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Brain-derived neurotrophic factor rs6265(Val66Met)single nucleotide polymorphism as a master modifier of human pathophysiology

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Neural Regeneration Research 2023年第1期18卷 102-106页

作者： Van Thuan Nguyen Braxton Hill Naiya Sims Aaron Heck Marcus Negron Claire Lusk Cristi LGalindo Department of Biology Western Kentucky UniversityBowling GreenKYUSA

Brain-derived neurotrophic factor is the most prevalent member of the nerve growth factor family.Since its discovery in 1978,this enigmatic molecule has spawned more than 27,000 publications,most of which are focused on neurological disorders.Brain-derived neurotrophic factor is indispensable during embryogenesis and postnatally for the normal development and function of both the central and peripheral nervous systems.It is becoming increasingly clear,however,that brain-derived neurotrophic factor likewise plays crucial roles in a variety of other biological functions independently of sympathetic or parasympathetic involvement.Brain-derived neurotrophic factor is also increasingly recognized as a sophisticated environmental sensor and master coordinator of whole organismal physiology.To that point,we recently found that a common nonsynonymous(Val66→Met)single nucleotide polymorphism in the brain-derived neurotrophic factor gene(rs6265)not only substantially alters basal cardiac transcriptomics in mice but subtly influences heart gene expression and function differentially in males and females.In addition to a short description of recent results from associative neuropsychiatric studies,this review provides an eclectic assortment of research reports that support a modulatory role for rs6265 including and beyond the central nervous system.

关键词： brain-derived neurotrophic factor neuropsychiatric disorders rs6265 Val66Met

众脑之力:通过开放神经影像数据和大规模协作催化神经精神疾病的创新发现

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Science Bulletin 2024年第10期69卷 1536-1555页

作者：鲁彬陈骁 Francisco Xavier Castellanos Paul M.Thompson 左西年臧玉峰严超赣 CAS Key Laboratory of Behavioral Science Institute of PsychologyBeijing 100101China Department of Psychology University of Chinese Academy of SciencesBeijing 100101China Department of Child and Adolescent Psychiatry NYU Grossman School of MedicineNew York 10016USA d Nathan Kline Institute for Psychiatric Research Orangeburg 10962USA Imaging Genetics Center Mark&Mary Stevens Institute for Neuroimaging&InformaticsKeck School of MedicineUniversity of Southern CaliforniaLos Angeles 90033USA Developmental Population Neuroscience Research Center IDG/McGovern Institute for Brain ResearchBeijing Normal UniversityBeijing 100875China National Basic Science Data Center Beijing 100190China Centre for Cognition and Brain disorders The Affiliated Hospital of Hangzhou Normal UniversityHangzhou 310004China Institute of Psychological Science Hangzhou Normal UniversityHangzhou 310030China Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairment Hangzhou 311121China International Big-Data Center for Depression Research Institute of PsychologyChinese Academy of SciencesBeijing 100101China Magnetic Resonance Imaging Research Center Institute of PsychologyChinese Academy of SciencesBeijing 100101China

Recent advances in open neuroimaging data are enhancing our comprehension of neuropsychiatric disorders.By pooling images from various cohorts,statistical power has increased,enabling the detection of subtle abnormalities and robust associations,and fostering new research methods.Global collaborations in imaging have furthered our knowledge of the neurobiological foundations of brain disorders and aided in imaging-based prediction for more targeted treatment.Large-scale magnetic resonance imaging initiatives are driving innovation in analytics and supporting generalizable psychiatric studies.We also emphasize the significant role of big data in understanding neural mechanisms and in the early identification and precise treatment of neuropsychiatric disorders.However,challenges such as data harmonization across different sites,privacy protection,and effective data sharing must be addressed.With proper governance and open science practices,we conclude with a projection of how large-scale imaging resources and collaborations could revolutionize diagnosis,treatment selection,and outcome prediction,contributing to optimal brain health.

关键词： Magnetic resonance imaging neuropsychiatric disorders Big data Open science Artificial intelligence

Synaptic development of layer V pyramidal neurons in the prenatal human prefrontal neocortex: a Neurolucida-aided Golgi study

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Neural Regeneration Research 2020年第8期15卷 1490-1495页

作者： Li-Xin He Lily Wan Wei Xiang Jian-Ming Li An-Hua Pan Da-Hua Lu Xiangtan Medicine and Health Vocational College XiangtanHunan ProvinceChina Department of Neurology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Changde Vocational Technical College ChangdeHunan ProvinceChina Department of Anatomy Changsha Medical UniversityChangshaHunan ProvinceChina Department of Anatomy and Neurobiology Xiangya School of MedicineCentral South UniversityChangshaHunan ProvinceChina

The prefrontal neocortex is involved in many high cognitive functions in humans.Deficits in neuronal and neurocircuitry development in this part of the cerebrum have been associated with various neuropsychiatric disorders in adolescents and adults.There are currently little available data regarding prenatal dendrite and spine formation on projecting neurons in the human prefrontal neocortex.Previous studies have demonstrated that Golgi silver staining can identify neurons in the frontal lobe and visual cortex in human embryos.In the present study,five fetal brains,at 19,20,26,35,and 38 gestational weeks,were obtained via the body donation program at Xiangya School of Medicine,Central South University,China.Golgi-stained pyramidal neurons in layer V of Brodmann area 46 in fetuses were quantitatively analyzed using the Neurolucida morphometry system.Results revealed that somal size,total dendritic length,and branching points of these neurons increased from 26 to 38 gestational weeks.There was also a large increase in dendritic spines from 35 to 38 gestational weeks.These findings indicate that,in the human prefrontal neocortex,dendritic growth in layer V pyramidal neurons occurs rapidly during the third trimester of gestation.The use of human fetal brain tissue was approved by the Animal Ethics Committee of Xiangya School of Medicine,Central South University,China(approval No.2011-045)on April 5,2011.

关键词： Golgi staining human brain banking neurodevelopment Neurolucida neuropsychiatric disorders prefrontal cortex synaptogenesis three-dimensional reconstruction

Implication of Neuronal Versus Microglial P2X4 Receptors in Central Nervous System disorders

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Neuroscience Bulletin 2020年第11期36卷 1327-1343页

作者： Alexia Duveau Eleonore Bertin Eric Boue-Grabot Universite de Bordeaux Institut des Maladies NeurodegenerativesUMR 529333000 BordeauxFrance CNRS Institut des Maladies NeurodegenerativesUMR 529333000 BordeauxFrance

The P2X4 receptor(P2X4)is an ATP-gated cation channel that is highly permeable to Ca2+and widely expressed in neuronal and glial cell types throughout the central nervous system(CNS).A growing body of evidence indicates that P2X4 plays key roles in numerous central disorders.P2X4 trafficking is highly regulated and consequently in normal situations,P2X4 is present on the plasma membrane at low density and found mostly within intracellular endosomal/lysosomal compartments.An increase in the de novo expression and/or surface density of P2X4 has been observed in microglia and/or neurons during pathological states.This review aims to summarize knowledge on P2X4 functions in CNS disorders and provide some insights into the relative contributions of neuronal and glial P2X4 in pathological contexts.However,determination of the cell-specific functions of P2X4 along with its intracellular and cell surface roles remain to be elucidated before its potential as a therapeutic target in multiple disorders can be defined.

关键词： Purinergic signaling P2X ATP Ligandgated ion channels Chronic pain Brain trauma Ischemia Neurodegenerative diseases Alcohol neuropsychiatric disorders

Brain Banks Spur New Frontiers in neuropsychiatric Research and Strategies for Analysis and Validation

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Genomics, Proteomics & Bioinformatics 2019年第4期17卷 402-414页

作者： Le Wang Yan Xia Yu Chen Rujia Dai Wenying Qiu Qingtuan Meng Liz Kuney Chao Chen Center for Medical Genetics&Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangsha 410078China Child Health Institute of New Jersey Department of NeuroscienceRutgers Robert Wood Johnson Medical SchoolNew BrunswickNJ 08901USA Psychiatry Department SUNY Upstate Medical UniversitySyracuseNY 13210USA Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100101China Affiliated Hospital of Guilin Medical University Guilin 541000China National Clinical Research Centre for Geriatric disorders Xiangya HospitalCentral South UniversityChangsha 410000China

neuropsychiatric disorders affect hundreds of millions of patients and families worldwide.To decode the molecular framework of these diseases,many studies use human postmortem brain samples.These studies reveal brain-specific genetic and epigenetic patterns via highthroughput sequencing technologies.Identifying best practices for the collection of postmortem brain samples,analyzing such large amounts of sequencing data,and interpreting these results are critical to advance neuropsychiatry.We provide an overview of human brain banks worldwide,including progress in China,highlighting some well-known projects using human postmortem brain samples to understand molecular regulation in both normal brains and those with neuropsychiatric disorders.Finally,we discuss future research strategies,as well as state-of-the-art statistical and experimental methods that are drawn upon brain bank resources to improve our understanding of the agents of neuropsychiatric disorders.

关键词： neuropsychiatric disorders Brain bank Postmortem brain Expression quantitative trait loci GWAS interpretation

Does COVID-19 increase the risk of neuropsychiatric sequelae? Evidence from a mendelian randomization approach

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World Journal of Psychiatry 2022年第3期12卷 536-540页

作者： Alfonsina Tirozzi Federica Santonastaso Giovanni de Gaetano Licia Iacoviello Alessandro Gialluisi Department of Epidemiology and Prevention IRCCS Istituto Neurologico Mediterraneo NeuromedPozzilli 86077Italy Department of Medicine and Surgery University of InsubriaVarese 21100Italy

Observational studies based on electronic health records (EHR) report anincreased risk of neurological/neuropsychiatric sequelae for patients who havehad coronavirus disease 2019 (COVID-19). However, these studies may sufferfrom biases such as unmeasured confounding, residual reverse causality, or lackof precision in EHR-based diagnoses. To rule out these biases, we tested causallinks between COVID-19 and different potential neurological/neuropsychiatricsequelae through a two-sample Mendelian randomization analysis of summarystatistics from large Genome-Wide Association Scans of susceptibility to COVID-19 and different neurological and neuropsychiatric disorders, including majordepression, anxiety, schizophrenia, stroke, Parkinson’s and Alzheimer’s diseases.We found robust evidence suggesting that COVID-19 – notably the hospitalizedand most severe forms – carries an increased risk of neuropsychiatric sequelae,particularly Alzheimer’s disease, and to a lesser extent anxiety disorder. In linewith a large longitudinal EHR-based study, this evidence was stronger for moresevere COVID-19 forms. These results call for a targeted screening strategy totackle the post-COVID neuropsychiatric pandemic.

关键词： COVID-19 Sars-CoV-2 Neurological disorders neuropsychiatric disorders Alzheimer’s disease Anxiety Mendelian randomization

neuropsychiatric issues after stroke: Clinical significance and therapeutic implications

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World Journal of Psychiatry 2020年第6期10卷 125-138页

作者： Shuo Zhang Michael Xu Zhi-Jun Liu Juan Feng Yan Ma Department of Neurology Shengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina Department of Clinical Medicine International Education SchoolChina Medical UniversityShenyang 110004Liaoning ProvinceChina Department of Ultrasound Shengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina

A spectrum of neuropsychiatric disorders is a common complication from stroke.neuropsychiatric disorders after stroke have negative effects on functional recovery,increasing the rate of mortality and disability of stroke survivors.Given the vital significance of maintaining physical and mental health in stroke patients,neuropsychiatric issues after stroke have raised concerns by clinicians and researchers.This mini-review focuses on the most common non-cognitive functional neuropsychiatric disorders seen after stroke,including depressive disorders,anxiety disorders,post-traumatic stress disorder,psychosis,and psychotic disorders.For each condition,the clinical performance,epidemiology,identification of the therapeutic implication,and strategies are reviewed and discussed;the main opinions and perspectives presented here are based on the latest controlled studies,meta-analysis,or updated systematic reviews.In the absence of data from controlled studies,consensus recommendations were provided accordingly.

关键词： Stroke neuropsychiatric disorders Depression Anxiety Post-traumatic stress disorder Psychosis

Personalized closed-loop brain stimulation system based on linear state space model identification

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Personalized closed-loop brain stimulation system based on l...

Quality of Life with Flotation Therapy for a Person Diagnosed with Attention Deficit Disorder,Atypical Autism,PTSD,Anxiety and Depression

第三十九届中国控制会议

作者： Xile Wei Moyuan Huang Meili Lu Siyuan Chang Jiang Wang Bin Deng School of Electrical and Information Engineering Tianjin University School of Information Technology Engineering Tianjin University of Technology and Education

The closed-loop brain stimulation system can adjust stimulation parameters based on neural activity feedback, so as to provide precise and personalized treatment for neurological and neuropsychiatric diseases. The design of a model-based closed-loop system requires the choice of a suitable system identification framework to learn a dynamic mapping from input and output data to quantify the effect of input stimulation on output neural activity, and design the controller with the identification model. We first designed a control-theory system identification framework to build a dynamic input-output（IO） model of neural activity suitable for closed-loop control design. To achieve effective model-based control, we use a linear state space model（LSSM）, which uses low-dimensional hidden neural states to characterize the effect of inputs on neural activity. Secondly, in order to train the model parameters, we choose a pulse sequence with independent modulation of parameters by pseudorandom sequence（PRS）, and proved that this is the best choice for collecting informational IO data sets in system identification. The input waveform can be used as a deep brain stimulation（DBS） for treating neuropsychiatric diseases while meeting clinical safety requirements. Thirdly, we take the beta frequency band of the local field potential（LFP） as a biomarker of Parkinson’s disease（PD） and system feedback signal to identify the system and design a closed-loop controller. The simulation results show that the closed-loop controller designed based on the LSSM model identified by the PRS modulation waveform can achieve the ideal control effect, and the performance of the model is similar to that of a real physiological IO model describing neural activity. The new PRS modulation waveform and system identification framework can help develop future model-based closed-loop stimulation systems, which is of great significance for the treatment of neuropsychiatric diseases.

关键词： Closed-loop control deep brain stimulation system identification neuropsychiatric disorders

来源： cnki会议评论

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Open Journal of Medical Psychology 2013年第3期2卷 134-138页

作者： Anette Kjellgren Hanna Edebol Tommy Norden Torsten Norlander Department of Psychology Karlstad UniversityKarlstadSweden Nutrition Gut Brain Interactions Research Centre Orebro UniversityOrebroSweden Evidens Research and Development Center GoteborgSweden Department of Clinical Neuroscience Karolinska InstitutetSolnaSweden Evidens Research and Development Center GoteborgSweden

The aim of this single-subject study was to report experiences from one and a half years of regular floating as described by a person with neuropsychiatric and mental health disorders. Floating, or Flotation Restricted Environmental Stimulation Technique, involves relaxation and sensory deprivation by means of resting in a tank with highly salted and body-tempered water. The subject, a 24-year-old woman diagnosed with attention deficit hyperactivity disorder, atypical autism, post-traumatic stress disorder, anxiety and depression floated regularly for one and a half years. Interviews regarding her experiences were analyzed and the main findings involved a subjective sense of improved quality of life, wellbeing and healthy behavior. There were no negative effects from treatment. Results suggest that floating may have beneficial therapeutic effects on mental health. Further studies that evaluate the efficacy and possible effects of floating with regard to mental health are needed.

关键词： Flotation Relaxation Mental Health neuropsychiatric disorders