Introduction
Anxiety and depression as high-rate psychiatric comorbidities are more common in people with epilepsy (PWE) (prevalence: 20%–50%) than in the general population (prevalence: 7%–20%) (1–5)]. The relationship between epilepsy and psychiatric disturbance is bidirectional; specifically, PWE are more prone to develop psychiatric comorbidities, while patients with certain primary psychiatric disorders are at higher risk of developing epilepsy (6). This bidirectional relation may be explained by the common pathogenesis of both epilepsy and psychiatric disorders (7). Psychiatric comorbidities, especially depression and anxiety, impact seizure disorders and the lives of PWE. To improve quality of life and promote efficiency in the treatment of epilepsy, screening for anxiety and depression and seeking for possible causes should become a necessary clinical routine. Unfortunately, psychiatric comorbidities often go unrecognized and untreated in PWE (8).
Although studies have found that women usually experience higher levels of anxiety and depression than men in the general population (9, 10), little is known about the gender differences in comorbid psychological disorders in epilepsy. So far, only one study has estimated the gender differences in the incidence of comorbid anxiety and depression in PWE and found that female patients with epilepsy are more susceptible to be affected by depression than male patients, but there is no gender difference in the prevalence of anxiety [(10). Therefore, more evidence is needed to increase the understandings of the gender differences in comorbid anxiety and depression in PWE.
Based on the gender discrepancy in psychiatric disorders, we hypothesized that there should be differences between male and female PWE in comorbid anxiety and depression. So the objective of the present study was to seek out gender differences in sociodemographic, clinical, incidence and risk factors of epilepsy comorbid anxiety/depression symptoms by investigating adult PWE in our hospital located in northwest China. Using statistical analyses of data obtained by self-rating questionnaires, we found differences between genders in the most predictors but not prevalence of epilepsy comorbid negative emotions.
Subjects and Methods
Participants and Recruitment
All 158 (male 93, female 65) adult PWE were recruited from the outpatient and inpatient Department of Clinical Neurology, the 940th Hospital of Joint Logistics Support Force of People’s Liberation Army (Lanzhou, Gansu Province, China). Patients were consecutively enrolled in this study between March 2017 and November 2017. The included patients should meet following criteria: (1) older than 18 years, (2) no other systemic disease, and (3) epilepsy was diagnosed by experienced epileptologists according to the International League against Epilepsy, (4) cognitively capable of communicating with physicians and understanding the questionnaires. After recruited the patients, resident doctors sent the questionnaires to the patients and helped them to fill in; physicians, attending doctors were responsible for collecting and analyzing data.
This study was approved by the Institutional Review Board prior to initiation, and each participant was consent and signed the patient’s medical notes to collect demographic and clinical information, including age, gender, years of education, occupational status, age at onset, duration of seizures, the number of antiepileptic drugs (AEDs) used daily, frequency of AED use, self-reported adverse effects of AEDs and frequency of seizures.
Assessment Scales
Self-Rating Anxiety Scale and Self-Rating Depression Scale
We adopted the Self-rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS) to assess anxiety and depression in the enrolled PWE. The SAS and SDS are widely used questionnaires among PWE, and their Chinese versions were administered in a previous study (11, 12). Either the SAS or the SDS composes 20-item symptom inventories, and each item is rated on a scale from 1 to 4. The total score is multiplied by 1.25 and is then converted into a standardized score ranging from 25 to 100, with higher scores reflecting more severe anxiety and depression. The criteria of severities applied in China are as the following: mild anxiety (score 50–60) and mild depression (score 53–62), moderate anxiety (score 61–70) and moderate depression (score 63–72), and severe anxiety (score>70) and severe depression (score>72) (13).
Quality of Life in Epilepsy-31 Inventory
Quality of life was assessed using the Chinese version of the Quality of Life in Epilepsy-31 (QOLIE-31) inventory, which is widely acknowledged epilepsy-specific QOL instruments and shows good validity and reliability in Chinese populations (14–16). The QOLIE-31 contains seven multi-item scales: seizure worry, overall quality of life (QOL), emotional well-being, energy/fatigue, cognitive function, medication effects and social function. The QOLIE-31 overall score is the sum of the weighted average of each subscale score, ranging from 1 to 100, with higher scores meaning a more favorable QOL (17, 18).
Pittsburgh Sleep Quality Inventory
The Pittsburgh Sleep Quality Inventory (PSQI) is a self-report questionnaire for assessing sleep. The global score ranges from 0 to 21, with a higher score indicating poorer sleep quality. The scale consists of seven subscales, comprising subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, use of sleep medications and daytime dysfunction. A total PSQI score of 5 or more points indicates poor sleep quality, and more than 10 points is considered severely disturbed sleep (19).
Statistical Analysis
All data were analyzed using the software package SPSS 23.0. Descriptive statistics were calculated for all variables. Quantitative data are expressed as the mean ± standard deviation (SD). Qualitative data are shown and summarized as numbers and proportions.
Gender differences were compared using Student’s t-test for continuous variables and Chi-square tests for categorical variables. To explore the relationships between depression/anxiety and sociodemographic, psychosocial and clinical variables, Pearson’s r was calculated. The independent variables correlating with anxiety or depression, which were defined as the scores of SAS (≥ 50) and SDS (≥ 53), respectively, were introduced into a logistic regression model with stepwise selection. All tests for statistical significance were two-sided, and p < 0.05 was considered significant.
Discussion
Gender discrepancy usually exists in psychiatric disorders. However, that difference(s) between genders may not always be the same in all kinds of scenarios. The current study investigated gender differences in the demographic variables, incidence and risk factors of comorbid anxiety and depression in PWE and have three key findings in the present study: (1) Expected gender differences in the prevalence of anxiety and depression are not actually seen in PWE. (2) Most of the important predictors for anxiety and depression in PWE vary by gender. (3) QOL energy/fatigue is the common influential factor of anxiety and depression in PWE and influences male and female PWE to different extents.
Large-scale epidemiological studies suggest that anxiety disorders are much more prevalent in women than in men, and this gender disparity is even more pronounced in other neuropsychiatric disorders, such as sleep disturbance (20). However, this study revealed no gender difference in the high prevalence rates of comorbid anxiety in PWE, which was consistent with previous studies (21, 22). Women in general are also documented to be more prone to depression than men (9, 10, 23), and recent evidence (22) also showed the female PWE had a higher ratio of comorbid depressive symptoms than the male. Paradoxically, the present study showed that men with epilepsy were just as likely as female patients to exhibit markedly higher levels of depression in comparison to the general population. Such discrepancies may be attributed to the different features of the selected samples among these studies. Significantly, the patients in this study were mainly from Gansu, a province of northwest China where economy and healthcare conditions are relatively under-developed. The unemployed and poorly educated situations may greatly impact the emotions of those participants. Nevertheless, our findings indicate that psychiatric comorbidities in male PWE must be concerned as important as in female patients, and the psychological state of PWE should not be equated with that of the general population.
Although the expected gender difference in the prevalence of anxiety and depression in PWE was not observed in this study, the important predictors of comorbid anxiety were found in this study quite complex and differed between male and female PWE. In men with epilepsy, poor sleep is the most dangerous factor in comorbid anxiety disorders. Sleep problems occur more frequently in PWE than in healthy controls (24). Sleep disturbance is a well-documented risk factor for developing or worsening anxiety disorders (25, 26), and women in the general population are more likely than men to report insomnia (25–27). Surprisingly, this study showed that men and women with epilepsy suffered equally from sleep problems. In contrast, the frequency of seizures was the most important indicator that independently related to anxiety in women with epilepsy in this study. Anxiety and depression are always correlated with seizure frequency, both before and after treatment, and depressive symptoms and seizure frequency influence mutually, indicated by both cross-sectional and longitudinal studies (28, 29). Our data are consistent with this finding in terms of anxiety but not depression. The analysis showed that anxiety symptoms associated seizure frequency stronger in women than in men in this study. This phenomenon may result from women’s higher level of psychological burden when facing a higher frequency of seizures, compared with male patients. Therefore, seizure-related factors impact the anxious status of women much more in comparison with men. For female PWE, good control of epilepsy and maintaining a positive and optimistic attitude toward seizures may help to reduce anxiety.
Predictors of depressive symptoms in PWE also varied by gender. It was notable in this study that depression was independently associated with education years and QOL social function in men with epilepsy but not in women. As reported, epilepsy often leads to poorer educational and vocational outcomes including unemployment and limited career prospects, especially for male patients (30). Data in the present study indicated that longer education years and better social function meant a lower risk of depression; on the contrary, poorly educated male PWE may have more psychological barriers and less-flexible coping strategies. In general, social support means differently to men and women. Women commonly relied on searching for social and religious support, while most men showed alexithymia and more difficulties on coping negative emotions (31), which may explain the gender differences in the predictors of depression in PWE in our study.
Our findings also suggest the importance of the relationship between fatigue and mental comorbidity in people with epilepsy. QOL medication effects, as the most important indicators of depression in both genders (32), were significant in our regression model of men with epilepsy. In women with epilepsy, rather than sociodemographic factors, QOL energy/fatigue almost exclusively account for the variance in depression. The degree of fatigue was found higher in adult PWE than in the general population (4, 33). In this study, the bidirectional relationship between negative emotions and epilepsy was well established: QOL energy/fatigue was confirmed as the common predictor of comorbid anxiety and depression in both genders with epilepsy. Moreover, the male patients were influenced by QOL energy/fatigue to a greater extent than the female patients. Although the mechanism of fatigue remains unclear, previous studies have found that fatigue was prominent in people with major depressive disorder even when depression was atypical (34). Thus, the association between depression (or anxiety) and fatigue should be fully understood, and fatigue should particularly be ameliorated in epilepsy patients. Seizure frequency and sleep-related problems have been found crucial risk factors for fatigue in epilepsy patients (33, 35), which may help to explain why PWE with anxiety disorders share fatigue as a common risk factor without gender differences.
In clinical practice, the main reason for psychiatric disorders in PWE usually is orchestration of large number of factors. However, our findings uncovered some interesting correlations between those factors, most of which serving as predictors for depression seem regulatable. Our study suggests that male and female PWE should be treated differently, particularly regard to negative emotional comorbidities. Further social support for male PWE and effective health education on epilepsy for female PWE may increase their confidence in treatment and relieve their anxiety about seizures.
Limitations
The following limitations should be considered when our data are being interpreted. (1) The cases were acquired from a single epilepsy center, and the sample size was relatively small. Thus the conclusion from these data cannot be applied to other patient groups directly. (2) A definitive diagnosis of depression or anxiety disorders should meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria by a comprehensive clinical examination. The SAS and SDS are brief screening instruments to assess the severity of anxiety or depressive symptoms and more appropriate for epidemiological research. (3) The data in our study were collected by participants’ self-reports with no confirmation by professional psychiatric staff. Therefore, the patients may have over-evaluated or underreported their actual situation of epilepsy. (4) The main type of epilepsy in most PWE of our sample is generalized epilepsy, while focal epilepsy has a higher prevalence in the adults.