Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

The role of axon guidance molecules in the pathogenesis of epilepsy

Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.

Physical rehabilitation for sensorineural hearing loss in childhood:Progress and challenges

Early intervention for sensorineural hearing loss(SNHL)in childhood is crucial for auditory and language development.In recent years,innovative auditory stimulation techniques and speech therapy strategies,such as middle ear implants,cochlear implants,auditory brainstem implants,and midbrain implants,have provided new avenues for improving patient outcomes.Additionally,basic research advancements in cell reprogramming and regeneration,stem cell therapy,and targeted drug delivery offer promising approaches to meet the individualized needs of children with SNHL.However,many challenges and unresolved issues remain in the treatment of SNHL.This article comments on the case report,which describes a female pediatric patient with SNHL who underwent foot reflexology which led to the normalization of hearing thresholds.Reflexology is considered to have potential benefits in physical rehabilitation,but its efficacy in hearing restoration requires further scientific validation through rigorous clinical trials and large-scale prospective studies.

Interleukin-6 in epilepsy and its neuropsychiatric comorbidities: How to bridge the gap

There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.

Childhood epilepsy and sleep

Sleep and epilepsy are two well recognized conditions that interact with each other in a complex bi-directional way. Some types of epilepsies have increased activity during sleep disturbing it; while sleep deprivation aggravates epilepsy due to decreased seizure threshold. Epilepsy can deteriorate the sleep-related disorders and at the same time; the parasomnias can worsen the epilepsy. The secretion of sleep-related hormones can also be affected by the occurrence of seizures and supplementation of epileptic patients with some of these sleep-related hormones may have a beneficial role in controlling epilepsy.

Multi-scale phase average waveform of electroencephalogram signals in childhood absence epilepsy using wavelet transformation

BACKGROUND： Recent studies have focused on various methods of wavelet transformation for electroencephalogram （EEG） signals. However, there are very few studies reporting characteristics of multi-scale phase waves during epileptic discharge.OBJECTIVE： To extract multi-scale phase average waveforms from childhood absence epilepsy EEG signals between time and frequency domains using wavelet transformation, and to compare EEG signals of absence seizure with pre-epileptic seizure and normal children, and to quantify multi-scale phase average waveforms from childhood absence epilepsy EEG signals. DESIGN, TIME AND SETTING： The case-comparative experiment was performed at the Department of Neuroelectrophysiology, Tianjin Medical University from August 2002 to May 2005. PARTICIPANTS： A total of 15 patients with childhood absence epilepsy from the General Hospital of Tianjin Medical University were enrolled in the study. The patients were not administered anti-epileptic drugs or sedatives prior to EEG testing. In addition, 12 healthy, age- and gender-matched children were also enrolled.METHODS： EEG signals were tested on 15 patients with childhood absence epilepsy and 12 normal children. Epileptic discharge signals during clinical and subclinical seizures were collected 10 and 20 times, respectively. The collected EEG signals were treated with wavelet transformation to extract multi-scale characteristics during absence epilepsy seizure using a conditional sampling method. Multi-scale phase average waveforms were collected using a conditional phase averaging technique. Amplitude of phase average waveform from EEG signals of epilepsy seizure, subclinical epileptic discharge, and EEG signals of normal children were compared and statistically analyzed in the first half-cycle.MAIN OUTCOME MEASURES： Multi-scale wavelet coefficient and the evolution of EEG signals were observed during childhood absence epilepsy seizures using wavelet transformation. Multi-scale phase average waveforms from EEG signals were observed using a conditional sampling method and phase averaging technique.RESULTS： Multi-scale characteristics of EEG signals demonstrated that 12-scale （3 Hz） rhythmical activity was significantly enhanced during childhood absence epilepsy seizure and co-existed with background structure （〈1 Hz, low frequency discharge）. The phase average wave exhibited opposed phase abnormal rhythm at 3 Hz. Prior to childhood absence epilepsy seizure, EEG detected opposed abnormal a rhythm and 3 Hz composition, which were not detected with traditional EEG. Compared to EEG signals from normal children, epileptic discharges from clinical and subclinical childhood absence epilepsy seizures were positive and amplitude was significantly greater （P〈0.05）.CONCLUSION： Wavelet transformation was used to analyze EEG signals from childhood absence epilepsy to obtain multi-scale quantitative characteristics and phase average waveforms. Multi-scale wavelet coefficients of EEG signals correlated with childhood absence epilepsy seizure, and multi-scale waveforms prior to epilepsy seizure were similar to characteristics during the onset period. Compared to normal children, EEG signals during epilepsy seizure exhibited an opposed phase model.

Localization of epileptic foci in Children with childhood absence epilepsy by magnetoencephalography combined with synthetic aperture magnetometry

This present study was aimed to investigate the localizable diagnostic value of magnetoencephalography （MEG） combined with synthetic aperture magnetometry （SAM） in childhood absence epilepsy （CAE）. Thirteen CAE patients underwent MEG detection at resting state and after hyperventilation, and then the epileptic loci were located by SAM. In the thirteen CAE patients, epileptic foci were found in five cases （38.5%）, and they were all located in the bilateral frontal lobe, suggesting that the frontal lobe in some CAE patients may serve as the epileptic foci. Our findings indicate that MEG combined with SAM could be of diagnostic value in localizing the epileptic foci in certain CAE patients.

BRAIN ELECTROENCEPHALOGIC ACTIVITY MAPPING ON CHILDHOOD EPILEPSY

With EEG, Computed Topography (CT) and Brain Electroencephalogic Activity Mapping (BEAM), we researched the changes on 64 epileptic children aged 4～14 years, to explore a clinical diagnostic significance. The BEAM technique-has proved to be particularly useful in establishing the focal origin of paroxystic activity in a high percentage of cases of partial epilepsies (91.2% ) and generalized epilepsies (90% ) and has shown particularly valuable and sensitive in localizing areas of brain function abnormality not detected by other diagnostic techniques.

Predictive Factors for Abnormal Brain CT-Scan in Childhood Epilepsy at Yaoundé(Cameroon)

Purpose: Despite irradiation, CT-scan remains an important diagnostic tool in epilepsy in poor countries where MRI is neither available nor affordable. But many causes of epilepsy are not accessible to CT-scan and this technique remains expensive for many poor families in countries with limited resources. The aim of this study was to determine clinical or electroencephalogram variables which could predict brain CT-scan abnormalities in childhood epilepsy. Methods: It was a cross-sectional study including 151 epileptic children who underwent head CT-scan from October 2011 to march 2012, in one university-affiliated hospital in Cameroon (YGOPH). The data collected were clinical, type of seizure, Electroencephalogram and head CT-scans results. Independent predictive factors for CT abnormalities were sought by logistic regression. A p value : Of the 151 children, 54.3% (82/151) were boys (sex ratio: 1.18 M/1F). The median age was 54 months [2 - 190 months];74.8% of children were more than 2 years old but at the onset of epilepsy they were 2 years old or less. Birth asphyxia, mental retardation and neurologic deficit were respectively associated in 62.4%, 54.3% and 51.7% of cases. Eighty-five had focal epilepsy (56.3%), 61.6% had abnormal head CT-scan, 68.9% had abnormal EEG, with no significant gender difference. The factors most significantly associated with abnormal head CT-scan were: child age ≤ 2 years, maternal hypertension/eclampsy, cerebral palsy, and child microcephaly, with 89% to 92% abnormal CT. The two independent predictors of abnormal CT were patients’ age ≤ 2 years and microcephaly. The two main CT-scan lesions were cerebral atrophy (28.5%) and brain infarct (16.6%). None of these abnormalities was correlated to any type of epilepsy. Conclusion: Almost two-thirds of head CT-scan performed in epileptic children are abnormal in our setting. Patients of 2 years old or less and those with microcephaly are very likely to have brain anomalies on CT-scan. The most common brain lesions are atrophy, cerebral infarction and porencephalic cavities. Action to reduce birth asphyxia may lead to the reduction of the incidence of epilepsy in children.

Nrf2 as a potential target for the treatment of epilepsy

Epilepsy is a prevalent chronic brain disorder that is characterized by a persistent predisposition to recurrently generate epileptic seizures and is often associated with cognitive and psychological consequences.Epilepsy affects approximately 65 million individuals,including both males and females of all ages worldwide,and poses a significant burden on patients,their families,and the health system(Vezzani et al.,2019).

Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

Flexible,high-density,laminated ECoG electrode array for high spatiotemporal resolution foci diagnostic localization of refractory epilepsy

High spatiotemporal resolution brain electrical signals are critical for basic neuroscience research and high-precision focus diagnostic localization,as the spatial scale of some pathologic signals is at the submillimeter or micrometer level.This entails connecting hundreds or thousands of electrode wires on a limited surface.This study reported a class of flexible,ultrathin,highdensity electrocorticogram(ECoG)electrode arrays.The challenge of a large number of wiring arrangements was overcome by a laminated structure design and processing technology improvement.The flexible,ultrathin,high-density ECoG electrode array was conformably attached to the cortex for reliable,high spatial resolution electrophysiologic recordings.The minimum spacing between electrodes was 15μm,comparable to the diameter of a single neuron.Eight hundred electrodes were prepared with an electrode density of 4444 mm^(-2).In focal epilepsy surgery,the flexible,high-density,laminated ECoG electrode array with 36 electrodes was applied to collect epileptic spike waves inrabbits,improving the positioning accuracy of epilepsy lesions from the centimeter to the submillimeter level.The flexible,high-density,laminated ECoG electrode array has potential clinical applications in intractable epilepsy and other neurologic diseases requiring high-precision electroencephalogram acquisition.

Association between childhood obesity and gut microbiota:16S rRNA gene sequencing-based cohort study

BACKGROUND This study aimed to identify characteristic gut genera in obese and normal-weight children(8-12 years old)using 16S rDNA sequencing.The research aimed to provide insights for mechanistic studies and prevention strategies for childhood obesity.Thirty normal-weight and thirty age-and sex-matched obese children were included.Questionnaires and body measurements were collected,and fecal samples underwent 16S rDNA sequencing.Significant differences in body mass index(BMI)and body-fat percentage were observed between the groups.Analysis of gut microbiota diversity revealed lowerα-diversity in obese children.Differences in gut microbiota composition were found between the two groups.Prevotella and Firmicutes were more abundant in the obese group,while Bacteroides and Sanguibacteroides were more prevalent in the control group.AIM To identify the characteristic gut genera in obese and normal-weight children(8-12-year-old)using 16S rDNA sequencing,and provide a basis for subsequent mechanistic studies and prevention strategies for childhood obesity.METHODS Thirty each normal-weight,1:1 matched for age and sex,and obese children,with an obese status from 2020 to 2022,were included in the control and obese groups,respectively.Basic information was collected through questionnaires and body measurements were obtained from both obese and normal-weight children.Fecal samples were collected from both groups and subjected to 16S rDNA sequencing using an Illumina MiSeq sequencing platform for gut microbiota diversity analysis.RESULTS Significant differences in BMI and body-fat percentage were observed between the two groups.The Ace and Chao1 indices were significantly lower in the obese group than those in the control group,whereas differences were not significant in the Shannon and Simpson indices.Kruskal-Wallis tests indicated significant differences in unweighted and weighted UniFrac distances between the gut microbiota of normal-weight and obese children(P<0.01),suggesting substantial disparities in both the species and quantity of gut microbiota between the two groups.Prevotella,Firmicutes,Bacteroides,and Sanguibacteroides were more abundant in the obese and control groups,respectively.Heatmap results demonstrated significant differences in the gut microbiota composition between obese and normal-weight children.CONCLUSION Obese children exhibited lowerα-diversity in their gut microbiota than did the normal-weight children.Significant differences were observed in the composition of gut microbiota between obese and normal-weight children.

Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study

BACKGROUND The interplay between inflammation,immune dysregulation,and the onset of neurological disorders,including epilepsy,has become increasingly recognized.Interleukin(IL)-6,a pro-inflammatory cytokine,is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients.The role of IL-6 receptor(IL6R)blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes.neuropsychiatric conditions due to neuroinflammation.METHODS Mendelian randomization(MR)analysis employing single nucleotide poly-morphisms(SNPs)in the vicinity of the IL6R gene(total individuals=408225)was used to evaluate the putative causal relationship between IL6R blockade and epilepsy(total cases/controls=12891/312803),focal epilepsy(cases/controls=7526/399290),and generalized epilepsy(cases/controls=1413/399287).SNP weights were determined by their effect on C-reactive protein(CRP)levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects.To address potential outlier and pleiotropic influences,sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions.RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk[inverse variance weighting:Odds ratio(OR):0.827;95%confidence interval(CI):0.685-1.000;P=0.05].Subtype analysis showed variability,with no significant effect observed in generalized,focal,or specific childhood and juvenile epilepsy forms.Beyond the primary inflammatory marker CRP,the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy,hinting at possible links to neuroinflammation,psychiatric symptoms,and associated mental disorders.CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence,likely mediated via complex neuroinflammatory pathways.These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy.The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

Total hip arthroplasty for sequelae of childhood hip disorders:Current review of management to achieve hip centre restoration

Adults requiring total hip arthroplasty(THA)for childhood disorder sequelae present with shortening,limp,pain,and altered gait.THA,which can be particularly challenging due to altered anatomy,requires careful planning,assessment,and computed tomography evaluation.Preoperative templating is essential to establish the appropriate acetabular and femoral size.Information regarding neck length and offset is needed to ensure the proper options are available at THA.Hip centre restoration must be planned preoperatively and achieved intraoperatively with appropriate exposure,identification,and stable fixation with optimum-size components.Identifying the actual acetabular floor is essential as changes include altered anatomy,distortion of the margins and version changes.Proximal femur changes include anatomical variation,decreased canal diameter,cortical thickness,changes in anteversion,and metaphyseal and diaphyseal mismatch.Preoperative assessment should consist of limb assessment for variations due to prior surgical procedures.Evaluation of the shortening pattern with the relationship of the lesser trochanter to the teardrop would help identify and plan for subtrochanteric shortening osteotomy,especially in high-riding hips.The surgical approach must ensure adequate exposure and soft tissue release to achieve restoration of the anatomical hip centre.The femoral components may require modularity to enable restoration of anteversion and optimum fixation.

Aberrant adult neurogenesis in intractable epilepsy:can GABAergic progenitor transplantation normalize this process?

Temporal lobe epilepsy(TLE) is a common type of focal epilepsy characterized by seizure foci within the temporal lobes.While surgical resection of the foci is an established and effective approach for controlling seizures,both temporal lobes cannot be removed,due to their prominent roles in learning and memory.Additionally,seizures induce changes to the temporal lobes that contribute to hyperexcitability,including mossy fiber sprouting,astrogliosis.

Astrocyte chloride,excitatory-inhibitory balance and epilepsy

Excitation and inhibition are at the core of brain function and malfunction.To sustain the activity of neuronal networks over time and space,glutamatergic excitation is balanced by GABAergic inhibition.The equipoise of excitation and inhibition,known as the excitation/inhibition(E/I)balance,is crucial for proper brain function.The E/I balance is highly dynamic and shifts across different brain states:wakefulness primarily augments excitatory activity,while sleep promotes a decrease in excitation and an increase in inhibition(Bridi et al.,2020).Neuronal activity during various brain states is primarily regulated by neurotransmitters(Schiemann et al.,2015),alongside non-synaptic mechanisms that operate on a slower timescale.The non-synaptic mechanisms are many,with the ionic composition of the extracellular space playing a significant role;altering extracellular ion concentrations affects sleep,arousal,electroencephalogram patterns,and behavioral states(Ding et al.,2016).

Iron supplementation during malaria infection in pregnancy and childhood:A review

Malaria presents a significant global public health challenge,with severe malarial anaemia being a primary manifestation of the disease.The understanding of anaemia caused by malaria remains incomplete,making the treatment more complex.Iron is a crucial micronutrient essential for haemoglobin synthesis,oxygen delivery,and other vital metabolic functions in the body.It is indispensable for the growth of human beings,as well as bacteria,protozoa,and viruses in vitro and in vivo.Iron deficiency is among the most common nutritional deficiencies and can have detrimental effects during developmental stages of life.Malaria-induced iron deficiency occurs due to the hemolysis of erythrocytes and the suppression of erythropoiesis,leading to anaemia.Meeting iron requirements is particularly critical during pivotal life stages such as pregnancy,infancy,and childhood.Dietary intake alone may not suffice to meet adequate iron requirements,thus highlighting the vital role of iron supplementation.While iron supplementation can alleviate iron deficiency,it can exacerbate malaria infection by providing additional iron for the parasites.However,in the context of pregnancy and childhood,iron supplementation combined with malaria prevention and treatment has been shown to be beneficial in improving birth outcomes and ensuring proper growth and development,respectively.This review aims to identify the role and impact of iron supplementation in malaria infection during the life stages of pregnancy and childhood.

Atherosclerosis originating from childhood:Specific features

Atherosclerosis is extremely widespread.Traditionally,it is considered a disease of older people,who most often experience problems with the heart and blood vessels.While much attention from the scientific community has been paid to studying the association between aging and atherosclerosis,as well as its consequences,there is evidence that atherosclerosis occurs at an early age.Atherosclerosis may form both during intrauterine development and in childhood.Nutrition plays an important role in childhood atherosclerosis,along with previous infectious diseases and excess weight of both the child and the mother.In the present review,we examined the development of atherosclerosis and the prerequisites in childhood.

Psychiatric comorbidities in epilepsy:population co-occurrence,genetic correlations and causal effects

Background Psychiatric comorbidities are common in patients with epilepsy.Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.Aim We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.Methods Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy.We then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression.Finally,we assessed the potential bidirectional relationships using two-sample Mendelian randomisation.Results In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions.For example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,p<0.001)—a correlation that was more pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,p<0.001).Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric conditions.Conclusions Psychiatric comorbidities are common in patients with epilepsy.Genetic correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric conditions.These findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psychiatric comorbidities in epilepsy.