
standardized behavior questionnaires regarding depression, anxiety,
family, school, self-concept, and behavioral problems at baseline and
follow-up.
The intervention includes 12 weekly computer-assisted modules
to be completed as part of a 50- to 60-minute session to mirror the
requirements dictated by many health insurance policies. After
completing each module, we review the concepts with the child to
assess understanding and reinforce learning. The rst 6 modules
introduce concepts related to CBT and symptoms of anxiety, and
provide a foundation for the nal 6 modules, which are considered to
be the application phase of the intervention. Parent involvement is
encouraged throughout the intervention, particularly during the nal
6 modules. Finally, we also follow participants who complete all
12 modules 3 months after the intervention to monitor treatment
outcomes over time.
The preliminary ndings have revealed that children with epilepsy
have separation anxiety, social phobia, and specic phobias, as well as
generalized anxiety disorder similar to children in the general
population. Some children worry about their seizures, whereas others
may not. Additionally, some children report that anxiety, not seizures,
limits their ability to make friends and be more like their peers.
Children with epilepsy also have a high rate of learning problems [36],
and as a result, it is important to monitor each child's level of
comprehension and understanding throughout the intervention to
ensure successful application of techniques to achieve symptom
reduction. Finally, early results indicate that the children are reporting
fewer symptoms of anxiety at the 3-month follow-up and that parents
are also endorsing fewer symptoms of anxiety in their child with
improved behavioral functioning.
3.3.1. Future directions
It will be important to continue to design and develop evidence-
based interventions for depression and anxiety disorders in children
with epilepsy. This will entail using validated intervention models
from the general population to determine if and when changes are
necessary to accommodate the needs of children with epilepsy. As
previously described, there have been a number of large-scale clinical
trials of CBT in the general population in which a vast amount of
knowledge has been gleaned. However, as researchers in epilepsy, it
may behoove us to start from a solid knowledge base and design
modications based on the specic needs of children with epilepsy. In
that manner, effective treatment interventions will be more rapidly
available to youth with epilepsy.
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