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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.
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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.