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Keywords:

  • Refractory epilepsy;
  • Temporal lobe epilepsy;
  • Psychiatric disorders;
  • Major depression

Summary

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Disclosure
  9. References

We aim to investigate whether temporal origin of epilepsy increases the risk of developing a psychiatric disorder and more specifically a major depressive disorder. The lack of standardized diagnostic instruments and the methodologic differences between studies highlight the fact that this issue warrants further, systematic, study. Three-hundred eight patients with complex partial seizures were classified according to temporal or extratemporal origin, following the Commission on Classification and Terminology of the International League Against Epilepsy (ILAE), 1989 localization-related concept. All patients were assessed using the Structured Interview for DSM-IV axis I psychiatric disorders (SCID-I). Lifetime and previous-year prevalence of psychiatric disorders were compared in temporal and extratemporal subgroups, using multivariate analysis. Previous-year major depression was significantly associated with temporal lobe origin. Our results do not support the hypothesis that patients with temporal lobe epilepsy (TLE) have more psychiatric illness in general, although they do suggest a specific connection between TLE and major depression.

The fact that patients with intractable epilepsy have the highest rates of psychiatric comorbidity, of which mood disorders are the most common diagnosis, has been consistently reported in the literature (Swinkels et al., 2005).

The role of the temporal lobe and the limbic system in the pathogenesis of psychopathologic disturbances, particularly major depression, is especially controversial. Some authors have found higher rates of psychiatric disorders in patients with temporal lobe epilepsy (TLE) compared with extratemporal lobe epilepsy (extra-TLE), whereas other authors have not supported this association (Swinkels et al., 2005). Heterogeneity regarding classification and origin of seizures, lack of standardized instruments used for the assessment of psychiatric disorders, in addition to differences in patient groups and small sample sizes, make it difficult to compare the results between studies.

Recent reports by the same research team (Swinkels et al., 2001, 2006) have tried to overcome the methodologic limitations of prior investigations. When comparing TLE and extra-TLE subgroups (Commission on Classification and Terminology of the International League Against Epilepsy (ILAE), 1989) among patients with complex partial seizures assessed with a standardized diagnostic instrument for psychiatric disorders, patients with TLE were not found to have significantly more from any psychiatric disorder. However, prevalence of mood disorders tended to be higher in patients with TLE.

The lack of comparable studies highlights the fact that this issue warrants further exploration.

We aim to examine whether psychiatric disorders, and specifically major depression, are more prevalent in TLE patients. For this purpose, homogeneous subgroups of patients with TLE and extra-TLE are compared, following a similar methodology to that used in the previously mentioned studies.

Methods

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Disclosure
  9. References

Subjects

Four hundred forty-nine adult patients were consecutively admitted to the Epilepsy Inpatient Unit of the Department of Neurology, Hospital Clinic of Barcelona, between 2001 and 2005, for assessment of drug-resistant epilepsy (Pintor et al., 2007). Drug-resistance was defined as “frequency of seizures of at least once a month, despite polytherapy with up to three different anti-convulsants, for a period of at least 2 years” (Engel, 2001).

Patients with refractory epilepsy are referred to the Hospital Clinic Epilepsy Unit from all over the country, and admitted for seizure assessment under continuous video-EEG (electroencephalography) monitoring for >1 week. Epilepsia diagnoses are based on the 1989 ILAE Classification of Epilepsies and Epilepsy Syndromes. Complex partial and generalized seizures are classified according to temporal or extratemporal origin and according to left, right, or bilateral location, on the basis of neuroimaging findings magnetic resonance imaging (MRI), EEG, and video-EEG observation of seizures. In our sample, the origin of the seizures could not be ascertained in 17 patients.

The study was approved by the Hospital Clinic of Barcelona Ethical and Research Committee. All patients provided informed written consent. Seventy-two patients with nonepileptic seizures and 17 patients with intellectual disability or severe medical conditions were excluded. Twenty-four patients presented with psychotic symptoms related to an increase of seizures during the admission period. Of these, only eight patients, those with other comorbid psychiatric disorders, were included. Ictal psychoses were not considered in the analysis of prevalence of psychiatric disorders.

Consistent with prior studies, 31 subjects with primarily generalized seizures were excluded. For temporal and extratemporal subgroup comparisons, we included 216 patients (69.7%) with a diagnosis of complex partial epilepsy only, and 92 (30.3%) with complex partial epilepsy as main seizure type, in association with secondary generalized seizures. The final sample consisted of 308 patients [mean age 35.15 years (standard deviation, 12.01), 56.5% females]. Epidemiologic and seizure characteristics of the sample are shown in Table 1.

Table 1.   Comparison of demographic and seizure features between TLE and Extra-TLE patients
VariableTotal (n = 344)TLE group (n = 185)Extra-TLE group (n = 123)p-value
n (%)n (%)n (%)
  1. TLE, temporal lobe epilepsy; extra-TLE, extratemporal lobe epilepsy.

  2. aN=308 (patients with complex partial seizures).

  3. b(mean, SD) Student’s t-test.

  4. (n %) Chi-square statistics with Yates’ correction and Fisher’s exact test.

Average age (years)a35.07 (12.08)35.83 (11.20)34.64 (13.15)0.39
Gender
 Female193 (56.1)103 (56.1)70 (56.8)0.50
Marital status
 Single160 (46.8)79 (42.7)62 (50.4)0.39
 Married/living together120 (34.9)69 (37.3)41 (33.3)
 Divorced/widow64 (18.3)37 (20.0)20 (16.3)
Education
 Primary education207 (60)111 (60.2)78 (63.0)0.69
 Secondary education99 (28.5)50 (27.3)34 (28.0)
 Higher education38 (10.7)23 (12.4)11 (9.0)
Labor
 Employed (paid)132 (38.7)72 (39.0)50 (40.4)0.80
 Disability pension/unemployment125 (36.2)65 (35.2)46 (37.4)
 Housekeeping/ student87 (25.1)48 (25.8)27 (22.2)
Epilepsy etiology
 Idiopathic213 (62.2)109 (59.3)84 (68.6)0.11
Main seizure type
 Partial seizure313 (91.1)185 (100)123 (100)0.44
  Only partial216 (69.7)133 (71.8)83 (67.5)
  Secondary generalized92 (30.3)52 (28.1)40 (32.5)
 Primary generalized31 (9.0)  
Number of crises
 1–5 per month134 (38.9)79 (42.9)43 (34.9)0.27
 >5 month210 (61.1)106 (57.1)80 (65.1)
Localization
 Temporal195 (56.7)   
 Extratemporal132 (38.4)   
 Nonestablished17 (4.9)   
Lateralizationa
 Left147 (47.0)89 (48.1)55 (44.7)0.36
 Right136 (44.7)84 (45.3)53 (43.5)
 Bilateral25 (8.3)12 (6.6)15 (11.8)
Duration of illnessb21.22 (12.01)22.18 (11.89)20.40 (11.20)0.29

Instruments

Patients were assessed by the epilepsy unit psychiatrist, who was blinded to epilepsy origin, using the Structured Clinical Interview for DSM-IV axis I diagnoses (SCID-I clinician version) (Spitzer et al., 1992). Lifetime and previous-year prevalence of any DSM-IV psychiatric disorder was ascertained. Epidemiologic, social, and occupational functioning data, in addition to seizure-related features, were obtained by the neurologists in charge of the patients.

Statistical analysis

Temporal and extratemporal groups were compared in relation to a number of sociodemographic and seizure variables (Table 1). Comparison between lifetime and previous-year prevalence of psychiatric disorders was also carried out between groups (Table 2). Chi-square statistics with Yates’ correction and Fisher’s exact text were used for the comparison of categorical data, whereas Student’s t-test was used for normally distributed dimensional variables. A logistic regression analysis was performed so as to investigate the magnitude of independent relationships with seizure origin. Lifetime and previous-year major depression were included as independent variables Because major depression has been associated with anxiety disorders, female gender, unemployment, marital status, age, duration of illness, and laterality, any interactions between major depression and these variables were also included as independent variables. Significance was set at p < 0.05. Odds ratios (ORs) and confidence intervals (CIs) were also calculated so as to determine the independent contribution of each factor.

Table 2.   Comparison of lifetime and last-year prevalence of psychiatric disorders between TLE and Extra-TLE patients
VariableTotal epilepsy groupTLE groupExtra-TLE groupp-value
n = 344n (%)n = 185n (%)n = 123n (%)  
LifetimeLast yearLifetimeLast yearLifetimeLast yearLifetimeLast year
  1. Chi-square statistics with Yates’ correction and Fisher’s exact text. Bold indicates p < 0.05.

Mood disorders126 (36.6)81 (23.5)71 (38.4)43 (23.2)40 (32.5)26 (21.1)0.330.67
 Major depression67 (19.5)41 (11.9)41 (22.2)27 (14.6)18 (14.6)8 (6.5)0.100.02
 Depression NOS17 (4.9)10 (2.9)11 (3.9)5 (2.7)4 (3.6)4 (3.3)0.740.74
 Dysthymia36 (10.5)25 (7.3)18 (9.7)10 (5.4)13 (10.6)10 (8.1)0.810.34
 Bipolar disorder 5 (1.5)3 (0.9)3 (1.6)2 (1.1)2 (1.6)2 (1.6)0.990.81
Anxiety disorders95 (27.7)68 (19.8)47 (25.4)39 (21.1)35 (28.5)21 (19.5)0.590.77
 Panic disorder19 (5.5)11 (3.2)8 (4.3)7 (3.8)4(3.3)0.490.53
 Generalized anxiety disorder47 (13.7)31 (9.0)24 (13.0)20 (10.8)15 (12.2)10 (8.1)0.840.51
 Anxiety NOS22 (6.4)16 (4.7)10 (5.4)8 (4.3)8 (6.5)6 (4.9)0.800.55
 Obsessive compulsive disorder7 (2.0)3 (0.9)5 (2.7)2 (1.1)2 (1.6)1 (0.8)0.700.51
 Social phobia28 (8.1)18 (5.2)11 (5.9)9 (4.9)11 (8.9)7 (5.7)0.360.79
Schizophrenia4 (1.2)2 (0.6)3 (1.6)1 (0.5)1 (0.8)1 (0.8)0.470.64
Somatoform disorders19 (5.5)11 (3.2)8 (4.3)6 (3.2)7 (5.7)5 (4.1)0.580.64
Psychoactive substance use disorders18 (5.2)4 (1.2)9 (4.6)2 (1.0)5 (3.8)00.780.51
 Alcohol dependence11 (3.2)2 (0.6)5 (2.6)03 (2.3)00.86 
 Drug dependence7 (2.0)2 (0.6)4 (2.1)2 (1.0)2 (1.5)00.720.51

Results

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Disclosure
  9. References

Total sample prevalence for lifetime and previous-year interictal psychiatric disorders are shown in Table 2.

One hundred eighty-eight patients (54.4%) had at least one psychiatric disorder throughout their lifetime, and 83 patients (24.1%) fulfilled criteria for more than one past psychiatric diagnosis.

Mood, followed by anxiety disorders, were the most prevalent lifetime and previous-year diagnoses. The highest comorbidity was found to be between these two disorders. Among the patients with affective disorders, 22.2% had lifetime comorbidity with an anxiety disorder.

Sixty-five patients (18.9%) were receiving pharmacologic treatment at the time of assessment. A total of 27.2% of patients with current affective disorders were on antidepressants, whereas nearly 17% of patients with anxiety disorders were taking antidepressants and 15.3% benzodiazepines. All patients with current comorbid mood and anxiety disorders (n = 16) were on antidepressants. Twenty-one patients without current anxiety or depressive disorder were on antidepressants (90% of these had history of a mood disorder). TLE and extra-TLE groups did not differ in rates of pharmacologic treatment.

When comparing lifetime and previous-year prevalence of psychiatric disorders, no significant differences were found between the groups in any of the main categories (mood, anxiety, psychotic, or somatoform disorders) (Table 2)

After logistic regression analysis, previous-year prevalence of major depression was significantly associated with temporal origin seizure (OR 3.84, CI 95% 1.23–9.86, p = 0.008). No other significant associations were found.

Discussion

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Disclosure
  9. References

In our sample, mood and anxiety disorders were the most prevalent psychiatric diagnoses. However, despite their high prevalence, a low proportion of patients were receiving specific treatment. This is consistent with previous reports, and highlights the fact that in epileptic patients psychiatric symptoms are underestimated and undertreated (Jones et al., 2005, 2007).

Regarding TLE and extra-TLE comparisons, our discussion will focus on the findings of the Dutch studies (Swinkels et al., 2001, 2006). Tertiary setting recruitment, sample size, inclusion criteria, and the classification of seizures according to temporal or extratemporal origin, are similar. Moreover, both studies used reliable and widely used instruments, consisting of structured interviews designed to assess psychiatric disorders (Spitzer et al., 1992; Smeets & Dingesmans, 1993).

Similarly to the prior studies, we did not find higher rates of previous-year or lifetime prevalence of anxiety disorders or psychotic disorders in the TLE group. However, when focusing on mood disorders, we observed a statistically higher previous-year prevalence of major depression in patients with TLE. The prior group also reported a higher prevalence of mood disorders in patients with TLE, especially as regards previous-year prevalence, although without reaching statistical significance (Swinkels et al., 2001).

Our findings support a possible connection between major depression and temporal structures, not influenced by demographic factors, other seizure-related features such as lateralization, or other psychiatric disorders, since potential confounders were controlled for in a multiple regression analysis. It must be noted that temporolimbic structures are considered to be more specifically involved in the nature of depressive symptoms, especially major depression. Recent neuroimaging studies have identified abnormalities in structures of the limbic system in patients with depression associated with TLE (Briellmann et al., 2007; Shamim et al., 2009). Nevertheless, our results must be interpreted with caution, since no differences have been found in lifetime prevalence of either major depressive disorders, other mood disorders, or mood disorders as a group. We have also failed to classify temporal and extratemporal groups into subgroups according to the etiology of the seizures. However, a recent study did not find higher rates of depression in mesial temporal sclerosis compared with lesional or cryptogenic, temporal, and extratemporal epilepsy (Adams et al., 2008). In the present study, the different subtypes of focal temporal epilepsy have not been investigated individually.

A further limitation to be considered is that the classification of the seizures is based on ILAE criteria (1989), which use noninvasive techniques for the localization and lateralization of seizures. Another shortcoming is the cross-sectional and retrospective assessment of lifetime Axis-I disorders without a follow-up design. Furthermore, the instrument used for assessment (SCID-I) has not been validated in patients with epilepsy, and does not include disorders such as attention deficit-hyperactivity disorder (ADHD), which has also been found to be more prevalent in patients with epilepsy. On the other hand, personality disorders were not assessed, and their influence on psychopathology was not taken into account. Finally, our drug-resistant sample limits the generalization of the findings.

Conclusions

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Disclosure
  9. References

Temporal structures may have a role in the pathogenesis of major depression in epilepsy. However, according to the Hermann and Withman model (Hermann et al., 2000), predisposition for psychiatric disorders in epilepsy may be the result of a combination of a complex variety of individual and seizure-related factors.

In conclusion, further research focusing on the role and interplay of the specific factors involved is warranted. Improvements in the classification of the different subtypes of epilepsy and integration of neuroimaging findings are key in this process.

Acknowledgments

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Disclosure
  9. References

This study was supported by a grant from the Ministry of Health of Spain (FIS 2004 Sanity Investigation Found, project PI040418) and in part by Catalonia Government, DURSI (Departament d’Universitats, Recerca i Societat de la Informació) 2009SGR1119. We thank O. Puig and F. Castro for the statistical support and manuscript preparation.

We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Disclosure

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Disclosure
  9. References

The authors have no conflict of interest to declare.

References

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Disclosure
  9. References
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