Functional seizures and binge eating disorder: A cross-sectional study

Objective: Functional seizures (FS) are brief, involuntary changes in behaviour or consciousness, distinct from epileptic seizures, potentially associated with psychological dissociation. Binge eating disorder (BED) was linked to psychological and somatic dissociation also. However, any connection between FS and BED is insufficiently explored. We aimed to assess BED prevalence in individuals with FS, anxiety/depression (AD)


Introduction
Functional seizures (FS) are paroxysmal changes, limited in time, in responsiveness, motor and sensory activity or behaviour which resemble several medical conditions, namely epileptic seizures, but are the result of complex neuropsychiatric dysfunctions [1].
Some authors [4] had identified several candidate mechanisms for FS, on the basis of diverse psychological theories: 1) FS as a manifestation of the breakdown of the integration of consciousness due to multimodal traumatic information dissociated from consciousness; 2) FS as stress-coping innate behavioural tendencies, similar to other defensive reactions; 3) FS as a physical manifestation of emotional distress which allow subjects to segregate the psychological origins of their affliction; 4) FS as learned behaviours maintained by operant conditioning and/or due to a secondary gain.
If interpreted as dissociative phenomena, FS may result in a breakdown in psychological integration due to separation or "dissociation" of traumatic experiences from awareness because of the anxiety associated with recalling them.According to this approach, FS are thought as sensorimotor flashbacks arising as acute response to threat, emotional distress and/or alteration in arousal [4].
In neurological settings, FS are often underdiagnosed or mistaken with epilepsy: barely 20 % to 40 % of patients receive a correct FS diagnosis, with a diagnostic delay estimated in about seven to nine years on average [5,6].A correct diagnosis is strictly dependent on specific diagnostic procedures and clinical expertise.According to ILAE Nonepileptic Seizures Task Force, a "gold standard" diagnosis is based on a history consistent with FS in the absence of epileptiform activity immediately before, during or after an event captured on ictal video-EEG with typical FS semiology [7,8].
Multicentre studies showed that patients with FS are 70 % women, other risk factors consisting in young age, economic and socio-cultural lower conditions, traumatic childhood experiences (including sexual, physical and psychological abuse and neglect), history of trauma and stressful life events, such as bereavement or illness [9,10].
Psychiatric comorbidities are very common in FS, such as other dissociative and somatoform disorders, functional or "medically unexplained" symptoms, depression and anxiety disorders, post-traumatic stress disorders (PTSD) and a high prevalence of personality disorders, especially borderline personality disorder (BPD) [11,12,13].
Given the high prevalence of these psychiatric manifestations in patients with FS, it is difficult to establish whether they represent comorbidities, predispositions, or underlying causes of FS.
According to DSM-5 [14], binge eating disorders (BED) is characterized by "recurrent (≥1 per week for 3 months), brief (≤2 h), psychologically distressing binging episodes, during which patients feel out of control and consume larger amounts of food than most people under similar circumstances, in the absence of regular compensatory behaviours to prevent weight gain".Binge eating episodes are also associated with eating rapidly, eating until feeling uncomfortably full, eating large quantities of food when not feeling physically hungry, eating alone because one feels embarrassed about how much one is eating, and feeling disgusted with oneself, depressed or guilty afterwards.
Several research observed that patients with BED report a history of trauma as childhood sexual and emotional abuse and elevated rates of depressive and dissociative symptoms [15][16][17][18].Indeed, many dissociative symptoms including identity fragmentation and/or possession experiences, dissociative escapes, episodes of derealization and depersonalization, dissociative stupor and trance, amnesia and memory losses are detectable in eating disorders including BED [19,20].
Both FS and BED are associated with somatic dissociation and high degrees of psychiatric comorbidity, trauma, and PTSD, however, any association between these disorders has been scarcely investigated [21,22].To date, only few case-reports and one retrospective study describe patients suffering from FS and eating disorders [22][23][24][25].
The primary objective of this multicentre, cross-sectional study is to evaluate the frequency of clinically manifest BED and of binge eating behaviour in three groups: people with FS, people with anxiety/ depression and healthy subjects.The decision to include patients with anxiety and depression was based on the high prevalence of these symptoms as a comorbidity in patients with FS.
We also aim to investigate the psychopathological profiles of individuals with FS in comparison with patients suffering from depression and/or anxiety (DA) and healthy subjects, and in particular to explore psychopathological risk factors for binge eating symptoms.

Participants
We recruited three different groups of participants: patients with FS (n = 48); patients with DA (n = 35) and healthy subjects (HS, n = 44).Patients with FS and patients with anxiety and depression disorders were engaged by the Regional Epilepsy Centre of Great Metropolitan Hospital of Reggio Calabria, the Department of Medical and Surgical Sciences "Magna Graecia" University of Catanzaro and the Department of Mental Health, AUSL Romagna, among out-patients requesting medical assistance, between February 2021 and December 2022.Healthy subjects were enrolled among health personnel, patients' companions and volunteers.Control sample was verified by psychiatrists through testing results of neuropsychiatric battery administered to all participants.
FS were diagnosticated by physicians (neurologists and psychiatrists) with experience in epilepsy and functional disorders, according to the latest ILAE guidelines.In particular, all FS patients underwent a video-EEG recording of a typical episode, that documented the absence of paroxysmal abnormalities during and after the episode.The diagnosis of BED, depressive and anxiety disorders was posed by psychiatrists according to DSM-5 criteria [14].
Included patients were over 18 years of age and received FS or depressive and/or anxiety disorders diagnosis for the first time.Exclusion criteria comprised previous history of epilepsy, serious medical conditions, drug or alcohol abuse in the last 3 years, use of anti-seizure medications, anti-depressants, antipsychotics or any medications known to induce alterations in eating behaviour.
All patients from the epilepsy centre with FS were included; possible comorbidity of anxiety and depressive disorders were diagnosed at the enrolment by psychiatrists according to DSM-5.
Participants were informed of all the procedures and signed an informed consent form prior to participation in the study.All procedures were approved by ethics committees of participant centres and conformed to the standards set by the Declaration of Helsinki.

Instruments and procedure
For all participants, we collected a series of personological and psychopathological data such as the presence of binge eating, anxiety and mood disorders, attitudes towards food and the tendency to eat compulsively, specific aspects and traits of the personality and the frequency to experience mental dissociation.All the participants filled out the several clinical instruments independently for about an hour and a half, the clinician was available for any doubts or clarifications.

Binge eating scale (BES)
The BES [26] was originally developed to identify binge eaters within an obese population.It consists of 16 items evaluating the behavioural manifestations, feelings and thoughts regarding a binge episode.Total score is determined by summing up the 16 items and it can range between 0 and 46.A cut-off point of ≥ 18 is used in the literature to indicate the possible presence of BED, with scores ≤ 17 considered as non-bingeing, 18-26 moderate bingeing, and > 27 severe bingeing [27].The BES have exhibited a good test-retest reliability (r = 0.87, p < 0.001) and a moderate association with binge eating symptoms severity (r = 0.20-0.40,p < 0.05) [27,28].

Personality inventory Disorder-5 (PID-5)
The Personality Inventory for DSM-5 (PID-5) [29] is a 220-item selfreport questionnaire aimed to assess maladaptive personality features according to the DSM-5 Section III model of personality psychopathology.Items are rated on a 4-point Likert scale (0 = very false or often false to 3 = very true or often true).The inventory includes 25 first-order facets that can be grouped into five second-order domains: Negative Affect, Detachment, Antagonism, Disinhibition, and Psychoticism.Internal consistencies have been found to be generally good.

Dissociative experiences scale-II (DES-II)
The DES-II [30,31] is a self-administered 28-item questionnaire based on DSM dissociation characterization.It measures dissociative experiences in daily life related to depersonalization, derealization, amnesia, and absorption.Each item is answered on a Likert-type scale ranging from 0 %, meaning never, to 100 %, meaning always.The total DES-II score is the mean of all 28 items scores.DES-II has good reliability and validity and a strong ability to identify dissociative disorders in a patient population (test-retest = 0.79 < r < 0.84; split-half = 0.83 < r < 0.93; Cronbach's α = 0.95) [31].

Beck depression inventory (BDI-2)
BDI-2 [32] is a 21-item self-report measure of attitudes and symptoms of depression over the previous 2-week period.Each symptom is applicable on a 3-point Likert scale from 0 (absence of symptom) to 3 (intense presence of symptom), with a possible range of 0 to 63.Higher scores indicate greater symptom severity, scores of 0-13 indicate minimal depression, 14-19 mild, 20-28 moderate and 29-63 severe depression.BDI-2 has an excellent test-retest reliability and high criterion validity [32,33].

State-trait anxiety inventory (STAI)
The STAI [34] is a 40-items self-administered assessment scale developed to measure an individual's tendency to experience somatic, affective, and cognitive aspects of anxiety.The STAI yields two different scores, one represents a temporary condition of state anxiety, the other one a more general and long-standing quality of trait anxiety.STAI has an elevated construct validity and present high test-rest reliability [35].

Statistical analysis
Data were analysed using SPSS version 28.0 (IBM Corp., Armonk, NY, USA) for all statistical procedures.Continuous data were presented as mean ± standard deviation or as median and interquartile range, depending on data distribution.Dichotomic data were presented as percent frequency.The Fisher's exact test was used to compare proportions for dichotomic variables in the groups.ANOVA F test with Tukey post-hoc tests and Welch's procedure with Games-Howell posthoc tests were used for analysis of variance for continuous variables with equal and non-equal variance, respectively (Levene's test of equality of variances was performed).Kruskal-Wallis test and post-hoc tests (Dwass-Steel-Critchlow-Fligner test) were used for comparisons between non-normally distributed data (normally distributed data were evaluated with Shapiro-Wilk test).Significance values have been adjusted by the Bonferroni correction for multiple tests.In the whole study sample as well as in patients with DA and FS, the relationship between clinical binge eating attitudes (dependent variable) and the other clinical variables was tested by univariable and multivariable logistic regression analysis.A p value < 0.05 was considered statistically significant, all tests were two-tailed.

Socio-demographical data
Relevant demographic data are reported in Table 1.The three groups were homogeneous in terms of age, whereas AD and FS groups showed a female preponderance as compared with HS.Compared with HS, FS people had lower level of education and higher rates of unemployment in addition to several psychiatric comorbidities such as depression, anxiety, dissociative and personality disorders and a family history of FS and other psychiatric disorders.A semi-structured questionnaire, developed to detect the presence of traumatic experiences in childhood, showed greater levels of emotional neglect, physical and psychological abuse, violence climate in family and sexual abuse in patients with FS than HS.In FS subjects we found greater body mass index, a higher rate of obese people and more frequency of other medical conditions including chronic pain, sleep and gastrointestinal disorders in comparison with both AD and HS groups.A greater presence of emotional neglect in childhood was detected in FS subjects compared with AD.Other demographic data are reported in Table S1 on Supplementary materials.

Differentiation among the groups
Compared to HS, people with FS reported more frequent and severe binge eating attitudes although only 3 patients with FS obtained a score in the range of severe symptoms (BES score > 27) and one of them was diagnosed the BED according to the DSM 5 criteria (Fig. 1).
The analysis of the whole sample's personality traits showed significant differences between FS and HS (with greater scores for FS people) in four out of five PID-5 domains (negative affectivity, detachment, disinhibition, and psychoticism) and in several PID-5 facets including distractibility, eccentricity, emotional lability, irresponsibility and perceptual dysregulation (See Fig. 2 and Table S2 in Supplementary materials for all significant differences among groups in PID-5 facets).The personality domain 'disinhibition', which includes a significantly higher distractibility facet, is significantly different between AD and FS groups.
Notable anxious-depressive symptoms and high frequency and intensity of dissociative experiences emerged from the questionnaires detecting psychopathological symptoms in FS people (all scores were significantly higher than HS).Table 2 lists all intergroup comparisons in clinical symptoms and in personality traits.
Univariable logistic regression models revealed that depressive and dissociative symptoms increase the odds of binge eating attitudes in people with FS, as well as some personality facets as emotional lability and perseveration (See Supplementary Table S3).
In the multivariable logistic regression model, the PID-5 facet 'Perseveration' resulted as only independent risk factor of clinical binge eating symptoms in people with FS (Table 3).

Discussion
The results of this cross-sectional study demonstrate that people with FS have a significantly higher frequency and severity of binge-eating symptoms than HS, although not in comparison to the AD group.Also, some patients with FS obtained a score at BED questionnaire in the range of severe symptoms (BES score > 27) and one of them was diagnosed BED according to the DSM 5 criteria.
The lack of a statistically significant difference in binge-eating symptoms between FS and AD groups may be due to the high prevalence of depression and anxiety as a comorbidity in people with FS (between 50 % and 75 %) or to the limited sample size, which may have impacted upon the ability to detect differences between the pathological samples.
Another possible reason for lack of differences could be attributed to the link between binge eating symptoms and the traumatic-dissociative dimension, which is often present both in people with FS and in several clinical subgroups with a history of traumatic development.Although dissociative phenomena are generally more frequent in some diagnostic categories characterized by traumatic etiopathogenesis (conversion disorders, PTSD, borderline personality disorders and dissociative disorders), the presence of dissociative manifestations was also described in subgroups of patients with history of traumatic development with varied psychopathology including schizophrenia, personality disorders, eating disorders, anxiety, and depression [36].In line with this hypothesis, we found a high presence of traumatic experiences in childhood as emotional neglect, psychological and physical abuse, violence climate in family and sexual abuse in both patients with FS and AD.
We demonstrated that the tendency towards depression and dissociation is associated with binge-eating symptoms in patients with FS and this could reinforce the hypothesis of a relationship between dissociation and eating disorders.In these patients some personality traits, such as emotional lability and perseveration, are associated with the tendency to experience binge-eating behaviours, also.
Furthermore, the PID-5 facet "perseveration" was able to independently predict the presence of binge-eating symptoms in people with FS.Perseveration is a relatively automatic process, and it can be considered a component of the compulsive behaviors [37].It is a maladaptive personality trait, characterized by the tendency to continue the same behaviour despite repeated failures, even when it ceases to be effective, rewarding or functional.Compulsivity is a typical feature of various mental disorders including addictive disorders and BED; particularly, it was found that rash-spontaneous behaviour in general, and specifically towards food, is increased in BED [38,39].We found a strong relationship between compulsivity and binge-eating behaviours in people with FS but not in people with AD (data not shown).This could support the existence of a compulsive dimension, rather than an affective dimension already widely demonstrated in the literature, underlying the tendency to engage in binge-eating behaviour in this medical population.
The study also revealed some characteristics in the personality of people with FS, which may offer a deeper insight into their psychological profile, such as the tendency to experiment dissociative states, negative affectivity with emotional lability, anxiousness, depression, disinhibition and psychoticism as the tendency toward eccentricity and perceptual dysregulation.The assessment of these personality dimensions, associated with specific psychopathological pictures, may improve the overall management of these patients assisting the clinician in the formulation of ad hoc pharmacological and psychotherapeutic intervention projects.
Eventually, the high prevalence of binge-eating symptoms in patients searching health care for FS should be considered.These symptoms may be underrecognized, as in most cases they are not spontaneously reported by patients.Thus, the clinicians should purposely ask for the presence of these disturbances, either with unstructured interview or by the administration of specific questionnaires.Indeed, binge-eating behaviours may constitute a source of stress and embarrassment for the patients, and they can induce inappropriate weight gain.
This study has several limitations.First, the limited sample size may have impacted the ability to detect differences between the people with FS and AD.However, the inclusion of only untreated patients with FS and DA resulted in considerable difficulties in enrolling a greater number of participants.Then, the three groups were not comparable in gender distribution, BMI, education level, employment and marital status.However, no correction techniques for these confounding variables (such as sample stratification or restriction) were allowed because of the small sample size, so the potential confounding effects of these differences should be considered for the reliability of the results.These differences may influence the results they are deemed as predisposing factors to binge eating.Regarding the differences in sex distribution among groups, females were more represented in FS and AD group than HS.Since several studies showed that a female to male ratio in BED is quite balanced [40,41], we may hypothesize that this difference has a limited effect on our results.In contrast, BED results associated with high BMI [42] and more than 75 % of individuals with BED also are overweight or obese [43], it is not surprising given the absence of inappropriate compensatory behaviours in BED.People in our FS sample resulted with higher BMI and rate of obesity compared with both controls and people with AD, however it is hard to establish whether both BMI and obesity in FS people represent risk factors or a consequence of binge eating symptoms.
Regarding differences in the education level and employment.FS sample showed high rate of unemployment, lower education level and higher rates of divorced status as compared to HS, but not to people with DA.Previous studies indicated that BED is associated with impaired daily functioning, impaired social role functioning and work productivity, however these data seem correlated to a broad range of psychopathology rather than specific to BED [44][45][46][47][48].
Another limit of our research FS is linked to the high comorbidity of other psychopathology including depressive and anxiety symptoms in people with FS.Hence, our results could not be closely related to FS symptomatology, although logistic regressions allowed us to limit the impact of this confounding variable.
Lastly, even though patients with FS showed more frequent and severe binge eating symptoms than healthy controls, only one patient was diagnosed a BED according to DSM-5 criteria, so more data is required to prove a strong relationship between FS and BED.
The findings of this research provide the importance of further investigating the association and relationship between dissociation and Fig. 2. PID-5 domains median scores of the three groups.Post-hoc analysis revealed significant results between FS and HS subjects for all the indicated domains (p value < 0.001).A significant difference between FS and AD people was found in disinhibition domain.(p value = 0.03).

Table 2
Clinical symptoms and personality traits comparisons as a function of group.

Fig. 1 .
Fig.1.Binge eating scale (BES) median scores of three groups.Greater binge behavior in FS people than HS was found (p value < 0.001).No differences were found between FS and AD people.

Table 1
Relevant demographical and clinical features in three groups (total sample = 127).

Table 3
Multivariable logistic regression model of Estimate as odds of presence/absence of binge eating symptoms in people with FS.