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Focus laterality and interictal psychiatric disorder in temporal lobe epilepsy

Vladimir V. Kalinin *, Dmitriy A. Polyanskiy

Department of Brain Organic Disorders and Epilepsy of Moscow Research Institute of Psychiatry of Ministry of Health, Russia

1. Introduction

Concomitant psychopathological states such as affective and

personality disorders seem to be the most frequent comorbid

psychiatric pathology among patients with temporal lobe epilepsy

(TLE). Despite their frequent prevalence that achieves about 850%

among patients with epilepsy15 the data on the type of affective

disorder in relation to focus laterality in temporal lobe epilepsy

remain obscure and rather controversial.

Thus, Flor-Henry6 was the first who showed the more frequent

occurrence of depressive disorder in the right focus, while

psychoses with schizophrenic symptoms in the left-sided focus

in temporal lobe epilepsy. On the other hand, Kanner5 rejected any

relation between focus laterality and depression development,

while according to Schmitz7,8 the opposite rule is true, and

depression in epilepsy has occurred more frequently in patients

with left temporal foci. In addition, Schmitz has stressed that left

temporal focus with hypofunction of frontal lobes seems to be

conditio sine qua non for development of interictal depression in

epilepsy.7,8

Data on anxiety disorder in relation to focus laterality in

patients with TLE are not less complicated than information ondepression.911 Thus, according to findings by Dobrochotova and

Bragina, depression more frequently prevails in patients with

right-sided foci while in patients with left-sided foci, as a rule,

more frequently anxiety occurs than depression.10 Here should be

stressed that these results10 were obtained analyzing the aura

semiotics in patients with epilepsy and cerebral tumors, andin this

context these data may be not properly comparable with

mentioned above findings since data obtained in patients rather

with depression or anxiety states in interictal period are required.

Interestingly, the results by Altshuler et al.11 obtained on patients

with TLE in interictal period are consistent with mentioned above

paradigm. In their study anxiety disorders were registered more

frequently in patients with left than right-sided focus epilepsy.11

Devinskyand DEsposito in this context indicatedthat in cases with

left-sided focus anxiety is developing more frequently simulta-

neously with depression, while in right-focus epilepsy isolated

depression appears more frequently.12

Dysphoric mood or dysphoria continues to be rather the

prerogative of epilepsy in terms of specific and most frequent

affective disorder. This syndrome is known in psychiatry since

works by Kraepelin and Bleuler and includes a pleomorphic

pattern of symptoms including such affective symptoms as

prominent irritability intermixed with euphoric mood, fear,

anxiety, as well as anergia, pain and insomnia.13,14 Blumer has

offered a special diagnostic category for patients with persistent

dysphoric mood in epilepsy, and called it Interictal dysphoric

Seizure 18 (2009) 176179

A R T I C L E I N F O

Article history:

Received 6 April 2008

Received in revised form 19 August 2008Accepted 22 August 2008

Keywords:

Temporal lobe epilepsy

Foci laterality

Affective disorder

Anxiety disorder

Interictal dysphoric disorder

Mild cognitive impairment

Behavioral disorder

A B S T R A C T

The current study was carried out in order to find the possible associations between foci laterality and

kindof prevailed psychopathological disorder in patients with temporal lobe epilepsy (TLE). One hundred

and ten patients with TLE (40 men and 70 women) were included into the study. Among all studiedpatients the left-focus activity was detected in 67 patients, right-sided fociin 43 patients. No

relationships between chronology variables of epilepsy (age,age at epilepsy onset, epilepsy duration) and

different subtypes of psychopathology in studied patients were revealed. Diagnosis of organic affective

disorder was observed more frequently in patients with right-sided foci, while diagnosis of organic

anxiety disorderin patients with left-sided foci (x2 = 7.0,p = 0.0081; Fishers exact testp = 0.018). The

comparison of dysphoric disorder with anxiety or affective disorder could not reveal any statistically

significant association with focus laterality. Obtained results are discussed in terms of association

between the different subtypes of studied psychiatric disorders and foci laterality in patients with TLE.

2008 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

* Corresponding author at: Head of Department, Moscow Research Institute of

Psychiatry of Ministry of Health, 3, Poteshnaya str., 107076 Moscow, Russia.

Tel.: +7 495 963 76 37; fax: +7 495 963 76 37.

E-mail addresses: doct.kalinin@mail.ru, research-kalinin@yandex.ru

(V.V. Kalinin).

Contents lists available atScienceDirect

Seizure

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / y s e i z

1059-1311/$ see front matter 2008 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

doi:10.1016/j.seizure.2008.08.012

mailto:doct.kalinin@mail.rumailto:research-kalinin@yandex.ruhttp://www.sciencedirect.com/science/journal/10591311http://dx.doi.org/10.1016/j.seizure.2008.08.012http://dx.doi.org/10.1016/j.seizure.2008.08.012http://www.sciencedirect.com/science/journal/10591311mailto:research-kalinin@yandex.rumailto:doct.kalinin@mail.ru

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disorder, although that category unfortunately has not been

included in DSM-IY or ICD-10.14 Unlike the sadness, the dysphoric

mood has outward vectorof blame that is directed to surroundings

of patient. In addition it may be accompanied by symptoms of

anger, gloomy affect, fury, hostility and aggression with destruc-

tive deeds.15

Understanding of relationship between personality in epileptic

patients and foci laterality is not less ambiguous.1618 The

prominent personality characteristics including viscosity, exces-

sive religiosity, hypergraphia and other epileptic features have

been observed more frequently in patients with left-sided focus in

study by Brandt et al.16 On the other hand, in study by Bear andFedio17 no differences between left and right foci in viscosity

values have been observed, although the majority of authors

confirmed the higher level of viscosity in patients with left-sided

foci.18,19

If the left focus determines both affective and personality

disorder, then the relationship between them may be presumed.

Along with this the duration of epilepsy in relation to personality

disorder and cognitive deterioration should also be taken into

account.2023

2. Objective

The current study was carried out in order to find the possible

effect of foci lateralization and epilepsy duration on kind ofpsychiatric disorder with emphasis on interictal affective and

anxiety in patients with temporal lobe epilepsy.

3. Material and methods

The study has been carried out on 110 patients with TLE.

Among all studied patients were 40 men and 70 women. The

focus laterality was detected strictly by visual EEG-method, and

data on ictal semiotics have not been used for this purpose. The

left-sided foci were detected in 67 patients, right-sided fociin

43 patients. The symptomatic form of TLE was diagnosed in 12

men and 36 women, cryptogenic formin 28 men and 34

women, respectively.

Psychiatric assessment was performed in order to set strictlyone of the next psychiatric diagnostic categories in accordance

with ICD-10: (1) organic affective disorder (F06.3) (14 patients);

(2) organic anxiety disorder (F06.4) (55 patients); (3) mild

cognitive impairment (F06.7) (44 patients); (4) personality

disorder due organic causes (i.e. epilepsy) (F07.0) (66 patients).

Along with above-mentioned ICD-10 criteria the diagnosis of

Interictal dysphoric disorder also was used. Principally, the

concomitant existence of dual diagnostic category per one patient

was allowed, including one affective and one personality or

cognitive disorder. All psychiatric categories primary were

diagnosed based upon psychiatric interview, and physician

(D.P.), who performed this interview, was blind to EEG findings.

In addition the Hamilton Rating Scale for Depression24 and

Hamilton Rating Scale for Anxiety

25

also were used for assessment

of degree depression and anxiety, respectively. The cutoff scores

for depression and anxiety in the current study were 15 points for

depression and 14 points for anxiety. In cases of both affective and

anxiety symptoms, the final diagnostic decision was dependent on

prevailed psychopathology.

The data on age of patients and epilepsy onset were also

obtained and included in the final analysis.

4. Statistics

All data were processed by Statistica program (6th version) on

personal computer. x2 statistics was used in to find the possible

discrepancies between diagnostic subgroups in relation to focus

laterality.

In addition the means of such variables as age of patient, age at

epilepsy onset and epilepsy duration in different diagnostic

subgroups were also analyzed using t-test.

5. Results

The main results are listed in the next several tables. Table 1

contains so-called chronology variables of epilepsy in different

subtypes of psychopathology in studied patients. As can be seen no

statistically significant discrepancies in chronology variables

between different diagnostic subgroups were obtained. It implies

that studied chronology variables have no relationship withdevelopment of mentioned diagnostic categories in patients with

epilepsy.

In Table2, relationship between foci laterality and development

of organic affective disorder or organic anxiety disorder is shown.

As can be seen, a category of organic affective disorder was

observed more frequently in patients with right-sided foci, while

diagnosis of organic anxiety disorderin patients with left-sided

foci. Fishers exact test (p= 0.018) and x2 statistics (x2 = 7.0

p= 0.0081) detected statistically significant discrepancies between

patients with diagnosis of organic affective disorder (organic

depression) and diagnosis of organic anxiety disorder. The odds

ratio (v = 4.6) indicates that patients with left-sided foci are on

average five times more frequently to have diagnosis organic

anxiety disorder than diagnosis of organic affective disorder,compared with patients, who have right-sided foci. On the

contrary, the probability for organic anxiety disorder development

in patients with right-sided foci is five times lesser than fororganic

affective disorder.

Table 1

Chronology variables in different subtypes of psychopathology in studied patients with TLE

Diagnosis Age of patients Age at epilepsy onset Epilepsy duration

Organic affective disorder 32.86 9.03 14.21 10.69 18.64 8.61

Organic anxiety disorder 34.18 12.21 18.05 9.08 15.91 11.48

Interictal dysphoric disorder 32.22 12.41 15.24 12.62 16.97 10.10

Mild cognitive impairment 32.68 12.39 12.68 9.96 19.98 10.71

Pers ona lity dis order du e orga nic caus es (epilepsy) 31.75 6.52 14.25 8.55 17.5 8.03

No statistically significant differences were obtained between groups.

Table 2

Focus laterality in patients with organic depression and organic anxiety

Psychopathological disorder Left-sided focus Right-sided focus Total

Organic depression 6 11 17

Organic anxiety 35 14 49

Total 41 25 66

x

2

=7.0, p = 0.0081; Fishers exact test two-tailed p = 0.0184; odds ratio v = 4.6.

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Principally, the comparison of dysphoric disorder with anxiety

or affective disorder could not reveal any statistically significant

association with focus laterality. It implies that focus lateralization

is important strictly for contrasting depression and anxiety, but

neither for dysphoria and depression, nor for dysphoria and

anxiety in TLE.

Similarly, no differences in relation to focus laterality were

obtained between personality disorder group and group with

cognitive impairment (Table 3). In other words,focuslateralization

does not determine development neither personality disorder, nor

cognitive impairment in patients with epilepsy.

6. Discussion

The current study has been carried out in order to find a

possible association between foci laterality and type of dominant

affective symptoms(dysphoria, depression or anxiety) in patients

with TLE. The study has certain limitations and may be criticized

at several reasons. First, in the final analysis of results the data on

antiepileptic (AED) drug therapy has not been included, although

some AED are thought to cause depression or anxiety develop-

mentand cognitive impairment in patientswith epilepsytoo.2630

The second reason concerns the fact that patients with left- orright-sided foci were strictly included in study,while patients with

bilateral focus activity were excluded intently from the trial.

The third reason for critical comments potentially may concern

the fact that quantified data of psychometric scales have not been

included in the current trial, although the evidence-based medicine

rules are required in modern scientific studies.

In order toprovea right for suchdesign ofstudy the nextseveral

reasons can be proposed. Thus, the study was intended to evaluate

strictly the foci laterality influence on depression or anxiety

development in epilepsy irrespective of used AEDs. The majority of

patients were taking such traditional AEDs as Valproates and

Carbamazepin which are thought to be mood stabilizer along

with antiepileptic properties, and choice of these AED has been

made in line with Ketters hypothesis of psychotropic properties ofdifferent AEDs.26 Moreover, themajorityof patients didnot receive

such drugs, as phenobarbital andphenyitoin, which are considered

to cause depressogenic effect.2731

If the patients with bilateral focus activity were included in

study the final results could not differentiate the isolate effect of

each hemisphere focus upon studied psychopathological symp-

toms, although the data on bilateral foci activity are also needed to

evaluate with unilateral foci influences for comparison purposes,

and such comparison will be made in the future.

The psychometric quantified scales (Hamiltons rating scale for

depression and Hamiltons rating scale for anxiety) were used for

patient selectiononly beforethe patients were included into study.

Nevertheless, the psychometric data have not been taken into

account in the final results of study, since the controversial rate fortheir use exists, and some authors argue against their expansive

use in psychiatry.32,33,34

The main findings of current study have shown that left-sided

foci are associated with anxiety, while the right-sided foci mainly

are connected with depression development. Obtained results

are consistent with data of other authors1012 and imply the role

of right hemisphere in genesis of depression, and left hemi-

spherein genesis of anxiety. Nevertheless obtained findings in

some way contradict to data by Kanner4,5 and Schmitz.7,8

Obviously, the mentioned discrepancies may be explained partly

by high degree of overlap between depression andanxiety, andin

patients with left-sided foci the final detection of prevailed

affective symptoms is complicated due these causes, and in

similar cases with TLE with left-sided foci the concomitant

appearance both anxiety and depression has been reported.11,12

In the current study, we tried to make only one diagnosis among

the three possible categories (affective, anxiety or dysphoric

disorder) on the basis of prevailed symptoms, while the dual

diagnosis for co-morbidity states (i.e. affective disorder + anxiety

disorder) was intentionally avoided.

Interestingly, that similar to ours results were obtained in

patients with stroke.35,36 Some authors in this context stressed

that in cases of right hemisphere stroke depression with apathy

and indifference appear more frequently, while in patients with

left hemisphere stroke depression and concomitant anxiety(catastrophic reaction), as a rule, develop,3537 although not all

authors could confirm such a relationship.37

Unfortunately our study was not able to reveal the neuropsy-

chological basis for dysphoric mood in patients with epilepsy, and

neither left-,nor right-sided foci seem to determine theoccurrence

of interictal dysphoric disorder. One of the possible explanations

for the lack of foci association with dysphoric disorder may be that

interictal dysphoric disorder seems to represent more complex

affective and behavioral syndrome, including both signs of

depression and anxiety. In this context, here should be mentioned

the diagnostic questionnaire by Blumer,14 in which dysphoria is

regarded as complex psychopathological state and eight key

criteria for its diagnosis are proposed.14

Similarly, the foci laterality did not determine neitherpersonality changes, nor mental deterioration in the present

study, although the certain data exist that patients with left-sided

foci activity, as a rule, are characterized by more pronounced

personality disorder compared with persons with right-sided

foci.12,18,19 Perhaps the current discrepancies with findings by

other authors may be partly explained by fact that we have not

used quantified evaluation for the rating of personality disorder

and mental deterioration in the present study.

In addition, some clinical and neuropsychological variables

important for dysphoria development might be overlooked in

current study and more meticulous trial is needed to find the

robust predictors for dysphoria development.

Principally the chronological variables could not differentiate

any affective, behavioral and cognitive diagnostic categories instudied patients that, in turn, may be partly explained by

concomitant appearance of affective and behavioral and cognitive

disorders in studied cohort of patients. In such cases the similar

chronological variables can be revealed in different categories, and

really a complex of several syndromes may be present.

Obtained findings stress the role of foci laterality in genesis of

affective and anxiety disorders in TLE, and may be presumably

extrapolated on brain mechanisms of affective and anxiety

disorders irrespective of epilepsy. If the proposed hypothesis

was true, then the right hemisphere involvement in the

mechanisms of depression and the left hemisphere involvement

in the pathogenesis of anxiety disorders should be expected,

although that speculative statement must be proved in special

studies.

Table 3

Focus laterality in patients with personality disorder and cognitive impairment

Psychopathological disorder Left-sided

focus

Right-sided

focus

Total

Personality disorder 38 24 62

Mild cognitive impairment 28 20 48

Total 66 44 110

No statistically significant differences between subgroups in relation to focus

laterality have been observed (x2 = 0.1, p= 0.75; Fishers exact test two-tailed

p= 0.84).

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