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Handedness, alexithymia, and focus laterality as risk factors for psychiatric comorbidity in patients with epilepsy
Epilepsy & Behavior 17 (2010) 389–394
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Handedness, alexithymia, and focus laterality as risk factors for psychiatric comorbidity in patients with epilepsy Vladimir V. Kalinin *, Anna A. Zemlyanaya, Oleg E. Krylov, Elena V. Zheleznova Department of Brain Organic Disorders and Epilepsy, Moscow Research Institute of Psychiatry, Ministry of Health and Social Development, Moscow, Russian Federation
a r t i c l e
i n f o
Article history: Received 16 November 2009 Revised 30 December 2009 Accepted 30 December 2009
Keywords: Temporal lobe epilepsy Comorbid psychiatric disorders Focus laterality Handedness Alexithymia SCL-90 constructs
a b s t r a c t The aim of the current study was to evaluate the effect of seizure lateralization, handedness, and alexithymia on psychopathology in patients with temporal lobe epilepsy. One hundred five patients were included in the study. The Hopkins Symptom Checklist—90 (SCL-90) and Toronto Alexithymia Scale (TAS-26) were used for psychopathological assessment of patients. Handedness was evaluated using Annett’s scale. Among the patients studied were 74 right-handers and 31 left-handers, and 25 alexithymic and 80 nonalexithymic persons. Left-sided foci were observed in 52, and right-sided foci in 53 persons. MANOVA was used for analysis of the interrelationship between nominal fixed factors (handedness, alexithymia, and focus laterality) and the dependent variables SCL-90, Hamilton Rating Scale for Depression, and Hamilton Rating Scale for Anxiety. MANOVA revealed that alexithymia exerts maximal effect on psychopathological variables, and maximal values of SCL-90 constructs were observed for persons with alexithymia/left-handedness and alexithymia/right-sided seizure focus combinations. Ó 2010 Elsevier Inc. All rights reserved.
1. Introduction Psychiatric comorbidities mainly in the form of affective and anxiety disorders seem to be the most frequent complications of epilepsy, particularly localization-related and temporal lobe epilepsy (TLE). Perini et al. have shown that patients with TLE have higher rates of affective and personality disorders compared with persons with juvenile myoclonic epilepsy [1]. Despite their frequent occurrence, about 8–50% among patients with epilepsy [2– 6], risk factors for the development of psychiatric disorders in TLE remain obscure and rather controversial. Flor-Henry was the first to show that depressive disorder in epilepsy occurs more frequently in patients with a right-sided focus, whereas psychoses with schizophrenic symptoms are attributed to a left-sided focus [7]. On the other hand, Kanner [6] and Manchanda et al. [8] rejected any relationship between side of focus and development of depression, whereas according to Schmitz [9,10], the opposite—depression in epilepsy occurs more frequently in patients with left temporal foci—is true. In addition, Schmitz stressed that a left temporal focus with hypofunction of the frontal lobes seems to be necessary for the development of interictal depression in epilepsy [9,10].
* Corresponding author. Address: Department of Brain Organic Disorders and Epilepsy, Moscow Research Institute of Psychiatry, Ministry of Health, Moscow 107076, Russian Federation. E-mail address: [email protected] (V.V. Kalinin). 1525-5050/$ - see front matter Ó 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2009.12.028
In a previous article, we reported that right-sided foci are associated with the development of depressive disorders, whereas leftsided foci, contrarily, are related to anxiety in TLE [12]. Obviously, that strict left/right foci dichotomy is not always enough to predict the precise type of psychopathology in TLE, as comorbid affective and anxiety disorders may equally develop irrespective of focus laterality. Moreover, some overlooked factors in addition to focus laterality may be important for the development of concomitant psychopathology in patients with epilepsy. Sensory and motor asymmetries seem to be examples of such poorly appreciated variables in neuropsychiatry. In this context, left-handedness and ambidexterity are thought to be phenomena that complicate neuropsychiatric assessment, and all left-handed and ambidextrous patients, as a rule, are intentionally withdrawn from such studies. Such an approach has certain limitations because interesting data are eliminated from further analysis, and results on cerebral organization of motor functions are not taken into account. Left-handedness itself seems to represent one pole in the neuropsychological continuum of Homo sapiens, where right-handedness occupies the other pole, and ambidexterity lies between these two poles. This continuum in handedness is thought to depict gradual changes in sensorial and motor function in human brain, and may be one of the factors that influence mental properties and psychic phenomena. Moreover, the exact interaction between focus laterality and handedness remains rather obscure. The term alexithymia, coined in 1972 by Sifneos [13], implies an inability to recognize and differentiate subtle emotional states combined with concrete thinking directed to the nearest surroundings
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and a paucity of dreaming and fantasies. Alexithymia is regarded as a constellation of personality traits that predispose to the development of psychosomatic and affective disorders. At least two neuropsychological models of alexithymia have been proposed to date. According to the first model, alexithymia is thought to be the result of reduced interconnections between the right and left hemispheres and, subsequently, interruption of the normal flow of information. In other words, alexithymia represents a state of ‘‘functional commissurotomy,” as was supposed by Hoppe et al. [13–16]. According to the second model, alexithymia is associated with a diminished ability to recognize facial expressions of basic emotions that is linked to dysfunction of the right hemisphere [17,18]. Despite the fact that these theoretical speculations are well known, there have not yet been any studies on possible relationships between alexithymia and epilepsy, except for that by Bewley et al. [19], although in that study patients with epilepsy and those with nonepileptic seizures and normal controls could not be distinguished based on the Toronto Alexithymia Scale (total score) [19]. In addition, to date, data on possible associations between alexithymia and psychopathological phenomena, in particular anxiety and depression, in patients with epilepsy have also been lacking. The principal aim of the current study was to find possible associations between motor lateralization (handedness), focus laterality, and alexithymia as risk factors for the development of psychopathological disorders in patients with localization-related forms of epilepsy.
2. Material and methods The study was carried out on 105 patients with TLE, 37 men and 68 women. The female preponderance in this group might be explained by the high proportion of females among persons admitted in the Department of Brain Organic Disorders and Epilepsy in which the current study was carried out, and intentional bias in patient selection was avoided. All consecutive cases within a 1-year period (May 2008–April 2009) were included. Symptomatic epilepsy was diagnosed in 40 patients, cryptogenic epilepsy in 53 patients, and idiopathic TLE in 12 patients. Focus laterality was determined strictly by the visual EEG method; data on ictal semiology were not taken into account. Left-sided foci were detected in 52 patients (15 men, 37 women), and right-sided foci in 53 patients (22 men, 31 women). MRI was used to verify diagnosis and, among those with symptomatic epilepsy, revealed mesiotemporal sclerosis in 26 patients and posttraumatic cysts in 14 cases. Here it should be stressed that MRI data were intentionally not included in further analysis, because the influence of structural brain pathology on psychopathology and handedness represents an independent issue, which must be the subject of further research. All patients were evaluated by psychiatrists to establish a psychiatric diagnosis. ICD-10 criteria were used for these purposes. In line with these criteria, the following disorders were diagnosed: (1) Organic Affective Disorder (F06.3) (24 patients), (2) Organic Anxiety Disorder (F06.4) (48 patients), and (3) Interictal Dysphoric Disorder (33 patients). For the assessment of depression and anxiety, the Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) respectively were used. For assessment of other psychopathological symptoms, the Hopkins Symptom Checklist—90 (SCL-90) scale was completed by the patients themselves [20,21]. Raw data from the SCL-90 were then transformed into nine constructs that were included in the final analysis of the interaction between affective and anxiety syndromes. In accordance with SCL-90 design, the nine constructs
are: Somatization, Obsessive–Compulsive, Interpersonal Sensitivity, Depression, Anxiety, Hostility, Phobic Anxiety, Paranoid ideation, and Psychoticism [20,21]. For the assessment of handedness, Annett’s scale was used [22]. Persons whose global Annett’s scale score was lower than 5 points were regarded as left-handers, and those whose score exceeded +5 points, as right-handers. Among all patients studied, 74 were considered right-handers (mean ± SD = 19.2 ± 6.0) and 31 left-handers ( 11.2 ± 10.9). The observed high proportion of lefthandedness among the patients studied (30%) raises a question on selection bias. This question is answered in the Discussion. The Toronto Alexithymia Scale (TAS-26) [13,23,24] was used to assess alexithymia. This scale consists of 26 items, and each item can be scored from 1 to 5 points. The TAS-26 global score ranges from 26 to 130 points. All patients whose global TAS-26 score exceeded 74 points were regarded as alexithymic. The mean average TAS-26 score in the nonalexithymic group (N = 80) was 58.5 ± 11.5, and in the alexithymic group (N = 25), 80.0 ± 4.8 points. 2.1. Statistics All data were statistically processed with the SPSS Version 11 program on a personal computer. For the first step, Student’s t test was used to assess differences in psychopathological variables (SCL-90, HAM-D, and HAM-A scores) in right-handers versus lefthanders, in alexithymic versus nonalexithymic patients, and in patients with a left-sided focus versus those with a right-sided focus. In the final step, MANOVA was used to analyze the interrelationship between nominal independent variables (fixed factors) and dependent quantitative variables. MANOVA represents a variant of multivariate analysis that is widely used to assess the influence of certain nominal variables (fixed factors) on variance of quantitative dependent variables. That analysis, estimating the variance, allows a single simultaneous comparison of three or more groups. The result becomes a type of screening test that indicates whether at least one group differs significantly from the others [25]. In addition, the interrelationship between nominal fixed factors and its influence on dependent variables may be revealed. MANOVA was chosen because this test has many advantages in comparison with the widely used t or z test [25], although each is designed to find possible discrepancies between the groups being compared; MANOVA is able to reveal discrepancies between groups that cannot be detected with t tests [25]. The variables handedness, alexithymia, and focus laterality of epilepsy were selected as independent factors. The nine constructs of the SCL-90, mentioned earlier, were considered dependent variables. In the current study, intentional selection of certain variables for purposes of analysis was avoided. The a priori hypothesis was that there should exist certain interrelationships between handedness, focus laterality, and alexithymia, on the one hand, and psychiatric syndromes, on the other hand. 3. Results The main results are summarized in the tables. In Table 1, psychopathological variables are compared between persons with leftsided foci and those with right-sided foci. As can be seen there were no significant differences. In Table 2, psychopathological variables are compared relative to handedness. Here it can be seen that left-handed and righthanded persons differ statistically significantly on three variables: Somatization, Depression, and SCL-90 total score. Principally, righthanded patients scored higher on these variables, and it can be concluded that right-handed patients with epilepsy usually experience more severe psychopathological symptoms compared with
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left-handed patients. In addition to the variables mentioned, a trend toward differences was also observed for Sensitivity (P = 0.06) and Anxiety (P = 0.07). In both cases, right-handed patients scored higher than left-handed patients. Table 3 summarizes the data on comparison of psychopathological variables in alexithymic and nonalexithymic patients, and statistically significant differences on all variables except the HAM-A score were observed. Principally, compared with nonalexithymic
Table 1 Comparison of psychopathological variables in patients with left-sided and rightsided foci. Variable
Left-sided focus (N = 52)
Right-sided focus (N = 53)
Significance
HAM-D HAM-A
6.70 ± 5.91 5.08 ± 3.87
6.49 ± 4.66 6.47 ± 5.45
N.S. N.S.
SCL-90 Somatization Obsession Sensitivity Depression Anxiety Aggression Phobia Paranoia Psychoticism
7.37 ± 5.11 8.59 ± 5.94 8.96 ± 7.17 8.09 ± 7.05 6.80 ± 5.44 3.80 ± 3.36 3.43 ± 3.29 4.37 ± 3.52 3.30 ± 4.36
8.72 ± 8.02 8.79 ± 6.85 8.70 ± 6.90 9.70 ± 8.93 8.04 ± 7.42 4.60 ± 4.84 4.08 ± 4.63 4.60 ± 5.07 4.70 ± 5.81
N.S. N.S. N.S. N.S. N.S. N.S. N.S. N.S. N.S.
56.11 ± 43.41
59.98 ± 49.27
N.S.
Total score
Table 2 Comparison of psychopathological variables in left-handed and right-handed patients. Variable
Left-handed patients (N = 31)
Right-handed patients (N = 74)
Significance
HAM-D HAM-A
5.42 ± 4.81 5.00 ± 4.25
7.05 ± 5.22 6.14 ± 4.91
N.S. N.S.
SCL-90 Somatization Obsession Sensitivity Depression Anxiety Aggression Phobia Paranoia Psychoticism
5.90 ± 5.29 7.13 ± 6.18 6.87 ± 6.66 6.52 ± 7.72 5.61 ± 5.99 3.68 ± 5.52 3.00 ± 4.17 4.03 ± 5.28 3.32 ± 5.22
9.15 ± 7.09 9.26 ± 6.24 9.61 ± 6.89 9.86 ± 7.90 8.11 ± 6.52 4.39 ± 3.40 4.05 ± 3.85 4.69 ± 3.87 4.34 ± 5.07
P = 0.024 N.S. P = 0.06 P = 0.049 P = 0.07 N.S. N.S. N.S. N.S.
42.23 ± 47.25
63.93 ± 43.88
P = 0.026
Total score
Note. Statistically significant differences are marked in boldface.
Table 3 Comparison of psychopathological variables in nonalexithymic and alexithymic patients. Variable
Nonalexithymic patients (N = 80)
Alexithymic patients (N = 25)
Significance
HAM-D
5.81 ± 4.28
9.00 ± 6.76
P = 0.006
HAM-A Somatization Obsession Sensitivity Depression Anxiety Aggression Phobia Paranoia Psychoticism
5.34 ± 4.20 7.03 ± 5.66 7.70 ± 5.92 7.34 ± 6.35 7.40 ± 6.84 6.29 ± 6.03 3.26 ± 2.94 3.03 ± 3.45 3.76 ± 3.53 3.08 ± 4.23
7.28 ± 6.00 11.92 ± 8.54 11.6 ± 6.56 12.2 ± 7.62 13.6 ± 9.48 10.84 ± 6.62 7.12 ± 5.80 6.04 ± 4.62 6.84 ± 5.68 7.12 ± 6.42
P = 0.07 P = 0.001 P = 0.006 P = 0.002 P = 0.005 P = 0.002 P = 0.003 P = 0.005 P = 0.002 P = 0.006
84.16 ± 55.20
P = 0.006
Total score
49.20 ± 39.20
Note. Statistically significant differences are marked in boldface.
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patients, alexithymic patients are characterized by higher SCL-90 construct and HAM-D scores. The main results of the MANOVA are summarized in Table 4, and as can be seen, the three factors studied influence psychopathological variables differently. Thus, alexithymia is thought to be the factor with maximum effects on all psychopathological variables. Noteworthy, alexithymia itself exerts maximum influence on each variable, and the g2 values for alexithymia were the highest among all the fixed factors studied, implying that alexithymia itself determines the appearance of all psychopathological symptoms in patients with epilepsy. On the other hand, focus laterality and handedness had lesser influence. This may be due to the smaller number of dependent variables: three for focus laterality (Aggression, Phobia, Paranoia) and two for handedness (Aggression and Paranoia). In addition, the effects of focus laterality and handedness as assessed with g2 values also were much smaller than the influence of alexithymia alone. Moreover, interactions between alexithymia and the other factors, if they were present, had less influence on dependent psychopathological symptoms compared with alexithymia alone. Here it should be stressed that the alexithymia score itself does not depend on either handedness or focus laterality, implying the independence of these three factors from each other, although they could interact to influence dependent psychopathological variables. The mean values of the psychopathological variables under the influence of the three fixed factors are listed in Tables 5 and 6. In Table 5 are listed the mean values of dependent psychopathological variables under the influence of handedness and alexithymia/ nonalexithymia. As can be seen, the maximum values of some variables were observed in alexithymic patients with left-handedness, whereas the minimum values were observed in left-handed but nonalexithymic patients. Right-handed patients were, as a whole, characterized by intermediate values of dependent psychopathological items irrespective of whether they were alexithymic or nonalexithymic. Notably, comparison of alexithymic left-handers with nonalexithymic left-handers revealed statistically significant differences on most of the variables including HAM-D and all SCL-90 constructs except Somatization. Table 6 lists the mean values of the dependent psychopathological items under the influence of focus laterality and alexithymia/ nonalexithymia. From this table it can be concluded that the maximum values of SCL-90 constructs were seen in patients with rightsided foci and alexithymia, whereas the minimum values were observed in nonalexithymic patients with right-sided foci. The patients with left-sided foci were, as a rule, characterized by intermediate values of SCL-90 constructs irrespective of the presence or absence of alexithymia. Comparison of alexithymic patients with a right-sided focus with nonalexithymic patients with a right-sided focus, on the one hand, and with alexithymic patients with a leftsided focus, on the other hand, revealed statistically significant differences.
4. Discussion Research on the significance of some basic epilepsy characteristics, that is, seizure semiology, seizure frequency and types, and antiepileptic drugs, as potential risk factors for the development of certain psychiatric comorbidities remains rather controversial and has not led to a definite conclusion. This implies that the basic variables cited are not sufficient to explain properly the development of certain psychiatric comorbidities in epilepsy. The current study seems to be the first in which handedness, alexithymia, and focus laterality have been evaluated in terms of
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their individual and joint influence on psychopathological symptoms in patients with epilepsy. The study may be criticized for its lack of a control group (patients without epilepsy) for comparison of the prevalence of alexithymia and handedness in persons with epilepsy. Nevertheless, the principal aim of the study was evaluation of the interaction of three different neurobiological factors on expression of different psychopathological variables strictly in patients with epilepsy. Although data on the prevalence of left-handedness in epilepsy were not within the principal aim of the carried study, the high proportion of left-handedness in patients with epilepsy (30%) obtained should be explained, as it could be interpreted to be the result of bias in patient selection. Here it should be stressed that according to data of other authors, the prevalence of left-handedness in the general population is about 11.2% in Holland [28] and 13% in Australia and New Zealand [27]. In Russia, similar data have been obtained, as left-handedness occurs in 10% of the general population [28]. On the other hand, the proportion of left-handedness in persons with epilepsy is thought to be higher, 1.6- to 2.0-fold that of the general population [28]. This implies that nearly 20% of persons with epilepsy could be left-handed. Our results indicate that the proportion of left-handedness in epilepsy is 30%. Obviously, this may be partly explained by our desire to include in the study the maximal number of patients with left-handedness so as to obtain a cohort size sufficient for comparison purposes. In other words, a bias in patient selection, if it really existed, could not be seriously exaggerated because of the objective high proportion of left-handedness among patients with epilepsy. Results of the present study have shown that some personality and neurobiological variables in patients with epilepsy are related to certain psychopathological disorders and could be used to predict psychiatric comorbidity, mainly affective and anxiety states. Alexithymia itself represents the strongest personality construct among the factors studied that influence psychopathological variables in epilepsy. On the other hand, focus laterality and handed-
ness individually had much less influence, and these factors could not completely explain the occurrence of psychopathological symptoms. Moreover, the data obtained might, at first glance, be seen as controversial and rather paradoxical. Thus, based on the data in Table 2, it could be concluded that right-handed patients with epilepsy are characterized by greater severity of some psychopathological variables (depression, somatization) compared with left-handers. However, this is not the case, as left-handed patients with high alexithymia scores had the maximum severity SCL-90 construct scores (Table 5). Obviously, alexithymia itself interacts with the other factors studied, and the results of such interactions may differ with respect to the psychopathology manifested. Thus, patients who were alexithymic and left-handed, on the one hand, or were alexithymic and had right-sided foci, on the other hand, scored the highest on most of the SCL-90 constructs. On the contrary, the minimum SCL90 construct scores were obtained by nonalexithymic left-handed patients and nonalexithymic patients with right-sided foci. In other words, alexithymia combined with left-handedness or with right-sided focus is thought to be a conditio sine qua non and risk factor for the development of psychopathological disorders in patients with epilepsy. Here it must be stressed that the effects of alexithymia, handedness, and focus laterality were not differentiated with respect to concrete SCL-90 constructs, and practically each SCL-90 construct could develop, and a plethora of psychopathological symptoms could result under their influence. The degree of alexithymia, in turn, depended on neither focus laterality nor handedness in the patients studied, implying that all three factors should be regarded as independent in terms of their origin, although their combination can explain the occurrence of psychopathological symptoms in patients with epilepsy. In this context it may be suggested that the effect of alexithymia is complementary to those of right-sided foci and left-handedness. The hypothesis that alexithymia originates as a result of pathology in the right hemisphere should be incorporated into the current discussion. Thus, patients with right hemisphere strokes are
Table 4 Results of MANOVA: Influence of different factors and their interaction on psychopathological variables. Variable
Focus
HAM-D
P = 0.958 g2 = 0.001 P = 0.150 g2 = 0.039
HAM-A SCL-90 Somatization Obsession Sensitivity Depression Anxiety Aggression Phobia Paranoia Psychoticism Total score
P = 0.194 g2°= 0.034 P = 0.996 g2 = 0.000 P = 0.588 g2°= 0.011 P = 0.108 g2 = 0.046 P = 0.074 g2 = 0.053 P = 0.0001 g2 = 0.206 P = 0.031 g2 = 0.07 P = 0.009 g2 = 0.095 P = 0.063 g2 = 0.056 P = 0.828 g2 = 0.004
Handedness
Alexithymia
P = 0.942
P = 0.001 g2 = 0.118 P = 0.017 g2 = 0.059
g2 = 0.000 P = 0.679
g2 = 0.002 P = 0.690
g2 = 0.002 P = 0.642
g2°= 0.002 P = 0.307
g2°= 0.011 P = 0.412
g2 = 0.007 P = 0.337
g2 = 0.010 P = 0.008
g2 = 0.073 P = 0.202
g2 = 0.017 P = 0.032
g2 = 0.048 P = 0.061
g2 = 0.036 P = 0.794
g2 = 0.001
P = 0.004 g2°= 0.084 P = 0.001 g2°= 0.117 P = 0.0001 g2 = 0.155 P = 0.0001 g2 = 0.200 P = 0.0001 g2 = 0.176 P = 0.0001 g2 = 0.396 P = 0.0001 g2 = 0.194 P = 0.0001 g2 = 0.265 P = 0.0001 g2 = 0.239 P = 0.0001 g2 = 0.153
Focus handedness
Focus alexithymia
Handedness alexithymia
Focus handedness alexithymia
P = 0.773
P = 0.682 g2 = 0.002 P = 0.317 g2 = 0.011
P = 0.016 g2 = 0.060 P = 0.097 g2 = 0.029
P = 0.873 g2 = 0.0001 P = 0.400 g2 = 0.007
P = 0.686
g2 = 0.005 P = 0.575
g2 = 0.012 P = 0.212
g2°= 0.032 P = 0.301
g2°= 0.025 P = 0.657
g2 = 0.009 P = 0.852
g2 = 0.003 P = 0.777
g2 = 0.005 P = 0.004
g2 = 0.109 P = 0.520
g2 = 0.014 P = 0.066
g2 = 0.056 P = 0.716
g2 = 0.007 P = 0.229
g2 = 0.031
P = 0.089 g2°= 0.030 P = 0.773 g2°= 0.001 P = 0.207 g2 = 0.017 P = 0.036 g2 = 0.045 P = 0.018 g2 = 0.058 P = 0.0001 g2 = 0.230 P = 0.007 g2 = 0.074 P = 0.0001 g2 = 0.122 P = 0.055 g2 = 0.038
P = 0.001 g2 = 0.105 P = 0.001 g2 = 0.108 P = 0.001 g2 = 0.104 P = 0.0001 g2 = 0.256 P = 0.002 g2 = 0.095 P = 0.0001 g2 = 0.199 P = 0.0001 g2 = 0.143
P = 0.273 g2°= 0.013 P = 0.336 g2°= 0.001 P = 0.609 g2 = 0.003 P = 0.701 g2 = 0.002 P = 0.352 g2 = 0.009 P = 0.0001 g2 = 0.0183 P = 0.732 g2 = 0.001 P = 0.029 g2 = 0.049 P = 0.799 g2 = 0.001
P = 0.580 g2 = 0.003
P = 0.011 g2 = 0.067
P = 0.185 g2 = 0.018
g2°= 0.002 P = 0.010
g2°= 0.068
Note. P = probability of null hypothesis; g2 = effect of studied factors on dependent variables; usually this parameter is equal to quota of variance caused by appropriate influence of fixed factor (factors) studied. All statistically significant values are marked in boldface.
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V.V. Kalinin et al. / Epilepsy & Behavior 17 (2010) 389–394 Table 5 Results of MANOVA: Mean values of dependent psychopathological variables for persons with different combinations of handedness and alexithymia. Variable
LH/A (N = 5)
LH/NA (N = 26)
RH/A (N = 20)
RH/NA (N = 54)
HAM-D
12.4 ± 6.0
8.2 ± 6.8
6.6 ± 4.5
HAM-A
9.2 ± 6.4
4.1 ± 3.2 P = 0.0001 (1) 4.2 ± 3.3 P = 0.013 (1)
6.8 ± 6.0
5.9 ± 4.5
SCL-90 Somatization
10.6 ± 5.4
12.3 ± 9.2
8.0 ± 5.8
Obsession
16.2 ± 8.3
10.5 ± 5.7
8.8 ± 6.4
Sensitivity
17.8 ± 9.1
10.8 ± 6.7
9.2 ± 7.0
Depression
19.6 ± 10.3
12. ± 8.9
9.0 ± 7.4
Anxiety
15.6 ± 8.6
9.7 ± 5.7
7.5 ± 7.8
Aggression
12.4 ± 9.3 9.0 ± 4.5
5.8 ± 3.9 P = 0.0195 (2) 5.3 ± 4.4
3.9 ± 3.1
Phobia Paranoia
12.4 ± 8.0 12.8 ± 6.9
5.5 ± 4.2 P = 0.0122 (2) 5.7 ± 5.6 P = 0.0234 (2)
4.4 ± 3.8
Psychoticism
5.0 ± 4.9 P = 0.028 (1) 5.4 ± 3.9 P = 0.0001 (1) 4.8 ± 3.4 P = 0.00001 (1) 4.0 ± 3.7 P = 0.00001 (1) 3.7 ± 2.8 P = 0.00001 (1) 2.0 ± 2.2 P = 0.00001 (1) 1.8 ± 3.0 P = 0.0001 (1) 2.4 ± 2.6 P = 0.00001 (1) 1.5 ± 1.9 P = 0.00001 (1) 28.9 ± 20.4 P = 0.0001 (1)
77.4 ± 46.1
59.0 ± 42.4
Total score
111.4 ± 83.8
3.6 ± 3.5
3.8 ± 4.8
Note. LH/A, left-handed and alexithymic; LH/NA, left-handed and nonalexithymic; RH/A, right-handed and alexithymic; RH/NA, right-handed and nonalexithymic. Comparisons were made between LH/A and LH/NA (1) and between LH/A and RH/A (2). Statistically significant differences are followed by P values.
usually characterized by a higher alexithymia score than patients with left hemisphere strokes [29]. Moreover, the right hemisphere is believed to be responsible for the origin and processing of negative emotions [30]. All SCL-90 constructs involve mainly negative feelings or states that are accompanied by negative emotions, such as depression, obsession, interpersonal sensitivity, anxiety, phobic anxiety, aggressiveness, and paranoid ideations, which can explain the greater severity of these syndromes in patients with epilepsy
with high alexithymia scores and right-sided foci. In other words, such poorly differentiated emotions can develop in persons with epilepsy who have a special predisposition in terms of right-sided focus, left-handedness, and alexithymia. Notably, the famous Russian neurologist M.I. Astvatsaturov described the emotional state called ‘‘dark basic feeling” [31]. Certainly, an analogy exists between Astvatsaturov’s ‘‘dark basic feeling” and the cluster of negative emotions in alexithymic patients with epilepsy in the current study. The existence of such a bundle of strictly negative emotions attributed to the right hemisphere seems to reflect ancient protective mechanisms in Homo sapiens that helped them to avoid danger. In this context, alexithymia can be considered an ancient and protective personality construct that has maintained its significance to the present. The real interaction mechanisms between alexithymia, lefthandedness, and right-sided foci in epilepsy with psychiatric comorbidity should also be considered. Unfortunately no plausible concept exists that could explain such mutual tropism. According to a hypothesis proposed by Geschwind and Galaburda, the right hemisphere is thought to be more conservative in terms of earlier development and plays an essential role in survival of H. sapiens [32,33]. In addition, the right hemisphere is thought to exert some influence on the left hemisphere, and this leads to retardation of left hemisphere maturation that, in turn, can cause left-handedness [32,33]. From this point of view, the brain of left-handers is not a simple mirror image of the brain of right-handers, but, rather, comprises two right and not properly matured hemispheres. This can explain the similarity of the interaction between alexithymia and left-handedness, on the one hand, to the interaction between alexithymia and right-sided focus, on the other hand, although this suggestion remains purely speculative and should be confirmed in a specific study. The results obtained may be used for the purpose of predicting concomitant psychopathological disorders in patients with epilepsy as psychiatric comorbid syndromes are thought to complicate the course and treatment of epilepsy itself. Further study/analysis of the origin of alexithymia/nonalexithymia in patients with epilepsy is required and could shed light on the pathogenesis of psychiatric disorders in epilepsy.
Table 6 Results of MANOVA: Mean values of dependent psychopathological variables for persons with different combinations of focus laterality and alexithymia. Variable
LF/A (N = 13)
LF/NA (N = 39)
RF/A (N = 12)
RF/NA (N = 41)
HAM-D HAM-A
9.5 ± 8.3 6.1 ± 5.8
5.6 ± 4.3 4.7 ± 2.8
8.5 ± 4.9 8.6 ± 6.2
5.9 ± 4.5 5.9 ± 5.1
7.1 ± 5.2
16.2 ± 9.7
Obsession
8.0 ± 5.1 P = 0.014 (1) 10.3 ± 7.8
7.9 ± 5.0
13.0 ± 4.9
Sensitivity
10.3 ± 8.3
8.4 ± 6.7
14.3 ± 6.5
Depression
9.9 ± 8.2 P = 0.0402 (1) 7.9 ± 4.9 P = 0.0183 5.1 ± 3.7
7.4 ± 6.6
17.6 ± 9.5
6.4 ± 5.7
14.0 ± 7.0
3.3 ± 3.1
9.3 ± 6.9
3.2 ± 3.6
8.3 ± 5.4
Paranoia
3.9 ± 2.4 P = 0.0137 (1) 5.1 ± 3.8
4.1 ± 3.4
8.8 ± 6.9
Psychoticism
4.8 ± 5.5
2.7 ± 3.8
9.7 ± 6.6
6.5 ± 6.0 P = 0.0001 (2) 7.6 ± 6.9 P = 0.0148 (2) 7.1 ± 6.2 P = 0.001 (2) 7.4 ± 7.4 P = 0.0003 (2) 6.3 ± 6.7 P = 0.0011 (2) 3.2 ± 2.9 P = 0.00001 (2) 2.8 ± 3.6 P = 0.0001 (2) 3.4 ± 3.7 P = 0.0007 (2) 3.2 ± 4.7 P = 0.0004 (2)
69.6 ± 54.2
50.8 ± 38.0
99.9 ± 54.0
SCL-90 Somatization
Anxiety Aggression Phobia
Total score
48.3 ± 41.6 P = 0.0009 (2)
Note. LF/A, Left-sided focus and alexithymic; LF/NA, left-sided focus and nonalexithymic; RF/A, right-sided focus and alexithymic; RF/NA, right-sided focus and nonalexithymic. Comparisons were made between LF/A and RF/A (1) and between RF/A and RF/NA (2). Statistically significant differences are followed by P values.
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[17] Parker JDA, Taylor GJ, Bagby RM. Alexithymia and the recognition of facial expressions of emotions. Psychother Psychosom 1993;59:197–202. [18] Lane RD, Sechrest L, Reidel R, Weldon V, Kazniak A, Schwartz GE. Impaired verbal and nonverbal emotion recognition in alexithymia. Psychosom Med 1996;58:203–10. [19] Bewley J, Murphy P, Mallows J, Baker GA. Does alexithymia differentiate between patients with nonepileptic seizures, patients with epilepsy, and nonpatient controls? Epilepsy Behav 2005;7:430–7. [20] Derogatis LR, Lipman R, Covi L. SCL-90: an outpatient psychiatric rating scale: preliminary report. Psychopharmacol Bull 1973;9:13–28. [21] Derogatis LR, Cleary PA. Confirmation of the dimensional structure of SCL-90: a study of construct validation. J Clin Psychol 1977;33:981–9. [22] Annett M. A classification of hand preference by association analysis. Br J Psychol 1970;61:303–21. [23] Bagby RM, Taylor GJ, Ryan D. The measurement of alexithymia: psychometric properties of the Schalling–Sifneos Personality Scale. Compr Psychiatry 1986;27:287–94. [24] Bagby R, Taylor G, Parker J. Cross-validation of the factor structures of the Toronto Alexithymia Scale. J Psychosom Res 1990;34:47–51. [25] Feinstein AR. Principles of medical statistics. Boca Raton, FL: Chapman & Hall/ CRC; 2002. [27] Brackenbridge CJ. Secular variation in handedness over ninety years. Neuropsychologia 1981;19:493–508. [28] Dobrochotova TA, Bragina NP. The left-handed persons. Moscow: Kniga; 1994 [in Russian]. [29] Spalletta G, Pasini A, Costa A, et al. Alexithymic features in stroke: effects of laterality and gender. Psychosom Med 2001;63:944–50. [30] Rolls ET. The brain and emotion. New York: Oxford University Press; 1999. p. 257. [31] Astvatsaturov MI. The handbook of neurological diseases. Moscow: Medgiz; 1939 [in Russian]. [32] Geschwind N, Galaburda A. Cerebral lateralization: biological mechanisms, associations and pathology. I. A hypothesis and program for research. Arch Neurol 1985;42:428–59. [33] Geschwind N, Galaburda A. Cerebral lateralization: biological mechanisms, associations and pathology. II. A hypothesis and program for research. Arch Neurol 1985;42:521–52.
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Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Handedness, alexithymia, and focus laterality as risk factors for psychiatric comorbidity in patients with epilepsy Vladimir V. Kalinin *, Anna A. Zemlyanaya, Oleg E. Krylov, Elena V. Zheleznova Department of Brain Organic Disorders and Epilepsy, Moscow Research Institute of Psychiatry, Ministry of Health and Social Development, Moscow, Russian Federation
a r t i c l e
i n f o
Article history: Received 16 November 2009 Revised 30 December 2009 Accepted 30 December 2009
Keywords: Temporal lobe epilepsy Comorbid psychiatric disorders Focus laterality Handedness Alexithymia SCL-90 constructs
a b s t r a c t The aim of the current study was to evaluate the effect of seizure lateralization, handedness, and alexithymia on psychopathology in patients with temporal lobe epilepsy. One hundred five patients were included in the study. The Hopkins Symptom Checklist—90 (SCL-90) and Toronto Alexithymia Scale (TAS-26) were used for psychopathological assessment of patients. Handedness was evaluated using Annett’s scale. Among the patients studied were 74 right-handers and 31 left-handers, and 25 alexithymic and 80 nonalexithymic persons. Left-sided foci were observed in 52, and right-sided foci in 53 persons. MANOVA was used for analysis of the interrelationship between nominal fixed factors (handedness, alexithymia, and focus laterality) and the dependent variables SCL-90, Hamilton Rating Scale for Depression, and Hamilton Rating Scale for Anxiety. MANOVA revealed that alexithymia exerts maximal effect on psychopathological variables, and maximal values of SCL-90 constructs were observed for persons with alexithymia/left-handedness and alexithymia/right-sided seizure focus combinations. Ó 2010 Elsevier Inc. All rights reserved.
1. Introduction Psychiatric comorbidities mainly in the form of affective and anxiety disorders seem to be the most frequent complications of epilepsy, particularly localization-related and temporal lobe epilepsy (TLE). Perini et al. have shown that patients with TLE have higher rates of affective and personality disorders compared with persons with juvenile myoclonic epilepsy [1]. Despite their frequent occurrence, about 8–50% among patients with epilepsy [2– 6], risk factors for the development of psychiatric disorders in TLE remain obscure and rather controversial. Flor-Henry was the first to show that depressive disorder in epilepsy occurs more frequently in patients with a right-sided focus, whereas psychoses with schizophrenic symptoms are attributed to a left-sided focus [7]. On the other hand, Kanner [6] and Manchanda et al. [8] rejected any relationship between side of focus and development of depression, whereas according to Schmitz [9,10], the opposite—depression in epilepsy occurs more frequently in patients with left temporal foci—is true. In addition, Schmitz stressed that a left temporal focus with hypofunction of the frontal lobes seems to be necessary for the development of interictal depression in epilepsy [9,10].
* Corresponding author. Address: Department of Brain Organic Disorders and Epilepsy, Moscow Research Institute of Psychiatry, Ministry of Health, Moscow 107076, Russian Federation. E-mail address: [email protected] (V.V. Kalinin). 1525-5050/$ - see front matter Ó 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2009.12.028
In a previous article, we reported that right-sided foci are associated with the development of depressive disorders, whereas leftsided foci, contrarily, are related to anxiety in TLE [12]. Obviously, that strict left/right foci dichotomy is not always enough to predict the precise type of psychopathology in TLE, as comorbid affective and anxiety disorders may equally develop irrespective of focus laterality. Moreover, some overlooked factors in addition to focus laterality may be important for the development of concomitant psychopathology in patients with epilepsy. Sensory and motor asymmetries seem to be examples of such poorly appreciated variables in neuropsychiatry. In this context, left-handedness and ambidexterity are thought to be phenomena that complicate neuropsychiatric assessment, and all left-handed and ambidextrous patients, as a rule, are intentionally withdrawn from such studies. Such an approach has certain limitations because interesting data are eliminated from further analysis, and results on cerebral organization of motor functions are not taken into account. Left-handedness itself seems to represent one pole in the neuropsychological continuum of Homo sapiens, where right-handedness occupies the other pole, and ambidexterity lies between these two poles. This continuum in handedness is thought to depict gradual changes in sensorial and motor function in human brain, and may be one of the factors that influence mental properties and psychic phenomena. Moreover, the exact interaction between focus laterality and handedness remains rather obscure. The term alexithymia, coined in 1972 by Sifneos [13], implies an inability to recognize and differentiate subtle emotional states combined with concrete thinking directed to the nearest surroundings
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and a paucity of dreaming and fantasies. Alexithymia is regarded as a constellation of personality traits that predispose to the development of psychosomatic and affective disorders. At least two neuropsychological models of alexithymia have been proposed to date. According to the first model, alexithymia is thought to be the result of reduced interconnections between the right and left hemispheres and, subsequently, interruption of the normal flow of information. In other words, alexithymia represents a state of ‘‘functional commissurotomy,” as was supposed by Hoppe et al. [13–16]. According to the second model, alexithymia is associated with a diminished ability to recognize facial expressions of basic emotions that is linked to dysfunction of the right hemisphere [17,18]. Despite the fact that these theoretical speculations are well known, there have not yet been any studies on possible relationships between alexithymia and epilepsy, except for that by Bewley et al. [19], although in that study patients with epilepsy and those with nonepileptic seizures and normal controls could not be distinguished based on the Toronto Alexithymia Scale (total score) [19]. In addition, to date, data on possible associations between alexithymia and psychopathological phenomena, in particular anxiety and depression, in patients with epilepsy have also been lacking. The principal aim of the current study was to find possible associations between motor lateralization (handedness), focus laterality, and alexithymia as risk factors for the development of psychopathological disorders in patients with localization-related forms of epilepsy.
2. Material and methods The study was carried out on 105 patients with TLE, 37 men and 68 women. The female preponderance in this group might be explained by the high proportion of females among persons admitted in the Department of Brain Organic Disorders and Epilepsy in which the current study was carried out, and intentional bias in patient selection was avoided. All consecutive cases within a 1-year period (May 2008–April 2009) were included. Symptomatic epilepsy was diagnosed in 40 patients, cryptogenic epilepsy in 53 patients, and idiopathic TLE in 12 patients. Focus laterality was determined strictly by the visual EEG method; data on ictal semiology were not taken into account. Left-sided foci were detected in 52 patients (15 men, 37 women), and right-sided foci in 53 patients (22 men, 31 women). MRI was used to verify diagnosis and, among those with symptomatic epilepsy, revealed mesiotemporal sclerosis in 26 patients and posttraumatic cysts in 14 cases. Here it should be stressed that MRI data were intentionally not included in further analysis, because the influence of structural brain pathology on psychopathology and handedness represents an independent issue, which must be the subject of further research. All patients were evaluated by psychiatrists to establish a psychiatric diagnosis. ICD-10 criteria were used for these purposes. In line with these criteria, the following disorders were diagnosed: (1) Organic Affective Disorder (F06.3) (24 patients), (2) Organic Anxiety Disorder (F06.4) (48 patients), and (3) Interictal Dysphoric Disorder (33 patients). For the assessment of depression and anxiety, the Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) respectively were used. For assessment of other psychopathological symptoms, the Hopkins Symptom Checklist—90 (SCL-90) scale was completed by the patients themselves [20,21]. Raw data from the SCL-90 were then transformed into nine constructs that were included in the final analysis of the interaction between affective and anxiety syndromes. In accordance with SCL-90 design, the nine constructs
are: Somatization, Obsessive–Compulsive, Interpersonal Sensitivity, Depression, Anxiety, Hostility, Phobic Anxiety, Paranoid ideation, and Psychoticism [20,21]. For the assessment of handedness, Annett’s scale was used [22]. Persons whose global Annett’s scale score was lower than 5 points were regarded as left-handers, and those whose score exceeded +5 points, as right-handers. Among all patients studied, 74 were considered right-handers (mean ± SD = 19.2 ± 6.0) and 31 left-handers ( 11.2 ± 10.9). The observed high proportion of lefthandedness among the patients studied (30%) raises a question on selection bias. This question is answered in the Discussion. The Toronto Alexithymia Scale (TAS-26) [13,23,24] was used to assess alexithymia. This scale consists of 26 items, and each item can be scored from 1 to 5 points. The TAS-26 global score ranges from 26 to 130 points. All patients whose global TAS-26 score exceeded 74 points were regarded as alexithymic. The mean average TAS-26 score in the nonalexithymic group (N = 80) was 58.5 ± 11.5, and in the alexithymic group (N = 25), 80.0 ± 4.8 points. 2.1. Statistics All data were statistically processed with the SPSS Version 11 program on a personal computer. For the first step, Student’s t test was used to assess differences in psychopathological variables (SCL-90, HAM-D, and HAM-A scores) in right-handers versus lefthanders, in alexithymic versus nonalexithymic patients, and in patients with a left-sided focus versus those with a right-sided focus. In the final step, MANOVA was used to analyze the interrelationship between nominal independent variables (fixed factors) and dependent quantitative variables. MANOVA represents a variant of multivariate analysis that is widely used to assess the influence of certain nominal variables (fixed factors) on variance of quantitative dependent variables. That analysis, estimating the variance, allows a single simultaneous comparison of three or more groups. The result becomes a type of screening test that indicates whether at least one group differs significantly from the others [25]. In addition, the interrelationship between nominal fixed factors and its influence on dependent variables may be revealed. MANOVA was chosen because this test has many advantages in comparison with the widely used t or z test [25], although each is designed to find possible discrepancies between the groups being compared; MANOVA is able to reveal discrepancies between groups that cannot be detected with t tests [25]. The variables handedness, alexithymia, and focus laterality of epilepsy were selected as independent factors. The nine constructs of the SCL-90, mentioned earlier, were considered dependent variables. In the current study, intentional selection of certain variables for purposes of analysis was avoided. The a priori hypothesis was that there should exist certain interrelationships between handedness, focus laterality, and alexithymia, on the one hand, and psychiatric syndromes, on the other hand. 3. Results The main results are summarized in the tables. In Table 1, psychopathological variables are compared between persons with leftsided foci and those with right-sided foci. As can be seen there were no significant differences. In Table 2, psychopathological variables are compared relative to handedness. Here it can be seen that left-handed and righthanded persons differ statistically significantly on three variables: Somatization, Depression, and SCL-90 total score. Principally, righthanded patients scored higher on these variables, and it can be concluded that right-handed patients with epilepsy usually experience more severe psychopathological symptoms compared with
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left-handed patients. In addition to the variables mentioned, a trend toward differences was also observed for Sensitivity (P = 0.06) and Anxiety (P = 0.07). In both cases, right-handed patients scored higher than left-handed patients. Table 3 summarizes the data on comparison of psychopathological variables in alexithymic and nonalexithymic patients, and statistically significant differences on all variables except the HAM-A score were observed. Principally, compared with nonalexithymic
Table 1 Comparison of psychopathological variables in patients with left-sided and rightsided foci. Variable
Left-sided focus (N = 52)
Right-sided focus (N = 53)
Significance
HAM-D HAM-A
6.70 ± 5.91 5.08 ± 3.87
6.49 ± 4.66 6.47 ± 5.45
N.S. N.S.
SCL-90 Somatization Obsession Sensitivity Depression Anxiety Aggression Phobia Paranoia Psychoticism
7.37 ± 5.11 8.59 ± 5.94 8.96 ± 7.17 8.09 ± 7.05 6.80 ± 5.44 3.80 ± 3.36 3.43 ± 3.29 4.37 ± 3.52 3.30 ± 4.36
8.72 ± 8.02 8.79 ± 6.85 8.70 ± 6.90 9.70 ± 8.93 8.04 ± 7.42 4.60 ± 4.84 4.08 ± 4.63 4.60 ± 5.07 4.70 ± 5.81
N.S. N.S. N.S. N.S. N.S. N.S. N.S. N.S. N.S.
56.11 ± 43.41
59.98 ± 49.27
N.S.
Total score
Table 2 Comparison of psychopathological variables in left-handed and right-handed patients. Variable
Left-handed patients (N = 31)
Right-handed patients (N = 74)
Significance
HAM-D HAM-A
5.42 ± 4.81 5.00 ± 4.25
7.05 ± 5.22 6.14 ± 4.91
N.S. N.S.
SCL-90 Somatization Obsession Sensitivity Depression Anxiety Aggression Phobia Paranoia Psychoticism
5.90 ± 5.29 7.13 ± 6.18 6.87 ± 6.66 6.52 ± 7.72 5.61 ± 5.99 3.68 ± 5.52 3.00 ± 4.17 4.03 ± 5.28 3.32 ± 5.22
9.15 ± 7.09 9.26 ± 6.24 9.61 ± 6.89 9.86 ± 7.90 8.11 ± 6.52 4.39 ± 3.40 4.05 ± 3.85 4.69 ± 3.87 4.34 ± 5.07
P = 0.024 N.S. P = 0.06 P = 0.049 P = 0.07 N.S. N.S. N.S. N.S.
42.23 ± 47.25
63.93 ± 43.88
P = 0.026
Total score
Note. Statistically significant differences are marked in boldface.
Table 3 Comparison of psychopathological variables in nonalexithymic and alexithymic patients. Variable
Nonalexithymic patients (N = 80)
Alexithymic patients (N = 25)
Significance
HAM-D
5.81 ± 4.28
9.00 ± 6.76
P = 0.006
HAM-A Somatization Obsession Sensitivity Depression Anxiety Aggression Phobia Paranoia Psychoticism
5.34 ± 4.20 7.03 ± 5.66 7.70 ± 5.92 7.34 ± 6.35 7.40 ± 6.84 6.29 ± 6.03 3.26 ± 2.94 3.03 ± 3.45 3.76 ± 3.53 3.08 ± 4.23
7.28 ± 6.00 11.92 ± 8.54 11.6 ± 6.56 12.2 ± 7.62 13.6 ± 9.48 10.84 ± 6.62 7.12 ± 5.80 6.04 ± 4.62 6.84 ± 5.68 7.12 ± 6.42
P = 0.07 P = 0.001 P = 0.006 P = 0.002 P = 0.005 P = 0.002 P = 0.003 P = 0.005 P = 0.002 P = 0.006
84.16 ± 55.20
P = 0.006
Total score
49.20 ± 39.20
Note. Statistically significant differences are marked in boldface.
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patients, alexithymic patients are characterized by higher SCL-90 construct and HAM-D scores. The main results of the MANOVA are summarized in Table 4, and as can be seen, the three factors studied influence psychopathological variables differently. Thus, alexithymia is thought to be the factor with maximum effects on all psychopathological variables. Noteworthy, alexithymia itself exerts maximum influence on each variable, and the g2 values for alexithymia were the highest among all the fixed factors studied, implying that alexithymia itself determines the appearance of all psychopathological symptoms in patients with epilepsy. On the other hand, focus laterality and handedness had lesser influence. This may be due to the smaller number of dependent variables: three for focus laterality (Aggression, Phobia, Paranoia) and two for handedness (Aggression and Paranoia). In addition, the effects of focus laterality and handedness as assessed with g2 values also were much smaller than the influence of alexithymia alone. Moreover, interactions between alexithymia and the other factors, if they were present, had less influence on dependent psychopathological symptoms compared with alexithymia alone. Here it should be stressed that the alexithymia score itself does not depend on either handedness or focus laterality, implying the independence of these three factors from each other, although they could interact to influence dependent psychopathological variables. The mean values of the psychopathological variables under the influence of the three fixed factors are listed in Tables 5 and 6. In Table 5 are listed the mean values of dependent psychopathological variables under the influence of handedness and alexithymia/ nonalexithymia. As can be seen, the maximum values of some variables were observed in alexithymic patients with left-handedness, whereas the minimum values were observed in left-handed but nonalexithymic patients. Right-handed patients were, as a whole, characterized by intermediate values of dependent psychopathological items irrespective of whether they were alexithymic or nonalexithymic. Notably, comparison of alexithymic left-handers with nonalexithymic left-handers revealed statistically significant differences on most of the variables including HAM-D and all SCL-90 constructs except Somatization. Table 6 lists the mean values of the dependent psychopathological items under the influence of focus laterality and alexithymia/ nonalexithymia. From this table it can be concluded that the maximum values of SCL-90 constructs were seen in patients with rightsided foci and alexithymia, whereas the minimum values were observed in nonalexithymic patients with right-sided foci. The patients with left-sided foci were, as a rule, characterized by intermediate values of SCL-90 constructs irrespective of the presence or absence of alexithymia. Comparison of alexithymic patients with a right-sided focus with nonalexithymic patients with a right-sided focus, on the one hand, and with alexithymic patients with a leftsided focus, on the other hand, revealed statistically significant differences.
4. Discussion Research on the significance of some basic epilepsy characteristics, that is, seizure semiology, seizure frequency and types, and antiepileptic drugs, as potential risk factors for the development of certain psychiatric comorbidities remains rather controversial and has not led to a definite conclusion. This implies that the basic variables cited are not sufficient to explain properly the development of certain psychiatric comorbidities in epilepsy. The current study seems to be the first in which handedness, alexithymia, and focus laterality have been evaluated in terms of
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their individual and joint influence on psychopathological symptoms in patients with epilepsy. The study may be criticized for its lack of a control group (patients without epilepsy) for comparison of the prevalence of alexithymia and handedness in persons with epilepsy. Nevertheless, the principal aim of the study was evaluation of the interaction of three different neurobiological factors on expression of different psychopathological variables strictly in patients with epilepsy. Although data on the prevalence of left-handedness in epilepsy were not within the principal aim of the carried study, the high proportion of left-handedness in patients with epilepsy (30%) obtained should be explained, as it could be interpreted to be the result of bias in patient selection. Here it should be stressed that according to data of other authors, the prevalence of left-handedness in the general population is about 11.2% in Holland [28] and 13% in Australia and New Zealand [27]. In Russia, similar data have been obtained, as left-handedness occurs in 10% of the general population [28]. On the other hand, the proportion of left-handedness in persons with epilepsy is thought to be higher, 1.6- to 2.0-fold that of the general population [28]. This implies that nearly 20% of persons with epilepsy could be left-handed. Our results indicate that the proportion of left-handedness in epilepsy is 30%. Obviously, this may be partly explained by our desire to include in the study the maximal number of patients with left-handedness so as to obtain a cohort size sufficient for comparison purposes. In other words, a bias in patient selection, if it really existed, could not be seriously exaggerated because of the objective high proportion of left-handedness among patients with epilepsy. Results of the present study have shown that some personality and neurobiological variables in patients with epilepsy are related to certain psychopathological disorders and could be used to predict psychiatric comorbidity, mainly affective and anxiety states. Alexithymia itself represents the strongest personality construct among the factors studied that influence psychopathological variables in epilepsy. On the other hand, focus laterality and handed-
ness individually had much less influence, and these factors could not completely explain the occurrence of psychopathological symptoms. Moreover, the data obtained might, at first glance, be seen as controversial and rather paradoxical. Thus, based on the data in Table 2, it could be concluded that right-handed patients with epilepsy are characterized by greater severity of some psychopathological variables (depression, somatization) compared with left-handers. However, this is not the case, as left-handed patients with high alexithymia scores had the maximum severity SCL-90 construct scores (Table 5). Obviously, alexithymia itself interacts with the other factors studied, and the results of such interactions may differ with respect to the psychopathology manifested. Thus, patients who were alexithymic and left-handed, on the one hand, or were alexithymic and had right-sided foci, on the other hand, scored the highest on most of the SCL-90 constructs. On the contrary, the minimum SCL90 construct scores were obtained by nonalexithymic left-handed patients and nonalexithymic patients with right-sided foci. In other words, alexithymia combined with left-handedness or with right-sided focus is thought to be a conditio sine qua non and risk factor for the development of psychopathological disorders in patients with epilepsy. Here it must be stressed that the effects of alexithymia, handedness, and focus laterality were not differentiated with respect to concrete SCL-90 constructs, and practically each SCL-90 construct could develop, and a plethora of psychopathological symptoms could result under their influence. The degree of alexithymia, in turn, depended on neither focus laterality nor handedness in the patients studied, implying that all three factors should be regarded as independent in terms of their origin, although their combination can explain the occurrence of psychopathological symptoms in patients with epilepsy. In this context it may be suggested that the effect of alexithymia is complementary to those of right-sided foci and left-handedness. The hypothesis that alexithymia originates as a result of pathology in the right hemisphere should be incorporated into the current discussion. Thus, patients with right hemisphere strokes are
Table 4 Results of MANOVA: Influence of different factors and their interaction on psychopathological variables. Variable
Focus
HAM-D
P = 0.958 g2 = 0.001 P = 0.150 g2 = 0.039
HAM-A SCL-90 Somatization Obsession Sensitivity Depression Anxiety Aggression Phobia Paranoia Psychoticism Total score
P = 0.194 g2°= 0.034 P = 0.996 g2 = 0.000 P = 0.588 g2°= 0.011 P = 0.108 g2 = 0.046 P = 0.074 g2 = 0.053 P = 0.0001 g2 = 0.206 P = 0.031 g2 = 0.07 P = 0.009 g2 = 0.095 P = 0.063 g2 = 0.056 P = 0.828 g2 = 0.004
Handedness
Alexithymia
P = 0.942
P = 0.001 g2 = 0.118 P = 0.017 g2 = 0.059
g2 = 0.000 P = 0.679
g2 = 0.002 P = 0.690
g2 = 0.002 P = 0.642
g2°= 0.002 P = 0.307
g2°= 0.011 P = 0.412
g2 = 0.007 P = 0.337
g2 = 0.010 P = 0.008
g2 = 0.073 P = 0.202
g2 = 0.017 P = 0.032
g2 = 0.048 P = 0.061
g2 = 0.036 P = 0.794
g2 = 0.001
P = 0.004 g2°= 0.084 P = 0.001 g2°= 0.117 P = 0.0001 g2 = 0.155 P = 0.0001 g2 = 0.200 P = 0.0001 g2 = 0.176 P = 0.0001 g2 = 0.396 P = 0.0001 g2 = 0.194 P = 0.0001 g2 = 0.265 P = 0.0001 g2 = 0.239 P = 0.0001 g2 = 0.153
Focus handedness
Focus alexithymia
Handedness alexithymia
Focus handedness alexithymia
P = 0.773
P = 0.682 g2 = 0.002 P = 0.317 g2 = 0.011
P = 0.016 g2 = 0.060 P = 0.097 g2 = 0.029
P = 0.873 g2 = 0.0001 P = 0.400 g2 = 0.007
P = 0.686
g2 = 0.005 P = 0.575
g2 = 0.012 P = 0.212
g2°= 0.032 P = 0.301
g2°= 0.025 P = 0.657
g2 = 0.009 P = 0.852
g2 = 0.003 P = 0.777
g2 = 0.005 P = 0.004
g2 = 0.109 P = 0.520
g2 = 0.014 P = 0.066
g2 = 0.056 P = 0.716
g2 = 0.007 P = 0.229
g2 = 0.031
P = 0.089 g2°= 0.030 P = 0.773 g2°= 0.001 P = 0.207 g2 = 0.017 P = 0.036 g2 = 0.045 P = 0.018 g2 = 0.058 P = 0.0001 g2 = 0.230 P = 0.007 g2 = 0.074 P = 0.0001 g2 = 0.122 P = 0.055 g2 = 0.038
P = 0.001 g2 = 0.105 P = 0.001 g2 = 0.108 P = 0.001 g2 = 0.104 P = 0.0001 g2 = 0.256 P = 0.002 g2 = 0.095 P = 0.0001 g2 = 0.199 P = 0.0001 g2 = 0.143
P = 0.273 g2°= 0.013 P = 0.336 g2°= 0.001 P = 0.609 g2 = 0.003 P = 0.701 g2 = 0.002 P = 0.352 g2 = 0.009 P = 0.0001 g2 = 0.0183 P = 0.732 g2 = 0.001 P = 0.029 g2 = 0.049 P = 0.799 g2 = 0.001
P = 0.580 g2 = 0.003
P = 0.011 g2 = 0.067
P = 0.185 g2 = 0.018
g2°= 0.002 P = 0.010
g2°= 0.068
Note. P = probability of null hypothesis; g2 = effect of studied factors on dependent variables; usually this parameter is equal to quota of variance caused by appropriate influence of fixed factor (factors) studied. All statistically significant values are marked in boldface.
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V.V. Kalinin et al. / Epilepsy & Behavior 17 (2010) 389–394 Table 5 Results of MANOVA: Mean values of dependent psychopathological variables for persons with different combinations of handedness and alexithymia. Variable
LH/A (N = 5)
LH/NA (N = 26)
RH/A (N = 20)
RH/NA (N = 54)
HAM-D
12.4 ± 6.0
8.2 ± 6.8
6.6 ± 4.5
HAM-A
9.2 ± 6.4
4.1 ± 3.2 P = 0.0001 (1) 4.2 ± 3.3 P = 0.013 (1)
6.8 ± 6.0
5.9 ± 4.5
SCL-90 Somatization
10.6 ± 5.4
12.3 ± 9.2
8.0 ± 5.8
Obsession
16.2 ± 8.3
10.5 ± 5.7
8.8 ± 6.4
Sensitivity
17.8 ± 9.1
10.8 ± 6.7
9.2 ± 7.0
Depression
19.6 ± 10.3
12. ± 8.9
9.0 ± 7.4
Anxiety
15.6 ± 8.6
9.7 ± 5.7
7.5 ± 7.8
Aggression
12.4 ± 9.3 9.0 ± 4.5
5.8 ± 3.9 P = 0.0195 (2) 5.3 ± 4.4
3.9 ± 3.1
Phobia Paranoia
12.4 ± 8.0 12.8 ± 6.9
5.5 ± 4.2 P = 0.0122 (2) 5.7 ± 5.6 P = 0.0234 (2)
4.4 ± 3.8
Psychoticism
5.0 ± 4.9 P = 0.028 (1) 5.4 ± 3.9 P = 0.0001 (1) 4.8 ± 3.4 P = 0.00001 (1) 4.0 ± 3.7 P = 0.00001 (1) 3.7 ± 2.8 P = 0.00001 (1) 2.0 ± 2.2 P = 0.00001 (1) 1.8 ± 3.0 P = 0.0001 (1) 2.4 ± 2.6 P = 0.00001 (1) 1.5 ± 1.9 P = 0.00001 (1) 28.9 ± 20.4 P = 0.0001 (1)
77.4 ± 46.1
59.0 ± 42.4
Total score
111.4 ± 83.8
3.6 ± 3.5
3.8 ± 4.8
Note. LH/A, left-handed and alexithymic; LH/NA, left-handed and nonalexithymic; RH/A, right-handed and alexithymic; RH/NA, right-handed and nonalexithymic. Comparisons were made between LH/A and LH/NA (1) and between LH/A and RH/A (2). Statistically significant differences are followed by P values.
usually characterized by a higher alexithymia score than patients with left hemisphere strokes [29]. Moreover, the right hemisphere is believed to be responsible for the origin and processing of negative emotions [30]. All SCL-90 constructs involve mainly negative feelings or states that are accompanied by negative emotions, such as depression, obsession, interpersonal sensitivity, anxiety, phobic anxiety, aggressiveness, and paranoid ideations, which can explain the greater severity of these syndromes in patients with epilepsy
with high alexithymia scores and right-sided foci. In other words, such poorly differentiated emotions can develop in persons with epilepsy who have a special predisposition in terms of right-sided focus, left-handedness, and alexithymia. Notably, the famous Russian neurologist M.I. Astvatsaturov described the emotional state called ‘‘dark basic feeling” [31]. Certainly, an analogy exists between Astvatsaturov’s ‘‘dark basic feeling” and the cluster of negative emotions in alexithymic patients with epilepsy in the current study. The existence of such a bundle of strictly negative emotions attributed to the right hemisphere seems to reflect ancient protective mechanisms in Homo sapiens that helped them to avoid danger. In this context, alexithymia can be considered an ancient and protective personality construct that has maintained its significance to the present. The real interaction mechanisms between alexithymia, lefthandedness, and right-sided foci in epilepsy with psychiatric comorbidity should also be considered. Unfortunately no plausible concept exists that could explain such mutual tropism. According to a hypothesis proposed by Geschwind and Galaburda, the right hemisphere is thought to be more conservative in terms of earlier development and plays an essential role in survival of H. sapiens [32,33]. In addition, the right hemisphere is thought to exert some influence on the left hemisphere, and this leads to retardation of left hemisphere maturation that, in turn, can cause left-handedness [32,33]. From this point of view, the brain of left-handers is not a simple mirror image of the brain of right-handers, but, rather, comprises two right and not properly matured hemispheres. This can explain the similarity of the interaction between alexithymia and left-handedness, on the one hand, to the interaction between alexithymia and right-sided focus, on the other hand, although this suggestion remains purely speculative and should be confirmed in a specific study. The results obtained may be used for the purpose of predicting concomitant psychopathological disorders in patients with epilepsy as psychiatric comorbid syndromes are thought to complicate the course and treatment of epilepsy itself. Further study/analysis of the origin of alexithymia/nonalexithymia in patients with epilepsy is required and could shed light on the pathogenesis of psychiatric disorders in epilepsy.
Table 6 Results of MANOVA: Mean values of dependent psychopathological variables for persons with different combinations of focus laterality and alexithymia. Variable
LF/A (N = 13)
LF/NA (N = 39)
RF/A (N = 12)
RF/NA (N = 41)
HAM-D HAM-A
9.5 ± 8.3 6.1 ± 5.8
5.6 ± 4.3 4.7 ± 2.8
8.5 ± 4.9 8.6 ± 6.2
5.9 ± 4.5 5.9 ± 5.1
7.1 ± 5.2
16.2 ± 9.7
Obsession
8.0 ± 5.1 P = 0.014 (1) 10.3 ± 7.8
7.9 ± 5.0
13.0 ± 4.9
Sensitivity
10.3 ± 8.3
8.4 ± 6.7
14.3 ± 6.5
Depression
9.9 ± 8.2 P = 0.0402 (1) 7.9 ± 4.9 P = 0.0183 5.1 ± 3.7
7.4 ± 6.6
17.6 ± 9.5
6.4 ± 5.7
14.0 ± 7.0
3.3 ± 3.1
9.3 ± 6.9
3.2 ± 3.6
8.3 ± 5.4
Paranoia
3.9 ± 2.4 P = 0.0137 (1) 5.1 ± 3.8
4.1 ± 3.4
8.8 ± 6.9
Psychoticism
4.8 ± 5.5
2.7 ± 3.8
9.7 ± 6.6
6.5 ± 6.0 P = 0.0001 (2) 7.6 ± 6.9 P = 0.0148 (2) 7.1 ± 6.2 P = 0.001 (2) 7.4 ± 7.4 P = 0.0003 (2) 6.3 ± 6.7 P = 0.0011 (2) 3.2 ± 2.9 P = 0.00001 (2) 2.8 ± 3.6 P = 0.0001 (2) 3.4 ± 3.7 P = 0.0007 (2) 3.2 ± 4.7 P = 0.0004 (2)
69.6 ± 54.2
50.8 ± 38.0
99.9 ± 54.0
SCL-90 Somatization
Anxiety Aggression Phobia
Total score
48.3 ± 41.6 P = 0.0009 (2)
Note. LF/A, Left-sided focus and alexithymic; LF/NA, left-sided focus and nonalexithymic; RF/A, right-sided focus and alexithymic; RF/NA, right-sided focus and nonalexithymic. Comparisons were made between LF/A and RF/A (1) and between RF/A and RF/NA (2). Statistically significant differences are followed by P values.
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