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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 biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The 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)groups.The 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 groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine 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 analysis.Results: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 response.The developed and externally validated prediction model,which incorporated clinical information,

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

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Enhanced Beta2-band Oscillations Denote Auditory Hallucination in Schizophrenia Patients and a Monkey Model of Psychosis

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Neuroscience Bulletin 2024年第3期40卷 325-338页

作者： Shuo Ma Tianzhen Chen Wenjun Jia Jie Liu Shihan Ding Puzhe Li Hong Gan Dapeng Zhang Shuxin Shao Mu-Ming Poo Min Zhao Bomin Sun Jian Jiang Department of Neurosurgery Ruijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200020China Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghai200030China Shanghai Center for Brain Science and Brain-inspired Technology Lingang LaboratoryShanghai201602China University of California at Berkeley BerkeleyCA94720USA School of Life Science and Technology ShanghaiTech UniversityShanghai201210China Institute of Neuroscience CAS Center for Excellence in Brain Science and Intelligence TechnologyCAS Key Laboratory of Primate NeurobiologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai200031China Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology Lingang LaboratoryShanghai201210China Fuyang Third People’s Hospital Fuyang Mental Health CenterFuyang236052China Shanghai Key Laboratory of Psychotic Disorders Shanghai200030China Institute of Psychological and Behavioral Science Shanghai Jiao Tong UniversityShanghai200030China Shanghai Quanlan Technology Co. LtdShanghai201602China

An electroencephalographic(EEG)signature of auditory hallucinations(AHs)is important for facilitating the diagnosis and treatment of AHs in Schizophrenia.We recorded EEG from 25 Schizophrenia patients with recurrent AHs.During the period of AHs,EEG recordings exhibited significantly elevated beta2-band power in the temporal region,as compared to those recorded in the absence of AHs or during stimulation with verbal sounds.We further generated methamphetamine-treated rhesus monkeys exhibiting psychosis-like behaviors,including repetitive sudden searching actions in the absence of external intrusion,suggesting the occurrence of AHs.Epidural EEG beta2-band power in the temporal region of these monkeys was enhanced immediately after methamphetamine treatment and positively correlated with the frequency of sudden searching actions.Thus,the enhancement of temporal beta2-band oscillations represents a signature for AHs in both patients and a monkey model of psychosis,and this monkey model can be used for developing closed-loop neuromodulation approaches for the treatment of refractory AHs in Schizophrenia.

关键词： Schizophrenia Auditory hallucinations Non-human primate Methamphetamine Electroencephalography

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Effectiveness of acupuncture-related therapies on Schizophrenia:a Bayesian network Meta-analysis

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Journal of Traditional Chinese Medicine 2023年第2期43卷 239-251页

作者： HUANG Zhaohan FANG Yuan WANG Xiaolu HAN Yue YU Qi WANG Tong School of Traditional Chinese Medicine Beijing University of Chinese MedicineInstitute of traditional Chinese medicineBeijing 102488China Maternal and women’s health department Shanghai Center for Women and Children’s HealthShanghai 200062China

OBJECTIVE:To create the hierarchical model for the comparison of efficacy of different ATs for Schizophrenia.METHODS:PubM ed,Web of Science,Embase,The Cochrane Library,ClinicalTrials,China National Knowledge Infrastructure Database,China Science and Technology Journal Database,Wanfang Database,and SinoM ed were searched using a specified search strategy to identify relevant studies up to December 2021.The data were extracted independently by two reviewers.The quality of included trials was evaluated based on the guidelines of“Cochrane Handbook for Systematic Reviews of Interventions”.Bayesian network metaanalysis was conducted by statistical analysis software Addis 1.16.6 and Stata 15.1.RESULTS:In total,60 randomized controlled trials covering 4810 patients were enrolled.The network metaanalysis result showed that Body Acupuncture(BA),BA+Electro-acupuncture(EA),Scalp Acupuncture(SA)+EA,Auricular Acupuncture(AA),Low-dose medication and Acupuncture(LA),Acupoint Injection(AI),and Acupoint Catgut Embedding(ACE),when combined with Western Medications(WM),demonstrated a better clinical effect at improving the symptoms of Schizophrenia,compared to WM alone.Results of rank probability showed that BA,when combined with WM,was the most optimal AT for Schizophrenia at decreasing three aspects of PANSS scale score.CONCLUSIONS:Acupuncture-related therapies help improve the symptoms of Schizophrenia,and BA combined with WM may be a better therapy for Schizophrenia.

关键词： Schizophrenia Acupuncture Acupuncture-related therapy Network Meta-analysis

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Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine‑resistant treatment‑refractory Schizophrenia:a 12‑week randomized,double‑blind,placebo‑controlled trial

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军事医学研究:英文版 2023年第4期10卷 431-443页

作者： Ming‑Huan Zhu Zhen‑Jing Liu Qiong‑Yue Hu Jia‑Yu Yang Ying Jin Na Zhu Ying Huang Dian‑Hong Shi Min‑Jia Liu Hong‑Yang Tan Lei Zhao Qin‑Yu Lv Zheng‑Hui Yi Feng‑Chun Wu Ze‑Zhi Li Clinical Research Center for Mental Disorders School of MedicineShanghai Pudong New Area Mental Health CenterTongji UniversityShanghai 200124China Qingdao Mental Health Center Qingdao 266034ShandongChina Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghai 200030China Department of Psychiatry the Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhou 510370China Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders Guangzhou 510370China

Background:Although clozapine is an effective option for treatment-resistant Schizophrenia(TRS),there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine.The main purpose of this randomized,double-blind,placebocontrolled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory Schizophrenia(CTRS)patients.Methods:A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride(amisulpride group)or clozapine plus placebo(placebo group).Positive and Negative Syndrome Scale(PANSS),Scale for the Assessment of Negative Symptoms(SANS),Clinical Global Impression(CGI)scale scores,Repeatable Battery for the Assessment of Neuropsychological Status(RBANS),Treatment Emergent Symptom Scale(TESS),laboratory measurements,and electrocardiograms(ECG)were performed at baseline,week 6,and week 12.Results:Compared with the placebo group,amisulpride group had a lower PANSS total score,positive subscore,and general psychopathology subscore at week 6 and week 12(PBonferroni<0.01).Furthermore,compared with the placebo group,the amisulpride group showed an improved RBANS language score at week 12(PBonferroni<0.001).Amisulpride group had a higher treatment response rate(P=0.04),lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group(PBonferroni<0.05).There were no differences between the groups in body mass index(BMI),corrected QT(QTc)intervals,and laboratory measurements.This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients.

关键词： Schizophrenia Clozapine-resistant treatment-refractory Schizophrenia Clozapine Amisulpride Augmentation

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Shared and distinct abnormalities of brain magnetization transfer ratio in Schizophrenia and major depressive disorder:a comparative voxel-based meta-analysis

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Chinese Medical Journal 2023年第23期136卷 2824-2833页

作者： Huan Lan Xueling Suo Chao Zuo Weishi Ni Song Wang Graham JKemp Qiyong Gong Department of Radiology Huaxi MR Research Center(HMRRC)West China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamenFujian 361000China Research Unit of Psychoradiology Chinese Academy of Medical SciencesChengduSichuan 610041China Department of Radiology Shengjing Hospital of China Medical UniversityShenyangLiaoning 110004China Functional and Molecular Imaging Key Laboratory of Sichuan Province West China Hospital of Sichuan UniversityChengduSichuan 610041China Liverpool Magnetic Resonance Imaging Centre(LiMRIC)and Institute of Life Course and Medical Sciences University of LiverpoolLiverpool L693BXUnited Kingdom

Background:Patients with Schizophrenia(SCZ)and major depressive disorder(MDD)share significant clinical overlap,although it remains unknown to what extent this overlap reflects shared neural profiles.To identify the shared and specific abnormalities in SCZ and MDD,we performed a whole-brain voxel-based meta-analysis using magnetization transfer imaging,a technique that characterizes the macromolecular structural integrity of brain tissue in terms of the magnetization transfer ratio(MTR).Methods:A systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in PubMed,EMBASE,International Scientific Index(ISI)Web of Science,and MEDLINE for relevant studies up to March 2022.Two researchers independently screened the articles.Rigorous scrutiny and data extraction were performed for the studies that met the inclusion criteria.Voxel-wise meta-analyses were conducted using anisotropic effect size-signed differential mapping with a unified template.Meta-regression was used to explore the potential effects of demographic and clinical characteristics.Results:A total of 15 studies with 17 datasets describing 365 SCZ patients,224 MDD patients,and 550 healthy controls(HCs)were identified.The conjunction analysis showed that both disorders shared higher MTR than HC in the left cerebellum(P=0.0006)and left fusiform gyrus(P=0.0004).Additionally,SCZ patients showed disorder-specific lower MTR in the anterior cingulate/paracingulate gyrus,right superior temporal gyrus,and right superior frontal gyrus,and higher MTR in the left thalamus,precuneus/cuneus,posterior cingulate gyrus,and paracentral lobule;and MDD patients showed higher MTR in the left middle occipital region.Meta-regression showed no statistical significance in either group.Conclusions:The results revealed a structural neural basis shared between SCZ and MDD patients,emphasizing the importance of shared neural substrates across psychopathology.Meanwhile,distinct disease-specific characteristics could have implic

关键词： Magnetization transfer imaging Major depressive disorder Meta-analysis Neuroimaging Psychoradiology Schizophrenia

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Domesticated HERV-W env contributes to the activation of the small conductance Ca^(2+)-activated K^(+)type 2 channels via decreased 5-HT4 receptor in recent-onset Schizophrenia

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Virologica Sinica 2023年第1期38卷 9-22页

作者： Xiulin Wua Qiujin Yan Lianzhong Liu Xing Xue Wei Yao Xuhang Li Wenshi Li Shuang Ding Yaru Xia Dongyan Zhang Fan Zhu State Key Laboratory of Virology and Department of Medical Microbiology School of Basic Medical SciencesWuhan UniversityWuhan430071China Wuhan Mental Health Center Wuhan430071China Hubei Province Key Laboratory of Allergy&Immunology Wuhan UniversityWuhan430071China

The human endogenous retroviruses type W family envelope(HERV-W env)gene is located on chromosome 7q21-22.Our previous studies show that HERV-W env is elevated in Schizophrenia and HERV-W env can increase cal-cium influx.Additionally,the 5-HTergie system and particularly 5-hydroxytryptamine(5-HT)receptors play a prominent role in the pathogenesis and treatment of Schizophrenia.5-hydroxytryptamine receptor 4(5-HT4R)agonist can block calcium channels.However,the underlying relationship between HERV-W env and 5-HT4R in the etiology of Schizophrenia has not been revealed.Here,we used enzyme-linked immunosorbent assay to detect the concentration of HERV-W env and 5-HT4R in the plasma of patients with Schizophrenia and we found that there were decreased levels of 5-HT4R and a negative correlation between 5-HT4R and HERV-W env in Schizophrenia.Overexpression of HERV-W env decreased the transcription and protein levels of 5-HT4R but increased small conductance Ca^(2+)-activated K^(+)type 2 channels(SK2)expression levels.Further studies revealed that HERV-w env could interact with 5-HT4R.Additionally,luciferase assay showed that an essential region(-364 to-176 from the transcription start site)in the SK2 promoter was required for HERV-W env-induced SK2 expression.Importantly,5-HT4R participated in the regulation of SK2 expression and promoter activity.Electrophysiological recordings suggested that HERV-Wenv could increase SK2 channel currents and the increase of SK2 currents was inhibited by 5-HT4R.In condusion,HERV-W env could activate SK2 channels via decreased 5-HT4R,which might exhibit a novel mechanism for HERV-Wenv to influence neuronal activity in Schizophrenia.

关键词： Human endogenous retroviruses type W(HERV-W) Env Small conductance Ca^(2+)-activated K^(+)type 2 channels(SK2) 5-Hydroxytryptamine receptor 4(5-HT4R) Schizophrenia

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The burden of depression,anxiety and Schizophrenia among the older population in ageing and aged countries:an analysis of the Global Burden of Disease Study 2019

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General Psychiatry 2024年第1期37卷 83-93页

作者： Ying Cheng Yu Fang Jinxin Zheng shiyang Guan Meiti Wang Wu Hong Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Nephrology Rujin HospitalInstitute of NephrologyInstitute of NephrologyShanghai Jiao Tong University School of MedicineShanghaiChina School of Global Health Chinese Center for Tropical Diseases ResearchShanghai Jiao Tong University School of MedicineShanghaiChina Department of Epidemiology and Biostatistics School of Public HealthAnhui Medical UniversityHefeiAnhuiChina

Background Depression,anxiety and Schizophrenia among older persons have become global public health challenges.However,the burden of these disorders in ageing and aged countries has not been analysed.Aims To investigate the burden of depression,anxiety and Schizophrenia among older adults in ageing and aged countries.Methods Using data from the Global Burden of Disease Study 2019,we calculated the estimated annual percentage change(EAPC)in the age-standardised incidence rates(ASiR)and age-standardised disability-adjusted life years(DALYs)rates(ASDR)for depression,anxiety and Schizophrenia of older people in ageing countries(China,India,Indonesia)and aged countries(Japan,Italy,Portugal)between 1990 and 2019.Trends in incidence and DALYs were analysed by gender and age.Results In 2019,the highest incidence of depression,anxiety and Schizophrenia in the older population in aged countries was in Japan(927271.3(752552.3-1125796.5),51498.2(37625.7-70487.3)and 126.0(61.0-223.2),respectively),while the highest incidence in ageing countries was in China(5797556.9(4599403.4-7133006.5),330256.1(246448.9-445987.4)and 1067.7(556.2-1775.9),respectively).DALYs for these disorders were similar,with the highest in Japan and China.From 1990 to 2019,the ASIR for depressive disorders decreased in aged countries but increased in ageing countries;the ASIR for anxiety disorders and Schizophrenia declined in both ageing and aged countries.The ASDR for depressive disorders was consistent with the ASIR but not for anxiety disorders and Schizophrenia.The ASIR for depressive disorders was higher in older women,while the opposite was observed in anxiety disorders and Schizophrenia.Notably,the conditions of burden of depressive disorders,anxiety disorders and Schizophrenia in the 65-70-year-old age group were the most burdensome.Conclusions The incidence and DALYs of these three mental disorders increased while exhibiting differences between ageing and aged countries.Raising awareness about formulating health policies for preventing and trea

关键词： Schizophrenia burden ageing

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Aripiprazole in the treatment of acute episode of Schizophrenia: a real-world study in China

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Chinese Medical Journal 2023年第9期136卷 1126-1128页

作者： Qian Li Yun’ai Su Xuemei Liao Maosheng Fang Jianliang Gao Jia Xu Mingjun Duan Haiying Yu Yang Yang Zhiyu Chen Jintong Liu Shaoxiao Yan Peifen Yao Shuying Li Changhong Wang Bin Wu Congpei Zhang Tianmei Si Department of Psychopharmacology Peking University Sixth Hospital(Institute of Mental Health)NHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Beijing 100191China Department of Psychiatry Wuhan Mental Health CenterWuhanHubei 430012China Department of Child and Adolescent Psychology the Fourth People’s Hospital of HefeiHefeiAnhui 230022China Mental Health Center the First Psychiatric Hospital of HarbinHarbinHeilongjiang 150056China Department of Science and Education the Fourth People’s Hospital of ChengduChengduSichuan 610036China Department of Psychiatry the Chinese People’s Liberation Army 904th HospitalChangzhouJiangsu 213003China Department of Psychiatry Beijing Anding HospitalBeijing 100029China Department of Psychiatry Hangzhou Seventh People’s HospitalHangzhouZhejiang 310063China Department of Adolescent and Child Psychological Behavior Shandong Mental Health CenterJinanShandong 250014China Department of Integrated Chinese and Western Medicine Beijing Huilongguan HospitalBeijing 102208China Department of Psychiatry Shanghai Mental Health CenterShanghai 201109China Department of Psychiatry the First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenan 456750China Department of Psychiatry Xi’an Mental Health CenterXi’anShaanxi 710067China

To the Editor:Schizophrenia is a progressive,debilitating disease.[1]Safe and effective treatment performed during the acute phase is the first step to improve prognosis,and it is critically important.Aripiprazole is known as a dopamine system stabilizer,and it exerts partial agonism with high affinity at dopamine D2 and serotonin-1A(5-HT1A)receptors as well as antagonism at serotonin-2A(5-HT2A)receptors.[2]It has been shown to be efficacious in amelioration of both positive and negative symptoms of acute Schizophrenia,and it shows better tolerance than most antipsychotics.[3]We conducted a real-world study to further confirm the efficacy and safety of aripiprazole in patients with acute episodes of Schizophrenia in China and tried to explore the clinical variables,including various drug regimens,which may be correlated with the efficacy of aripiprazole,and provide a basis for the optimization of aripiprazole treatment for patients with acute Schizophrenia.

关键词： Schizophrenia acute dopamine

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Histamine H1 Receptor in Basal Forebrain Cholinergic Circuit:A Novel Target for the Negative Symptoms of Schizophrenia?

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Neuroscience Bulletin 2022年第5期38卷 558-560页

作者： Shuangshuang Wu Chenshu Gao Feng Han Heming Cheng Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou 310053China Key Laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China

Schizophrenia is a common and severe mental disorder with a lifetime prevalence of~1%[1]Apart from the typical positive symptoms,such as hallucinations and delusions,which mainly make patients seek medication,60%-70%of patients are tortured by negative symptoms(e.***.apathy and alogia)and cognitive deficits that impose a long-term burden on patients[2].

关键词： Schizophrenia patients medication

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Consensus on potential biomarkers developed for use in clinical tests for Schizophrenia

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General Psychiatry 2022年第1期35卷 42-52页

作者： Ping Lin Junyu Sun Xiaoyan Lou Dan Li Yun Shi Zhenhua Li Peijun Ma Ping Li Shuzi Chen Weifeng Jin Shuai Liu Qing Chen Qiong Gao Lili Zhu Jie Xu Mengyuan Zhu Mengxia Wang Kangyi Liang Ling Zhao Huabin Xu Ke Dong Qingtian Li Xunjia Cheng Jinghong Chen Xiaokui Guo Department of Clinical Laboratory Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Medical Microbiology and Parasitology Fudan University School of Basic Medical SciencesShanghaiChina Department of Psychosis Institute of PsychiatryPsychology and NeuroscienceKing’s College LondonLondonUK Clinical Laboratory Affiliated Hospital of West Anhui Health Vocational CollegeLu’anAnhuiChina School of Global Health Chinese Center for Tropical Diseases ResearchShanghai Jiao Tong University School of MedicineShanghaiChina Editorial Office of General Psychiatry Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Shanghai Key Laboratory of Psychotic Disorders Shanghai Jiao Tong University School of MedicineShanghaiChina

Background Schizophrenia is a serious mental illness affecting approximately 20 million individuals globally.Both genetic and environmental factors contribute to the illness.If left undiagnosed and untreated,Schizophrenia results in impaired social function,repeated hospital admissions,reduced quality of life and decreased life expectancy.Clinical diagnosis largely relies on subjective evidence,including self-reported experiences,and reported behavioural abnormalities followed by psychiatric evaluation.In addition,psychoses may occur along with other conditions,and the symptoms are often episodic and transient,posing a significant challenge to the precision of diagnosis.Therefore,objective,specific tests using biomarkers are urgently needed for differential diagnosis of Schizophrenia in clinical practice.Aims We aimed to provide evidence-based and consensus-based recommendations,with a summary of laboratory measurements that could potentially be used as biomarkers for Schizophrenia,and to discuss directions for future research.Methods We searched publications within the last 10 years with the following keywords:‘Schizophrenia’,‘gene’,‘inflammation’,‘neurotransmitter’,‘protein marker’,‘gut microbiota’,‘pharmacogenomics’and‘biomarker’.A draft of the consensus was discussed and agreed on by all authors at a round table session.Results We summarised the characteristics of candidate diagnostic markers for Schizophrenia,including genetic,inflammatory,neurotransmitter,peripheral protein,pharmacogenomic and gut microbiota markers.We also proposed a novel laboratory process for diagnosing Schizophrenia in clinical practice based on the evidence summarised in this paper.Conclusions Further efforts are needed to identify Schizophrenia-specific genetic and epigenetic markers for precise diagnosis,differential diagnosis and ethnicity-specific markers for the Chinese population.The development of novel laboratory techniques is making it possible to use these biomarkers clinically to diagnose disease.

关键词： diagnosis Schizophrenia impaired

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