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Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military Medical Research 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi Su Yu-Ya-Nan Zhang Hao Yu Zhe Lu Wen-Qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun Li Yun-Dan Liao Zhe-Wei Kang Li-Fang Wang Yue Li Ming Li Bing Liu Hai-Liang Huang Lu-Xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang Zhuo Huang Dai Zhang Wei-Hua Yue Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental disorders Peking University Sixth HospitalBeijing 100191China NHC Key Laboratory of Mental Health and Research Unit of Diagnosis and Treatment of mood Cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking University Huilongguan Clinical Medical School Beijing Huilongguan HospitalBeijing 100096China Department of Psychiatry Jining Medical UniversityJining 272067ShandongChina Henan Key Lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China Chinese Institute for Brain Research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective *** studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been ***,further research is imperative to enhance precision medicine in SCZ ***:Participants with SCZ were recruited from two randomized *** discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)*** external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole ***,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic *** genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,*** study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve ***:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment *** developed and externally validated predictio

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

Atypical features and treatment choices in bipolar disorders:a result of the National Bipolar Mania Pathway Survey in China

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Neuroscience Bulletin 2015年第1期31卷 22-30页

作者： Daihui Peng Ting Shen Linda Byrne Chen Zhang Yueqi Huang Xin Yu Jingping Zhao Marita McCabe David Mellor Yiru Fang Division of mood disorders Shanghai Clinical Center for Mental DisorderDepartment of PsychiatryShanghai Mental Health CenterShanghai Jiao Tong University School of Medicine School of Psychology (Burwood Campus) Deakin University Institute of Mental Health Peking University Mental Health Institute The Second Xiangya Hospital of Central South University

In this study,we examined the point prevalence rate of atypical features in bipolar disorder,and estimated the potential impact of these features on treatment practices in China. Using the atypical features criteria of the Diagnostic and Statistical Manual of the American Psychiatric Association（DSM-IV）,we documented the atypical symptoms in 3 906 consecutive participants with bipolar disorder enrolled at 26 psychiatric services across China. We further assessed the association between atypical features and the treatment approaches,including the prescription of antidepressants. The overall point prevalence rate of atypical features was 9.1% among patients with various bipolar disorder subtypes. When the definition was broadened to include atypical features B,the overall rate increased to 11.8%. Interestingly,among patients with the mixed state and remission subtypes,there was a significant difference in the rates of antidepressant medication usage between patients who met and those who did not meet the criteria for atypical features B. These fi ndings indicate a trend of using antidepressants for these two types of patients with atypical features. Further,for both mixed state and remission patients,treatment approaches were related to atypicalfeatures B. Our findings provide evidence to assist clinicians to readily recognize atypical features in bipolar subtypes and can propose treatments based on these diagnoses.

关键词： atypical features bipolar treatment antidepressant

Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease

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Neural Regeneration Research 2025年第6期20卷 1628-1643页

作者： Yimiao Jiang Zengxin Qi Huixian Zhu Kangli Shen Ruiqi Liu Chenxin Fang Weiwei Lou Yifan Jiang Wangrui Yuan Xin Cao Liang Chen Qianxing Zhuang Department of Physiology School of MedicineNantong UniversityNantongJiangsu ProvinceChina Department of Neurosurgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina National Center for Neurological disorders ShanghaiChina Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration ShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institute of Brain ScienceFudan UniversityShanghaiChina

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the comp

关键词： anxiety basal ganglia bradykinesia deep brain stimulation depression globus pallidus externus globus pallidus internus lateral globus pallidus medial globus pallidus neural circuit Parkinson's disease

Neuromodulation of the peripheral nervous system:Bioelectronic technology and prospective developments

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BMEMat(BioMedical Engineering Materials) 2024年第1期2卷 88-114页

作者： Hayoung Song Moohyun Kim Enji Kim Jakyoung Lee Inhea Jeong Kyeonghee Lim Seoung Young Ryu Myoungjae Oh Younhee Kim Jang-Ung Park Department of Materials Science and Engineering Yonsei UniversitySeoulSouth Korea Center for Nanomedicine Institute for Basic Science(IBS)SeoulSouth Korea Department of Neurosurgery Yonsei University College of MedicineSeoulSouth Korea Graduate program of Nano Biomedical Engineering(NanoBME) Advanced Science InstituteYonsei UniversitySeoulSouth Korea

The peripheral nervous system(PNS)is a fascinatingly complex and crucial component of the human body,responsible for transmitting vital signals throughout the body's intricate network of *** efficient functioning is paramount to our health,with any dysfunction often resulting in serious medical conditions,including motor disorders,neurological diseases,and psychiatric *** strides in science and technology have made neuromodulation of the PNS a promising avenue for addressing these health *** involves modifying nerve activity using a range of techniques,such as electrical,chemical,optical,and mechanical *** plays a critical role in this effort,allowing for precise,controlled,and sustained stimulation of the *** paper provides an overview of the PNS,discusses the current state of neuromodulation devices,and presents emerging trends in the field,including advances in wireless power transfer and materials,that are shaping the future of neuromodulation.

关键词： bioelectronics neuromodulation peripheral nervous system

Glyphosate Exposure Associated with Human Neurodegenerative disorders: A Scoping Review

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Journal of Behavioral and Brain Science 2024年第7期14卷 187-209页

作者： Hannah Hutchins David M. Compton Kris Dougherty Behavioral Neuroscience program Palm Beach Atlantic University West Palm Beach Florida USA Department of Biology Palm Beach Atlantic University West Palm Beach Florida USA

Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a number of serious human health disorders. This rapid literature review aims to accumulate and analyze research from the last ten years, focusing specifically on the effects of exposure to glyphosate-based herbicide products such as Roundup as associated with the formation of various neurological disorders. Specifically, this review focuses on laboratory research using animal models or human cell cultures as well as human population-based epidemiological studies. It associates exposure to glyphosate or glyphosate-based products with the formation or exacerbation of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, seizures, and autism spectrum disorder. In addition, it examines the correlation between the gut-brain axis, exposure to glyphosate, and neurodegeneration.

关键词： Herbicide Glyphosate Roundup Neurodegeneration Neurodegenerative Disorder Parkinson’s Disease Alzheimer’s Disease Seizures Autism Spectrum Disorder Gut-Brain Axis

Pathophysiological significance of increased α-synuclein deposition in sympathetic nerves in Parkinson’s disease: a post-mortem observational study

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Translational Neurodegeneration 2022年第1期11卷 737-746页

作者： Risa Isonaka Patti Sullivan David S.Goldstein Autonomic Medicine Section Clinical Neurosciences ProgramDivision of Intramural ResearchNational Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaMD 20892USA

Background: Parkinson’s disease (PD) is characterized by intra-neuronal deposition of the protein α-synuclein (α-syn) and by deficiencies of the catecholamines dopamine and norepinephrine (NE) in the brain and heart. Accumulation of α-syn in sympathetic noradrenergic nerves may provide a useful PD biomarker;however, whether α-syn buildup is pathophysiological has been unclear. If it were, one would expect associations of intra-neuronal α-syn deposition with catecholaminergic denervation and with decreased NE contents in the same samples. Methods: We assayed immunoreactive α-syn and tyrosine hydroxylase (TH, a marker of catecholaminergic innerva-tion) concurrently with catecholamines in coded post-mortem scalp skin, submandibular gland (SMG), and apical left ventricular myocardial tissue samples from 14 patients with autopsy-proven PD and 12 age-matched control subjects who did not have a neurodegenerative disease. Results: The PD group had increased α-syn in sympathetic noradrenergically innervated arrector pili muscles (5.7 times control, P < 0.0001), SMG (35 times control, P = 0.0011), and myocardium (11 times control, P = 0.0011). Myocar-dial TH in the PD group was decreased by 65% compared to the control group (P = 0.0008), whereas the groups did not differ in TH in either arrector pili muscles or SMG. Similarly, myocardial NE was decreased by 92% in the PD group (P < 0.0001), but the groups did not differ in NE in either scalp skin or SMG. Conclusions: PD entails increased α-syn in skin, SMG, and myocardial tissues. In skin and SMG, augmented α-syn deposition in sympathetic nerves does not seem to be pathogenic. The pathophysiological significance of intra-neuronal α-syn deposition appears to be organ-selective and prominent in the heart.

关键词： Synuclein Tyrosine hydroxylase Norepinephrine Immunofluorescence Parkinson Post-mortem

Hypothalamic-Pituitary-End-Organ Axes:Hormone Function in Female Patients with Major Depressive Disorder

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Neuroscience Bulletin 2021年第8期37卷 1176-1187页

作者： Yuncheng Zhu Xiaohui Wu Rubai Zhou Oliver Sie Zhiang Niu Fang Wang Yiru Fang Division of mood disorders Shanghai Hongkou Mental Health CenterShanghai200083China Clinical Research Center Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai200030China Shanghai Medical College Fudan UniversityShanghai200032China Shanghai Yangpu Mental Health Center Shanghai200093China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai200031China Shanghai Key Laboratory of Psychotic disorders Shanghai201108China

Classic hypothalamic-pituitary-end-organ feedback loops–the hypothalamic-pituitary-adrenal axis(HPAA),hypothalamic-pituitary-thyroidal axis(HPTA),and hypothalamic-pituitary-gonadal axis(HPGA)–are associated with the neuroendocrine and immune systems in major depressive disorder(MDD).Female patients with MDD present with evident neuroendocrine and immunological ***,thyroid hormone,and reproductive steroid levels fluctuate with menstrual cycles,which might lead to glucocorticoid receptor resistance,impairment of triiodothyronine conversion,and sex hormone secretion *** this review,we summarize the independent and interactive functions of these three axes in female MDD *** similar molecular structure of steroids implies an interrelationship between the hypothalamic-pituitary-end-organ axes and the competitive inhibitory effects at the receptor level,especially when considering the HPAA and HPGA.

关键词： Major depressive disorder Neurosecretory systems Sex steroid hormones

Storylines of family medicine Ⅸ:people and places—diverse populations and locations of care

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Family Medicine and Community Health 2024年第S3期12卷 79-88页

作者： William B Ventres Leslie A Stone Emad R Abou-Arab Julio Meza David S Buck Jerome W Crowder Jennifer Y C Edgoose Alexander Brown Ellen J Plumb Amber K Norris Jay J Allen Lauren E Giammar John E Wood Scott M Dickson G Austin Brown Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family Medicine University of Michigan Medical SchoolAnn ArborMichiganUSA Family Medicine University of California Los AngelesDavid Geffen School of MedicineLos AngelesCaliforniaUSA Community Medicine University of HoustonTilman J Fertitta Family College of MedicineHoustonTexasUSA Social and Behavioral Sciences University of HoustonTilman J Fertitta Family College of MedicineHoustonTexasUSA Family Medicine and Community Health University of Wisconsin-Madison School of Medicine and Public HealthMadisonWisconsinUSA NH Dartmouth Family Medicine Residency ConcordNew HampshireUSA San Francisco VA Medical Center San FranciscoCaliforniaUSA Duluth Family Medicine Residency program University of Minnesota Medical School Duluth CampusDuluthMinnesotaUSA UAMS Northeast Regional Campus Family Medicine Residency program JonesboroArkansasUSA Cascades East Family Medicine Residency program Oregon Health&Science University School of MedicineKlamath FallsOregonUSA

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅸ:people and places—diverse populations and locations of care’,authors address the following themes:‘LGBTQIA+health in family medicine’,‘A family medicine approach to substance use disorders’,‘Shameless medicine for people experiencing homelessness’,“Difficult”encounters—finding the person behind the patient’,‘Attending to patients with medically unexplained symptoms’,‘Making house calls and home visits’,‘Family physicians in the procedure room’,‘Robust rural family medicine’and‘Full-spectrum family medicine’.May readers appreciate the breadth of family medicine in these essays.

关键词： illustration family dimensions

Alterations of Audiovisual Integration in Alzheimer’s Disease

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Neuroscience Bulletin 2023年第12期39卷 1859-1872页

作者： Yufei Liu Zhibin Wang Tao Wei Shaojiong Zhou Yunsi Yin Yingxin Mi Xiaoduo Liu Yi Tang Department of Neurology and Innovation Center for Neurological disorders Xuanwu HospitalCapital Medical UniversityNational Center for Neurological DisordersBeijing100053China

Audiovisual integration is a vital information process involved in cognition and is closely correlated with aging and Alzheimer’s disease(AD).In this review,we evaluated the altered audiovisual integrative behavioral symptoms in *** further analyzed the relationships between AD pathologies and audiovisual integration alterations bidirectionally and suggested the possible mechanisms of audiovisual integration alterations underlying AD,including the imbalance between energy demand and supply,activity-dependent degeneration,disrupted brain networks,and cognitive resource ***,based on the clinical characteristics including electrophysiological and imaging data related to audiovisual integration,we emphasized the value of audiovisual integration alterations as potential biomarkers for the early diagnosis and progression of *** also highlighted that treatments targeted audiovisual integration contributed to widespread pathological improvements in AD animal models and cognitive improvements in AD ***,investigation into audiovisual integration alterations in AD also provided new insights and comprehension about sensory information processes.

关键词： Audiovisual integration-Aging Alzheimer's disease Cognition Sensory information process