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Keywords:

  • Epilepsy surgery;
  • Depression;
  • Personality inventory;
  • Partial epilepsy

Abstract

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. References

Summary:  Purpose: Depression sometimes occurs after surgical treatment for medically intractable partial epilepsy. The risk of pre- and postsurgical depression may vary by laterality of seizure focus. We reviewed the pre- and postsurgical psychological assessments and clinical courses of patients to identify those at highest risk for postsurgical mood disorders.

Methods: Depression status was assessed in a consecutive series of epilepsy patients before and 1 year after epilepsy surgery with the use of Scale 2 of the MMPI-2 and a clinical depression index (CDI) scoring the occurrence of depressive symptoms, psychiatric referral, or attempted/completed suicide. Outcome at 1 year was modeled by regression techniques as functions of preoperative mood measurements, side of epilepsy surgery, and preoperative verbal intelligence.

Results: The CDI and Scale 2 MMPI-2 correlated significantly (r = 0.341; p ≤ 0.01). Left (n = 54 subjects) and right (n = 53) surgery groups did not differ by sex, seizure outcome, age, education, age at first seizure, duration of epilepsy, or intellect. Higher presurgical depressive morbidity (p = 0.0037) and right-sided surgery (p = 0.0003) predicted higher postoperative CDI. Higher preoperative Scale 2 scores, indicating worse depressive traits, predicted worse postoperative Scale 2 scores (p < 0.0001). Although side of surgery did not predict Scale 2 scores, Scale 2 scores of patients with preoperative right-sided foci tended to have worse postsurgical Scale 2 scores (p = 0.08). Findings for the temporal lobectomy subgroup (n = 90) were similar to those of the overall sample.

Conclusions: Patients undergoing right hemispheric epilepsy surgery, especially those with high presurgical depression–related morbidity, may be particularly susceptible to clinical depression. Our findings support other studies that show an interhemispheric modulation of depressive traits and symptoms.

Improvements in psychosocial functioning and quality of life after surgical treatment for medically intractable epilepsy may come at the risk of postsurgical psychiatric complications. Psychiatric morbidity includes the emergence of depression, anxiety, or psychosis after epilepsy surgery (1–5).

Whether the side of epilepsy surgery predicts postsurgical problems with mood disorders remains a controversy. Specifically, among patients with focal, symptomatic epilepsies, interictal depression may be more prevalent in those with left-sided seizure foci than in those with right-sided foci (6,7). In disagreement are later studies that show no effect of laterality of seizure focus on results of personality inventories (8), and conversely, a tendency for right-sided seizure foci to have greater association with presurgical depression (9,10). The side of epilepsy surgery may affect subsequent psychiatric morbidity, with depression having a greater prevalence after right-sided surgery (3,9–11).

To test the hypothesis that depression and its severe sequelae (suicide attempt or completion or other symptoms requiring psychiatric intervention) may vary with side of seizure focus and subsequent surgery, we reviewed the psychological assessments and clinical courses of patients with medically intractable partial epilepsy at two time points, before and 1 year after epilepsy surgery. These findings can be used to counsel patients before epilepsy surgery and to identify those at risk for postsurgical mood disorders.

METHODS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. References

Subjects

Subjects were drawn from consecutive epilepsy surgery candidates who were referred for neuropsychological evaluation from February 1991 through January 1998 as part of a standard, presurgical protocol for epilepsy surgery. Patients were reassessed at 1 year after epilepsy surgery. Patients younger than 18 years and those with functional illiteracy were excluded from this study, as they were unable to participate in the full assessment protocol. Patients who completed personality profiles but produced invalid protocols because of response bias or inconsistent responding also were excluded. Qualified neuropsychologists or supervised fellows of a registered training program performed neuropsychological evaluations. The University of Virginia Human Investigation Committee approved the study.

Subjects were divided into two groups by the hemisphere of epilepsy surgery. Because patients with mesial temporal lobe epilepsy may have higher rates of mood disorders than do those with other epilepsies (12), we repeated analyses with the subgroup of subjects who underwent anterior temporal lobectomy (ATL).

Depression indices

Pre- and postsurgical depression were measured by using two complementary methods. To quantify indicators of depression from information obtained via a clinical interview, one point was coded for each instance of (a) self-reported depressive symptoms, (b) psychiatric intervention for depression, or (c) attempted or completed suicide. Although highly specific for psychiatric morbidity, the small range of possible values for this clinical depression index necessarily limits sensitivity.

The quantitative assessment of depression consisted of the Depression scale (Scale 2) from the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) (13). Scale 2 of the MMPI-2 is empirically demonstrated to be a valid measure of depression in clinical populations (14–16), including epilepsy patients with a known psychiatric history (17). Scale 2 also is a valid measure of depressive symptoms in an outpatient population, suggesting that it also is sensitive in detecting milder levels of depression (16).

In both indices, higher scores indicated more severe depressive symptoms.

Data analysis

To determine if postsurgical depression varied by the hemisphere of epilepsy surgery, we used regression techniques to model postoperative outcome determined either by postoperative clinical depression index or by Scale 2 MMPI. Variables included in the model were (a) preoperative clinical depression index or Scale 2, (b) the hemispheric side of epilepsy surgery, and (c) preoperative verbal IQ score (VIQpre). Our model took the last into account because preliminary data suggested that VIQpre varied by side of surgery and might affect the ability of subjects to report symptoms of depression. So as not to assume linearity of this variable, VIQpre was modeled by using a restricted cubic spline function (18). Because the clinical depression index is an ordinal variable, we used a proportional odds logistic model (18). A linear regression function modeled Scale 2, a continuous variable. Because valid VIQpre and some postoperative MMPI-2 scores were not available for all subjects, missing data were multiply imputed with the use of customized software (19) so that no subjects with otherwise valid data were discarded (20). Analysis of variance was then used to determine interactions among variables.

Other subject characteristics were evaluated by using Student's t tests for continuous and Fisher's exact tests for categoric variables.

RESULTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. References

Clinical depression index correlated with Scale 2 of the MMPI-2

Of the gross sample of 128 subjects, 21 were excluded for incomplete follow–up. The remaining 107 subjects had valid clinical data allowing accurate determination of pre- and postsurgical clinical depression index scores. Ninety of the sample of 107 patients had valid pre- and postoperative Scale 2 scores after exclusions for literacy, compliance, or death.

Correlation between combined pre- and postsurgical clinical depression indices and Scale 2 scores showed that an increasing clinical depression score accurately reflected the severity of depression predicted by Scale 2 scores (Pearson correlation coefficient, 0.341; p ≤ 0.01). The significant correlation suggested that the clinical depression index was a meaningful measurement of the severity of clinical depression despite the restricted range of the index.

Demographics of subjects did not differ

Table 1 shows the distribution of sites and sides of epilepsy surgery in the total sample of 107 patients. Subject characteristics are shown in Tables 2 and 3. Regarding hemispheric dominance, 10 patients (9% of the total sample) were left-handed, but only two subjects showed right hemispheric language dominance as demonstrated by bilateral intracarotid amytal testing. Left and right surgery subjects did not differ by sex, surgery outcome, age at time of presurgical assessment, years of education, age at first seizure, duration of epilepsy, or presurgical intellect. ATL subjects were similarly matched, but the presurgical verbal intellect of left-sided subjects was significantly inferior to that of right-sided subjects (p = 0.02).

Table 1.  Distribution of sites of epilepsy surgery
Location of surgeryLeftRightTotal
  1. Temporal patients underwent anterior temporal lobectomy. Extratemporal lobe patients underwent resection of cortically based epileptic lesions in regions other than the temporal lobe.

Temporal464490
Extratemporal   
 Frontal527
 Parietal369
 Occipital011
 Total8917
Total5453107
Table 2.  Characteristics of epilepsy surgery subjects by side of epilepsy surgery
CategoryNo.LeftRightTotalp Value
  1. Mean ± standard error of the mean. IQ Verbal, IQ Performance, Kaufman Brief Intelligence vocabulary and matrices tests: Surgical outcome, Engel's class 1 seizure free with and without aura (29) during the year after surgery. Scale 2 MMPI, Scale of MMPI-2; CDI, clinical depression index; pre, before epilepsy surgery; post, 1 year after epilepsy surgery.

Sex     
 Male 262450 
 Female 2829570.85
Surgical outcome     
 Seizure free 394180 
 Not seizure free 1512270.66
Age (yr)10731.9 ± 1.233.1 ± 1.5 0.54
Education (yr)10713.1 ± 0.412.3 ± 0.5 0.26
First seizure (yr)10715.6 ± 1.313.3 ± 1.5 0.26
Duration (yr)10716.8 ± 1.319.9 ± 1.5 0.12
IQ Verbal pre9688.8 ± 1.992.9 ± 1.4 0.06
IQ Performance pre9692.7 ± 2.795.6 ± 2.0 0.35
Scale 2 MMPI pre9961.9 ± 1.959.1 ± 1.6  
Scale 2 MMPI post9058.8 ± 1.660.3 ± 2.2  
CDI pre1020.58 ± 0.130.49 ± 0.01  
CDI post1040.35 ± 0.080.89 ± 0.12  
Table 3.  Characteristics of the anterior temporal lobectomy subgroup
CategoryNo.LeftRightTotalp Value
  • a

     Statistically significant.

Sex     
 Male 182240 
 Female 2822500.40
Surgical outcome     
 Seizure free (class 1) 343771 
 Not seizure free 127190.30
Age (yr)9031.7 ± 1.332.6 ± 1.6 0.64
Education (yr)9013.2 ± 0.512.5 ± 0.4 0.28
First seizure (yr)9015.9 ± 1.612.0 ± 1.4 0.07
Duration (yr)9016.4 ± 1.420.6 ± 1.7 0.07
IQ Verbal8188.2 ± 1.693.3 ± 1.5 0.02a
IQ Performance8193.4 ± 2.198.0 ± 1.8 0.10
Scale 2 MMPI pre7962.6 ± 2.157.7 ± 1.9  
Scale 2 MMPI post8559.1 ± 1.858.2 ± 2.5  
CDI pre900.65 ± 0.150.52 ± 0.15  
CDI post900.37 ± 0.100.93 ± 0.14  

Depression indices vary by side of surgery and by surgical state

As determined from preoperative clinical interviews, nine subjects with temporal lobe foci (five left-sided foci, four right-sided foci) had a history of attempted suicide. Thirty-three (31%) of 107 subjects had nonzero clinical depression index preoperatively. Postoperatively, one left-hemispheric surgery subject and three right-hemispheric surgery subjects attempted or completed suicide within the first year of follow-up. Forty-seven (44%) subjects postoperatively had nonzero clinical depression index scores. One of the postoperative subjects had a right extratemporal lobe resection; all others underwent ATL.

Figure 1 shows the mean values for the clinical depression index and Scale 2 compared between sides and surgical states. The figures suggested that patients who had left-sided epileptic foci had higher mean clinical depression indices and mean Scale 2 scores than did those with right-sided partial epilepsy. After epilepsy surgery, however, right-hemisphere epilepsy surgery patients had higher clinical depression indices and Scale 2 scores than did left-hemisphere surgery patients.

image

Figure 1. Effects of side of epilepsy surgery and pre- or postsurgical state on the depression scale of the MMPI-2 (Scale 2) and a 3-point clinical depression index (CDI) in a sample of epilepsy surgery patients (all subjects) and in the subgroup of anterior temporal lobectomy patients (atl). Error bars, standard error of the mean.

Download figure to PowerPoint

To confirm these impressions, multiple regression results are shown in Table 4. The side of epilepsy surgery was significantly associated with the severity of the clinical depression index, with right-sided patients showing significantly worse depressive morbidity (p = 0.0003). Higher presurgical clinical depression indices predicted higher postsurgical scores (p = 0.0037).

Table 4.  Analysis of variance after regression to postoperative depressive outcome modeled by preoperative depressive outcome
Variableχ2dfp Value
  1. CDI, Clinical depression index; S2, scale 2 of the MMPI-2; Side, hemisphere of epilepsy surgery; VIQ pre, preoperative verbal IQ determined by Kaufman Brief Intelligence Test.

Logistic regression of postsurgical CDI   
 No.108  
 CDI13.4630.0037
 Side12.9610.0003
 VIQ pre1.5330.676
Linear regression of postsurgical Scale 2 of MMPI-2   
 No.90  
 S2121.36<0.0001
 Side all interactions 12.120.08
 S2 * Side13.030.08
 VIQ Pre30.520.67

Higher presurgical Scale 2 scores were associated with higher postsurgical scores (p < 0.0001). The side of epilepsy surgery tended to predict postsurgical Scale 2 scores (p = 0.08), reflecting the pattern of convergence of postsurgical Scale 2 scores shown in Fig. 1. However, presurgical Scale 2 scores of patients with left-sided epileptic foci tended to be higher than those in patients with right-sided epilepsy (p = 0.08). The effect of side tended to differ by the severity of preoperative Scale 2 scores; postsurgical Scale 2 scores diverged most notably by side for higher preoperative scores (p = 0.08; Fig. 2).

image

Figure 2. The relation between preoperative and postoperative Scale 2 scores of the MMPI-2 diverge by side of surgery most notably with higher values of preoperative Scale 2 scores. Scores are adjusted for preoperative verbal IQ score of 90.

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The subset of ATL subjects experienced similar changes in the clinical depression indices and Scale 2 scores, except that the smaller sample size limited significance of findings (Table 4).

DISCUSSION

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. References

Our study of the psychological outcomes of patients with medically intractable epilepsy followed up for 1 year after epilepsy surgery revealed several important associations among depression, laterality of seizure focus, and laterality of surgery.

First, Scale 2 of the MMPI–2, a well validated and commonly used personality assessment, correlated significantly with the severity of depression as measured by a clinical depression index.

Second, preoperative symptoms of depression, psychiatry visits, or suicide attempts predicted a worsening of symptoms within the first year after epilepsy surgery as modeled by regression analyses. Right-sided epilepsy surgery patients had significantly more postsurgical psychiatric morbidity than did left-sided patients.

Third, preoperative Scale 2 scores predicted the severity of Scale 2 scores determined 1 year after surgery. Both left- and right-sided surgery patients had similar postoperative Scale 2 scores, but patients with preoperative left-sided seizure foci tended to have worse Scale 2 scores than did those with right-sided foci at the time of the presurgical assessment.

Overall, the present study suggested that the modulation of depression was affected by the laterality of epileptic pathology and its surgical removal. Patients with preoperative depression, especially those with right-sided seizure foci, may be at greater risk for depressive symptoms after surgical intervention.

Presurgical measurements of depressive traits in the present study agree with the majority of previous studies that show that persons with epilepsy with left-hemispheric foci have symptoms of interictal depression at higher rates than do those with right-sided foci (6,7,21). Other studies, however, found that the interictal, presurgical rate of depression is higher in right-sided temporal lobe epilepsy (9,10).

Epilepsy surgery appears to alter the relation between mood and laterality of partial epilepsy. The present study agrees with multiple case series in which the incidence of depression, suicide, psychosis, or intractability to treatment is higher after right-sided surgery (3,10,11,22). Studies are not uniform in conclusions; some series show no effect of laterality on suicide rates in long-term follow-up of epilepsy surgery patients (23). However, in the current study, the significantly worse depression-related outcomes in right-sided surgery patients occurred despite a tendency in right-sided patients to have more favorable presurgical Scale 2 scores. After surgery, left-sided Scale 2 scores in the present study converged with right-sided scores. These findings contrast with those from a previous study that showed that there are no differences in MMPI-2 scales between left- and right-hemisphere groups either before or after surgery (8). Those authors suggest that neurologic factors play a minimal role in depression and that psychological factors likely account for the depression experienced by epilepsy patients.

Both Scale 2 and the clinical depression index underwent parallel changes: left-sided surgery subjects showed improvements, and right-sided subjects, decrements after surgery. However, whereas Scale 2 scores converged, depression-related outcomes by surgical hemisphere diverged. Because our statistical model takes into account the possible effects of verbal intelligence, underreporting on the basis of poor verbal skills is not a likely explanation for these observations.

The more parsimonious interpretation lies in the differences in the two indices. Whereas Scale 2 is a point determination, the clinical depression index captured both point and interval symptoms. The interval of our study was ≥1 year. Findings may differ depending on the duration of postsurgical follow–up, with the immediate postoperative period—4 to 8 weeks—possibly being the period of highest risk of psychiatric morbidity (24,25). Scale 2 administered 1 year after surgery, therefore, may underestimate the peak morbidity of depression.

A second interpretation can be theorized from the findings of Bear and Fedio (26), who reported that patients with right-sided foci tend to deny negative behaviors, and left-sided patients, to emphasize them (21). Likewise, in the present study, right-sided patients tended to underreport presurgical depressive traits, but they were more likely to experience depression-related outcomes.

The implication of our findings is that there is an interhemispheric modulation of depressive traits and symptoms. Most studies on the lateralization of depression center on the effects of stroke on mood. A proposed anatomic model of poststroke depression holds that strokes involving the left hemisphere, especially those of the anterior regions, are more likely to lead to significant depression (27). A recent meta–analysis of all reports on poststroke depression, however, offers no support for the hypothesis that the location of infarct affects development of depression (28). Epileptic lesions and their subsequent removal, our study suggests, may affect mood differently from destructive lesions.

We conclude that patients undergoing resection in the right hemisphere for epilepsy surgery are particularly susceptible to the severe sequelae of depression. This conclusion is underscored by the unfortunate fact that, of our sample, three right temporal lobectomy patients who were seizure free committed suicide before their 1-year anniversary. Our findings suggest that counseling of presurgical candidates and monitoring of postsurgical patients should be tailored to the side of resection. Patients with right-sided epileptic foci or those with high scores on depression indices may need closer monitoring after surgery, or at least may need to be counseled before epilepsy surgery on the risk of postoperative depression. Notably, psychiatric status after surgical intervention may be independent of seizure control. Certainly patients acknowledging symptoms of depression, anxiety, or other psychiatric symptoms should be immediately referred for psychological or psychiatric evaluation and treatment.

Acknowledgment: We thank Susan Goode, R.N., of the F.E. Dreifuss Comprehensive Epilepsy Program for her dedicated care of our epilepsy patients. We thank Frank E. Harrell, Ph.D., of the Department of Health Evaluation Services, for his consultation in statistical methods. M.Q. is supported in part by NINDS K08 NS02021.

References

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. References
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