Epilepsy Research 177 (2021) 106784 Contents lists available at ScienceDirect Epilepsy Research journal homepage: www.elsevier.com/locate/epilepsyres Personality changes in patients suffering from drug-resistant epilepsy after surgical treatment: a 1-year follow-up study Elena Iurina a, *, Eva Bailles b, Mar Carreño c, d, e, Antonio Donaire c, d, e, Jordi Rumià c, d, Teresa Boget c, d, e, Núria Bargalló d, e, Xavier Setoain c, d, e, f, Pedro Roldan c, d, Estefanía Conde-Blanco c, d, e, María Centeno c, d, e, Luis Pintor c, d, e, g a Department of Psychiatry and Forensic Medicine, Autonomous University of Barcelona (UAB), Barcelona, 08007, Spain b Mental Health Service, Nostra Senyora de Meritxell Hospital, Andorra c Clinical Institute of Neurosciences, Hospital Clinic of Barcelona, Barcelona, 08036, Spain d Epilepsy Unit, Hospital Clinic of Barcelona, Barcelona, 08036, Spain e Biomedical Research Institute August Pi i Sunyer (IDIBAPS), Hospital Clinic of Barcelona, Barcelona, 08036, Spain f Biomedical Imaging Group, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 08034, Barcelona, Spain g Department of Medicine, University of Barcelona (UB), 08036, Barcelona, Spain A R T I C L E I N F O A B S T R A C T Keywords: Objective: To determine changes in dimensions of personality in a sample of patients suffering from drug-resistant Drug-resistant epilepsy epilepsy at the 1-year follow-up following surgery, compared to non-surgically treated controls. Refractory epilepsy Methods: We conducted a prospective comparative controlled study, including drug-resistant epilepsy surgery Epilepsy surgery candidates. Demographic, psychiatric, neurological, and psychological data were recorded. Presurgical and 12- Personality months follow-up evaluations were performed. Personality dimensions were measured by the NEO Five-Factor Inventory, Revised version (NEO-FFI-R), anxiety and depression symptoms were assessed by the Hospital Anx­ iety and Depression Scale (HADS: HADA-Anxiety and HADD-Depression), psychiatric evaluations were per­ formed using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) Axis-I disorders classification. Statistical analysis consisted of comparative tests, correlation analysis, and the stepwise multiple regression test (ANOVA). Results: A 1-year follow-up was completed by 70 out of 80 patients. Through the study, the surgical group decreased in neuroticism and increased in agreeableness. The controls increased in consciousness, and these changes were predicted by the earlier age of epilepsy onset and lesser score in HADD at the baseline. No per­ sonality changes were associated with seizure frequency. The presurgical evaluation concluded that both groups had no differences in demographic, psychiatric, or neurological variables with the only exception being for the number of seizures per month, which was higher in the surgical group. Psychiatric comorbidity in patients was associated with their higher degree of neuroticism and agreeableness at the baseline. Comparing control and surgical groups at the one-year follow-up, the agreeableness personality variable was higher in the surgical group, and as expected, HADS scores were higher in the control group, and seizure fre­ quency was also higher in the control group. Significance: Higher agreeableness was the most relevant difference in personality dimensions in patients who underwent surgical treatment compared with the non-surgical treatment group. After surgery patients decreased in neuroticism and increased in agreeableness scores. 1. Introduction % of patients with epilepsy who do not have an adequate response to antiepileptic pharmacotherapy (Kwan and Brodie, 2000). Drug-resistant Epilepsy is a common neurological disorder affecting more than 50 (or refractory) epilepsy is defined when attempts to choose an appro­ million people all over the world (Ngugi et al., 2011). There are about 30 priate drug treatment are unsuccessful after two different antiepileptic * Corresponding author. E-mail address: iurinaelena1990@gmail.com (E. Iurina). https://doi.org/10.1016/j.eplepsyres.2021.106784 Received 12 July 2021; Received in revised form 29 September 2021; Accepted 4 October 2021 Available online 7 October 2021 0920-1211/© 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). E. Iurina et al. Epilepsy Research 177 (2021) 106784 drug therapies and uncontrolled seizures continue (Kwan et al., 2010). a study group of drug-resistant epileptic patients, who underwent sur­ Drug-resistant epilepsy is associated with a high burden on health gical treatment, was compared with a control group consisting of pa­ care, patients’ low index of quality of life, and high comorbidity, espe­ tients suffering from drug-resistant epilepsy treated with antiepileptic cially with psychiatric diseases (Janson and Bainbridge, 2021; Hitiris drugs. Both groups were followed up to 1 year after being included in the et al., 2007). Surgery is the treatment of choice in the case of diagnosed study. drug-resistant epilepsy, and it aims to achieve a seizure-free outcome and improve the quality of a patient’s life (Duncan et al., 2006; Wiebe 2.2. Setting and participants et al., 2002). It is known that, compared to the general population, epileptic pa­ This research was conducted at the Hospital Clinic of Barcelona. The tients can exhibit specific features of personality; for instance, a high study was approved by the Hospital Ethics Committee. Subjects were level of aggression (Shehata and Bateh, 2009) and dysfunctional per­ recruited from the Epilepsy Unit of the Neurology Service, which re­ sonality patterns (Novais et al., 2019; Bear and Fedio, 1977). As for ceives referrals from the whole of Spain. non-pathological personality dimensions, epileptic patients can show a The general evaluation protocol consisted of the following points: all high level of neuroticism (Rivera Bonet et al., 2019) and a low level of participants signed informed consent; the patients were evaluated to openness to experience (Leong et al., 2019), compared to the general confirm the diagnosis of drug-resistant epilepsy according to the Inter­ population. national League Against Epilepsy protocol (Scheffer et al., 2017) and After analyzing personality changes in patients with drug-resistant were assessed for the possibility of surgical intervention. Patients with epilepsy following successful surgical treatment, the decrease in the one or more of the clinical conditions listed below were excluded from expression of pathological personality traits and the reductions of sub­ the current study: scales of neuroticism and organic psycho-syndrome were reported (Novais et al., 2019; Witt et al., 2008). Such pathological personality 1) history of serious medical pathology except for epilepsy; patterns such as social introversion, paranoia, psychasthenia, hypo­ 2) mental retardation: IQ < 70; chondriasis, and schizophrenia significantly decreased following surgi­ 3) presence of severe dementia previously diagnosed; cal treatment in patients suffering from drug-resistant epilepsy in 4) schizophrenia or other chronic psychosis; observational follow-up studies using the Minnesota Multiphasic Person­ 5) non-epileptic psychogenic seizures; ality Inventory (MMPI) (Meldolesi et al., 2007; Derry et al., 2002; Wachi 6) surgical intervention for control of previous epileptic seizures. et al., 2001; Meier and French, 1965). In contrast, some researchers revealed no personality changes in patients with epilepsy following Those, who met the inclusion criteria of the study, but had contra­ surgical treatment (Engman and Malmgren, 2012; King and Tranel, indications for surgery according to the Epilepsy Committee report, 2017). constituted the control group. Epileptic patients show higher neuroticism compared to the general population (Rassart et al., 2020), and some studies focused on this 2.3. Clinical assessments dimension. Some authors reported neuroticism did not change following surgery (Engman and Malmgren, 2012; Rose et al., 1996), but Witt with Demographic, clinical, psychiatric, and psychological variables were colleagues (Witt et al., 2008) demonstrated changes in some subscales of collected. Demographic data collection form included age, gender, ed­ this dimension in their research. A recent systematic review (Iurina ucation, occupation, and marital state. Clinical data consisted of infor­ et al., 2021), studied personality changes in patients with drug-resistant mation about the age of the epilepsy onset in months, etiology of epilepsy following surgical treatment, and came to the conclusion, that epilepsy, localization, and laterization of epileptogenic foci, type of some personality dimensions could change following surgery. These epileptic seizures, dichotomic measure of a number of seizures at the changes can differ according to the localization of the epileptogenic baseline (“5 or less per month” or “more than 5 per month”), and a area; for example, the insular resection group became more emotionally number of seizures per month in the last 6 months. Psychiatric evalua­ labile despite seizure freedom, compared to the temporal group who tions were performed by a psychiatrist, and they included DSM-IV Axis-I increased in lack of stamina scale (Hébert-Seropian et al., 2017). disorders and HADS – depression and anxiety scale. Evaluation of per­ Seizure freedom as an outcome of surgical treatment can influence sonality dimensions was performed by using NEO-FFI-R (Aluja et al., the existence of adaptive personality changes and their severity. 2005). The revised NEO-FFI (NEO Five-Factor Inventory) is a short Favourable personality changes can be seen from early follow-up as­ version of the NEO-PI-R (Revised NEO Personality Inventory) ques­ sessments even in patients who were not seizure-free, though further tionnaire and has 60 items (12 per domain) for self-assessing the five follow-ups showed that improvements after 1–2 years were specific to major personality dimensions: neuroticism, extraversion, openness to seizure-free patients. Taking into account that pathological personality experience, agreeableness, and conscientiousness. features are the result of a continuing interictal process and brain The patient must indicate his/her degree of agreement with the structure damage caused by epileptic activity or side effects of antiepi­ statement using a score from 0 to 4 from “total disagreement” to «totally leptic treatment (Hessen et al., 2007), it is expected that achieving agree» respectively. The minimum score for any domain is 0, and the seizure freedom may lead to changes in the severity of these personality maximum is 48. The average scores of each variable in the Spanish traits in patients and recovery from several psychiatric symptoms. population are: Neuroticism: Mean = 23.48, SD = 9.04; Extraversion: Reviewing current literature revealed a lack of studies to analyse Mean = 29.73, SD = 7.50; Openness to experience: Mean = 30.66, SD = changes in non-pathological personality features following surgery in 7.22; Agreeableness: Mean = 36.15, SD = 6.63; Conscientiousness: drug-resistant epilepsy. The present study aimed to evaluate the changes Mean = 33.38, SD = 7.66. Neuroticism is a disposition to experience in dimensions of personality using the NEO-FFI-R questionnaire in negative effects, such as anger, irritability, emotional instability, anxi­ drug-resistant epilepsy patients who underwent surgical treatment, ety, and depression. Extraversion is characterized by sociability, asser­ compared to a control group in one-year follow-up. tiveness, high activity level, positive emotions, and in search of stimulation. Openness trait involves being creative, curious, interested 2. Methods in new experiences and being emotionally and artistically sensitive. Agreeableness is the domain of emphatic emotion, expressing the ability 2.1. Design to help and cooperate for the well-being of society. Conscientiousness reflects the tendency to be responsible, strong willed, persistent, orga­ We carried out an observational, prospective cohort study, in which nized, goal-directed, and adherence to rules and ethical principles. 2 E. Iurina et al. Epilepsy Research 177 (2021) 106784 Anxiety and depressive symptoms were assessed by Hospital Anxiety test, and Spearman correlation analysis was run for all the independent and Depression Scale (HADS). The Spanish version of HADS was applied variables to reveal how they are initially associated with the personality for evaluating depression (HAD - D) and anxiety (HAD - A) (Herrero profile. The independent variables included age, gender, type of epi­ et al., 2003). It contains 14 items, 7 of which are for self-assessing the lepsy, location, laterality, etiology, age at epilepsy onset, HADS, and level of depression and 7 for anxiety. Every subscale should be scored by mental disorders (existence or absence: yes/no).To evaluate changes in the patient from 0 to 3 according to the severity of the item. Accordingly, psychological and psychiatric test results from baseline to 1-year follow- the patient can score from 0 to 21 points on each scale. More than 10 up, Student’s t-test, within-subjects Wilcoxon signed-rank test, and points out of 21 in every subscale is considered as a probable indicator of Spearman correlation tests were performed. Adjustments for multiple clinical anxiety or depression. tests were performed using the Games-Howell procedure. The clinician version of the Structured Clinical Interview for DSM-IV Those variables of personality test that reached statistical signifi­ (SCID-CV; Spanish version) (First et al., 1996) was used to assess DSM-IV cance in 1-year follow-up were introduced into stepwise multiple Axis-I disorders. We grouped psychiatric comorbidity into two clusters: regression analysis. Multiple regression was used to determine the “yes”/”no”. The following psychiatric conditions were evaluated: 1) contribution of each variable at the baseline on the changes in person­ affective disorders, including major depressive episodes, recurrent ality dimensions at the 1-year follow-up. Also, such data as seizure fre­ depression, dysthymic disorder, affective disorder due to a medical quency at the baseline, seizure frequency at the 1-year follow-up, and condition or substance disorder, adjustment disorder, and bipolar dis­ the variable reflecting changes in this item in pre/post follow-up period order; 2) anxiety disorders, including panic disorder, phobia, were included in the Spearman correlation tests to be compared with obsessive-compulsive disorder, posttraumatic stress disorder, and other variables indicating changes in personality dimensions. anxiety disorders; 3) schizophrenia or schizoaffective disorder and other psychosis; 4) eating disorders; 5) conduct disorder; and 6) substance use 3. Results disorder. Of 80 eligible patients, 70 completed the neuropsychiatric assess­ 2.4. Procedure ment at the 1-year follow-up, 28 underwent surgery, and 42 were not suitable for surgery (control group). In the intention to treat approach, All participants provided written informed consent at the time of no statistical differences in sociodemographic, clinical, or neuropsy­ their enrollment in the outpatient setting of the Epilepsy Unit. Drug- chiatric variables were revealed between patients who completed the resistant epilepsy was diagnosed according to the International League study and patients who were lost to 1-year follow-up (n = 10). Against Epilepsy protocol. Accepted patients were referred for admis­ sion to a neurology ward for a week evaluation. 3.1. Descriptive analysis at baseline and comparison between groups Clinical evaluation included video-electroencephalography (EEG) monitoring, a 3 - Tesla brain magnetic resonance with an epilepsy Sociodemographic, clinical, and neuropsychiatric variables at the protocol, functional magnetic resonance imaging (fMRI), positron baseline in the whole sample and the differences between groups are emission tomography scans to indicate the epileptogenic zone, neuro­ shown in Table 1. psychological tests, the psychiatric evaluation, and a psychological Given that we found the baseline differences in the number of sei­ evaluation through the NEO-FFI-R. Taking all these results into account zures at the basal time (per month), we analyzed this variable affection the committee board made a decision on the surgery suitability for every on the personality dimensions. Thus, in Table 2, we compared person­ patient. The epilepsy committee comprises neurologists, psychiatrists, ality dimensions according to the basal seizure frequency dichotomized, neurosurgeons, neuroradiologists, neuropsychologists, psychologists, and no differences between both groups were observed. Tables 3A and and nuclear medicine specialists. 3B presents the analysis of how personality dimensions were associated Those who had contraindications for surgical intervention formed with all the independent sociodemographic and clinical variables at the the control cohort. Surgical candidates were paired with the same time baseline. following patients, who composed the control group and underwent all assessment procedures at the same time interval respectively to the 3.2. Longitudinal analysis of one-year follow-up outcomes surgical intervention at the baseline and in 1 year after surgery. Non- surgical patients were maintained on a standard medication regimen Table 4 shows longitudinal changes in personality, mood, and during the follow-up period. The postoperative evaluation 1-year seizure frequency in the surgical and non-operated group through the following surgical treatment involved the following procedures: the study, as well as differences between groups at the one-year follow-up. psychiatric evaluation (HADS), the clinical psychology assessment Significant differences between basal and 1-year meanings in the sur­ (NEO-FFI-R), and a clinical interview to collect neurological data. gical group were observed in decreased neuroticism (Mean = 4.46, SD = 6.05, p = 0.001*), and increased agreeableness scores (Mean=-2.16, SD 2.5. Statistical analysis = 4.20, p = 0.011*). Conscientiousness increased in the control group through the 1-year follow-up: Mean=-2.36, SD = 4.71, p = 0.002*. Statistical analysis was performed using Version 22 of SPSS for The comparison of control and surgical groups revealed the only Windows and differences were considered significant at p < 0.05. significant difference in agreeableness personality variable, being higher Distributions of variables were examined by Shapiro-Wilk Test ac­ in the operated group (p = 0.007*). cording to our sample size and appropriate tests were applied for further The number of seizures diminished significantly in the surgical group analysis. only (Mean = 26.04, SD = 37.52, p = 0.000**). Differences were The intention to treat approach was carried out in order to see if the observed in the number of seizures per month comparing both groups of 10 drop-out patients were different from patients finishing the follow- patients at the one-year follow-up, with higher scores in the controls: up. A descriptive analysis of all variables was performed at the base­ z=-5.394, p = 0.000**. line. The group of controls and the surgical group were compared to We evaluated how the variable, reflected personality changes from detect initial differences between groups, using a Student’s t-test, the baseline to the 1-year after surgery, depended on the number of Pearson’s chi-square test, Mann–Whitney U test according to the type of seizures at the one-year follow-up and pre-post differences in seizures every variable and its distributions. When a difference was found, how it frequency: no statistically significant associations with these variables affected personality was examined using Kruskal-Wallis tests and Stu­ were observed either in the surgical group or the control group. dent’s t-test. Also, stepwise multiple regression (ANOVA), Student’s t- Table 5 demonstrates changes in mood and differences between 3 E. Iurina et al. Epilepsy Research 177 (2021) 106784 Table 1 Sociodemographic and clinical variables at baseline and differences between groups. Whole sample group Surgical group Control group Differences between surgical and control (n = 70) (n = 28) (n = 42) group, p-value % Mean SD % Mean SD % Mean SD Sociodemographic Age 36.94 10.93 35.00 8.49 38.24 12.22 0.195 Gender: 0.728 Women 55.7 53.6 57.1 Men 44.3 46.4 42.9 Education: 0.768 Basic education 45.7 46.4 45.2 Secondary education 37.1 39.3 35.7 Higher education 17.1 14.3 19 Occupation: 0.073 Inactive 28.6 14.3 38.1 Housewife/student 21.4 21.4 21.4 Active 50 64.3 40.5 Marital status: 0.519 Married 57.1 64.3 52.4 Separated/widowers 12.9 7.1 16.7 Single 28.6 28.6 28.6 No data 1.4 0 2.4 Neurologic 0.819 Idiopathic etiology 60.0 64.3 57.1 Type of seizures: 0.599 No seizures 1.4 0 2.4 Focal onset impaired awareness 50.0 57.1 45.2 seizures Other focal onset seizures 15.7 14.3 16.7 Unknown onset tonic- clonic seizures 20 14.3 23.8 Generalized seizures 10.0 14.3 7.1 Locus: 0.571 Temporal 57.1 64.3 52.4 Extratemporal 24.3 25.0 23.8 Unestablished 15.7 10.7 19 Hemisphere: 0.400 Right 44.3 42.9 45.2 Left 37.1 46.4 31 Bilateral 12.9 7.1 16.7 Unknown 1.4 0 2.4 Age (months) of epilepsy onset 193.6 180.34 139.57 120.77 229.62 204.46 0.068 Number of seizures at the basal time (per 21.11 35.71 26.04 37.52 17.83 34.52 0.040* month) Psychiatric assessment: Psychiatric comorbidity 37.1 50 12 HADS scale: HAD-Depression 3.93 3.41 4.59 4.09 3.49 2.86 0.308 HAD-Anxiety 6.59 3.52 7.16 3.87 6.18 3.21 0.203 Clinical psychology assessment NEO personality: Neuroticism 25.53 6.85 26.66 6.90 24.78 6.77 0.254 Extraversion 26.61 5.90 25.87 6.30 27.10 5.65 0.395 Openness to experience 27.55 6.27 27.46 6.51 27.60 6.19 0.923 Agreeableness 32.73 5.07 33.82 5.36 32.00 4.79 0.141 Conscientiousness 32.48 5.90 33.45 6.95 31.84 5.86 0.265 HADS scoring for each variable: Normal: 0–7; Borderline abnormal (borderline case): 8–10; Abnormal (case):11–21. The average scores of each NEO-FFI-R variable in the Spanish population are: Neuroticism: Mean = 23.48, SD = 9.04; Extraversion: Mean = 29.73, SD = 7.50; Openness to experience: Mean = 30.66, SD = 7.22; Agreeableness: Mean = 36.15, SD = 6.63; Conscientiousness: Mean = 33.38, SD = 7.66. surgical and control groups at the 1-year follow-up. HADA and HADD seizures at the one-year follow-up and pre-post differences in seizures scores were higher in the control group, comparing to the surgical group frequency: no statistically significant associations with these variables at the 1-year follow-up (p = 0.044* and p = 0.018* relatively for anxiety were observed either in the surgical group or the control group. and depression scores). The number of seizures diminished significantly in the surgical group only (Mean = 26.04, SD = 37.52, p = 0.000**). Differences were observed in the number of seizures per month 3.3. Predictive analysis from baseline variables to one-year follow-up comparing both groups of patients at the one-year follow-up, with outcomes higher scores in the controls: z=-5.394, p = 0.000**. We evaluated how the variable, reflected personality changes from The surgical group increased in neuroticism and agreeableness, the baseline to the 1-year after surgery, depended on the number of which was not predicted by any baseline variables of interest. The controls increased in consciousness; these changes were 4 E. Iurina et al. Epilepsy Research 177 (2021) 106784 Table 2 associated with seizure status. The most relevant features in our study Association of NEO-FFI personality dimensions and seizure frequency (intervals) were a decrease in neuroticism and an increase in agreeableness in the at the baseline (presurgical evaluation) in a 70 drug-resistant epilepsy patients’ surgical group through the follow-up, and higher agreeableness in the sample. surgical group compared with the control group one year after surgery. Seizure N of Mean SD Differences Decrease in neuroticism one year after surgical treatment in epileptic frequency patients between patients was presented in another study (Witt et al., 2008) with 151 groups, p-value epileptic patients, with a mean age of 37.1 years. However, the German 5 or less per 30 24.94 6.87 personality inventory was used for personality assessment in this case month instead of being performed with the NEO-FFI-R as we did. The German Neuroticism More than p = 0.532 5 per 40 25.98 6.88 personality inventory (Fragebogen zur Persцnlichkeit bei zerebralen Erk­ month rankungen) aims to identify behavioral and personality patterns in 5 or less per non-psychiatric patients with central nervous system disorders and ep­ 30 26.99 4.68 month ilepsy in particular. The scale of neuroticism corresponds to the identi­ Extraversion More than p = 0.634 cally named trait of the Big Five Personality Inventory, but includes 5 per 40 26.33 6.72 month some reflected pathological features subscales: vegetative symptoms, 5 or less per anxiety, somatization, hyperemotionality, reduced drive, obsession, and 30 26.37 6.36 Openness to month other-determination. Additionally, they reported on the personality More than p = 0.174 changes in seizure-free patients only. With reference to somatic and experience 5 per 40 28.43 6.14 psychic anxiety as items of the neuroticism-related scale, another study month 5 or less per (Engman and Malmgren, 2012) also found a decrease in these features 30 32.59 4.35 month evaluated by the Karolinska Scale of Personality in 57 epileptic patients, Agreeableness More than p = 0.846 with a mean age of the participants similar to ours, after surgical 5 per 40 32.83 5.59 treatment. These neuroticism-related subscales are quite similar to the month 5 or less per NEO - neuroticism item, but these items are part of a wider neuropsy­ 30 32.93 5.82 chological feature in the Karolinska Scale of Personality - from scales month Conscientiousness More than p = 0.589 related to neuroticism and anxiety proneness. Personality changes were 5 per 40 31.15 6.02 revealed in seizure-free patients only (Engel I). In another study (Rassart month et al., 2020) with 53 patients, and a mean age of 30 years the shortened Personality was not associated with the seizure frequency in our sample. Dutch version of the Big Five Inventory was used to evaluate personality. The Liverpool Seizure Severity Scale was used to assess seizure fre­ predicted by the earlier age of epilepsy onset and lower depression quency and severity. The association of a high level of neuroticism and a scores at the baseline (R2 = 27.8 %, p = 0.002, beta = - 0.363 and – low level of agreeableness with seizure frequency in epileptic patients 0.302 respectively). Also, the controls increased in HADS scores, which was detected in that research. In contrast, in our analysis, we found no was not predicted by any baseline variables of interest. association of these personality changes with the number of seizures per month neither pre- nor pre/post changes in seizure frequency variables. 4. Discussion Wachi et al. (2001) reported no differences between seizure-free and non-seizure-free groups in personality changes in a small sample of 26 It was revealed that personality traits in patients with drug-resistant epileptic patients following surgical treatment. But patients from the epilepsy change following surgical and pharmacological antiepileptic non-seizure-free group showed a reduction in seizure frequency of up to treatment at the 1-year follow-up, but in a different way depending on 90 % from a preoperative level. The authors applied the MMPI ques­ whether or not surgical treatment is carried out. This is the most tionnaire for personality assessment in their study and reported a important outcome of our study. These personality changes were not decrease in the scores of infrequency, hypochondriasis, psychasthenia, Table 3A Association of personality dimensions with neurological and sociodemographic variables at the baseline (presurgical evaluation) in a 70 drug-resistant epilepsy pa­ tients’ sample. Age Gender Etiology Type of Locus Hemisphere Age (month) of Number of seizures the (right vs left vs epilepsy onset at basal time (per seizures bilateral) month) Neuroticism Pearson F = 0.530t=- F = 0.108t = F= F= F = 0.366p = Correlation Correlation Correlation = 1.109df = 68p = 0.369df = 65p 1.535p = 0.310p = 0.695 coefficient = coefficient = 0.040p = 0.743 0.271 = 0.694 0.214 0.735 0.238p = 0.047* 0.074p = 0.543 Extraversion Pearson F = 1.753t=- F = 0.064t = F= F= F = 0.346p = Correlation Correlation Correlation=- 1.413df = 68p = 0.800df = 65p 0.745p = 0.282p = 0.709 coefficient=- coefficient=- 0.218p = 0.070 0.162 = 0.925 0.529 0.755 0.273p = 0.022* 0.038p = 0.755 Openness to Pearson F = 0.000t=- F = 0.025t = F= F= F = 0.504p = Correlation Correlation experience Correlation=- 0.806df = 68p = 1.017df = 65p 0.833p = 2.114p = 0.606 coefficient=- coefficient = 0.014p = 0.907 0.423 = 0.313 0.480 0.129 0.102p = 0.401 0.139p = 0.252 Agreeableness Pearson F = 0.256t=- F = 0.003t=- F= F= F = 3.898p = Correlation Correlation Correlation=- 2.383df = 68p = 1.467df = 65p 0.263p = 0.407p = 0.025* (R > L > coefficient=-0.59p coefficient = 0.106p = 0.382 0.020* (W > M) = 0.313 0.852 0.668 B) = 0.626 0.146p = 0.228 Conscientiousness Pearson F = 0.356t=- F = 0.029t = F= F= F = 0.880p = Correlation Correlation Correlation = 3.512df = 68p = 0.535df = 65p 0.819p = 0.835p = 0.420 coefficient=- coefficient=- 0.189p = 0.117 0.001** (W > M) = 0.595 0.488 0.439 0.029p = 0.810 0.039p = 0.750 W: women; M: men; R: right, L: left; B: bilateral. Age of the epilepsy onset, hemisphere of the epileptogenic focus, and gender were associated with personality in our sample. * p < 0,05. ** p < 0.001. 5 E. Iurina et al. Epilepsy Research 177 (2021) 106784 Table 3B frequency. We did not have a “seizure-free” group in our analysis: we Association of personality dimensions and mood and psychiatric comorbidity at indicated the number of seizures for every patient or 2 groups according the baseline (presurgical evaluation) in the sample of 70 drug-resistant epilepsy to the seizure frequency (“5 or less per month” and “more than 5 per patients. month”) for different statistical calculations. HAD- HAD-Anxiety Psychiatric In our research, the control group increased in consciousness at the Depression comorbidity (yes/no) one-year follow-up, which was predicted by an earlier age of epilepsy Neuroticism Correlation Correlation F = 0.297, t=-2.444, onset and lower depression symptoms measured by HADD at the coefficient = coefficient = df = 68, p = 0.017* baseline. 0.441 p = 0.000 0.528 p = 0.000 (Neuroticism is higher Consciousness is defined as an individual’s organization, persistence, ** ** in patients with psychiatric and motivation in achieving a goal (Roberts et al., 2009). Increase in this comorbidity) complex trait of character in a control group appears as an adaptive Extraversion Correlation Correlation F = 4.926, df = process and psychologically tackling disease-associated stress, which coefficient=- coefficient=- 38.674, t = 1.895, p = goes better in more emotionally stable individuals, who are less 0.501 p = 0.000 0.080 p = 0.518 0.066 depressed. ** Openness to Correlation Correlation F = 1.202, t = 0.228, Conscientiousness and agreeableness were significantly higher in experience coefficient=- coefficient=- df = 68, p = 0.821 women than in men at the baseline in our sample. We cannot completely 0.278 p = 0.022 0.141 p = 0.252 confirm or deny the idea of personality gender differences in epileptic * patients vs the general population, as there are different results reported Agreeableness Correlation Correlation F = 0.801, t=-2.357, in the literature. Some general population studies (Chapman et al., 2007; coefficient=- coefficient = df = 68, p = 0.021* 0.235 p = 0.054 0.095 p = 0.439 (Agreeableness is Costa et al., 2001) indicated women being higher in agreeableness and higher in patients with neuroticism scores than men; one research (Weisberg et al., 2011) re­ psychiatric ported on higher extraversion additionally to the features mentioned comorbidity) above. Nostro et al. (2017) reported that neuroticism and consciousness Conscientiousness Correlation Correlation F = 0.031, t=-0.008, coefficient=- coefficient = df = 68, p = 0.993 were higher in women than in men in the general population. According 0.101 p = 0.413 0.101 p = 0.411 to the research of Mac Giolla and Kajonius (2019) women typically score higher than men in all five trait factors in the general population. All the Psychiatric comorbidity and mood were associated with personality in our above-mentioned studies reported women being more neurotic than sample. * p < 0,05. men in the general population. However, this differs from our results ** p < 0.001. which revealed no significant gender differences in the neuroticism scores. It could be due to the fact that epilepsy is associated with and schizophrenia in patients following surgical treatment. Thus, the increased neuroticism in patients compared with the general population improvement in pathological personality traits can be observed even in regardless of gender (Rivera Bonet et al., 2019), so epileptic men become the case of reduction in seizure frequency, rather than complete seizure more neurotic compared with men without epilepsy. elimination. Agreeableness was lower in the bilateral epileptogenic foci locali­ These differences between our and other studies may occur due to zation subgroup in comparison to the right and left hemispheres. There the different inventories applied to assess personality and seizure are no personality differences between the right and left localized epi­ lepsy foci, which is in line with another epileptic patient’s study results Table 4 Changes in NEO-FFI-R dimensions and seizure frequency at the one-year follow-up in the surgical and control groups of drug-resistant epilepsy patients. Surgical group Control group Results Differences (basal-1 year) Results Differences (basal-1 year) Differences between groups, p-value Mean SD Mean SD p Mean SD Mean SD p NEO-FFI-R: Neuroticism 22.19 9.50 4.46 6.05 0.001** 23.97 9.05 0.81 7.42 0.484 0.433 Extraversion 27.37 6.62 − 1.49 6.83 0.258 27.27 7.08 − 0.16 4.72 0.826 0.954 Openness to experience 28.22 8.12 − 0.77 5.70 0.484 28.03 6.20 − 0.42 5.51 0.624 0.909 Agreeableness 35.98 5.27 − 2.16 4.20 0.011* 32.17 5.92 − 0.17 5.12 0.828 0.007* Conscientiousness 35.36 6.18 − 1.91 5.53 0.079 34.19 6.60 − 2.36 4.71 0.002* 0.460 Seizure frequency 0.96 2.99 26.04 37.52 0.000** 15.56 21.21 2.68 25.54 0.866 0.000** Personality and seizure frequency changed in both groups of patients at the 1-year follow-up. * p < 0,05. ** p < 0,001. Table 5 Changes in HADS at the one-year follow-up in the surgical and control groups of drug-resistant epilepsy patients. Surgical group Control group Results Differences (basal-1 year) Results Differences (basal-1 year) Differences between groups, p-value Mean SD Mean SD p Mean SD Mean SD p HADS scale: HAD-Depression 3.08 3.24 1.51 3.33 0.146 5.15 3.97 − 1.66 4.17 0.015* 0.018* HAD-Anxiety 5.60 4.42 1.56 4.14 0.072 7.73 4.42 − 1.55 3.64 0.010* 0.044* Control group increased in depression and anxiety levels at the 1-year follow-up. * p < 0,05. 6 E. Iurina et al. Epilepsy Research 177 (2021) 106784 (Leong et al., 2019). According to the results of two studies with healthy 6. Limitations participants, special anatomic areas were associated with high agree­ ableness: larger areas in the left superior temporal gyrus (Li et al., 2017) The main limitation of this study occurs due to the small sample size. or larger regional gray matter volume right orbitofrontal cortex (Kapo­ Due to ethical reasons the distribution for groups of surgical treatment giannis et al., 2013). Our research did not provide enough data for a or controls depended on patient suitability and was not randomized, detailed discussion on this topic, but it seems that anatomical and which could cause bias in our sample. Furthermore, one of the limita­ functional brain features in epileptic patients, who have bilateral tions of the study was the lack of an instrument which could inform localization of epileptogenic foci, can negatively influence about various pathological personality traits. Only through this assess­ agreeableness. ment (and consequent statistical analysis) could we talk about “normal/ Neuroticism and agreeableness were higher in patients with psy­ pathological” personality traits. There are instruments capable of chiatric comorbidities at the baseline in our research. The neuroticism measuring pathological personality, such as DAPP-BQ or NBI. domain presented a positive correlation with psychiatric symptoms in both mesial temporal lobe epilepsy related to hippocampal sclerosis in 7. Conclusion 100 patients and also in a study with 100 juvenile myoclonic epilepsy patients (Alonso et al., 2019). This study demonstrates that personality traits in patients with drug- Agreeableness dimension scores negatively correlated with psychi­ resistant epilepsy change following surgery at the 1-year follow-up. atric diseases in studies with non-epileptic participants: in a non-clinical Agreeableness was the most relevant difference between the surgical sample of 3147 subjects between 17 and 25 years old, who had a psy­ and control group, being higher in the former. chotic experience in the past (Shi et al., 2018); in 3785 patients between The surgical group became less neurotic and increased in agree­ 21 and 46 years old suffering from addictive disorders (Dash et al., ableness scores, while the control group increased in the consciousness 2019); and in a sample of 6140 patients with borderline personality scale, especially if a patient was young at the onset of epilepsy and was disorder (Distel et al., 2009). Our patients suffering from drug-resistant not depressed according to the baseline presurgical evaluation. The epilepsy showed a high level of agreeableness in the subgroup with changes in personality dimensions were not associated with the seizure psychiatric comorbidities, and this result does not correspond to the frequency, either at the baseline or at the follow-up. other non-epileptic studies, which evaluated the association of person­ ality and psychiatric disorders. Funding The most prevalent psychiatric comorbidity in epileptic patients associated with high neuroticism is mood disorders. Our sample showed This research did not receive any specific grant from funding that neuroticism was associated with higher HADS scores. The higher agencies in the public, commercial, or not-for-profit sectors. the neuroticism is, the more depressive and anxious the patient is; which is in line with many previous studies with both epileptic patients and healthy participants (Rivera Bonet et al., 2019; Lee et al., 2018; Kim Declaration of Competing Interest et al., 2016; Endermann and Zimmermann, 2009; Wilson et al., 2009). Extraversion and openness to experience personality dimensions were None of the authors has any conflict of interest to disclose. We negatively associated with depression scores in our research, which is in confirm that we have read the Journal’s position on issues involved in line with previous studies with healthy participants (Kim et al., 2016), ethical publication and affirm that this report is consistent with those and with neurologic diseases subjects (Magyar et al., 2017). guidelines. Our study shows the association between earlier onset of epilepsy and higher conscientiousness scores. 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