The mechanisms behind comorbid symptoms of depression in persons with epilepsy (PWE) remain largely unknown. Our study aimed to learn whether seizures moderate fluctuations in depressive symptoms in PWE when controlling for preictal symptoms of depression. We enrolled 57 adult PWE admitted to the New York University (NYU) Langone Epilepsy Monitoring Unit (EMU) from 2021 to 2024. Thirty-seven participants had a seizure. Twenty of the admitted patients did not have seizures during the admission period and therefore served as controls. All participants were seizure free for > 7 days prior to participation. Upon admission, all participants completed the Montgomery-Asberg Depression Rating Scale (MADRS) to evaluate baseline mood. The MADRS was repeated acutely (4-24 h post seizure or admission) and subacutely (2-7 days post seizure or discharge) for both groups. Linear regression models revealed that individuals with higher baseline MADRS scores (indicating higher depressive symptoms) experienced worse mood acutely post-seizure, while lower baseline MADRS scores were associated with acute mood improvement (R2 = 0.59, p < 0.001). Experiencing a seizure was not associated with subacute mood outcomes, which were instead driven by acute mood state (R2 = 0.56, p < 0.001). In conclusion, we found that seizures exacerbate pre-ictal depressive symptoms and that post-ictal depressive symptoms persist up to 7 days after seizure resolution. This study may provide evidence for a bidirectional relationship and demonstrate a vicious cycle between depression and epilepsy.

Epilepsy, one of the most common neurological diseases, affects more than 70 million people worldwide. Anti-seizure drugs targeting membrane ion channels or GABAergic neurotransmission are the first choices for controlling seizures, whereas the high incidence of pharmacoresistance and adverse effects largely restrict the availability of current anti-seizure drugs (ASDs). Traditional Chinese Medicine (TCM) has shown historical evidence-based therapeutic effects for neurological diseases including epilepsy. But until the late 1990s, great efforts in both clinical and experimental fields advanced TCM interventions for epilepsy from evidence-based practices to more systematic neuropharmacological significance, and show new lights on preferable management of epilepsy in the last decade. This review summarized the advances of applying TCM interventions (ranging from herbal medicines and their active ingredients to other strategies such as acupuncture) for epilepsy, followed by associated mechanism theories. The therapeutic potential of TCM interventions for epilepsy as well as its comorbidities turns from somehow debatable to hopeful. Finally, some prospects and directions were proposed to drive further clinical translational research. The future directions of TCM should aim at not only deriving specific anti-epileptic molecules but also illustrating more precise mechanisms with the assistance of advanced multifaceted experimental tools.

Psychiatric comorbidities are frequent in people with epilepsy (PWE) or psychogenic nonepileptic seizures (PNES), and the use of validated screening instruments to identify respective symptoms is recommended. Our aim was to investigate the recommendations resulting from routine screening for depression, anxiety and suicidality with the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the Generalized Anxiety Disorder Scale (GAD-7) in the outpatient clinic of a tertiary epilepsy center.

We retrospectively analyzed NDDI-E and GAD-7 scores (German versions) of 264 outpatients at a tertiary epilepsy center and extracted recommendations regarding psychopathology from the outpatient letters.

The screening revealed a likely major depression (NDDI-E ≥17) in 15.2% of PWE (without PNES, 30/197) and an NDDI-E score ≥17 in 51.2% of patients with PNES ± epilepsy (21/41), moderate to severe symptoms of generalized anxiety (GAD-7 ≥10) in 20.3% of PWE (40/197) and 56.1% of patients with PNES (23/41), and a high risk of suicidality (NDDI-E item 4 ≥3) in 8.1% of PWE (16/197) and in 24.4% of patients with PNES (10/41). The most frequently given recommendations regarding depression or anxiety were a psychiatric/psychotherapeutic treatment for PWE and an admission to the psychotherapy ward of the epilepsy center for patients with PNES. No evidence for active suicidal tendencies was found in any of the patients with a positive screening for suicidality.

Routine screening with NDDI-E and GAD-7 for depression, anxiety and suicidality is efficient and feasible and leads to individual recommendations for further assessment and treatment.

Background: Mental health conditions and epilepsy frequently coexist and have independently been associated with severe maternal morbidity (SMM). Since little is known about the risks of these conditions when they occur together in pregnancy, we evaluated the associations of mental health conditions, epilepsy, and SMM. Methods: We conducted a population-based study of births in California between 2007 and 2018. Antenatal epilepsy and mental health conditions (defined as depression, anxiety, posttraumatic stress disorder, and other) were identified using billing codes. We categorized individuals into the following mutually exclusive exposure groups: no epilepsy or mental health conditions (referent), mental health conditions alone, epilepsy alone, or both epilepsy and mental health conditions. Our primary outcome was SMM, defined by the 20-indicator Centers for Disease Control and Prevention Index. We conducted multivariable logistic regression models adjusted for sociodemographic and clinical confounding factors. Results: In a cohort of 5,275,994 births, SMM occurred more frequently in individuals with mental health conditions alone, epilepsy alone, and both mental health conditions and epilepsy (1.8%, 3.0%, 4.2%, respectively) compared with the referent group (0.8%). The odds of SMM were significantly increased for each exposure group: adjusted odds ratio (aOR) 2.13, 95% confidence interval (CI) 2.05-2.22 for mental health conditions; aOR 3.79, 95% CI 3.45-4.18 for epilepsy; and aOR 4.91, 95% CI 4.01-6.00 for both. Conclusion: Epilepsy and mental health conditions were independently associated with SMM, and individuals carrying both diagnoses had the highest odds of SMM. Our results highlight the need for awareness of SMM risks in this population.

Drug-resistant temporal lobe epilepsy (TLE) is a neurological disorder characterized by cognitive deficits. This study examined whether patients with TLE and different cognitive phenotypes differ in cortisol levels and affectivity while controlling for demographic and clinical variables. Methods: In this cross-sectional study, 79 adults with TLE underwent neuropsychological evaluation in which memory, language, attention/processing speed, executive function, and affectivity were assessed. Six saliva samples were collected in the afternoon to examine the ability of the hypothalamic-pituitary-adrenal (HPA) axis to descend according to the circadian rhythm (C1 to C6). The cortisol area under the curve concerning ground (AUCg) was computed to examine global cortisol secretion.

Three cognitive phenotypes were identified: memory impairment, generalized impairment, and no impairment. The memory-impairment phenotype showed higher cortisol levels at C4, C5, and C6 than the other groups (p = 0.03, η2 = 0.06), higher cortisol AUCg than the generalized-impairment phenotype (p = 0.004, η2 = 0.14), and a significant reduction in positive affectivity after the evaluation (p = 0.026, η2 = 0.11). Higher cortisol AUCg and reductions in positive affectivity were significant predictors of the memory-impairment phenotype (p < 0.001; Cox and Snell R2 = 0.47).

Patients with memory impairment had a slower decline in cortisol levels in the afternoon, which could be interpreted as an inability of the HPA axis to inhibit itself. Thus, chronic stress may influence hippocampus-dependent cognitive function more than other cognitive functions in patients with TLE.

This study was conducted to examine the relationship between intrinsic spirituality, resilience and hopelessness in patients with epilepsy and to investigate the mediating role of resilience in the relationship between intrinsic spirituality and hopelessness.

This study is a descriptive correlational research. The study was conducted with 120 patients who met the inclusion criteria between January 2023 and July 2023. Data were collected by using Personal Information Form, Intrinsic Spirituality Scale (ISS), Beck Hopelessness Scale (BHS) and Brief Resilience Scale (BRS).

According to the results of the study, it was found that the mean ISS score (β = 0.730) affected the mean BRS score positively and the mean BHS score (β = -0.497) negatively (p > 0.05). It was found that the mean BRS score affected the mean BHS score (β = -0.178) negatively (p > 0.05). The indirect effect (β = -0.129) and total effect (β = -0.626) of intrinsic spirituality on hopelessness mediated by the mean BRS score were found to be negative and significant. It was determined that the tested model provided a good fit and explained the direct and indirect effects of the study variables.

According to the results of the study, it was found that intrinsic spirituality affected resilience positively and hopelessness negatively. Resilience was found to have a negative effect on hopelessness. It was determined that resilience partially mediated the relationship between intrinsic spirituality and hopelessness and this situation reduced hopelessness more.

Epilepsy presents a significant global health challenge, impacting millions worldwide. Alarmingly, over half of individuals living with epilepsy (PWE) also face concurrent medical conditions, with psychiatric complications, particularly depression, standing out as prevalent issues. The relationship between epilepsy and depression is complex and bidirectional, with approximately a quarter of adults with epilepsy receiving a diagnosis of depression. This complexity underscores the challenges in diagnosing depression in epilepsy patients, hindered by overlapping symptoms and distinct manifestations of depression in this population. Our review highlights that the use of most antidepressant pharmacotherapies does not increase the risk of seizure occurrences. On the contrary, compelling evidence suggests that such treatments may even decrease seizure frequency, offering hope for patients. In addition to pharmacology, non-pharmacological interventions are emerging as vital alternatives, enriching the therapeutic landscape. However, despite these promising avenues, a significant gap in our understanding persists, characterized by a lack of comprehensive, prospective research. Our review rigorously explores the latest pathophysiological insights linking depression and epilepsy while critically evaluating contemporary treatment paradigms for individuals grappling with these comorbid conditions. By focusing on the most current developments, this review aims to equip clinicians with cutting-edge knowledge, fostering a more nuanced and effective approach to managing the intricate interplay between epilepsy and comorbid depression.

Several psychiatric disorders have been found to occur more frequently in persons with epilepsy (PWE) than in persons without epilepsy.

To summarize the prevalence of 20 psychiatric disorders in PWE compared with persons without epilepsy.

The search included records from inception to February 2024 in Ovid, MEDLINE, Embase, and PsycINFO.

Published epidemiological studies examining the prevalence of psychiatric disorders among PWE compared with persons without epilepsy were systematically reviewed. There were no restrictions on language or publication date.

Abstracts were reviewed in duplicate, and data were extracted using a standardized electronic form. Descriptive statistics and meta-analyses are presented.

Data were recorded on the prevalence of 20 psychiatric disorders among PWE compared with persons without epilepsy. Meta-analyses were performed along with descriptive analyses.

The systematic search identified 10 392 studies, 27 of which met eligibility criteria. The meta-analyses included 565 443 PWE and 13 434 208 persons without epilepsy. The odds of most psychiatric disorders studied were significantly increased in PWE compared with those without epilepsy, including anxiety (odds ratio [OR], 2.11; 95% CI, 1.73-2.58); depression (OR, 2.45; 95% CI, 1.94-3.09); bipolar disorder (OR, 3.12; 95% CI, 2.23-4.36); suicidal ideation (OR, 2.25; 95% CI, 1.75-2.88) but not suicide attempt (OR, 3.17; 95% CI, 0.49-20.46); psychotic disorder (OR, 3.98; 95% CI, 2.57-6.15); schizophrenia (OR, 3.72; 95% CI, 2.44-5.67); obsessive-compulsive disorder (OR, 2.71; 95% CI, 1.76-4.15); posttraumatic stress disorder (OR, 1.76; 95% CI, 1.14-2.73); eating disorders (OR, 1.87; 95% CI, 1.73-2.01); alcohol misuse (OR, 3.64; 95% CI, 2.27-5.83) and alcohol dependence (OR, 4.94; 95% CI, 3.50-6.96) but not alcohol abuse (OR, 2.10; 95% CI, 0.60-7.37); substance use disorder (OR, 2.75; 95% CI, 1.61-4.72); autism spectrum disorder (OR, 10.67; 95% CI, 6.35-17.91); and attention-deficit/hyperactivity disorder (OR, 3.93; 95% CI, 3.80-4.08).

In this comprehensive study, most psychiatric comorbidities examined were significantly more prevalent in PWE than in those without epilepsy. These findings show the high burden of psychiatric comorbidities in PWE. This, in turn, underscores the need for appropriately identifying and treating psychiatric comorbidity in epilepsy to manage patients effectively and improve quality of life.

To investigate phenotypes of comorbidity before and after an epilepsy diagnosis in a national cohort of post-9/11 Service Members and Veterans and explore phenotypic associations with mortality.

Among a longitudinal cohort of Service Members and Veterans receiving care in the Veterans Health Administration (VHA) from 2002 to 2018, annual diagnoses for 26 conditions associated with epilepsy were collected over 5 years, ranging from 2 years prior to 2 years after the year of first epilepsy diagnosis. Latent class analysis (LCA) was used to identify probabilistic comorbidity phenotypes with distinct health trajectories. Descriptive statistics were used to describe the characteristics of each phenotype. Fine and Gray cause-specific survival models were used to measure mortality outcomes for each phenotype up to 2021.

Six distinct phenotypes were identified: (1) relatively healthy, (2) post-traumatic stress disorder, (3) anxiety and depression, (4) chronic disease, (5) bipolar/substance use disorder, and (6) polytrauma. Accidents were the most common cause of death overall, followed by suicide/mental health and cancer, respectively. Each phenotype exhibited unique associations with mortality and cause of death, highlighting the differential impact of comorbidity patterns on patient outcomes.

By delineating clinically meaningful epilepsy comorbidity phenotypes, this study offers a framework for clinicians to tailor interventions. Moreover, these data support systems of care that facilitate treatment of epilepsy and comorbidities within an interdisciplinary health team that allows continuity of care. Targeting treatment toward patients with epilepsy who present with specific heightened risks could help mitigate adverse outcomes and enhance overall patient care.

At present, little is known about the outcomes measured in studies assessing the effectiveness of treatments for adults with epilepsy. As part of a wider project developing a Core Outcome Set for clinical trials for adults with epilepsy, we summarised the current outcomes and measurement instruments used in completed phase III and IV clinical trials registered in the clinicaltrials.gov and International Standard Randomised Controlled Trial Number (ISRCTN) databases. Of the reviewed studies 104 were deemed eligible. The outcomes that were measured were recorded, and trial registry entries cross referenced against associated peer review publications. In total, 374 unique granular outcome terms were identified, which grouped into 45 outcome concepts across the following domains: seizures, cognitive/behavioural/psychiatric, sleep, general symptom, functional status / disability, emotional functioning, social functioning, delivery of care, life impact, trial processes, side effects / adverse events, pregnancy / offspring, and death. We identified evidence of outcome measurement heterogeneity, with just 10/45 outcome concepts measured in more than half of the identified studies. This association remained when assessing studies grouped by epilepsy chronicity (newly diagnosed vs. chronic/treatment refractory) and epilepsy classification (focal vs. other). These findings highlight the need for a Core Outcome Set for interventional studies for adults with epilepsy to improve consistency of outcome measurement and reporting.

Patient-reported outcome measures (PROMs) such as the Neurological Disorders Depression Inventory in Epilepsy (NDDI-E), a 6-item epilepsy-specific PROM, is used to screen for major depressive disorder symptoms for patients with epilepsy (PWE). The validity and interpretation of PROMs can be affected by differential item functioning (DIF), which occurs when subgroups of patients with the same underlying health status respond to and interpret questions about their health status differently. This study aims to determine whether NDDI-E items exhibit DIF and to identify subgroups of PWE that exhibit DIF in NDDI-E items.

Data were from the Calgary Comprehensive Epilepsy Program database, a clinical registry of adult PWE in Calgary, Canada. A tree-based partial credit model based on recursive partitioning (PCTree) was used to identify subgroups that exhibit DIF on NDDI-E items using patients' characteristics as covariates. Differences in the identified subgroups were characterized using multinomial logistic regression.

Of the 1,576 patients in this cohort, 806 (51.1%) were female, and the median age was 38.0 years. PCTree identified four patient subgroups defined by employment status, age, and sex. Subgroup 1 were unemployed patients ≤ 26 years old, subgroup 2 were unemployed patients > 26 years, subgroup 3 were employed females, while subgroup 4 were employed male patients. The subgroups exhibited significant differences on education level, comorbidity index scores, marital status, type of epilepsy, and driving status.

PWE differed in their interpretation and responses to questions about their depression symptoms, and these differences were a function of sociodemographic and clinical characteristics.

Mental health issues are widespread and significant among individuals with serious illness. Among patients receiving palliative care (PC), psychiatric comorbidities are common and impact patient quality of life. Despite their prevalence, PC clinicians face challenges in effectively addressing the intricate relationship between medical and psychiatric disorders due to their complex, intertwined and bidirectionally influential nature. This article, created collaboratively with a team of psychiatric-palliative care experts, is the second in a two-part series examining the bidirectional relationship between medical and psychiatric illness in PC. This article explores 10 prevalent psychiatric manifestations associated with severe illness and its treatment. Building upon the first article, which focused on 10 common physical manifestations of psychiatric illness among patients receiving PC, these two articles advocate for an integrated approach to PC that prioritizes mental and emotional wellbeing across the continuum of serious illness.

Despite the introduction of several first-in-class antiseizure medications in the last 15 years and the recent generation of new hypotheses to explain the drug-resistant phenotype in epilepsy, the proportion of patients with refractory epilepsy remains apparently unchanged. Therefore, it is essential to provide new perspectives (or, perhaps, revive old perspectives) to develop more effective therapeutic interventions. Some of the complex comorbid disorders associated with epilepsy, which present similar rates of unresponsive patients and whose refractoriness is possibly mediated by similar causes, could provide keys to implement novel therapeutic interventions. In this article, based on Swanson's ABC model to develop scientific hypotheses, we establish (or rescue) some interesting connections between depression and epilepsy, focusing on the relationship between drug-resistant epilepsy and depression.

Management of severe (drug-resistant) epilepsy and epilepsy in other serious illnesses is multidimensional and requires consideration of both physical symptoms and psychosocial distress that require individualized treatment. Palliative care offers a holistic approach to disease that focuses on all dimensions of suffering to maintain quality of life. Integration of a palliative care mind- and skillset in the management of severe epilepsy and epilepsy in other serious illnesses can provide person-centered care and support for families and caregivers.

To assess whether children with febrile seizures and/or epilepsy were at increased risk of experiencing internalizing symptoms or psychotic-like experiences at age 11 years.

This cohort study includes 44 819 children from the 11-year follow up of the Danish National Birth Cohort. Information on childhood seizures was retrieved from the Danish National Patient Registry, whereas child psychiatric symptoms were assessed in a web-based questionnaire using the Adolescent Psychotic-like Symptom Screener and the Strength and Difficulties Questionnaire. Adjusted odds ratios (aORs) with corresponding 95% confidence intervals (CIs) for the association between childhood seizures and internalizing symptoms (symptom score ≥8) and psychotic-like experiences (≥2 definite experiences) were obtained using logistic regression models.

A total of 1620 children with febrile seizures (3.6%), and 311 children with epilepsy (0.7%) were identified. When adjusted for potential confounders, no association between febrile seizures and psychiatric symptoms was observed, and no association was observed between epilepsy and psychotic-like experiences. However, the OR for internalizing symptoms was 1.76 (95% CI: 1.20-2.58) in children with epilepsy compared to children without. This higher risk was evident mainly in boys (OR 2.30, 95% CI 1.37-3.85), children with ≥2 epilepsy-related hospital admissions (OR 2.79, 95% CI 1.81-4.32), and children whose age at first epilepsy-related hospital admission was 0-3 years (OR 2.47, 95% CI 1.45-4.19).

No association was found between febrile seizures and psychiatric symptoms or epilepsy and psychotic-like experiences at age 11. However, boys with epilepsy were at higher risk of experiencing internalizing symptoms.

Although several studies have examined a diagnostic conversion from major depressive disorder (MDD) to bipolar disorder (BD), only a few studies specifically focused on adolescents and young adults who are at the peak ages of BD onset. Data from participants (N = 130,793) aged 10-29 years who were diagnosed with MDD were extracted from the Taiwan National Health Insurance Research Database. We applied demographic analyses, survival analysis, Aalen Johansen curves, and Cox regression, investigating the diagnostic conversion rate and factors that were most or less predictive of conversion. Among the adolescents and young adults with MDD, the number of participant conversion subsample is 14,187 and the conversion rate was 13.80% (95% confidence interval: 13.54-14.06%) during the 11-year follow-up. The conversion rate was highest in the first year (4.50%; 4.39-4.61%) and decreased over time. The significant predictors were younger age of diagnosis with MDD (p < 0.001), moderate and high antidepressant resistance (p < 0.001), obesity (p < 0.001), psychiatric comorbidities (attention-deficit/hyperactivity disorder, substance use disorder, and cluster B and C personality disorder, all p < 0.001), a family history of mental disorders (schizophrenia and mood disorders, all p < 0.05), lower monthly income (p < 0.001), and more mental health visits to the clinic each year (p < 0.001). A composite of demographic characteristics, antidepressant resistance, physical and psychiatric comorbidities, and family history significantly predicted diagnostic conversion from MDD to BD (area under the curve = 0.795, p < 0.001). Compared to adult population, the adolescents and young adults had different factors that were most or less predictive of conversion, which warrants further investigation.

Since epilepsy is often complicated by psychiatric symptoms, the contributions of psychiatry are indispensable for the care and improvement of the quality of life of individuals with epilepsy. Moreover, the existence of a bidirectional relationship between epilepsy and psychiatric symptoms was recently proposed, based on the evidence that not only are some psychiatric symptoms more likely than others to follow epilepsy, but also that psychiatric symptoms may precede the onset of epilepsy and the presence of psychiatric symptoms may influence the outcome of treatment for seizures. There has also been a gradual accumulation of neurobiological findings related to psychosis, depressive, and anxiety symptoms that are associated with epilepsy with respect to abnormalities in brain networks and neurotransmission. This mini-review focuses on the neuropsychiatric aspects of epilepsy and proposes that a reconsideration of neuropsychiatry in light of epilepsy findings could serve as a bridge between psychiatry and neurology.

How epilepsy surgery influences the bidirectional relationship of epilepsy and depression remains poorly defined.

For a better understanding of this question, we conducted a systematic review and meta-analysis of risk ratio on depression prevalence before and after epilepsy surgery, using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Three databases were comprehensively screened for all studies assessing depression before and after resective surgery in adult epileptic patients until 8 October 2022. Studies were included if depression was assessed before and after epilepsy surgery regardless of the time of follow-up. A total of 1917 studies were screened for eligibility and 91 full-texts up for inclusion; 35 studies were finally included, 25 studies and 2563 patients were included in main meta-analysis and 10 for exploratory analysis. Risk of bias was assessed using Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) from Cochrane. To derive the pooled depression rates before and after surgery, a meta-analysis with inversed-variance was performed using random-effects logistic models with Peto's correction and a 95% CI. Heterogeneity was assessed with Cochran's Q-test along with its derived measure of inconsistency I2.

Overall, the depression rates before and after resective epilepsy surgery were 0.70 (0.53 to 0.91) 95% CI, suggesting that the rate of depression at last follow-up evaluation tends to decrease after Resective Epilepsy Surgery (RES). Subgroup analysis suggest a positive long-term effect appears with a significant lower rates of depression already 6 months (0.61 (0.38 to 0.98)), after surgery which is maintained over time after 1 year (0.53 (0.31 to 0.90)), and after 2 years (0.62 (0.42 to 0.92)).

This important finding should be taken in consideration before resective surgery for drug-resistant epilepsies. However, prospective studies should be conducted to characterise which patient, at the individual level, might be at risk of de novo or worsening of depression.

CRD42022355386.

People with epilepsy (PWE) frequently experience sleep disturbances that can severely affect their quality of life. Depression is also a common symptom in the PWE population and can aggravate sleep problems. However, the interplay between epilepsy, depression, and sleep disturbances is not yet fully understood. Our study was designed to investigate the association between epilepsy and sleep disturbances in US adults and to determine whether depressive symptoms play a mediating role in this relationship.

We examined data from the National Health and Nutrition Examination Survey (NHANES) spanning January 1, 2015, to March 2020, before the pandemic.A total of 10,093 participants aged ≥ 20 years with complete data on epilepsy and sleep disturbance were included. Weighted multiple logistic regression and mediation analysis were used to explore the associations among depression, epilepsy, and sleep disturbance. Interaction effects of epilepsy with various covariates were also investigated.

Epilepsy was associated with depression and sleep disturbances. Weighted logistic regression analysis revealed a significant association between epilepsy and sleep disturbances (OR = 3.67, 95% CI = 1.68-8.04). Depression partially mediated this relationship, demonstrating a mediation effect of 23.0% (indirect effect = 0.037, P < 0.001). Subgroup analyses revealed variations in the relationship between epilepsy and sleep disturbances among different groups. Furthermore, interaction analyses revealed significant interactions between epilepsy and age (P = 0.049) and hypertension (P = 0.045).

Our study utilizing NHANES data confirmed that depression partially mediated the association between epilepsy and sleep disturbance. Additionally, we observed differences in this association across demographic groups. Addressing depressive symptoms in PWE may improve their sleep quality, but further research is needed to explore the underlying mechanisms.

Drug-resistant epilepsy (DRE) poses significant challenges in terms of effective management and seizure control. Neuromodulation techniques have emerged as promising solutions for individuals who are unresponsive to pharmacological treatments, especially for those who are not good surgical candidates for surgical resection or laser interstitial therapy (LiTT). Currently, there are three neuromodulation techniques that are FDA-approved for the management of DRE. These include vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). Device selection, optimal time, and DBS and RNS target selection can also be challenging. In general, the number and localizability of the epileptic foci, alongside the comorbidities manifested by the patients, substantially influence the selection process. In the past, the general axiom was that DBS and VNS can be used for generalized and localized focal seizures, while RNS is typically reserved for patients with one or two highly localized epileptic foci, especially if they are in eloquent areas of the brain. Nowadays, with the advance in our understanding of thalamic involvement in DRE, RNS is also very effective for general non-focal epilepsy. In this review, we will discuss the underlying mechanisms of action, patient selection criteria, and the evidence supporting the use of each technique. Additionally, we explore emerging technologies and novel approaches in neuromodulation, such as closed-loop systems. Moreover, we examine the challenges and limitations associated with neuromodulation therapies, including adverse effects, complications, and the need for further long-term studies. This comprehensive review aims to provide valuable insights on present and future use of neuromodulation.

The COVID-19 pandemic has affected the lives of people with epilepsy (PWE) in various ways. This systematic review and meta-analysis aims to assess the mental health status and prevalence of mental disorders including depression, anxiety, stress, and psychological distress among PWE. Furthermore, this study evaluates changes in sleep patterns and presence of sleep disturbances among them. The findings of this systematic review can help health organizations, policymakers, and health workers to better prepare and respond to future health crises for PWE and other chronic disease patients.

This systematic review was prepared using PRISMA reporting guidelines. We systematically searched PubMed, Web of Science, Scopus and Cochrane Library databases for studies that reported data on mental health parameters including depression, anxiety, stress, psychological distress, quality of life, and sleep quality, during the pandemic until May 2023. The analytical procedures were executed through the utilization of Comprehensive Meta-Analysis (CMA) software.

In our study, a total of 61 carefully selected studies were analyzed, yielding valuable insights into the prevalence and impact of various mental health indicators among PWE. The findings revealed that a significant proportion of PWE experienced distressing psychological symptoms, with depression being reported by 34% of participants. Additionally, anxiety was prevalent among 43% of individuals, while stress symptoms were reported by 49% of respondents. Moreover, a substantial portion of PWE, approximately 38%, reported experiencing poor sleep quality, further underscoring the multifaceted nature of the challenges faced by this population. These findings highlight the need for targeted interventions and comprehensive support systems to address the mental health concerns and sleep disturbances faced by individuals living with epilepsy.

The findings revealed that a substantial number of PWE experience symptoms of depression, anxiety, stress, and poor sleep quality. These results emphasize the importance of considering mental health and sleep assessments as integral components of care for individuals with epilepsy. The study underscores the need for further research and targeted interventions to address the mental health burden faced by this population. By prioritizing and addressing these challenges, healthcare providers can enhance the overall well-being and quality of life for individuals living with epilepsy.

Epilepsy is a common yet complex neurological disorder. Historically, antiseizure medications (ASMs) have faced challenges in crossing the blood-brain barrier (BBB) and targeting the epileptogenic zone, creating a bottleneck in seizure management. Certain nanomaterials can facilitate drug penetration through the BBB and enable stimulus-responsive drug release, thereby enhancing targeted and efficient drug utilization while reducing adverse reactions in other brain tissues and peripherally. This article reviews the current researches on stimulus-responsive nanosystems applicable in antiepileptic therapy, as well as nanotechnology applications that improve the brain delivery of ASMs.

To mitigate limitations of self-reported mood assessments, we introduce a novel affective bias task. The task quantifies instantaneous emotional state by leveraging the phenomenon of affective bias, in which people interpret external emotional stimuli in a manner consistent with their current emotional state. This study establishes task stability in measuring and tracking depressive symptoms in clinical and nonclinical populations. Initial assessment in a large nonclinical sample established normative ratings. Depressive symptoms were measured and compared with task performance in a nonclinical sample, as well as in a clinical cohort of individuals who were undergoing surgical evaluation for severe epilepsy. In both cohorts, a stronger negative affective bias was associated with a higher Beck Depression Inventory-II score. The affective bias task exhibited high stability and interrater reliability as well as construct validity in predicting depression levels in both cohorts, suggesting that the task is a reliable proxy for mood and a diagnostic tool for detecting depressive symptoms.

Research around the frequency of psychiatric diseases and psychosocial consequences caused by seizures and stigmatization in patients with epilepsy is important, in terms of multidimensional evaluation of the condition, increasing quality of life, and controlling the frequency of seizures. This prospective study aimed to evaluate relationship between comorbid psychiatric diseases and clinical and sociodemographic data, patients' quality of life and perceived stigma in patients with epilepsy.

In this prospective single-center study, we evaluated clinical and demographic data, and characteristics of epilepsy. We used the Symptom Check List 90-Revised (SCL-90-R) as a screening test for psychiatric comorbidities and the Mini International Neuropsychiatric Interview (MINI) test for patients who had an SCL90-R general symptom index (GSI) score of ≥1. The frequency of psychiatric comorbidities, the association between comorbid psychiatric disorders and quality of life, and the level of stigmatization in patients with epilepsy was assessed using the Quality of Life in Epilepsy Inventory (QOLIE-10) and Perceived Stigma Scale.

SCL90-R GSI scores of ≥1 were found in 122 of 300 patients. Psychiatric comorbidities were found in 24.8% (n = 69) of patients with epilepsy in the MINI test, major depression was found in 16.9 %, (n = 47), and generalized anxiety disorder was the most common (5.7 %, n = 16). The number of anti-seizure medications (p = 0.007), high seizure frequency (p = 0.01), seizure in previous 12 months (p = 0.003), history of epilepsy surgery (p = 0.032) and psychiatric disease (p < 0.001), and high perceived stigma (p < 0.001) and QOLIE-10 (p < 0.001) scores were all correlated with psychiatric comorbidities.

According to the results of our study, an important correlation was determined between psychiatric comorbidities and a history of psychiatric disease, poor quality of life, and high perceived stigma scores in patients with epilepsy. This suggests that screening patients for comorbid psychiatric conditions in epilepsy outpatient clinics is critical, as is establishing a strong collaboration with the psychiatry clinic, to reduce psychosocial issues and the economic burden of stigmatization and improve quality of life.

Patients with epilepsy are prone to cognitive decline, depression, anxiety and other behavioral disorders. Cognitive comorbidities are particularly common and well-characterized in people with temporal lobe epilepsy, while inconsistently addressed in epileptic animals. Therefore, the aim of this study was to ascertain whether there is good evidence of cognitive comorbidities in animal models of epilepsy, in particular in the rat pilocarpine model of temporal lobe epilepsy. We searched the literature published between 1990 and 2023. The association of spontaneous recurrent seizures induced by pilocarpine with cognitive alterations has been evaluated by using various tests: contextual fear conditioning (CFC), novel object recognition (NOR), radial and T-maze, Morris water maze (MWM) and their variants. Combination of results was difficult because of differences in methodological standards, in number of animals employed, and in outcome measures. Taken together, however, the analysis confirmed that pilocarpine-induced epilepsy has an effect on cognition in rats, and supports the notion that this is a valid model for assessment of cognitive temporal lobe epilepsy comorbidities in preclinical research.

A growing number of clinical and animal studies suggest that the nucleus accumbens (NAc), especially the shell, is involved in the pathogenesis of temporal lobe epilepsy (TLE). However, the role of parvalbumin (PV) GABAergic neurons in the NAc shell involved in TLE is still unclear. In this study, we induced a spontaneous TLE model by intrahippocampal administration of kainic acid (KA), which generally induce acute seizures in first 2 h (acute phase) and then lead to spontaneous recurrent seizures after two months (chronic phase). We found that chemogenetic activation of NAc shell PV neurons could alleviate TLE seizures by reducing the number and period of focal seizures (FSs) and secondary generalized seizures (sGSs), while selective inhibition of PV exacerbated seizure activity. Ruby-virus mapping results identified that the hippocampus (ventral and dorsal) is one of the projection targets of NAc shell PV neurons. Chemogenetic activation of the NAc-Hip PV projection fibers can mitigate seizures while inhibition has no effect on seizure ictogenesis. In summary, our findings reveal that PV neurons in the NAc shell could modulate the seizures in TLE via a long-range NAc-Hip circuit. All of these results enriched the investigation between NAc and epilepsy, offering new targets for future epileptogenesis research and precision therapy.

Episodic memory disruptions in epilepsy stem from shared neurocircuitry. While prior research has focused on retrospective memory (RM), prospective memory (PM; i.e. remembering to remember) also deserves consideration given its critical role in the management of daily activities. The current investigation assessed whether PM is associated with disability and quality of life in people with epilepsy.

This cross-sectional, correlational study included a consecutive series of 50 people with epilepsy presenting for neuropsychological evaluation who completed the Royal Prince Alfred Prospective Memory Test (RPA) and Prospective and Retrospective Memory Questionnaire (PRMQ) and 63 demographically comparable healthy adults. The participants with epilepsy also completed clinical measures of neuropsychological ability and questionnaires assessing disability and quality of life.

People with epilepsy had significantly more frequent memory symptoms as compared to healthy adults at a very large effect size. Worse mood was associated with lower PM ability at a medium effect size and more frequent PM symptoms at a large effect size. A hierarchical linear regression indicated that PM explained 52% of the variance in disability and 43% of the variance in quality of life after accounting for RM ability.

PM is associated with poorer everyday functioning among people with epilepsy and shows evidence of incremental value beyond RM ability in that regard. Future studies are needed to understand the complex pathways from PM to functional limitations to inform clinical intervention.

Epilepsies are a group of heterogeneous brain disorder, and antiseizure medications (ASMs) are the mainstay of treatment. Despite the availability of more than 30 drugs, at least one third of individuals with epilepsy are drug-resistant. This emphasizes the need for novel compounds that combine efficacy with improved tolerability.

A literature review on the pharmacology, efficacy, tolerability, and safety of azetukalner (XEN1101), a second-generation opener of neuronal potassium channels currently in Phase 3 development as ASM.

Results from the phase 2b clinical trial strongly support the ongoing clinical development of azetukalner as a new ASM. Its pharmacokinetic properties support convenient once-daily dosing, eliminating the need for titration at initiation or tapering at the conclusion of treatment. CYP3A4 is the main enzyme involved in its metabolism and drug-drug interactions can affect the drug exposure. Preliminary analysis of an ongoing open-label study reveals no reported pigmentary abnormalities. The upcoming Phase 3 clinical trials are expected to provide further insight into the efficacy, tolerability, and safety of azetukalner in treating focal-onset and primary generalized tonic-clonic seizures. Structurally distinct from currently marketed ASMs, azetukalner has the potential to be the only-in-class Kv7.2/7.3 opener on the market upon regulatory approval.

For approximately 30% of people with epilepsy, seizures are not well-controlled by anti-seizure medication (ASM). This condition, called treatment resistant epilepsy (TRE), is associated with increased morbidity and mortality, and substantially impacts the quality of life of both the individual and their family. Non-responsiveness to ASMs leads many people with TRE to seek alternative therapies, such as cannabinoid-based medication, particularly cannabidiol (CBD), with or without medical or professional advice. This is due in part to widespread reporting in the media about the benefits of CBD for seizures in some forms of epilepsy.

Adults with TRE, opting to add CBD to their existing treatment regime, completed this prospective, observational, longitudinal, quasi-experimental, time-series study. We hypothesized that adjunctive CBD use would positively impact participants' quality of life and psychological well-being in comparison to a baseline period without CBD use. Participants were followed for a period of approximately six months - for approximately one month of baseline prior to the initiation of CBD use and approximately five months after the initiation of CBD use. Participants provided urine samples and completed behavioral questionnaires that assessed quality of life, anxiety/depression, and adverse events during baseline and at two times during CBD use.

Complete case analyses (n = 10) showed a statistically significant improvement in quality of life, a statistically significant decrease in anxiety symptoms, and a statistically significant decrease in the experience of adverse events over time (p < 0.05). Improvements noted in the experience of depression symptoms did not reach statistical significance. Urinalysis revealed the majority of participants had no CBD/metabolites in their system at the beginning of the study, and confirmed the presence of CBD/metabolites in participants' urine after CBD was added to their treatment regime. Analysis of missing data using multiple imputation supported the findings of the complete case analysis.

For a small group of individuals with TRE of varying etiologies, adjunctive use of artisanal CBD was associated with improvements in the behavioral and psychological symptoms of TRE, as well as improved medication tolerability.

The effect of meditation on brain activity has been the topic of many studies in healthy subjects and in patients suffering from chronic diseases. These effects are either explored during meditation practice (state effects) or as a longer-term result of meditation training during the resting-state (trait). The topic of this article is to first review these findings by focusing on electroencephalography (EEG) changes in healthy subjects with or without experience in meditation. Modifications in EEG baseline rhythms, functional connectivity and advanced nonlinear parameters are discussed in regard to feasibility in clinical applications. Secondly, we provide a state-of-the-art of studies that proposed meditative practices as a complementary therapy in patients with epilepsy, in whom anxiety and depressive symptoms are prevalent. In these studies, the effects of standardized meditation programs including elements of traditional meditation practices such as mindfulness, loving-kindness and compassion are explored both at the level of psychological functioning and on the occurrence of seizures. Lastly, preliminary results are given regarding our ongoing study, the aim of which is to quantify the effects of a mindfulness self-compassion (MSC) practice on interictal and ictal epileptic activity. Feasibility, difficulties, and prospects of this study are discussed.

Anhedonia is clinically defined as difficulty or inability to feel pleasure or to be motivated to perform activities that were previously pleasurable. Anhedonia is a core feature of depressive disorders but can be present in other conditions such as substance use and anxiety disorders. Herein we report the case of a 34-year-old female who developed marked anhedonia after left cortico-amygdalohippocampectomy. Despite optimal seizure control, the person struggled with anhedonia and other depressive symptoms. After ruling out medico-neurologic complications, she was prescribed with a selective serotonin reuptake inhibitor and cognitive-behavioral therapy. Anhedonia can be a challenging neuropsychiatric presentation that requires ruling out the effects of antiseizure medications, neurosurgery, and other drugs before prescribing antidepressants.

Epilepsy is one of the most common neurologic conditions. Its clinical manifestations are not restricted to seizures but often include cognitive disturbances and psychiatric disorders. Prospective population-based studies have shown that people with epilepsy have an increased risk of developing mood disorders, and people with a primary mood disorder have an increased risk of developing epilepsy. The existence of common pathogenic mechanisms in epilepsy and mood disorders may explain the bidirectional relation between these two conditions. Recognition of a personal and family psychiatric history at the time of evaluation of people for a seizure disorder is critical in the selection of antiseizure medications: those with mood-stabilizing properties (e.g., lamotrigine, oxcarbazepine) should be favoured as a first option in those with a positive history while those with negative psychotropic properties (e.g., levetiracetam, topiramate) avoided. While mood disorders may be clinically identical in people with epilepsy, they often present with atypical manifestations that do not meet ICD or DSM diagnostic criteria. Failure to treat mood disorders in epilepsy may have a negative impact, increasing suicide risk and iatrogenic effects of antiseizure medications and worsening quality of life. Treating mood disorders in epilepsy is identical to those with primary mood disorders. Yet, there is a common misconception that antidepressants have proconvulsant properties. Most antidepressants are safe when prescribed at therapeutic doses. The incidence of seizures is lower in people randomized to antidepressants than placebo in multicenter randomized placebo-controlled trials of people treated for a primary mood disorder. Thus, there is no excuse not to prescribe antidepressant medications to people with epilepsy.

Depression is a major public health problem and negatively affects the quality of life of patients with epilepsy. Despite multiple studies investigating the magnitude and predictors, the results have been inconsistent. Therefore, this study aimed to estimate the pooled prevalence and factors associated with depressive symptoms among patients with epilepsy in Ethiopia.

The primary articles were searched using databases like PubMed, Google Scholar, CINAHL, SCOPUS, EMBASE, and African Journal Online. A total of 10 primary articles that assessed the prevalence and factors associated with depressive symptoms among patients with epilepsy in Ethiopia were included. A Microsoft Excel spreadsheet was used to extract the data, which was then exported to Stata version 14 for further analysis. The statistical heterogeneity was evaluated using the I2 test. Due to heterogeneity, a random effect meta-analysis model was employed. Publication bias was checked through Egger's weighted regression test and funnel plot.

A total of 10 primary studies with 3,532 participants were included. The pooled prevalence of depressive symptoms among patients with epilepsy was found to be 41.69% (95% CI, 37.70, 45.68). The pooled prevalence of depressive symptoms was 48.61, 42.98, 40.68, 38.27, and 34.80% in Oromia, SNNPs, Amhara, Addis Ababa, and Tigray, respectively, based on a sub-group analysis per regional state. Perceived stigma (AOR = 3.30, 95% CI: 1.40, 7.80), seizure frequency (AOR = 3.81, 95% CI: 1.03, 14.09), and perceived stress (AOR = 4.6, 95% CI: 1.05, 20.06) were factors associated with depressive symptoms.

We found that depressive symptoms affects at least four out of ten patients with epilepsy, indicating an immense burden. Depressive symptoms were extremely prevalent in those who had high levels of stigma, a monthly seizure frequency of once or more, and perceived stress. Therefore, physicians should take extra precautions when treating patients with epilepsy who have certain conditions.

This study was registered according to The International Prospective Register of Systemic Review (PROSPERO) with the registration ID (CRD42023484308).

Depression and anxiety are the most common psychiatric comorbidities in epilepsy and are known to increase healthcare utilization, the risk of refractory epilepsy, and anti-seizure medication intolerability. Despite this, depression and anxiety continue to be underrecognized and undertreated in people with epilepsy (PWE). Several barriers to the identification of depression and anxiety in PWE exist, including reliance on unstructured interviews rather than standardized, validated instruments. Moreover, there is a dearth of behavioral health providers to manage these comorbidities once identified. The use of validated screening instruments in epilepsy clinics can assist with both the identification of psychiatric symptoms and monitoring of treatment response by the epilepsy clinician for PWE with comorbid depression and/or anxiety. While screening instruments can identify psychiatric symptoms occurring within a specified time, they are not definitively diagnostic. Screeners can be time efficient tools to identify patients requiring further evaluation for diagnostic confirmation. This article reviews recent literature on the utility of depression and anxiety screening instruments in epilepsy care, including commonly used screening instruments, and provides solutions for potential barriers to clinical implementation. Validated depression and anxiety screening instruments can increase identification of depression and anxiety and guide epilepsy clinician management of these comorbidities which has the potential to positively impact patient care.

To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults with drug-resistant focal epilepsy.

Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6-month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment-related variables were assessed by using a stepwise logistic regression model.

At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was associated with a 2.3 times increased risk of an initially negative NDDIE screening result becoming positive at re-assessment after 6 months. In addition, the number of ASMs taken at baseline correlated with an increased risk of a change in depression screening test results from negative to positive during follow-up, whereas no association was identified with sociodemographic and epilepsy-related variables, including seizure outcomes. Approximately 6% of patients who were initially negative at screening for suicidal ideation became positive at the 6-month re-assessment. The risk of switch from a negative to a positive screening test result for suicidal ideation was increased more than two-fold in individuals who screened positive for depression at baseline, and was unrelated to the type of ASM introduced, sociodemographic variables, or seizure outcomes.

Almost 1 in 5 adults with drug-resistant focal epilepsy who screen negative for depression become positive when re-assessed 6 months after a treatment change. At re-assessment 6 months later, 6.1% who screen initially negative for passive suicidal ideation become positive. These changes in screening status are independent of type of ASM introduced or seizure outcomes but correlate with psychiatric status at baseline.

It is well established that epileptic disorders are associated with a wide range of psychosocial issues that overburden the affected individuals and limit their lifestyle. This study aimed to determine the commonalities between depression and anxiety symptoms among patients with epilepsy (PWE). In addition, we assessed whether depression and anxiety rates varied depending on factors related to the disease.

A cross-sectional study was conducted between October 2021 and March 2022 among all PWE at Prince Mohammed bin Abdulaziz Hospital, and 147 patients who responded to the questionnaires were included for analysis (65.6% response rate). Depression was measured using the Patient Health Questionnaire depression scale (PHQ-9), while anxiety levels were measured using the Generalized Anxiety Disorder scale (GAD-7). Demographic variables such as sex, age, marital status, and factors related to epilepsy were also recorded.

The results showed that 39.5% and 27.9% of participants had major depressive disorder (MDD) and generalized anxiety disorder (GAD), respectively. The presence of factors that increased susceptibility to seizures was associated with a greater expression of depression (P = 0.035) and anxiety (P = 0.002) symptoms. The presence of symptoms/signs that precede seizures was associated with a higher risk of moderate and severe depression (P = 0.001) and moderate and severe anxiety (P < 0.001). Irregular use of medications was associated with a higher risk of moderate and severe depression (P = 0.037); however, lamotrigine was associated with lower rates of depression among the participants (P = 0.023).

This study found that PWE had a higher prevalence of MDD and GAD than the general population. However, this accepted paradigm has yet to reflect a meaningful change in constructing condition-specific recommendations for PWE. Our study revealed that the presence of subjectively recognized signs of an impending ictal episode was significantly associated with a higher risk of moderate and severe depression and anxiety. Furthermore, factors that increase the susceptibility to seizures were associated with a higher risk of depression and anxiety. Irregular medication use was associated with a higher risk of moderate and severe depression. However, lamotrigine was associated with lower rates of depression among participants.

The relationship between epilepsy and depression is bidirectional. One condition exacerbates the other. However, there are no current guidelines for treating depression in epilepsy patients. In some cases, seizures worsen when antidepressants (AD) are prescribed or when they are discontinued due to adverse events. The Shugan Jieyu capsule, composed of Acanthopanax senticosus and Hypericum perforatum, is a widely used herbal medicine for treating depression. This study aimed to explore the effectiveness and safety of Shugan Jieyu capsules (SJC) in relieving depression in patients with epilepsy.

We searched English, Korean, Japanese, and Chinese databases in October 2023 to collect all relevant randomized clinical trials (RCTs). The primary outcomes were the depression scale scores and seizure frequency. The secondary outcomes were quality of life (QoL) and adverse events.

Nine RCTs were included in this meta-analysis. Compared with AD, SJC showed significant differences in the improvement of depression (SMD: 3.82, 95% CI: 3.25, 4.39) and reduction in seizure frequency (MD: 0.39 times/month, 95% CI: 0.28, 0.50). SJC showed more beneficial results than antiepileptic drugs (AED) in terms of antidepressant effects (SMD: 1.10, 95% CI: 0.69, 1.51) and QoL (MD: 11.75, 95% CI: 10.55, 12.95). When patients were prescribed AED, the additional administration of SJC improved depression symptoms (SMD: 0.96, 95% CI: 0.28, 1.63). The SJC treatment group had a lower incidence of side effects than the control group. However, the difference was not statistically significant.

Our results suggest that SJC may be effective in treating depression in patients with epilepsy. Additionally, SJC has the potential to help reduce seizure frequency in epilepsy patients with depression.

Organophosphate (OP) compounds are highly toxic and include pesticides and chemical warfare nerve agents. OP exposure inhibits the acetylcholinesterase enzyme, causing cholinergic overstimulation that can evolve into status epilepticus (SE) and produce lethality. Furthermore, OP-induced SE survival is associated with mood and memory dysfunction and spontaneous recurrent seizures (SRS). In male Sprague-Dawley rats, we assessed hippocampal pathology and chronic SRS following SE induced by administration of OP agents paraoxon (2 mg/kg, s.c.), diisopropyl fluorophosphate (4 mg/kg, s.c.), or O-isopropyl methylphosphonofluoridate (GB; sarin) (2 mg/kg, s.c.), immediately followed by atropine and 2-PAM. At 1-hour post-OP-induced SE onset, midazolam was administered to control SE. Approximately 6 months after OP-induced SE, SRS were evaluated using video and electroencephalography monitoring. Histopathology was conducted using hematoxylin and eosin (H&E), while silver sulfide (Timm) staining was used to assess mossy fiber sprouting (MFS). Across all the OP agents, over 60% of rats that survived OP-induced SE developed chronic SRS. H&E staining revealed a significant hippocampal neuronal loss, while Timm staining revealed extensive MFS within the inner molecular region of the dentate gyrus. This study demonstrates that OP-induced SE is associated with hippocampal neuronal loss, extensive MFS, and the development of SRS, all hallmarks of chronic epilepsy. SIGNIFICANCE STATEMENT: Models of organophosphate (OP)-induced SE offer a unique resource to identify molecular mechanisms contributing to neuropathology and the development of chronic OP morbidities. These models could allow the screening of targeted therapeutics for efficacious treatment strategies for OP toxicities.

Understanding rare genetic brain disorders with overlapping neurological and psychiatric phenotypes is of increasing importance given the potential for developing disease models that could help to understand more common, polygenic disorders. However, the traditional clinical boundaries between neurology and psychiatry result in frequent segregation of these disorders into distinct silos, limiting cross-specialty understanding that could facilitate clinical and biological advances. In this Review, we highlight multiple genetic brain disorders in which neurological and psychiatric phenotypes are observed, but for which in-depth, cross-spectrum clinical phenotyping is rarely undertaken. We describe the combined phenotypes observed in association with genetic variants linked to epilepsy, dystonia, autism spectrum disorder and schizophrenia. We also consider common underlying mechanisms that centre on synaptic plasticity, including changes to synaptic and neuronal structure, calcium handling and the balance of excitatory and inhibitory neuronal activity. Further investigation is needed to better define and replicate these phenotypes in larger cohorts, which would help to gain greater understanding of the pathophysiological mechanisms and identify common therapeutic targets.

 Patients with epilepsy (PWE) frequently have comorbid psychiatric disorders, the most common of which are depression and anxiety. Attention deficit disorder with hyperactivity (ADHD) is also more frequent among PWE, though that condition has been scarcely studied among the adult PWE population.

 This study aimed to compare the presence of ADHD symptoms between adult PWE and the general population.

 This was an observational case-control study. Ninety-five adult PWE from a tertiary center in southern Brazil were compared with 100 healthy controls. All subjects were submitted to three structured scales: 1) the World Health Organization Adult ADHD Self-Report Scale version 1.1 (ASRS); 2) the Hospital Anxiety and Depression Scale (HADS); and 3) the Adverse Events Profile (AEP). Dichotomic variables were analyzed through chi-square test and Fisher's exact test, as appropriate, and non-parametric variables were analyzed through the Mann-Whitney U test.

 Medians and interquartile ranges (IR) were: 1) ASRS: 26.00 (IR: 18 to 38) among PWE versus 17.00 (IR: 11 to 24) among controls, p < 0.001; 2) HADS: 14.00 (IR: 8 to 21) among PWE versus 11.00 (IR: 8 to 16) among controls, p = 0.007; 3) AEP: 3800 (IR: 31 to 49) among PWE versus 33.00 (IR: 23 to 43) among controls, p = 0.001.

 PWE showed a higher burden of symptoms of ADHD, depression, and anxiety when compared with controls, which replicates in the Brazilian population the findings of current literature that point toward a higher prevalence of such disorders among PWE.

To determine sex differences in the prevalence of depression and assess the risk factors for depression among adult patients with epilepsy from the Dali area of China.

We retrospectively analyzed the clinical data of adult patients with epilepsy who visited the First Affiliated Hospital of Dali University from January 2017 to January 2022. Patient Health Questionnaire-9 was used to assess depressive symptoms in patients with epilepsy. The risk factors of depression were analyzed by binary logistic regression among different sex in patients with epilepsy.

There were significant sex differences in depression in patients with epilepsy (p < 0.001), and females were 4.27 times more likely to suffer from depression than males (95% confidence interval: 3.70-4.92). The risk factors for depression among female patients with epilepsy included occupation (p < 0.001), years with epilepsy (p < 0.001), seizure frequency (p < 0.001), seizure type (p < 0.001), etiology (p < 0.001), number of antiseizure medications used (p < 0.001), antiseizure medications (p < 0.001), and electroencephalogram findings (p < 0.001). The risk factors for depression among male patients with epilepsy included age (p < 0.001), ethnicity (p < 0.001), occupation (p < 0.001), years with epilepsy (p < 0.001), seizure frequency (p < 0.001), seizure type (p < 0.001), etiology (p < 0.001), number of antiseizure medications used (p < 0.001), antiseizure medications (p < 0.001), and electroencephalogram findings (p < 0.001).

Adult female patients with epilepsy had a higher risk of depression than adult male patients with epilepsy. There were sex differences in the risk factors associated with depression among patients with epilepsy.

Depression, a common mental problem frequently detected in people with epilepsy (PWE), is a major factor that decreases the quality of life of PWE. The cognitive behavioral therapy (CBT) is the most commonly used non-pharmacological treatment for depressive disorders. The CBT for PWE with depression has not yet been studied in Korea. This study aimed to evaluate the effects of the CBT on depression in PWE in Korea.

This study included 16 PWE with depression who received CBT and 30 control PWE with depression who did not receive CBT. The mean number of CBT sessions per patient was 7.2 in the CBT group. The Beck Depression Inventory-II (BDI-II) and Patient Health Questionnaire-9 (PHQ-9) were administered before and after CBT sessions in the CBT group, whereas PHQ-9 was performed at baseline and follow-up in the control group. The difference in PHQ-9 and BDI-II scores were analyzed between the pre- and post-CBT periods in the CBT group. The difference between baseline and follow-up PHQ-9 scores was compared in the control group.

There was no significant difference in baseline variables between the CBT and control groups. The PHQ-9 score significantly decreased after the CBT sessions in the CBT group (pre-CBT PHQ-9 = 13.56 vs. post-CBT PHQ-9 = 8.56) but it did not change in the control group (Baseline PHQ-9 = 13.83 vs. follow-up PHQ-9 = 14.67). Twelve PWE had undergone four or more CBT sessions with pre-CBT and post-CBT BDI-II. The BDI-II score significantly decreased after CBT sessions (pre-CBT BDI-II = 30.75 vs. post-CBT BDI-II = 21.5). The CBT decreased the sub-field scores of cognitive and physical-emotional factors as well as suicidal ideation, but the score of sleep problems did not significantly improve. The CBT did not significantly change the seizure frequency.

The CBT significantly improved depression in Korean PWE. Therefore, it can be considered a treatment tool for depression in PWE. However, a study with more patients and a fixed number of CBT sessions is recommended to generalize this effect.