Epilepsy & Behavior 1, 184-190 (2000)
doi:10.1006/ebeh.2000.0066, available online at http://www.idealibrary.com on IDEAL

Comorbid Psychiatric Symptoms in Temporal
Lobe Epilepsy: Association with Chronicity
of Epilepsy and Impact on Quality of Life1

Bruce P. Hermann, Ph.D.,*,2 Michael Seidenberg, Ph.D., Brian Bell, Ph.D.,* Austin Woodard, Psy.D.,*,‡ Paul Rutecki, M.D.,*,‡ and Raj Sheth, M.D.*

*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; depression.


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. E-mail: hermann@neurology.wisc.edu.

undertreated 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-


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Comorbid Psychological Disorder 185

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-

roimaging, 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-

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186 Hermann et al.

Patient Characteristics

  Patients (n = 54) Controls (n = 38)

Age 37.9 (11.6) 35.1 (12.5)
Education 12.9 (2.2) 13.7 (2.3)
Full Scale IQ 94.7 (17.2)  109.6 (14.5)**
Gender 12M, 42F 16M, 22F*
Age of onset 16.3 (12.2)  
Duration 19.5 (10.6)  

   * 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.

Symptom Checklist-90-Revised

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 below.

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 included.

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 depression.

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 resentment.

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, and delusions.

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 symptom breadth.

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Comorbid Psychological Disorder 187

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 elsewhere (5).

Data Analyses

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)
  Mean SE Mean SE p

Somatization 55.7 1.2 49.9 1.5   .004
Obsessive–Compulsive 60.6 1.2 53.2 1.4   .001
Interpersonal sensitivity 58.6 1.2 53.6 1.5   .01
Depression 57.3 1.3 49.8 1.6   .001
Anxiety 54.3 1.4 48.8 1.7   .015
Hostility 53.3 1.3 48.1 1.6   .012
Phobic Anxiety 57.1 1.2 49.5 1.5   .001
Paranoid Ideation 53.3 1.4 50.4 1.6   .182
Psychoticism 57.7 1.5 50.5 1.7   .002
Global Severity Index 58.1 1.4 50.4 1.6   .001
Positive Symptom Distress 54.8 1.1 48.6 1.3   .001
Positive Symptom Total 57.7 1.3 50.9 1.6   .001

icantly 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 Symptom Total).

Clinical Seizure Features and Self-Reported
Emotional-Behavioral Distress

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,

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188 Hermann et al.

Partial Correlation of Duration of Epilepsy with SCL-90-R Scales

Scale r P

Somatization 0.29 0.045
Obsessive–Compulsive 0.42 0.003
Interpersonal Sensitivity 0.47 0.001
Depression 0.38 0.008
Anxiety 0.31 0.03
Hostility 0.32 0.03
Phobic Anxiety 0.41 0.004
Paranoid Ideation 0.46 0.001
Psychoticism 0.40 0.004
Global Severity Index 0.40 0.005
Positive Symptom Distress Index 0.31 0.034
Positive Symptom Total 0.47 0.002

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 relationship altered.

Secondary Analyses

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 were unaltered.


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


Health Perceptions -0.54** -0.57** -0.50**
Overall Quality of Life -0.60** -0.52** -0.63**
Physical Function -0.44** -0.41** -0.42**
Role Limitations: Physical -0.54** -0.43** -0.51**
Role Limitations: Emotional -0.63** -0.55** -0.63**
Pain -0.45** -0.40** -0.42**
Work/Driving/Social -0.61** -0.54** -0.56**
Energy/Fatigue -0.57** -0.62** -0.62**
Emotional Well-Being -0.70** -0.67** -0.67**
Attention/Concentration -0.70** -0.70** -0.63**
Health Discouragement -0.64** -0.57** -0.59**
Seizure Worry -0.41** -0.42** -0.38**
Memory -0.48** -0.48** -0.36**
Language -0.58** -0.51** -0.50**
Medication Effects -0.48** -0.40** -0.46**
Social Support -0.29* -0.17 -0.19
Social Isolation -0.64** -0.56** -0.63**
Total -0.84** -0.77** -0.79**

** P < 0.01.
   * P < 0.05.

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Comorbid Psychological Disorder 189

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
Emotional-Behavioral Distress

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) are covaried.

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 lobe epilepsy.

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190 Hermann et al.


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Authored Date: 
Tuesday, November 5, 2013