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Causal relationship between feelings and cognitive decline:An univariable and multivariable Mendelian randomization study

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World Journal of psychiatry 2024年第3期14卷 421-433页

作者： Juan Liu Lin Liu Yi-Xin Hu Jian-Hua Li Xiao Zou Hao-Yun Zhang Li Fan Department of Cardiology The Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China Department of Pulmonary and Critical Care Medicine The Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China The Fourth Department of geriatric Health Care The Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China Department of Anesthesiology First Medical Center of Chinese PLA General HospitalBeijing 100853China

BACKGROUND While the impact of depression on cognition is well-documented,the relationship between feelings and cognition has received limited attention.AIM To explore the potential association between feelings and cognition with a twosample Mendelian randomization(MR)analysis.METHODS Our analysis utilized genome-wide association data on various feelings(fed-up feelings,n=453071;worrier/anxious feelings,n=450765;guilty feelings,n=45-0704;nervous feelings,n=450700;sensitivity/hurt feelings,n=449419;miserableness,n=454982;loneliness/isolation,n=455364;happiness,n=152348)in the European population and their impact on cognitive functions(intelligence,n=269867).Conducting a univariable MR(UVMR)analysis to assess the relationship between feelings and cognition.In this analysis,we applied the inverse variance weighting(IVW),weighted median,and MR Egger methods.Additionally,we performed sensitivity analysis(leave-one-out analysis),assessed heterogeneity(using MR-PRESSO and Cochran’s Q test),and conducted multiple validity test(employing MR-Egger regression).Subsequently,a multivariable MR(MVMR)analysis was employed to examine the impact of feelings on cognition.IVW served as the primary method in the multivariable analysis,complemented by median-based and MR-Egger methods.RESULTS In this study,UVMR indicated that sensitivity/hurt feelings may have a negative causal effect on cognition(OR=0.63,95%CI:0.43-0.92,P=0.017).After adjustment of other feelings using MVMR,a direct adverse causal effect on cognition was observed(OR_(MVMR)=0.39,95%CI:0.17-0.90,P_(MVMR)=0.027).While a potential increased risk of cognitive decline was observed for fed-up feelings in the UVMR analysis(ORUVMR=0.64,95%CI:0.42-0.97,PUVMR=0.037),this effect disappeared after adjusting for other feelings(OR_(MVMR)=1.42,95%CI:0.43-4.74,P_(MVMR)=0.569).These findings were generally consistent across MV-IVW,median-based,and MR-Egger analyses.MR-Egger regression revealed pleiotropy in the impact of worrier/anxious feelings on cognition,presenting a challenge in

关键词： Mendelian randomization analysis Feelings Cognition Intelligence

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Deliberate self-harm among pediatric psychiatric inpatients in China:A single-center retrospective study

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World Journal of psychiatry 2024年第3期14卷 398-408页

作者： Xing-Zhi Jiang Huan-Huan Li Zhen-Zhen Yu Chen Wang Department of Child and Adolescent psychiatry Shenzhen Kangning HospitalShenzhen Mental Health CenterShenzhen Key Laboratory for Psychological Healthcare and Shenzhen Institute of Mental HealthShenzhen 518020Guangdong ProvinceChina Department of psychiatry Xiamen Xianyue HospitalXiamen 361012Fujian ProvinceChina Department of geriatric Medicine Dalian Medical UniversityDalian 116000Liaoning ProvinceChina Department of Neurology The Second Affiliated Hospital of Xiamen Medical CollegeXiamen 361000Fujian ProvinceChina Department of Neurology and Department of Neuroscience The First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361000Fujian ProvinceChina

BACKGROUND For children and adolescents,deliberate self-harm(DSH)is becoming a mental health problem of concern.Despite several studies on the prevalence and factors of DSH in the world,there is little information on DSH among children and adolescents in China.This study explores the prevalence,types,associated risk factors and tendency of DSH in pediatric psychiatric inpatients in China.AIM To understand the situation of DSH among hospitalized children and adolescents and its related factors.METHODS In this study,we retrospectively studied 1414 hospitalized children and adolescents with mental illness at Xiamen Mental Health Center from 2014 to 2019,extracted the demographic and clinical data of all patients,and analyzed clinical risk factors of DSH.RESULTS A total of 239(16.90%)patients engaged in at least one type of DSH in our study.Cutting(n=115,48.12%)was the most common type of DSH.Females(n=171,71.55%)were more likely to engage in DSH than males(n=68,28.45%).DSH was positively associated with depressive disorders[OR=3.845(2.196-6.732);P<0.01],female[OR=2.536(1.815-3.542);P<0.01],parental marital status[OR=5.387(2.254-12.875);P<0.01]and negative family history of psychiatric illness[OR=7.767(2.952-20.433);P<0.01],but not with occupation,substance use and history of physical abuse.CONCLUSION Our findings suggest that for patients with depression,females,an abnormal marriage of parents,and no history of mental illness,attention should be paid to the occurrence of DSH.

关键词： Deliberate self-harm Children Adolescent Psychiatric inpatients Retrospective study

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KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer’s disease

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World Journal of psychiatry 2024年第3期14卷 445-455页

作者： Qun-Shan Lu Lin Ma Wen-Jing Jiang Xing-Bang Wang Mei Lu Department of geriatric Medicine Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Key Laboratory of Cardiovascular Proteomics of Shandong Province Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and

关键词： Alzheimer's disease Diabetes Insulin resistance KAT7 Dual-specificity tyrosine phosphorylation-regulated kinase-1A HMGN1

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The role of inflammasomes in human diseases and their potential as therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 479-508页

作者： Jing Yao Keenan Sterling Zhe Wang Yun Zhang Weihong Song The National Clinical Research Center for geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Key Laboratory of Neurodegenerative Diseases Ministry of EducationBeijingP.R.China Zhejiang Clinical Research Center for Mental Disorders Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and The Affiliated Kangning HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325000China

Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune response.Each inflammasome complex has three major components:an upstream sensor molecule that is connected to a downstream effector protein such as caspase-1 through the adapter protein ASC.Inflammasome formation typically occurs in response to infectious agents or cellular damage.The active inflammasome then triggers caspase-1 activation,followed by the secretion of pro-inflammatory cytokines and pyroptotic cell death.Aberrant inflammasome activation and activity contribute to the development of diabetes,cancer,and several cardiovascular and neurodegenerative disorders.As a result,recent research has increasingly focused on investigating the mechanisms that regulate inflammasome assembly and activation,as well as the potential of targeting inflammasomes to treat various diseases.Multiple clinical trials are currently underway to evaluate the therapeutic potential of several distinct inflammasome-targeting therapies.Therefore,understanding how different inflammasomes contribute to disease pathology may have significant implications for developing novel therapeutic strategies.In this article,we provide a summary of the biological and pathological roles of inflammasomes in health and disease.We also highlight key evidence that suggests targeting inflammasomes could be a novel strategy for developing new disease-modifying therapies that may be effective in several conditions.

关键词： inflam therapeutic potential

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Depression among caregivers of patients with dementia:Associative factors and management approaches

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World Journal of psychiatry 2022年第1期12卷 59-76页

作者： Si-Sheng Huang Division of geriatric psychiatry Department of PsychiatryChanghua Christian HospitalChanghua 500Taiwan

As elderly people increasingly come to represent a higher proportion of the world’s population,various forms of dementia are becoming a significant chronic disease burden.The World Health Organization emphasizes dementia care as a public health priority and calls for more support for family caregivers who commonly play a significant,central role in dementia care.Taking care of someone with dementia is a long-term responsibility that can be stressful and may lead to depression among family caregivers.Depression and related behavioral and cognitive changes among caregivers could in turn affect the status and prognosis of the dementia patient.This review article explores depression in dementia caregivers and summarizes proposed mechanisms,associated factors,management and research findings,and proposes future research directions.

关键词： Dementia Depression Caregiver Caregiver burden Activities of daily living Functional status

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Abnormalities of electroencephalography microstates in patients with depression and their association with cognitive function

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World Journal of psychiatry 2024年第1期14卷 128-140页

作者： Rui-Jie Peng Yu Fan Jin Li Feng Zhu Qing Tian Xiao-Bin Zhang Suzhou Medical College Soochow UniversitySuzhou 215123Jiangsu ProvinceChina Department of psychiatry Suzhou Psychiatric HospitalThe Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina

BACKGROUND A growing number of recent studies have explored underlying activity in the brain by measuring electroencephalography(EEG)in people with depression.However,the consistency of findings on EEG microstates in patients with depression is poor,and few studies have reported the relationship between EEG microstates,cognitive scales,and depression severity scales.AIM To investigate the EEG microstate characteristics of patients with depression and their association with cognitive functions.METHODS A total of 24 patients diagnosed with depression and 32 healthy controls were included in this study using the Structured Clinical Interview for Disease for The Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.We collected information relating to demographic and clinical characteristics,as well as data from the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS;Chinese version)and EEG.RESULTS Compared with the controls,the duration,occurrence,and contribution of microstate C were significantly higher[depression(DEP):Duration 84.58±24.35,occurrence 3.72±0.56,contribution 30.39±8.59;CON:Duration 72.77±10.23,occurrence 3.41±0.36,contribution 24.46±4.66;Duration F=6.02,P=0.049;Occurrence F=6.19,P=0.049;Contribution F=10.82,P=0.011]while the duration,occurrence,and contribution of microstate D were significantly lower(DEP:Duration 70.00±15.92,occurrence 3.18±0.71,contribution 22.48±8.12;CON:Duration 85.46±10.23,occurrence 3.54±0.41,contribution 28.25±5.85;Duration F=19.18,P<0.001;Occurrence F=5.79,P=0.050;Contribution F=9.41,P=0.013)in patients with depression.A positive correlation was observed between the visuospatial/constructional scores of the RBANS scale and the transition probability of microstate class C to B(r=0.405,P=0.049).CONCLUSION EEG microstate,especially C and D,is a possible biomarker in depression.Patients with depression had a more frequent transition from microstate C to B,which may relate to more negative rumination and visual processing.

关键词： Depression Electroencephalography Microstates Cognitive functions

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Virtual reality-based cognitive-behavioural therapy for the treatment of anxiety in patients with acute myocardial infarction:a randomised clinical trial

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General psychiatry 2024年第2期37卷 189-196页

作者： Yuanyuan Li Juan Peng Pingyuan Yang Jiajun Weng Yan'e Lu Jiajia Liu Shikun Xu Lihua Guan Dong Huang Qibing Wang Juying Qian Zexin Zhao Yabin Wei Junbo Ge Xiao Huang Department of Psychological Medicine Zhongshan Hospital Fudan UniversityShanghaiChina Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesNational Clinical Research Center for Interventional MedicineShanghaiChina Department of Psychological Medicine Shanghai Geriatric Medical CenterShanghaiChina School of Nursing Peking UniversityBeijingChina Beijing Key Laboratory of Drug Dependence Research National Institute on Drug DependencePeking UniversityBeijingChina

Background The presence of mental health conditions is pervasive in patients who experienced acute myocardial infarction(AMI),significantly disrupting their recovery.Providing timely and easily accessible psychological interventions using virtual reality-based cognitive-behavioural therapy(VR-CBT)could potentially improve both acute and long-term symptoms affecting their mental health.Aims We aim to examine the effectiveness of VR-CBT on anxiety symptoms in patients with AMI who were admitted to the intensive care unit(ICU)during the acute stage of their illness.Methods In this single-blind randomised clinical trial,participants with anxiety symptoms who were admitted to the ICU due to AMI were continuously recruited from December 2022 to February 2023.Patients who were Han Chinese aged 18-75 years were randomly assigned(1:1)via block randomisation to either the VR-CBT group to receive VR-CBT in addition to standard mental health support,or the control group to receive standard mental health support only.VR-CBT consisted of four modules and was delivered at the bedside over a 1-week period.Assessments were done at baseline,immediately after treatment and at 3-month follow-up.The intention-to-treat analysis began in June 2023.The primary outcome measure was the changes in anxiety symptoms as assessed by the Hamilton Anxiety Rating Scale(HAM-A).Results Among 148 randomised participants,70 were assigned to the VR-CBT group and 78 to the control group.The 1-week VR-CBT intervention plus standard mental health support significantly reduced the anxiety symptoms compared with standard mental health support alone in terms of HAM-A scores at both post intervention(Cohen’s d=−1.27(95%confidence interval(CI):−1.64 to−0.90,p<0.001)and 3-month follow-up(Cohen’s d=−0.37(95%CI:−0.72 to−0.01,p=0.024).Of the 70 participants who received VR-CBT,62(88.6%)completed the entire intervention.Cybersickness was the main reported adverse event(n=5).Conclusions Our results indicate that VR-CBT can significantly reduce post-AMI anxiety at t

关键词： admitted behaviour treatment

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Consensus on rapid screening for prodromal Alzheimer's disease in China

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General psychiatry 2024年第1期37卷 1-16页

作者： Lin Huang Qinjie Li Yao Lu Fengfeng Pan Liang Cui Ying Wang Ya Miao Tianlu Chen Yatian Li Jingnan Wu Xiaochun Chen Jianping Jia Qihao Guo Department of Gerontology Shanghai Sixth People's Hospital Afiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina shanghai BestCovered ShanghaiChina ADepartment of Neurology Fujan Medical University Union HospitalFuzhouChina Department of Neurology National Clinical Research Center for Geriatric DiseasesBeijingChina

Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impairment(MCl)and evidence of AD's pathology.At this stage,disease-modifying interventions should be used to prevent the progression to dementia.Given the inherent heterogeneity of MCl,more specific biomarkers are needed to elucidate the underlying AD's pathology.Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology,their clinical applications are limited by their high costs and invasiveness,particularly in low-income areas in China.Therefore,to improve the early detection of Alzheimer's disease(AD)pathology through cost-effective screening methods,a panel of 45neurologists,psychiatrists andgerontologistswas invited to establish a formal consensus on the screening of pAD in China.The supportive evidence and grades of recommendations are based on a systematic literature review andfocus group discussion.National meetings were held to allow participants to review,vote and provide their expert opinions to reach a consensus.A majority(two-thirds)decision was used for questions for which consensus could not be reached.Recommended screening methods are presented in this publication,including neuropsychological assessment,peripheral biomarkers and brain imaging.In addition,a general workflow for Screening pAD in China is established,which will help clinicians identify individuals at high risk and determine therapeutic targets.

关键词： Alzheimer income screening

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Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its function.However,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain elusive.In this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent y-secretase.We identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in mice.Finaly,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout mice.This data demonstrates that the a-secretase is essential for CNTNAP2 processing and its function.Our study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

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Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia

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World Journal of psychiatry 2024年第6期14卷 794-803页

作者： Peng Chen Hai-Dong Yang Jun-Jie Wang Zhen-Hua Zhu Hui-Min Zhao Xu-Yuan Yin Yuan Cai Hong-LiangZhu Jia-Lin Fu Xin-Zhu Zhang Wen-Xi Sun Li Hui Xiao-Bin Zhang Suzhou Medical College of Soochow University Suzhou 215123Jiangsu ProvinceChina Department of psychiatry Suzhou Psychiatric HospitalInstitute of Mental HealthThe Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina Department of psychiatry The Fourth People’s Hospital of LianyungangThe Affiliated Kangda College of Nanjing Medical UniversityLianyungang 222003Jiangsu ProvinceChina Research Center of Biological psychiatry Suzhou Psychiatric HospitalInstitute of Mental HealthThe Affiliated Guangji Hospital of Soochow UniversitySuzhou 215137Jiangsu ProvinceChina Department of Neurology The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215002Jiangsu ProvinceChina

BACKGROUND Accumulating evidence suggests that the inflammatory cytokine interleukin-6(IL-6)contributes to the pathophysiology of psychiatric disorders.However,there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia(EOS).AIM To investigate the relationship between serum IL-6 concentration and the clinical features of EOS.METHODS We measured serum IL-6 Levels from 74 patients with chronic schizophrenia,including 33 with age at onset0.05)after controlling for age,body mass index,and other covariates.Negative symptom scores were higher in the EOS group than the AOS group(F=6.199,P=0.015).Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score(r=-0.389,P=0.032)and avolition/asociality subscore(r=-0.387,P=0.026).CONCLUSION Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness.IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

关键词： Early-onset schizophrenia Interleukin 6 Negative symptoms Avolition Asociality

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