Pub Date : 2024-12-26eCollection Date: 2024-01-01DOI: 10.1136/gpsych-2023-101220
Yuri de Castro Machado, Mariana Oliveira, Mateus Pereira Mundoca, Bernardo Viana, Debora Marques de Miranda, Marco Aurélio Romano-Silva
Background: Non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), may offer an alternative treatment strategy for impulsive behaviour. By modulating brain activity, these techniques could potentially enhance impulse control and mitigate impulsivity.
Aims: To provide a comprehensive analysis of the correlation between NIBS parameters, targeted brain regions and impulsivity.
Methods: We systematically searched PubMed, Scopus and Embase on 5 April 2023 for randomised controlled trials (RCTs) of NIBS on impulsivity. Unbiased Hedges' g with 95% CIs was used to define the effect size. Cochran Q test and I² statistics were used to assess for heterogeneity; p values inferior to 0.10 and I²>25% were considered significant for heterogeneity. Publication bias was investigated by funnel plot analysis of point estimates according to study weights, by Egger's regression test and by non-parametric rank correlation (Begg) test.
Results: A total of 18 studies were included, comprising 655 patients from 14 RCTs and four randomised crossover studies. The meta-analysis of effect sizes from 9 tDCS studies on impulsivity did not show a significant effect (g=-0.18; 95% CI -0.46 to 0.10; p=0.210) and from 9 repetitive TMS (rTMS) studies also did not yield a statistically significant effect (g=0.21; 95% CI -0.38 to 0.80; p=0.490). When analysing active tDCS using Barratt Impulsiveness Scale version 11, the scores showed a trend towards improvement with active tDCS over placebo (g=-0.54; 95% CI -0.97 to -0.12; p<0.05; I²=0%).
Conclusions: There is currently insufficient evidence to support the clinical use of rTMS or tDCS as a means of reducing impulsivity in individuals with mental disorders. The main limitations of this study are the lack of available patient-level data, a limited number of studies, the lack of consensus on the structure of impulsivity and variability in how impulsivity is measured and conceptualised.
Prospero registration number: CRD42023413684.
背景:非侵入性脑刺激(NIBS)技术,如经颅磁刺激(TMS)和经颅直流刺激(tDCS),可能为冲动行为提供另一种治疗策略。通过调节大脑活动,这些技术可以潜在地增强冲动控制和减轻冲动。目的:全面分析NIBS参数、目标脑区与冲动的相关性。方法:我们于2023年4月5日系统检索PubMed、Scopus和Embase,检索NIBS治疗冲动的随机对照试验(rct)。使用95% ci的无偏对冲来定义效应大小。采用Cochran Q检验和I²统计量评估异质性;p值小于0.10和I²>25%被认为具有显著的异质性。发表偏倚采用研究权重点估计的漏斗图分析、Egger回归检验和非参数秩相关(Begg)检验。结果:共纳入18项研究,包括来自14项随机对照试验和4项随机交叉研究的655例患者。对9个tDCS研究的冲动性效应大小的meta分析没有显示显著的影响(g=-0.18;95% CI -0.46 ~ 0.10;p=0.210),从9个重复性经颅磁刺激(rTMS)研究中也没有产生统计学上显著的影响(g=0.21;95% CI -0.38 ~ 0.80;p = 0.490)。当使用Barratt冲动性量表第11版分析活跃tDCS时,得分显示活跃tDCS比安慰剂有改善的趋势(g=-0.54;95% CI -0.97 ~ -0.12;结论:目前没有足够的证据支持临床使用rTMS或tDCS作为减少精神障碍患者冲动的一种手段。本研究的主要局限性是缺乏可用的患者水平数据,研究数量有限,对冲动性的结构缺乏共识,以及如何测量和概念化冲动性的可变性。普洛斯彼罗注册号:CRD42023413684。
{"title":"Effects of non-invasive brain stimulation on impulsivity in patients with mental disorders: a systematic review and meta-analysis of randomised clinical trials.","authors":"Yuri de Castro Machado, Mariana Oliveira, Mateus Pereira Mundoca, Bernardo Viana, Debora Marques de Miranda, Marco Aurélio Romano-Silva","doi":"10.1136/gpsych-2023-101220","DOIUrl":"10.1136/gpsych-2023-101220","url":null,"abstract":"<p><strong>Background: </strong>Non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), may offer an alternative treatment strategy for impulsive behaviour. By modulating brain activity, these techniques could potentially enhance impulse control and mitigate impulsivity.</p><p><strong>Aims: </strong>To provide a comprehensive analysis of the correlation between NIBS parameters, targeted brain regions and impulsivity.</p><p><strong>Methods: </strong>We systematically searched PubMed, Scopus and Embase on 5 April 2023 for randomised controlled trials (RCTs) of NIBS on impulsivity. Unbiased Hedges' g with 95% CIs was used to define the effect size. Cochran Q test and I² statistics were used to assess for heterogeneity; p values inferior to 0.10 and I²>25% were considered significant for heterogeneity. Publication bias was investigated by funnel plot analysis of point estimates according to study weights, by Egger's regression test and by non-parametric rank correlation (Begg) test.</p><p><strong>Results: </strong>A total of 18 studies were included, comprising 655 patients from 14 RCTs and four randomised crossover studies. The meta-analysis of effect sizes from 9 tDCS studies on impulsivity did not show a significant effect (g=-0.18; 95% CI -0.46 to 0.10; p=0.210) and from 9 repetitive TMS (rTMS) studies also did not yield a statistically significant effect (g=0.21; 95% CI -0.38 to 0.80; p=0.490). When analysing active tDCS using Barratt Impulsiveness Scale version 11, the scores showed a trend towards improvement with active tDCS over placebo (g=-0.54; 95% CI -0.97 to -0.12; p<0.05; I²=0%).</p><p><strong>Conclusions: </strong>There is currently insufficient evidence to support the clinical use of rTMS or tDCS as a means of reducing impulsivity in individuals with mental disorders. The main limitations of this study are the lack of available patient-level data, a limited number of studies, the lack of consensus on the structure of impulsivity and variability in how impulsivity is measured and conceptualised.</p><p><strong>Prospero registration number: </strong>CRD42023413684.</p>","PeriodicalId":12549,"journal":{"name":"General Psychiatry","volume":"37 6","pages":"e101220"},"PeriodicalIF":5.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-20eCollection Date: 2024-01-01DOI: 10.1136/gpsych-2023-101436
Yujia Xia, Zhangsheng Yu
{"title":"Thorny but rosy: prosperities and difficulties in 'AI plus medicine' concerning data collection, model construction and clinical deployment.","authors":"Yujia Xia, Zhangsheng Yu","doi":"10.1136/gpsych-2023-101436","DOIUrl":"10.1136/gpsych-2023-101436","url":null,"abstract":"","PeriodicalId":12549,"journal":{"name":"General Psychiatry","volume":"37 6","pages":"e101436"},"PeriodicalIF":5.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12eCollection Date: 2024-01-01DOI: 10.1136/gpsych-2024-101673
Trine Lise Bakken, Magnus Sandberg, Anna Axmon
Abstract:
Background: The knowledge about the prevalence of schizophrenia among people with intellectual disabilities (ID) is sparse, particularly concerning the distribution in different age groups.
Aims: To investigate the prevalence of diagnoses in the schizophrenia spectrum among people with ID compared with the general population (gPop).
Methods: This was an 8-year longitudinal register study. The participants were all residents of Skåne on 1 January 2014. People with a diagnosis of ID (F7 in International Statistical Classification of Diseases and Related Health Problems 10th Revision) or Down syndrome (DS; Q90), or service and support for people with ID/autism spectrum disorder (ASD) comprised the ID cohort (n=14 716). After excluding family members of people in the ID cohort, the remaining population of Skåne comprised the gPop cohort (n=1 226 955).The primary outcome measure was having at least one diagnosis in the schizophrenia spectrum (F20-F29). Secondary outcomes were single diagnoses within the schizophrenia spectrum.
Results: The prevalence of schizophrenia spectrum diagnoses was 7.2% in the ID cohort. This was more than an eightfold increase compared with the gPop (relative risk (RR) 8.45; 95% CI 7.94 to 9.00). The risk was also high among children (aged 0-18 years at the start of the study period; RR 9.42; 95% CI 7.36 to 12.05). In the subcohort comprising those with a diagnosis of DS, the risk of schizophrenia diagnosis was more than twice as high as in gPop. Concomitant ASD or genetic syndrome did not carry an excess risk among people with ID when compared with the gPop.
Conclusions: The findings of the present study support earlier assumptions that people with vulnerable brains develop psychotic disorders more frequently and that the onset age is lower than among people in the gPop. Habilitation services for children and adolescents, as well as general mental health services, should keep in mind that schizophrenia may be present when children and adolescents show severely decreased functioning, anxiety or aggressive behaviour.
摘要/ Abstract摘要:背景:关于精神分裂症在智障人群中的患病率,特别是在不同年龄组的分布方面的知识很少。目的:调查与一般人群(gPop)相比,ID人群中精神分裂症谱系诊断的患病率。方法:这是一项为期8年的纵向登记研究。参与者均为2014年1月1日skamatne的居民。诊断为ID(《国际疾病与相关健康问题统计分类》第十版F7)或唐氏综合征(DS)者;问题90),或对患有ID/自闭症谱系障碍(ASD)的人的服务和支持组成ID队列(n=14 716)。在排除ID队列中人群的家庭成员后,sk的剩余人群组成gPop队列(n=1 226 955)。主要结局指标是在精神分裂症谱系中至少有一种诊断(F20-F29)。次要结果是精神分裂症谱系内的单一诊断。结果:在ID队列中,精神分裂症谱系诊断的患病率为7.2%。与gPop相比,这是8倍多的增长(相对风险(RR) 8.45;95% CI 7.94 - 9.00)。儿童的风险也很高(研究开始时0-18岁;RR 9.42;95% CI 7.36 ~ 12.05)。在诊断为DS的亚队列中,诊断为精神分裂症的风险是gPop的两倍多。与gPop相比,伴随ASD或遗传综合征在ID患者中没有带来额外的风险。结论:目前的研究结果支持了先前的假设,即大脑脆弱的人更容易出现精神障碍,而且发病年龄低于gPop人群。儿童和青少年康复服务以及一般心理健康服务应牢记,当儿童和青少年表现出功能严重下降、焦虑或攻击性行为时,就可能存在精神分裂症。
{"title":"Schizophrenia in children, adults and older people with intellectual disability compared with the general population: a Swedish register study (IDcare).","authors":"Trine Lise Bakken, Magnus Sandberg, Anna Axmon","doi":"10.1136/gpsych-2024-101673","DOIUrl":"10.1136/gpsych-2024-101673","url":null,"abstract":"<p><strong>Abstract: </strong></p><p><strong>Background: </strong>The knowledge about the prevalence of schizophrenia among people with intellectual disabilities (ID) is sparse, particularly concerning the distribution in different age groups.</p><p><strong>Aims: </strong>To investigate the prevalence of diagnoses in the schizophrenia spectrum among people with ID compared with the general population (gPop).</p><p><strong>Methods: </strong>This was an 8-year longitudinal register study. The participants were all residents of Skåne on 1 January 2014. People with a diagnosis of ID (F7 in International Statistical Classification of Diseases and Related Health Problems 10th Revision) or Down syndrome (DS; Q90), or service and support for people with ID/autism spectrum disorder (ASD) comprised the ID cohort (n=14 716). After excluding family members of people in the ID cohort, the remaining population of Skåne comprised the gPop cohort (n=1 226 955).The primary outcome measure was having at least one diagnosis in the schizophrenia spectrum (F20-F29). Secondary outcomes were single diagnoses within the schizophrenia spectrum.</p><p><strong>Results: </strong>The prevalence of schizophrenia spectrum diagnoses was 7.2% in the ID cohort. This was more than an eightfold increase compared with the gPop (relative risk (RR) 8.45; 95% CI 7.94 to 9.00). The risk was also high among children (aged 0-18 years at the start of the study period; RR 9.42; 95% CI 7.36 to 12.05). In the subcohort comprising those with a diagnosis of DS, the risk of schizophrenia diagnosis was more than twice as high as in gPop. Concomitant ASD or genetic syndrome did not carry an excess risk among people with ID when compared with the gPop.</p><p><strong>Conclusions: </strong>The findings of the present study support earlier assumptions that people with vulnerable brains develop psychotic disorders more frequently and that the onset age is lower than among people in the gPop. Habilitation services for children and adolescents, as well as general mental health services, should keep in mind that schizophrenia may be present when children and adolescents show severely decreased functioning, anxiety or aggressive behaviour.</p>","PeriodicalId":12549,"journal":{"name":"General Psychiatry","volume":"37 6","pages":"e101673"},"PeriodicalIF":5.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-11eCollection Date: 2024-01-01DOI: 10.1136/gpsych-2024-101604
Elizabeth Roberts, Mala Watts, Safiya Riley, Kathryn Hart
{"title":"Scoping survey of dietetic resourcing for eating disorders: why is the dietitian's role marginalised in community eating disorders?","authors":"Elizabeth Roberts, Mala Watts, Safiya Riley, Kathryn Hart","doi":"10.1136/gpsych-2024-101604","DOIUrl":"10.1136/gpsych-2024-101604","url":null,"abstract":"","PeriodicalId":12549,"journal":{"name":"General Psychiatry","volume":"37 6","pages":"e101604"},"PeriodicalIF":5.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-07eCollection Date: 2024-01-01DOI: 10.1136/gpsych-2024-101608
Yaara Zisman-Ilani, Jessica G Kovach, Meera Chatterjee, Mary F Morrison
{"title":"Unlocking the door to supportive housing: addressing the challenge of post-discharge transitions in safety-net psychiatric care.","authors":"Yaara Zisman-Ilani, Jessica G Kovach, Meera Chatterjee, Mary F Morrison","doi":"10.1136/gpsych-2024-101608","DOIUrl":"10.1136/gpsych-2024-101608","url":null,"abstract":"","PeriodicalId":12549,"journal":{"name":"General Psychiatry","volume":"37 6","pages":"e101608"},"PeriodicalIF":5.3,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This paper aims to present a Statistical Analysis Software (SAS) macro %BBIplus, offering estimation and visualisation methods for the Bang's Blinding Index (BBI) for randomised controlled trials (RCTs) with various designs. We developed the SAS macro programme %BBIplus to facilitate the implementation of BBI. This user-friendly programme allows for easy and rapid estimation and visualisation of BBI across different scenarios, including pairwise comparison RCTs with two arms, double-dummy design RCTs with three arms and factorial design RCTs with four arms. The programme requires no pre-existing data set, and users only need to input the number of individuals of correct, uncertain or wrong guesses in each intervention or control group. We illustrate the functionality of %BBIplus using blinding assessment data from three previously published RCTs: BBR (adjunctive berberine reduces antipsychotic-associated weight gain and metabolic syndrome in patients with schizophrenia: a randomised controlled trial), SELECT-TDCS (the sertraline versus electrical current therapy for treating depression clinical study: results from a factorial, randomised controlled trial) and ELECT-TDCS (trial of electrical direct-current therapy versus escitalopram for depression) studies. The programme estimates the BBI for each arm, providing point estimates, 95% CI and associated p values. Additionally, %BBIplus can visualise the estimations through forest plots and make the judgement for the success of blinding easily and rapidly. This tool caters to the needs of clinical trial investigators, offering a comprehensive solution for estimating and visualising the blinding index under various RCT designs.
本文旨在介绍一个统计分析软件(SAS)宏%BBIplus,为各种设计的随机对照试验(rct)提供Bang's Blinding Index (BBI)的估计和可视化方法。我们开发了SAS宏程序%BBI +来促进BBI的实现。这个用户友好的程序允许在不同情况下轻松快速地估计和可视化BBI,包括两臂的两两比较rct,三臂的双假人设计rct和四臂的因子设计rct。该程序不需要预先存在的数据集,用户只需要输入每个干预组或对照组中正确、不确定或错误猜测的人数。我们使用三个先前发表的随机对照试验的盲性评估数据来说明%BBIplus的功能:BBR(辅助小檗碱减少精神分裂症患者抗精神病相关体重增加和代谢综合征:一项随机对照试验),SELECT-TDCS(舍曲林与电流治疗治疗抑郁症的临床研究:结果来自一项因子、随机对照试验)和ELECT-TDCS(电直流电治疗与艾司西酞普兰治疗抑郁症的试验)研究。该方案估计每个臂的BBI,提供点估计、95% CI和相关p值。此外,%BBIplus还可以通过森林样地将估算结果可视化,方便快捷地判断盲法是否成功。该工具满足临床试验研究者的需求,为各种RCT设计下的盲化指数估计和可视化提供了全面的解决方案。
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Low socioeconomic status (SES) is a well-established risk factor for general and mental health problems. However, there is no widely accepted definition or operationalisation for SES, leading to varied interpretations in research. In a critical review of the child and adolescent mental health literature, we map how SES is defined and measured. We examined 334 relevant papers from 2013 to 2024 and found significant variability in the operationalisation of SES. Our analysis revealed fundamental problems such as the lack of clear definitions, insufficient detail on variables used and limited measures directly reported by adolescents. We discuss issues related to measurement techniques and their impact on reproducibility, policy development and intervention design. Based on our findings, we recommend using SES measures that directly assess the socioeconomic position of children and adolescents. Additionally, we recommend researchers improve transparency and specificity in reporting the measures used and the rationale behind their selection. The wide range of distinct measures used to represent SES, coupled with insufficient reporting, likely hampers our understanding of which underlying factors truly drive observed effects and impedes the establishment of causal relationships. This, in turn, makes the path to effective health interventions more challenging.
低社会经济地位(SES)是导致一般和心理健康问题的一个公认的风险因素。然而,社会经济地位并没有一个广为接受的定义或操作方法,导致研究中的解释各不相同。在对儿童和青少年心理健康文献的批判性回顾中,我们描绘了如何定义和衡量 SES。我们研究了从 2013 年到 2024 年的 334 篇相关论文,发现 SES 的操作方法存在很大差异。我们的分析揭示了一些基本问题,如缺乏明确的定义、所用变量不够详细、青少年直接报告的测量方法有限等。我们讨论了与测量技术相关的问题及其对可重复性、政策制定和干预设计的影响。基于我们的研究结果,我们建议使用直接评估儿童和青少年社会经济地位的社会经济地位测量方法。此外,我们还建议研究人员在报告所使用的测量方法及其选择理由时提高透明度和具体性。用于代表社会经济地位的各种不同的测量方法,再加上报告的不充分,很可能会妨碍我们了解哪些基本因素真正推动了所观察到的效应,并阻碍因果关系的建立。这反过来又使有效的健康干预措施更具挑战性。
{"title":"What do we mean when we talk about socioeconomic status? Implications for measurement, mechanisms and interventions from a critical review on adolescent mental health.","authors":"Mirela Zaneva, Tsvetomira Dumbalska, Aaron Reeves, Lucy Bowes","doi":"10.1136/gpsych-2023-101455","DOIUrl":"10.1136/gpsych-2023-101455","url":null,"abstract":"<p><p>Low socioeconomic status (SES) is a well-established risk factor for general and mental health problems. However, there is no widely accepted definition or operationalisation for SES, leading to varied interpretations in research. In a critical review of the child and adolescent mental health literature, we map how SES is defined and measured. We examined 334 relevant papers from 2013 to 2024 and found significant variability in the operationalisation of SES. Our analysis revealed fundamental problems such as the lack of clear definitions, insufficient detail on variables used and limited measures directly reported by adolescents. We discuss issues related to measurement techniques and their impact on reproducibility, policy development and intervention design. Based on our findings, we recommend using SES measures that directly assess the socioeconomic position of children and adolescents. Additionally, we recommend researchers improve transparency and specificity in reporting the measures used and the rationale behind their selection. The wide range of distinct measures used to represent SES, coupled with insufficient reporting, likely hampers our understanding of which underlying factors truly drive observed effects and impedes the establishment of causal relationships. This, in turn, makes the path to effective health interventions more challenging.</p>","PeriodicalId":12549,"journal":{"name":"General Psychiatry","volume":"37 6","pages":"e101455"},"PeriodicalIF":5.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07eCollection Date: 2024-01-01DOI: 10.1136/gpsych-2024-101675
Hamer Bastidas-Bilbao, Ximena Palacios-Espinosa, Donna E Stewart, Vicky Stergiopoulos
{"title":"Mental illness segregation and truncated autonomy within medical assistance in dying legislative frameworks in Colombia and Canada.","authors":"Hamer Bastidas-Bilbao, Ximena Palacios-Espinosa, Donna E Stewart, Vicky Stergiopoulos","doi":"10.1136/gpsych-2024-101675","DOIUrl":"https://doi.org/10.1136/gpsych-2024-101675","url":null,"abstract":"","PeriodicalId":12549,"journal":{"name":"General Psychiatry","volume":"37 6","pages":"e101675"},"PeriodicalIF":5.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Kabuki syndrome (KS) is a rare developmental disorder characterised by multiple congenital anomalies and intellectual disability. UTX (ubiquitously transcribed tetratricopeptide repeat, X chromosome), which encodes a histone demethylase, is one of the two major pathogenic risk genes for KS. Although intellectual disability is a key phenotype of KS, the role of UTX in cognitive function remains unclear. Currently, no targeted therapies are available for KS.
Aims: This study aimed to investigate how UTX regulates cognition, to explore the mechanisms underlying UTX dysfunction and to identify potential molecular targets for treatment.
Methods: We generated UTX conditional knockout mice and found that UTX deletion downregulated calmodulin transcription by disrupting H3K27me3 (trimethylated histone H3 at lysine 27) demethylation.
Results: UTX-knockout mice showed decreased phosphorylation of calcium / calmodulin-dependent protein kinase II, impaired long-term potentiation and deficit in remote contextual fear memory. These effects were reversed by an Food and Drug Administration-approved drug desipramine.
Conclusions: Our results reveal an epigenetic mechanism underlying the important role of UTX in synaptic plasticity and cognitive function, and suggest that desipramine could be a potential treatment for KS.
{"title":"Desipramine reverses remote memory deficits by activating calmodulin-CaMKII pathway in a UTX knockout mouse model of Kabuki syndrome.","authors":"Lei Chen, Yuting Li, Minggang Liu, Zhaohui Lan, Xu Zhang, Xiujuan Yang, Qian Zhao, Shuai Wang, Longyong Xu, Ying Zhou, Yifang Kuang, Tatsuo Suzuki, Katsuhiko Tabuchi, Eiki Takahashi, Miou Zhou, Charlie Degui Chen, Tianle Xu, Weidong Li","doi":"10.1136/gpsych-2023-101430","DOIUrl":"10.1136/gpsych-2023-101430","url":null,"abstract":"<p><strong>Background: </strong>Kabuki syndrome (KS) is a rare developmental disorder characterised by multiple congenital anomalies and intellectual disability. <i>UTX</i> (ubiquitously transcribed tetratricopeptide repeat, X chromosome), which encodes a histone demethylase, is one of the two major pathogenic risk genes for KS. Although intellectual disability is a key phenotype of KS, the role of <i>UTX</i> in cognitive function remains unclear. Currently, no targeted therapies are available for KS.</p><p><strong>Aims: </strong>This study aimed to investigate how <i>UTX</i> regulates cognition, to explore the mechanisms underlying <i>UTX</i> dysfunction and to identify potential molecular targets for treatment.</p><p><strong>Methods: </strong>We generated <i>UTX</i> conditional knockout mice and found that <i>UTX</i> deletion downregulated calmodulin transcription by disrupting H3K27me3 (trimethylated histone H3 at lysine 27) demethylation.</p><p><strong>Results: </strong><i>UTX</i>-knockout mice showed decreased phosphorylation of calcium / calmodulin-dependent protein kinase II, impaired long-term potentiation and deficit in remote contextual fear memory. These effects were reversed by an Food and Drug Administration-approved drug desipramine.</p><p><strong>Conclusions: </strong>Our results reveal an epigenetic mechanism underlying the important role of <i>UTX</i> in synaptic plasticity and cognitive function, and suggest that desipramine could be a potential treatment for KS.</p>","PeriodicalId":12549,"journal":{"name":"General Psychiatry","volume":"37 5","pages":"e101430"},"PeriodicalIF":5.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}