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Nano-chromium picolinate and heat stress enhance insulin sensitivity in cross-bred sheep

Animal Nutrition 2023年第2期13卷 173-184页

作者： Alex T.Hung brian j.leury Matthew A.Sabin Fahri Fahri Kristy DiGiacomo Tu-Fa Lien Frank R.Dunshea Faculty of Veterinary and Agricultural Sciences The University of MelbourneParkvilleVIC 3010Australia Murdoch Children's Research Institute The University of MelbourneParkvilleVIC 3010Australia Department of Animal Science National Chiayi UniversityChiayiChina Faculty of Biological Sciences The University of LeedsLeeds LS29JTUnited Kingdom

This study evaluated the effects of heat stress(HS)and dietary nano chromium picolinate(nCrPic)on metabolic responses of sheep to an intravenous glucose tolerance test(IVGTT),an intravenous insulin tolerance test(ITT)and an intramuscular adrenocorticotropin hormone(ACTH)challenge in sheep.Thirty-six sheep housed in metabolic cages were randomly allocated within 3 dietary groups(0,400 and 800 mg/kg supplemental nCrPic)to either thermoneutral(22℃)or cyclic HS(22 to 40℃)conditions for 3 wk.Basal plasma glucose tended to be increased during HS(P=0.052)and decreased by dietary nCrPic(P=0.013)while plasma non-esterified fatty acid concentrations were decreased(P=0.010)by HS.Di-etary nCrPic reduced the plasma glucose area under the curve(P=0.012)while there were no significant effects of HS on plasma glucose area under the curve in response to the IVGTT.The plasma insulin response over the first 60 min after the IVGTT was decreased by HS(P=0.013)and dietary nCrPic(P=0.022)with the effects being additive.In response to the ITT plasma glucose reached a nadir sooner(P=0.005)in sheep exposed to HS,although there was no effect on the depth of the nadir.Dietary nCrPic decreased(P=0.007)the plasma glucose nadir after ITT.Over the duration of the ITT plasma insulin concentrations were lower in sheep exposed to HS(P=0.013)whereas there was no significant effect of supplemental nCrPic.There was no effect of either HS or nCrPic on cortisol response to ACTH.Dietary nCrPic supple-mentation decreased(P=0.013)mitogen-activated protein kinase-8(jNK)and increased(P=0.050)carnitine palmitoyltransferase 1B(CPT1B)mRNA expression in skeletal muscle.Results of this experiment demonstrated that animals under HS and supplemented with nCrPic had greater insulin sensitivity.

关键词： Chromium picolinate Sheep Heat stress Insulin sensitivity

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Gestational heat stress alters skeletal muscle gene expression profiles and vascularity in fetal pigs in a sexually dimorphic manner

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journal of Animal Science and Biotechnology 2022年第6期13卷 1785-1798页

作者： Weicheng Zhao Mark P.Green Christina D.Marth Fan Liu Hieu H.Le Gordon S.Lynch Alan W.Bell brian j.leury Frank R.Dunshea jeremy j.Cottrell School of Agriculture and Food Faculty of Veterinary and Agricultural SciencesThe University of MelbourneParkvilleVIC 3010Australia School of BioSciences Faculty of ScienceThe University of MelbourneParkvilleVIC 3010Australia Melbourne Veterinary School Faculty of Veterinary and Agricultural SciencesThe University of MelbourneWerribeeVIC 3030Australia Rivalea Australia Pty Ltd CorowaNSW 2646Australia Centre for Muscle Research Department of Anatomy and PhysiologyThe University of MelbourneParkville 3010Australia Department of Animal Science Cornell UniversityIthacaNY 14853-4801USA Faculty of Biological Sciences The University of LeedsLeeds LS29JTUK

Background: There is evidence that sow heat stress(HS) during gestation affects fetal development with implications for impaired muscle growth. We have previously demonstrated that maternal HS during early to midgestation compromised muscle fibre hyperplasia in developing fetal pigs. Thus, we hypothesised these phenotypic changes are associated with a change in expression of genes regulating fetal skeletal muscle development and metabolism. To test this, at d 60 of gestation, RNA sequencing and immunohistochemistry were performed on fetal longissimus dorsi(LD) muscle biopsies collected from pregnant gilts that had experienced either thermoneutral control(CON, 20 ℃, n = 7 gilts, 18 LD samples) or controlled HS(cyclic 28 to 33 ℃, n = 8 gilts, 23 LD samples)conditions for 3 weeks.Results: A total of 282 genes were differentially expressed between the HS and CON groups in female LD muscles(false discovery rate(FDR) ≤ 0.05), whereas no differentially expressed genes were detected in male LD muscles between the two groups(FDR > 0.05). Gestational HS increased the expression of genes associated with transcription corepressor activity, adipogenesis cascades, negative regulation of angiogenesis and pro-inflammatory signalling in female LD muscles. Immunohistochemical analyses revealed a decreased muscle vascularity density in fetuses from HS group for both sexes compared to those from the CON group(P = 0.004).Conclusions: These results reveal gilt HS during early to mid-gestation altered gene expression profiles in fetal LD muscles in a sexually dimorphic manner. The molecular responses, including transcription and angiogenesis repressions and enhanced adipogenesis cascades, were exclusively observed in females. However, the associated reductions in muscle vascularity were observed independently of sexes. Collectively this may indicate female fetal pigs are more adaptive to gestational HS in terms of gene expression changes, and/or there may be sexually dimorphic differences with respect to the timing of muscle molecular

关键词： Adipogenesis Angiogenesis Fetal pig Gestation Heat stress Sexual dimorphism Skeletal muscle Sows

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Acid-insoluble ash is a better indigestible marker than chromic oxide to measure apparent total tract digestibility in pigs

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Animal Nutrition 2021年第1期7卷 64-71页

作者： Susanto Prawirodigdo Neil j.Gannon brian j.leury Frank R.Dunshea Faculty of Veterinary and Agricultural Sciences The University of MelbourneParkvilleVictoria3010Australia Balai Pengkajian Teknologi Pertanian Central java SemarangCentral Java50552Indonesia Biomin Singapore PO Box 2419ToowoombaQLD4350Australia Faculty of Biological Sciences The University of LeedsLeedsLS29JTUnited Kingdom

The aim of this study was to determine the apparent total tract digestibility(ATTD)of nutrients in cottonseed meal(CSM)and soybean meal(SBM)in simple carbohydrate and more complex wheat-based diets using 2 indigestible markers and total faecal collection.Twenty-five Large White×Landrace boars(57.8 kg)were randomly allocated to either a pure wheat diet,40%CSM or SBM in either a sugar-starch-(1∶1)or wheat-based diet for 18 d.Acid-insoluble ash(AIA)and chromic oxide(Cr2O3)were included in all diets as indigestible markers.Diets were offered(1,800 g/d per pig)in 3 meals/d from d 1 to 11 and 8 meals/d from d 12 to 17.On d 9,the pigs were moved to individual metabolism cages to allow total faecal collection.On d 18,the pigs were fed hourly for 8 h.After the 8th meal,pigs were anaesthetized and digesta sampled from the terminal ileum and rectum before lethal injection.There were no differences between ATTD of nitrogen(N)determined using AIA as a marker and measured by total faecal collection.On the other hand,the ATrD of N of diets containing CSM in sugar-starch-or wheat-based diets and the pure wheat diet determined using Cr2O3 as a marker was less(-3.11%,-4.46%and-6.59%;P

关键词： Organic matter Pig Wheat Cottonseed meal Soybean meal Digestibility Nitrogen

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Basal diet and indigestible marker influence apparent digestibilities of nitrogen and amino acids of cottonseed meal and soybean meal in pigs

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Animal Nutrition 2019年第3期5卷 234-240页

作者： Susanto Prawirodigdo Neil j.Gannon brian j.leury Frank R.Dunshea Faculty of Veterinary and Agricultural Sciences The University of MelbourneParkvilleVictoria3010Australia BPTP Central java SemarangCentral Java50552Indonesia Biomin Singapore PO Box 2419ToowoombaQLD4350Australia

This study was to determine the apparent ileal nitrogen(N)and amino acid digestibilities of cottonseed meal(CSM)and soybean meal(SBM)in simple carbohydrate-based and more complex wheat-based diets.Twenty five Large White × Landrace boars(40.9 kg)were randomly allocated to one of 5 dietary treatments:a wheat diet,40% CSM in either a sugar:starch(1:1)or wheat-based diet,or 40% SBM in either a sugar:starch or wheat-based diet for 14 d.All diets contained vitamins,minerals,and contained acid-insoluble ash(AIA)and Cr2 O3 as indigestible markers.Rations were offered(1,800 g/pig per d)in3 meals/d on d 1-11 and 8 meals/d on d 12-13.On d 14,the pigs were fed hourly for 8 h.After the 8 th meal,pigs were anaesthetised with isoflurothane,and ileal and faecal digesta sampled from the terminal ileum and rectum before lethal injection of barbiturate.Apparent ileal digestibility(AID)of N was greater(12.1%)when CSM was fed in the wheat-based diet as compared to the simple carbohydrate-based diet,whereas apparent ileal N digestibility of SBM was slightly lower(-4.5%)in the wheat-based diet as compared to the sugar:starch-based diet.Apparent ileal amino acid digestibility generally respondeds similarly to N.Therefore,while there was a wide difference in apparent N and amino acid digestibilities of SBM and CSM when they were fed in the sugar:starch-based diets,these differences were less apparent when they were fed the wheat-based diet.There was an apparent net release of N into the hindgut of pigs fed CSM in both base diets.Conversely,there was quite substantial apparent digestion of N in the hindgut of pigs fed SBM in both base diets.The use of Cr2 O3 as an indigestible marker resulted in lower apparent ileal and faecal digestibilities than using AIA,particularly for diets containing CSM.These data demonstrate that the basal diet and choice of indigestible marker can substantially influence the estimate of apparent N digestibility,this response can differ for different protein meals.

关键词： Organic matter Pig Wheat Cottonseed meal Soybean meal Digestibility

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Dietary nano chromium picolinate can ameliorate some of the impacts of heat stress in cross-bred sheep

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Animal Nutrition 2021年第1期7卷 198-205页

作者： Alex T.Hung brian j.leury Matthew A.Sabin Fahri Fahri Kristy DiGiacomo Tu-Fa Lien Frank R.Dunshea Faculty of Veterinary and Agricultural Sciences The University of MelbourneParkvilleVIC3010Australia Murdoch Children's Research Institute The University of MelbourneParkvilleVIC3010Australia Department of Animal Science National Chiayi UniversityChina Faculty of Biological Sciences The University of LeedsLeeds LS29JTUnited Kingdom

Two studies were conducted to evaluate the effect of nano chromium picolinate(nCrPic)during heat stress(HS)in sheep.In the initial study,36 Merino×Poll cross-bred sheep were individually penned and allocated to 3 dietary treatments(0,400 and 800μg/kg nCrPic)for 8 wk.Body composition was determined at the beginning and end of the experiment using dual energy X-ray absorptiometry.The sheep remained in their dietary groups but were then placed in metabolic cages and randomly allocated within the dietary group to differing ambient temperature regimes,i.e.,thermo-neutral(TN)(n=18)and HS(n=18),for 3 wk.Dietary nCrPic had no effect on growth performance and body composition during the initial study conducted under TN conditions.Heat stress decreased average daily feed intake(ADFI)(P=0.002)whereas sheep under HS had reduced average daily gain(ADG)and indeed lost weight(P<0.001).Dietary nCrPic increased both ADFI(P=0.041)and ADG(P=0.049)under both TH and HS conditions such that the performance of sheep receiving supplemental nCrPic and exposed to HS was similar to that of control sheep maintained under TN conditions.Heat stress increased rectal temperature(P<0.001)and respiration rate(P<0.001),particularly during the hottest parts of the day as indicated by interactions(P<0.001)between time of day and thermal treatment.Rectal temperature was lower in sheep fed nCrPic(P=0.050),particularly under peak HS conditions during the afternoon as indicated by the interactions between dietary nCrPic and time of day(P<0.001)and dietary nCrPic,thermal treat-ment and time of day(P=0.010).Similarly,respiration rate was lower in sheep fed nCrPic under peak HS conditions during the afternoon as indicated by the interactions between dietary nCrPic and thermal treatment(P<0.001)and dietary nCrPic and time of day(P=0.030).In conclusion,dietary nCrPic can partially ameliorate the negative effects of HS as indicated by the maintenance of ADFI and decreased physiological responses,such as elevations in rectal temperature and respiration rate.

关键词： Chromium picolinate Sheep Heat stress Nanotechnology Physiology

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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel brian Zanotti Michael V.Volin M.Asif Amin Myles j.Lewis Costantino Pitzalis Shiva Arami joseph A.Karam Nadera j.Sweiss Shiva Shahrara jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR activation.Mechanistically,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR signaling.In Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative phosphorylation.Conversely,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP capacity.The enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 expression.We found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA explants.Similar to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient animals.Consistently,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by Syntenin-1.In conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Fetal Head Compression: Its Possible Role in Neurologic Injury

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Open journal of Obstetrics and Gynecology 2024年第1期14卷 124-143页

作者： Barry S. Schifrin brian j. Koos Wayne R. Cohen Department of Obstetrics and Gynecology The Western University of Health Sciences Pomona USA The David Geffen School of Medicine at UCLA Los Angeles USA The University of Arizona College of Medicine Tucson USA

It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.

关键词： Fetal Brain Injury Fetal Head Compression Ischemic Encephalopathy Neonatal Encephalopathy

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Aerosol jet printing of surface acoustic wave microfluidic devices

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Microsystems & Nanoengineering 2024年第1期10卷 231-242页

作者： joseph Rich brian Cole Teng Li Brandon Lu Hanyu Fu Brittany N.Smith jianping Xia Shujie Yang Ruoyu Zhong james L.Doherty Kanji Kaneko Hiroaki Suzuki Zhenhua Tian Aaron D.Franklin Tony jun Huang Department of Biomedical Engineering Duke UniversityDurhamNC 27708USA Department of Electrical and Computer Engineering Duke UniversityDurhamNC 27708USA Department of Mechanical Engineering Virginia Polytechnic Institute and State UniversityBlacksburgVA 24061USA Thomas Lord Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA Deptartment of Precision Mechanics Faculty of Science and EngineeringChuo UniversityTokyo 112-8551Japan Department of Chemistry Duke UniversityDurhamNC 27708USA

The addition of surface acoustic wave(SAW)technologies to microfluidics has greatly advanced lab-on-a-chip applications due to their unique and powerful attributes,including high-precision manipulation,versatility,integrability,biocompatibility,contactless nature,and rapid actuation.However,the development of SAW microfluidic devices is limited by complex and time-consuming micro/nanofabrication techniques and access to cleanroom facilities for multistep photolithography and vacuum-based processing.To simplify the fabrication of SAW microfluidic devices with customizable dimensions and functions,we utilized the additive manufacturing technique of aerosol jet printing.We successfully fabricated customized SAW microfluidic devices of varying materials,including silver nanowires,graphene,and poly(3,4-ethylenedioxythiophene)polystyrene sulfonate(PEDOT:PSS).To characterize and compare the acoustic actuation performance of these aerosol jet printed SAW microfluidic devices with their cleanroom-fabricated counterparts,the wave displacements and resonant frequencies of the different fabricated devices were directly measured through scanning laser Doppler vibrometry.Finally,to exhibit the capability of the aerosol jet printed devices for lab-on-a-chip applications,we successfully conducted acoustic streaming and particle concentration experiments.Overall,we demonstrated a novel solution-based,direct-write,single-step,cleanroom-free additive manufacturing technique to rapidly develop SAW microfluidic devices that shows viability for applications in the fields of biology,chemistry,engineering,and medicine.

关键词： printing wave fluid

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The endogenous progenitor response following traumatic brain injury:a target for cell therapy paradigms

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Neural Regeneration Research 2022年第11期17卷 2351-2354页

作者： Anna Badner brian j.Cummings Department of Psychiatry and Behavioral Sciences Stanford UniversityPalo AltoCAUSA Sue and Bill Gross Stem Cell Center University of California-IrvineIrvineCAUSA Institute for Memory Impairments and Neurological Disorders University of California-IrvineIrvineCAUSA Physical Medicine and Rehabilitation University of California-IrvineIrvineCAUSA Department of Anatomy and Neurobiology University of California-IrvineIrvineCAUSA

Although there is ample evidence that central nervous system progenitor pools respond to traumatic brain injury,the reported effects are variable and likely contribute to both recovery as well as pathophysiology.Through a better understanding of the diverse progenitor populations in the adult brain and their niche-specific reactions to traumatic insult,treatments can be tailo red to enhance the benefits and dampen the deleterious effects of this response.This review provides an overview of endogenous precursors,the associated effects on cognitive recovery,and the potential of exogenous cell therapeutics to modulate these endogenous repair mechanisms.Beyond the hippocampal dentate gyrus and subventricular zone of the lateral ventricles,more recently identified sites of adult neurogenesis,the meninges,as well as circumventricular organs,are also discussed as targets for endogenous repair.Importantly,this review highlights that progenitor prolife ration alone is no longer a meaningful outcome and studies must strive to better chara cterize precursor spatial localization,transcriptional profile,morphology,and functional synaptic integration.With improved insight and a more targeted approach,the stimulation of endogenous neurogenesis remains a promising strategy for recovery following traumatic brain injury.

关键词： cell therapy endogenous repair neurogenic niche progenitors traumatic brain injury

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

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General Psychiatry 2024年第1期37卷 103-111页

作者： Viktor H Ahlqvist Christina Dardani Paul Madley-Dowd Harriet Forbes jessica Rast Caichen Zhong Renee M Gardner Christina Dalman Kristen Lyal cRAIG Newschaffer Torbjorn Tomson Michael Lundberg Daniel Berglind Neil M Davies brian K Lee Cecilia Magnusson Dheeraj Rai Department of Global Public Health Karolinska InstitutetStockholmSweden Medical Research Council Integrative Epidemiology Unit Bristol Medical SchoolUniversity of BristolBristolUK Centre for Academic Mental Health Population Health SciencesBristol Medical SchoolUniversity of BristolBristolUK Faculty of Epidemiology and Population Health London School of Hygiene and Tropical MedicineLondonUK A.j.Drexel Autism Institute Drexel UniversityPhiladelphiaPAUSA Department of Epidemiology and Biostatistics School of Public HealthDrexel UniversityPhiladelphiaPAUSA College of Health and Human Development Pennsylvania State UniversityState CollegePAUSA Department of Clinical Neuroscience Karolinska InstitutetStockholmSweden Centre for Epidemiology and Community Medicine Region StockholmStockholmSweden K.G jebsen Center for Genetic Epidemiology Department of Public Health and NursingNorwegian University of Science and TechnologyTrondheimNorway Division of Psychiatry University Collge LondonLondonUK Department of Statistical Sciences University Cllge LondonLondonK NIHR Biomedical Research Centre University of BristoBristolUK Avon and Wiltshire Partnership NHS Mental Health TrustBristolUK

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.

关键词： epilepsy Psychiat lifetime

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