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 ...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,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).展开更多
To the editor:Major depressive disorder(MDD)is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoami...To the editor:Major depressive disorder(MDD)is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoamine neurotransmitters,hypothalamic-pituitary-adrenal axis,immune-inflammation and the glutamate system.展开更多
Background Youth suicide has been a pressing public mental health concern in China,yet there is a lack of gatekeeper intervention programmes developed locally to prevent suicide among Chinese adolescents.Aims The curr...Background Youth suicide has been a pressing public mental health concern in China,yet there is a lack of gatekeeper intervention programmes developed locally to prevent suicide among Chinese adolescents.Aims The current Delphi study was the first step in the systematic development of the Life Gatekeeper programme,the first gatekeeper programme to be developed locally in China that aims to equip teachers and parents with the knowledge,skills and ability to identify and intervene with students at high risk of suicide.Methods The Delphi method was used to elicit a consensus of experts who were invited to evaluate the importance of training content,the feasibility of the training delivery method,the possibility of achieving the training goals and,finally,the appropriateness of the training materials.Two Delphi rounds were conducted among local experts with diversified professional backgrounds in suicide research and practice.Statements were accepted for inclusion in the adjusted training programme if they were endorsed by at least 80%of the panel.Results Consensus was achieved on 201 out of 207 statements for inclusion into the adapted guidelines for the gatekeeper programme,with 151 from the original questionnaire and 50 generated from comments of the panel members.These endorsed statements were synthesised to develop the content of the Life Gatekeeper training programme.Conclusions This Delphi study provided an evidence base for developing the first gatekeeper training programme systematically and locally in China.We hope that the current study can pave the way for more evidence-based suicide prevention programmes in China.Further study is warranted to evaluate the effectiveness of the Life Gatekeeper training programme.展开更多
In early 2020,the COVID-19 outbreak complicated the diagnosis,treatm ent and rehabilitation of patients with substance use disorders and increased the risks of substance abuse and addictive behaviours,such as online g...In early 2020,the COVID-19 outbreak complicated the diagnosis,treatm ent and rehabilitation of patients with substance use disorders and increased the risks of substance abuse and addictive behaviours,such as online gaming disorders,in the general public.Substance use disorder is a chronic recurrent brain disease characterised by strong cravings,high recurrence rates,and a high proportion of comorbidity of mental and physical disorders.1 Therefore,regular long-term therapeutic interventions are critical to preventing dm g relapses while maintaining withdrawal.展开更多
基金supported by the National Natural Science Foundation of China(81825009,82071505,81901358)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2MC&T-B-099,2019-I2M-5–006)+2 种基金the Program of Chinese Institute for Brain Research Beijing(2020-NKX-XM-12)the King’s College London-Peking University Health Science Center Joint Institute for Medical Research(BMU2020KCL001,BMU2019LCKXJ012)the National Key R&D Program of China(2021YFF1201103,2016YFC1307000).
文摘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,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).
文摘To the editor:Major depressive disorder(MDD)is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoamine neurotransmitters,hypothalamic-pituitary-adrenal axis,immune-inflammation and the glutamate system.
基金funding from Research Fund of VankeSchool of Public Health(100009001)funding from Shuimu Tsinghua Scholarfunding from Beijing High Level Public HealthTechnical Specialist Development Fund(Discipline backbone-02-07).
文摘Background Youth suicide has been a pressing public mental health concern in China,yet there is a lack of gatekeeper intervention programmes developed locally to prevent suicide among Chinese adolescents.Aims The current Delphi study was the first step in the systematic development of the Life Gatekeeper programme,the first gatekeeper programme to be developed locally in China that aims to equip teachers and parents with the knowledge,skills and ability to identify and intervene with students at high risk of suicide.Methods The Delphi method was used to elicit a consensus of experts who were invited to evaluate the importance of training content,the feasibility of the training delivery method,the possibility of achieving the training goals and,finally,the appropriateness of the training materials.Two Delphi rounds were conducted among local experts with diversified professional backgrounds in suicide research and practice.Statements were accepted for inclusion in the adjusted training programme if they were endorsed by at least 80%of the panel.Results Consensus was achieved on 201 out of 207 statements for inclusion into the adapted guidelines for the gatekeeper programme,with 151 from the original questionnaire and 50 generated from comments of the panel members.These endorsed statements were synthesised to develop the content of the Life Gatekeeper training programme.Conclusions This Delphi study provided an evidence base for developing the first gatekeeper training programme systematically and locally in China.We hope that the current study can pave the way for more evidence-based suicide prevention programmes in China.Further study is warranted to evaluate the effectiveness of the Life Gatekeeper training programme.
基金This work was supported by the Program of Shanghai Academic Research Leader(17XD1403300)the Shanghai Key Laboratory of Psychotic Disorders(13DZ2260500)+1 种基金the Shanghai Intelligent Engineering Technology Research Center for Addiction and Rehabilitation(19DZ2255200)and the Shanghai Clinical Research Center for Mental Health(19MC1911100).
文摘In early 2020,the COVID-19 outbreak complicated the diagnosis,treatm ent and rehabilitation of patients with substance use disorders and increased the risks of substance abuse and addictive behaviours,such as online gaming disorders,in the general public.Substance use disorder is a chronic recurrent brain disease characterised by strong cravings,high recurrence rates,and a high proportion of comorbidity of mental and physical disorders.1 Therefore,regular long-term therapeutic interventions are critical to preventing dm g relapses while maintaining withdrawal.
