Comorbid psychiatric symptoms in temporal lobe epilepsy: association with chronicity of epilepsy and impact on quality of life
Comorbid Psychiatric Symptoms in Temporal
Lobe Epilepsy: Association with Chronicity
of Epilepsy and Impact on Quality of Life1
*Department of Neurology, University of Wisconsin, Madison, Wisconsin 53792; †Department
of Psychology, Chicago Medical School, North Chicago, Illinois 60064; and ‡Francis Forster
Epilepsy Center, Middleton Veterans Administration Hospital, Madison, Wisconsin 53705
Received May 8, 2000; accepted for publication May 16, 2000
Purpose. The goals of this work were to determine: (1) the nature and extent of differences in
self-reported psychiatric symptoms between patients with temporal lobe epilepsy and matched
healthy controls, (2) the relationship between chronicity (duration) of temporal lobe epilepsy and
comorbid interictal psychiatric symptoms, and (3) the impact of comorbid psychiatric symptoms on
self-reported health-related quality of life.
Methods. Patients with temporal lobe epilepsy (n = 54) and healthy controls (n = 38) were administered
the Symptom Checklist-90-Revised (SCL-90-R) to assess the nature and severity of psychiatric
symptomatology and epilepsy patients completed the Quality of Life in Epilepsy-89 (QOLIE-89) to
define health-related quality of life. Among epilepsy patients the SCL-90-R scales were examined in
relation to chronicity of temporal lobe epilepsy as well as the impact of comorbid emotional-behavioral
distress on health-related quality of life.
Results. Compared with healthy controls, patients with epilepsy exhibited significantly higher (worse)
scores across all but one of the 12 SCL-90-R scales. Among patients with epilepsy, increasing chronicity
was associated with significantly higher (worse) scores across all SCL-90-R scales and increased emotional-
behavioral distress was associated with lower (worse) scores across all 17 QOLIE-89 scales.
Conclusion. Comorbid interictal psychiatric symptoms are elevated among patients with temporal lobe
epilepsy compared with healthy controls and appear to be modestly associated with increasing chronicity
(duration) of epilepsy. This comorbid emotional-behavioral distress is specifically associated with a
significantly poorer health-related quality of life, and suggests that quality-of-life research should devote
greater attention to the potential impact of comorbid psychiatric distress. © 2000 Academic Press
Key Words: quality of life; temporal lobe epilepsy; complex partial seizures; behavior; mood;
In fields such as primary care, the degree to which
psychiatric comorbidity is underrecognized and un-
1 Supported in part by NIH 37738 and NARSAD.
2 To whom correspondence should be addressed at the Department
of Neurology, Matthews Neuropsychology Lab, University of
Wisconsin, 600 North Highland Avenue, Madison, WI 53792.
has been characterized with some precision
(cf. 10). Further, the degree to which psychiatric symptoms
contribute to additional psychosocial impairment
and reductions in health-related quality of life
beyond that attributable to physical disease has been
demonstrated as well. For example, the adverse effects
of comorbid psychiatric disorder on health-related
quality of life (HRQOL) have been demonstrated
among patients with specific chronic medical disorders
(e.g., diabetes) (11) as well among general neu-
Copyright © 2000 by Academic Press
All rights of reproduction in any form reserved.
|Comorbid Psychological Disorder
rology outpatients (1). While psychiatric comorbidity
is known to be more prevalent among patients with
chronic and intractable epilepsy (3, 4, 9, 16), the effects
of this psychiatric distress on quality of life are not
well characterized despite the fact that health-related
quality of life in epilepsy is a topic of wide interest.
Recent years have seen research efforts devoted to
better understanding the cognitive burdens associated
with increasing chronicity or years of epilepsy (6–8,
12). This interest is due, at least in part, to attempts to
better understand chronicity-driven morbidity among
patients with potential surgically remediable syndromes
of epilepsy. While research has been devoted
to identifying the effects of chronicity on neuropsychological
status, less direct evidence speaks to the
relationship between chronicity and the degree of comorbid
interictal emotional-behavioral distress. This
issue can be addressed using contemporary psychiatric
nosology and diagnostic methods (e.g., DSM-IV) as
well as by patient self-report of psychiatric symptoms.
This investigation undertook the following tasks.
First, patients with temporal lobe epilepsy were compared
with a closely matched group of healthy controls
on a standardized measure of emotional-behavioral
distress that has been shown to be particularly
sensitive to behavior change in epilepsy (Symptom
Checklist-90-Revised (SCL-90-R)) (21). Second, the relationship
between emotional-behavioral distress and
increasing years of epilepsy was specifically examined.
Third, the degree to which emotional-behavioral
distress influenced patients’ report of HRQOL was
examined using a conventional epilepsy-specific measure
of quality of life.
Subjects were patients with temporal lobe epilepsy
and healthy controls. Initial selection criteria for epilepsy
patients included the following: (a) chronological
age between 18 and 60, (b) WAIS-III Verbal, Performance,
or Full Scale IQ scores > 69, (c) complex
partial seizures of definite or probable temporal lobe
origin, (d) no MRI abnormalities other than atrophy
evident on clinical reading, and (e) no other neurological
disorder. Patients meeting initial selection criteria
had their medical records reviewed by a board-certified
neurologist with special expertise in epileptology
(P.R. or R.S.). This review included information pertaining
to seizure semiology, previous EEGs and neu-
and clinical history and course. Based on
this review, each patient was classified as having complex
partial seizures (CPS) of definite, probable, or possible
temporal lobe origin. Definite CPS/TL was defined
by continuous video-EEG monitoring demonstrating
temporal lobe (TL) seizure onset. Probable
CPS/TL was defined by review of clinical semiology
with features reported to reliably identify complex
partial seizures of temporal lobe of temporal lobe origin
versus onset in other regions (e.g., frontal) in
conjunction with interictal EEGs, neuroimaging findings,
and developmental and clinical history. Only
those patients meeting criteria for definite and probable
CPS/TL were recruited for study participation. Patients
with possible CPS/TL were excluded.
Selection criteria for the controls included the following:
(a) chronological age between 18 and 60, (b)
WAIS-III Full Scale, Verbal, or Performance IQ > 69,
(c) a relationship with the patient as either friend,
family member, or spouse, (d) no current substance
abuse or medical or psychiatric condition that could
affect cognitive functioning, (e) no psychotropic medications,
history of loss of consciousness (LOC) > 5
min, or history of developmental learning disorder.
Clinical information was extracted from the chart
while the examiner was blinded to the results of the
dependent measures. In addition, all patients underwent
direct interview regarding details of the presumed
etiology, course, treatment, and complications
of their epilepsy. Whenever possible, family members
were present (or were consulted by phone) to confirm
and elaborate on details of the clinical history. Permission
for release of information was obtained from the
patients so that all pertinent medical records could be
obtained from all previous epilepsy-related hospitalizations
as well as from physicians who had treated
the patients’ epilepsy. These medical records were
reviewed and abstracted by an individual blinded to
the dependent measures. Variables extracted from interview
with patients and significant others as well as
from review of medical records included age of onset
of recurrent seizures, duration of epilepsy, years of
active epilepsy (duration minus seizure-free intervals
of at least 1 year), presence and frequency of simple
and complex partial as well as secondarily generalized
seizures over the past year, estimated number of lifetime
secondarily generalized tonic– clonic seizures
(under or over 100), and history of status epilepticus
defined according to the guidelines developed by the
Working Group on Status Epilepticus.
Table 1 provides summary information regarding
the controls and epilepsy patients. Patients had signif-
||Patients (n = 54)
||Controls (n = 38)
|Full Scale IQ
|| 109.6 (14.5)**
|Age of onset
| * P = 0.06.
** P < 0.01.
icantly lower Full Scale IQ, but there were no significant
differences in age, gender, or education.
Patients and controls completed a self-report measure
of emotional-behavioral distress (SCL-90-R) (2)
and patients with epilepsy completed a comprehensive
measure of health-related quality of life (Quality
of Life in Epilepsy-89 item version (QOLIE-89)) (5).
Both measures are described in more detail below.
The SCL-90-R is a 90-item self-report inventory designed
to reflect the psychological symptom patterns
of community, medical, and psychiatric respondents.
Each item is rated on a five-point scale of distress
ranging from “not at all” to “extremely.” It is scored
and interpreted across nine primary symptom dimensions
and three global distress scales. The SCL-90-R is
especially sensitive to change among epilepsy patients,
temporal lobe epilepsy patients in particular
(21). The SCL-90-R scales are normed separately for
gender. A brief summary of the SCL-90-R scales follows
Somatization. Item content assesses complaints
arising from perceptions of bodily dysfunction with
complaints focusing on cardiovascular, gastrointestinal,
respiratory, and other systems with strong autonomic
mediation. Items also cover pain and discomfort
of the gross musculature and additional somatic
equivalents of anxiety.
Obsessive–compulsive. Item content assesses thoughts,
impulses, and actions that are experienced as unremitting
and irresistible and that are of an egoalien
or unwanted nature. Behavior and experiences of
a more general cognitive performance deficit are also
Interpersonal sensitivity. Item content assesses selfdeprecation,
self-doubt, and marked discomfort during
interpersonal interactions, self-consciousness, and
negative expectations concerning interpersonal behavior
with others and others’ perceptions of them.
Depression. Item content assesses dysphoric mood
and affect, withdrawal of life interest, lack of motivation
and energy, feelings of hopelessness, thoughts of
suicide, and other cognitive and somatic correlates of
Anxiety. Item content assesses nervousness, tension,
and trembling, as are panic attacks and feelings
of terror, apprehension, and dread. Somatic correlates
of anxiety are also assessed.
Hostility. Item content assesses thoughts, feelings,
or actions that are characteristic of the negative affect
state of anger. Items include the three modes of expression
and reflect aggression, irritability, rage, and
Phobic anxiety. Item content assesses persistent fear
responses to a specific person, place, object, or situation
that is irrational and disproportionate to the stimulus
and leads to avoidance or escape behavior. Items
focus on the more pathognomonic and disruptive
manifestations of phobic behavior.
Paranoid ideation. Item content assesses the cardinal
characteristics of projective thought, hostility, suspiciousness,
grandiosity, centrality, fear of loss of autonomy,
Psychoticism. Item content assesses behaviors that
reflect a withdrawn, isolated, and schizoid lifestyle
along with first-rank symptoms of schizophrenia including
hallucinations and thought control. Item content
assesses a gradual continuum ranging from mild
interpersonal alienation to frank psychosis.
Global severity index. This summary scale is the best
single indicator of the current level of depth of the
disorder it that it combines information concerning
the number of symptoms reported with the intensity
of perceived distress.
Positive symptom distress index. This summary scale
reflects the average level of distress reported for the
symptoms that were endorsed and can be interpreted
as a measure of symptom intensity.
Positive symptom total. This summary scale reflects
the number of symptoms endorsed regardless of the
level of distress and can be interpreted as a measure of
|Comorbid Psychological Disorder
Quality of Life in Epilepsy-89 (QOLIE-89)
The QOLIE-89 is a well-known measure of healthrelated
quality of life in epilepsy (5). It has 17 summary
scales: seizure worry, medication effects, health
discouragement, work/driving/social function, language,
attention/concentration, memory, overall
QOL, emotional well-being, role limitations—emotional,
social isolation, social support, energy/fatigue,
physical, role limitations—physical, and pain. Factor
analysis has shown the 17 scales to fall into four factors:
epilepsy targeted, cognitive, mental health, and
physical health. Details regarding the development,
reliability, and validity of the instrument are described
Three sets of analyses were performed. First, patients
with epilepsy were compared with controls
across all SCL-90-R scales using MANCOVA with age
as the covariate. It was hypothesized that increased
emotional-behavioral distress would be reported by
epilepsy patients compared with controls. Effect sizes
and confidence intervals were derived to determine
the relative magnitude of group differences across the
SCL-90-R scales. Second, to determine the relationship
between chronicity of temporal lobe epilepsy and
emotional-behavioral distress, partial correlations
were computed between duration (years) of epilepsy
and SCL-90-R scales with onset age as the covariate in
that age of onset and duration were significantly correlated
(r = 0.50). It was hypothesized that increased
emotional-behavioral distress would be associated
with increasing chronicity (years) of epilepsy. Third,
to examine the effects of comorbid interictal psychiatric
distress on health-related quality of life, selected
SCL-90-R measures of emotional-behavioral distress
were regressed on QOLIE-89 scales. It was hypothesized
that increased psychopathology would be associated
with broad and generalized reductions in perceived
quality of life.
Emotional-Behavioral Distress in Epilepsy
Compared with Healthy Controls
The MANCOVA resulted in a significant (P =
0.003) Hotelling’s T, and examination of univariate
effects showed the epilepsy patients to exhibit signif-
Mean SCL-90-R Scores
(n = 54)
(n = 38)
|Global Severity Index
|Positive Symptom Distress
|Positive Symptom Total
higher (worse) scores across all SCL-90-R
scales except Paranoid Ideation (see Table 2). For the
specific behavior problem scales, the effect sizes (from
high to low) were as follows: Phobic Anxiety, Obsessive–
Compulsive, Depression, Psychoticism, Somatization,
Interpersonal Sensitivity, Hostility, and Anxiety.
The 95% confidence intervals for the patients and
controls did not overlap for five of the nine specific
behavioral problem scales (Somatization, Obsessive–
Compulsive, Depression, Phobic Anxiety, Psychoticism)
or for all three SCL-90-R summary scales (Global
Severity Index, Positive Symptom Distress Index, Positive
Clinical Seizure Features and Self-Reported
Table 3 provides the partial correlations between
duration of epilepsy and SCL-90-R scores. Because age
of onset and duration were significantly correlated
(r = 0.50), onset was used as a covariate when examining
duration–psychopathology relationships. As
shown in Table 3, increasing duration of temporal lobe
epilepsy was significantly associated with increased
(worse) SCL-90-R scores across all scales. In terms of
proportion of variance, this relationship was relatively
modest and ranged from a low of 8% (Somatization) to
a high of 26% (Interpersonal Sensitivity, Positive
Symptom Total). The relationship between duration of
epilepsy and SCL-90-R scales remained significant
even when other clinical seizure variables were included
as covariates (e.g., overall seizure frequency,
Partial Correlation of Duration of Epilepsy with SCL-90-R Scales
|Global Severity Index
|Positive Symptom Distress Index
|Positive Symptom Total
lifetime secondary-generalized seizures, and history
of status epilepticus).
Relationship between Emotional-Behavioral
Distress and Health-Related Quality of Life
Table 4 provides the correlations between two SCL-
90-R summary measures of emotional-behavioral distress
(Global Severity Index, Positive Symptom Distress
Index) and one specific scale (Depression) with
perceived health-related quality of life (QOLIE-89).
These interrelationships were examined both directly
and by partial correlation with duration of epilepsy
and IQ as the covariates. The results were not substantially
different and the simple Pearson correlations are
presented below. As can be seen, there was a significant
relationship between significantly poorer healthrelated
quality of life in association with emotionalbehavioral
distress. Again, a secondary set of analyses
was conducted to confirm that this relationship was
not moderated by other factors. The relationship between
quality of life and comorbid psychopathology
was examined in the context of several covariates (e.g.,
overall seizure frequency, lifetime secondarily generalized
seizures, history of status epilepticus) and in no
set of additional analyses was the above-described
MANOVA was used to determine the relationship
between SCL-90-R scales and the frequency of simple
partial, complex partial, or secondarily generalized
seizures, as well as lifetime generalized seizures
(1001) and no significant findings emerged. While the
SCL-90-R provides gender-specific norms, a MANCOVA
was employed to examine epilepsy-versuscontrol
differences while controlling for gender given
the disparate distribution of gender in the epilepsy
and control groups. The results as described above
Three aspects of the current investigation are noteworthy:
(1) differences between controls and temporal
lobe epilepsy patients across the scales of the SCL-
90-R, (2) the risk of comorbid psychiatric distress with
increasing chronicity of temporal lobe epilepsy, and
(3) the impact of comorbid psychopathology on perceived
health-related quality of life.
Emotional-Behavioral Distress in Epilepsy
Compared with Healthy Controls
It is generally accepted that the risk of interictal
psychopathology is elevated among patients with
Correlations Between Emotional-Behavioral Distress
and Health-Related Quality of Life
|Overall Quality of Life
|Role Limitations: Physical
|Role Limitations: Emotional
|** P < 0.01.
* P < 0.05.
|Comorbid Psychological Disorder
chronic epilepsy attending tertiary care clinics (5, 6, 9,
16). Thus, the fact that patients with temporal lobe
epilepsy self-reported more emotional-behavioral distress
on the SCL-90-R is not surprising. However, the
generalized nature of the scale elevations is somewhat
unexpected. Moreover, across 8 of the 12 scales there
was no overlap of the 95% confidence intervals for
patients and controls. Inspection of effect sizes indicated
that symptoms of anxiety-related disorders and
depression yielded the greatest differences between
patients and controls (Phobic Anxiety, Obsessive–
Compulsive, Depression). These findings are also consistent
with the trends reported in the literature (13,
17, 18, 22). It should be remembered that the controls
were spouses, friends, or siblings of the patients and
were comparable in age and education and socioeconomic
status. Thus, even under these conditions there
were sizable differences between patients with temporal
lobe epilepsy and healthy controls in the number
and intensity of reported psychological symptoms.
Clinical Seizure Features and Self-Reported
While there is an extensive literature investigating
the known and suspected etiologies of interictal psychopathology,
this investigation was especially interested
in the effect of chronicity (increasing years of
duration) on comorbid interictal psychiatric symptoms.
Recent years have seen interest growing in regard
to the neuropsychological morbidities associated
with increasing chronicity/duration of epilepsy
among patients with surgically remediable syndromes
(6–8, 14). Relatively less is known about the emotional-behavioral
morbidity associated with increasingly
chronic temporal lobe epilepsy, hence the focus here.
In summary, the results of this study demonstrate that
increasing chronicity of temporal lobe epilepsy is
modestly associated with increased and generalized
self-reported emotional-behavioral distress. This relationship
remains significant even after the effects of
other pertinent and potentially confounding clinical
variables (e.g., age of onset, number of lifetime secondarily
generalized seizures, history of status epilepticus)
The SCL-90-R is only one of many self-report symptom
questionnaires, but it was selected for investigation
because of its demonstrated sensitivity to emotional-
behavioral change among patients with temporal
lobe epilepsy compared with other instruments
(21). Thus, replication of this finding using the SCL-
90-R with other samples of patients with temporal
lobe epilepsy would be especially helpful in determining
the reliability and generalizability of the reported
relationship between duration and psychopathology.
Relationship between Comorbid Interictal
Psychopathology and Health-Related
Quality of Life
During the past decade considerable research has
been devoted to developing measures of health-related
quality of life and examining the impact of clinical
epilepsy variables (e.g., seizure frequency, seizure
type, medications) on quality of life (5, 19, 20). The
potential effects of comorbid psychiatric disorder on
quality of life have been comparatively neglected compared
with disease-related factors. In the general medical
and psychiatric literature there is convincing evidence
that comorbid psychiatric disease is associated
with additional psychosocial impairment, impairments
beyond that which can be attributed to the
effects of the underlying medical disorder itself (cf.
10). This association has been reported in chronic
medical illnesses (e.g., diabetes) (11) and recently reported
in general neurology patients (1). There have
been but two very recent reports involving epilepsy
patients that have similarly suggested that comorbid
depressive symptoms or depressive disorder may adversely
affect perceived quality of life (15, 22). The
relationship observed here, that comorbid psychopathology
is associated with depressed quality of life,
was both strong in nature and generalized in effect,
and not limited to self-reported depression. Summary
SCL-90-R scales of psychological distress and symptom
intensity were highly predictive of significantly
lower health-related quality of life, with this relationship
detected across all QOLIE-89 scales.
The results of this investigation suggest the following.
First, efforts to recognize and detect comorbid
interictal psychological distress are important given
its apparent frequency and severity. Second, comorbid
psychological distress is a factor that clearly needs to
be considered and controlled for in studies of healthrelated
quality of life in epilepsy. Third, increased risk
of comorbid psychopathology appears to be another
burden associated with increasing chronicity of temporal
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