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Modifying Informed Consent to Help Address Functional Unmasking in Psychedelic Clinical Trials 修改知情同意有助于解决致幻剂临床试验中的功能揭露问题
IF 25.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2025-01-08 DOI: 10.1001/jamapsychiatry.2024.4312
Michelle Matvey, D. Parker Kelley, Ellen R. Bradley, Winston Chiong, Aoife O’Donovan, Josh Woolley
ImportanceThere is unprecedented clinician, industry, and patient interest in the therapeutic development of psychedelic drugs. This is due to a combination of promising clinical trial results, positive media coverage, and the lack of novel pharmacologic treatments for psychiatric disorders in recent decades. However, the field faces a key methodological challenge: masking participants to treatment conditions in psychedelic clinical trials has been largely unsuccessful.ObjectiveWhen participants can tell whether they received active drug or placebo, their responses to clinical assessments, questionnaires, and even their functional imaging and biological data can be influenced by preconceptions about treatment effects. Positive patient expectancies combined with ineffective masking may skew outcomes and inflate effect sizes. This complicates efforts to determine the safety and efficacy of psychedelic drugs. Here, we explore a method to help address this problem: modifying informed consent to obscure information about the study design.Evidence ReviewWe reviewed all contemporary (2000-2024) clinical trials of psychedelic or methylenedioxymethamphetamine (MDMA) therapy and corresponded with the investigators to compile information on the use of modifications to informed consent in these studies.FindingsModifying informed consent to obscure details of the study design has been implemented in several psychedelic clinical trials and may offer a way to strengthen masking. However, this approach poses significant ethical risks. We examine examples of modifications used in the psychedelic literature, discuss the current regulatory landscape, and suggest strategies to mitigate risks associated with modified informed consent.Conclusions and RelevanceIncorporating modified informed consent in future psychedelic clinical trials may improve interpretability and impact, but this has not been explicitly tested. Modifications to informed consent may not be appropriate in all cases, and risks to participants should be minimized by implementing appropriate guardrails.
临床医生、工业界和患者对致幻剂的治疗发展产生了前所未有的兴趣。这是由于有希望的临床试验结果,积极的媒体报道,以及近几十年来精神疾病缺乏新的药物治疗。然而,该领域面临着一个关键的方法论挑战:在迷幻药临床试验中,掩盖参与者的治疗条件在很大程度上是不成功的。目的:当参与者能够分辨出他们接受的是有效药物还是安慰剂时,他们对临床评估、问卷调查的反应,甚至他们的功能成像和生物学数据都可能受到对治疗效果的先入为主的影响。积极的患者期望与无效的掩蔽相结合可能会扭曲结果并夸大效应大小。这使得确定致幻剂的安全性和有效性的工作变得复杂。在这里,我们探索了一种方法来帮助解决这个问题:修改知情同意来模糊有关研究设计的信息。我们回顾了所有当代(2000-2024年)迷幻药或亚甲基二氧甲基苯丙胺(MDMA)治疗的临床试验,并与研究者进行了通信,以收集这些研究中知情同意修改的使用信息。修改知情同意以模糊研究设计的细节已经在几个迷幻药临床试验中实施,可能提供一种加强掩盖的方法。然而,这种方法带来了重大的伦理风险。我们研究了迷幻药文献中使用的修改实例,讨论了当前的监管格局,并提出了降低与修改后的知情同意相关的风险的策略。在未来的迷幻药临床试验中纳入修改后的知情同意可能会提高可解释性和影响,但这尚未得到明确的测试。对知情同意的修改可能并不适用于所有情况,应通过实施适当的护栏将参与者的风险降至最低。
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引用次数: 0
Genetic Analysis of Retinal Cell Types in Neuropsychiatric Disorders 神经精神疾病视网膜细胞类型的遗传分析
IF 25.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2025-01-08 DOI: 10.1001/jamapsychiatry.2024.4230
Emanuel Boudriot, Marius Stephan, Finn Rabe, Lukasz Smigielski, Andrea Schmitt, Peter Falkai, Michael J. Ziller, Moritz J. Rossner, Philipp Homan, Sergi Papiol, Florian J. Raabe
ImportanceAs an accessible part of the central nervous system, the retina provides a unique window to study pathophysiological mechanisms of brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric and neurological disorders, but it remains largely unclear which specific cell types and biological mechanisms are involved.ObjectiveTo determine whether specific retinal cell types are affected by genomic risk for neuropsychiatric and neurological disorders and to explore the mechanisms through which genomic risk converges in these cell types.Design, Setting, and ParticipantsThis genetic association study combined findings from genome-wide association studies in schizophrenia, bipolar disorder, major depressive disorder, multiple sclerosis, Parkinson disease, Alzheimer disease, and stroke with retinal single-cell transcriptomic datasets from humans, macaques, and mice. To identify susceptible cell types, Multi-Marker Analysis of Genomic Annotation (MAGMA) cell-type enrichment analyses were applied and subsequent pathway analyses performed. The cellular top hits were translated to the structural level using retinal optical coherence tomography (acquired between 2009 and 2010) and genotyping data in the large population-based UK Biobank cohort study. Data analysis was conducted between 2022 and 2024.Main Outcomes and MeasuresCell type–specific enrichment of genetic risk loading for neuropsychiatric and neurological disorder traits in the gene expression profiles of retinal cells.ResultsExpression profiles of amacrine cells (interneurons within the retina) were robustly enriched in schizophrenia genetic risk across mammalian species and in different developmental stages. This enrichment was primarily driven by genes involved in synapse biology. Moreover, expression profiles of retinal immune cell populations were enriched in multiple sclerosis genetic risk. No consistent cell-type associations were found for bipolar disorder, major depressive disorder, Parkinson disease, Alzheimer disease, or stroke. On the structural level, higher polygenic risk for schizophrenia was associated with thinning of the ganglion cell inner plexiform layer, which contains dendrites and synaptic connections of amacrine cells (B, −0.09; 95% CI, −0.16 to −0.03; P = .007; n = 36 349; mean [SD] age, 57.50 [8.00] years; 19 859 female [54.63%]). Higher polygenic risk for multiple sclerosis was associated with increased thickness of the retinal nerve fiber layer (B, 0.06; 95% CI, 0.02 to 0.10; P = .007; n = 36 371; mean [SD] age, 57.51 [8.00] years; 19 843 female [54.56%]).Conclusions and RelevanceThis study provides novel insights into the cellular underpinnings of retinal alterations in neuropsychiatric and neurological disorders and highlights the retina as a potential proxy to study synaptic pathology in schizophrenia.
作为中枢神经系统的一个可接近的部分,视网膜为研究人类大脑疾病的病理生理机制提供了一个独特的窗口。成像和电生理学研究已经揭示了几种神经精神和神经疾病的视网膜改变,但仍不清楚具体是哪种细胞类型和生物学机制参与其中。目的确定特定的视网膜细胞类型是否受到神经精神和神经疾病基因组风险的影响,并探讨基因组风险在这些细胞类型中聚集的机制。设计、环境和参与者:这项遗传关联研究结合了精神分裂症、双相情感障碍、重度抑郁症、多发性硬化症、帕金森病、阿尔茨海默病和中风的全基因组关联研究结果,以及来自人类、猕猴和小鼠的视网膜单细胞转录组数据集。为了鉴定易感细胞类型,应用了基因组注释的多标记分析(MAGMA)细胞类型富集分析和随后的途径分析。利用视网膜光学相干断层扫描(2009年至2010年间获得)和基于英国生物银行的大型人群队列研究的基因分型数据,将细胞顶部命中转化为结构水平。数据分析是在2022年至2024年间进行的。视网膜细胞基因表达谱中神经精神和神经疾病特征遗传风险负荷的细胞类型特异性富集。结果在不同哺乳动物物种和不同发育阶段,无突细胞(视网膜内的中间神经元)的表达谱在精神分裂症遗传风险中显著富集。这种富集主要是由参与突触生物学的基因驱动的。此外,视网膜免疫细胞群的表达谱在多发性硬化症遗传风险中丰富。双相情感障碍、重度抑郁症、帕金森病、阿尔茨海默病或中风没有发现一致的细胞类型关联。在结构水平上,较高的精神分裂症多基因风险与神经节细胞内丛状层变薄有关,其中包含无突细胞的树突和突触连接(B,−0.09;95% CI,−0.16 ~−0.03;P = .007;N = 36 349;平均[SD]年龄57.50[8.00]岁;19 859名女性[54.63%])。多发性硬化症的高多基因风险与视网膜神经纤维层厚度增加有关(B, 0.06;95% CI, 0.02 ~ 0.10;P = .007;N = 36 371;平均[SD]年龄57.51[8.00]岁;女性19 843人[54.56%])。结论和相关性本研究为神经精神和神经疾病视网膜改变的细胞基础提供了新的见解,并强调了视网膜作为研究精神分裂症突触病理的潜在代理。
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引用次数: 0
Social Determinants of Health and Suicide-Related Outcomes: A Review of Meta-Analyses. 健康和自杀相关结果的社会决定因素:荟萃分析综述
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2025-01-02 DOI: 10.1001/jamapsychiatry.2024.4241
Peter Jongho Na, Jeonghyun Shin, Ha Rim Kwak, Jaewon Lee, Dylan J Jester, Piumee Bandara, Jim Yong Kim, Christine Y Moutier, Robert H Pietrzak, Maria A Oquendo, Dilip V Jeste

Importance: Preventing suicide is one of the top priorities in public health policy. Identifying key social determinants of health (SDOH) in suicide risk is critical for informing clinical practices, future research, and policy solutions to prevent suicide.

Objective: To examine the associations of SDOH with suicide-related outcomes.

Data sources: Studies published before July 2023 were searched through PubMed, PsycINFO, Embase, and Web of Science. The date of the search was August 4, 2023.

Study selection: We included the most up-to-date meta-analyses reporting associations between SDOH and suicide-related outcomes.

Data extraction and synthesis: Three independent reviewers extracted data and conducted quality assessment using the Joanna Briggs Institute Checklist for Systematic Reviews and Research Syntheses.

Main outcomes and measures: The main outcomes of interest were suicide mortality, suicide attempt, and suicidal ideation.

Results: A total of 46 meta-analyses met inclusion criteria. For suicide mortality, justice system-involved individuals in the community, exposure to others' and parental suicide, firearm accessibility, divorce, experience in foster care, release from incarceration, and midlife (age 35-65 years) unemployment were the SDOH with consistently strong effects. Individuals released from incarceration demonstrated a high prevalence of suicide mortality (114.5 per 100 000 persons). With regard to suicide attempt, experience of childhood abuse and maltreatment and sexual assault, gender and sexual minority status, and parental suicide mortality were the strongest risk factors. The prevalence of suicide attempt among homeless individuals (28.9%; 95% CI, 21.7%-37.2%) and incarcerated female youths (27%; 95% CI, 20%-34%) and adults (12.2%; 95% CI, 7.1%-17.2%) was high. For suicidal ideation, identification as bisexual and intimate partner violence in women were the strongest risk factors. The prevalence of lifetime suicidal ideation in homeless individuals was 41.6% (95% CI, 28.6%-56.0%). Protective factors associated with reduced risk of suicide mortality were religious affiliation and being married. School connectedness showed protective associations against suicide attempt and suicidal ideation.

Conclusions and relevance: Tailoring interventions and future research for identified priority subpopulations, such as justice system-involved individuals in the community, and implementing policy measures addressing the SDOH that showed strong associations with suicide mortality, attempts, and ideation, such as gun licensing requirements, are critical to counteracting social and environmental forces that increase suicide risk.

重要性:预防自杀是公共卫生政策的优先事项之一。确定自杀风险中的健康关键社会决定因素(SDOH)对于告知临床实践、未来研究和预防自杀的政策解决方案至关重要。目的:探讨SDOH与自杀相关结局的关系。数据来源:通过PubMed, PsycINFO, Embase和Web of Science检索2023年7月之前发表的研究。搜索日期是2023年8月4日。研究选择:我们纳入了最新的荟萃分析,报告了SDOH与自杀相关结果之间的关联。数据提取和综合:三位独立的审稿人提取数据,并使用乔安娜布里格斯研究所系统评论和研究综合清单进行质量评估。主要结局和测量方法:主要结局为自杀死亡率、自杀企图和自杀意念。结果:共有46项meta分析符合纳入标准。就自杀死亡率而言,社区司法系统相关人员、接触他人和父母自杀、枪支可及性、离婚、寄养经历、出狱和中年(35-65岁)失业是具有持续强烈影响的SDOH。从监禁中释放出来的人显示出很高的自杀死亡率(每10万人中有114.5人 000人)。在自杀企图方面,儿童期遭受虐待和性侵犯的经历、性别和性少数身份以及父母自杀死亡率是最强的危险因素。无家可归者自杀未遂率(28.9%;95% CI, 21.7%-37.2%)和被监禁的女青年(27%;95% CI, 20%-34%)和成人(12.2%;95% CI(7.1% ~ 17.2%)较高。就自杀意念而言,女性的双性恋身份和亲密伴侣暴力是最强的危险因素。无家可归者的终生自杀意念患病率为41.6% (95% CI, 28.6%-56.0%)。与降低自杀死亡率风险相关的保护因素是宗教信仰和结婚。与学校的联系显示出对自杀企图和自杀意念的保护作用。结论和相关性:针对已确定的优先亚人群(如社区中涉及司法系统的个人)量身定制干预措施和未来研究,并实施政策措施,解决与自杀死亡率、企图和想法密切相关的SDOH问题,如枪支许可要求,对于抵消增加自杀风险的社会和环境力量至关重要。
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引用次数: 0
Deconstructing Cognitive Impairment in Psychosis With a Machine Learning Approach. 用机器学习方法解构精神病患者的认知障碍
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2025-01-01 DOI: 10.1001/jamapsychiatry.2024.3062
Robert A McCutcheon, Richard S E Keefe, Philip M McGuire, Andre Marquand
<p><strong>Importance: </strong>Cognitive functioning is associated with various factors, such as age, sex, education, and childhood adversity, and is impaired in people with psychosis. In addition to specific effects of the disorder, cognitive impairments may reflect a greater exposure to general risk factors for poor cognition.</p><p><strong>Objective: </strong>To determine the extent that impairments in cognition in psychosis reflect risk factor exposures.</p><p><strong>Design, setting, and participants: </strong>This cross-sectional study examined the relationship between exposures and cognitive function using data from the Bipolar-Schizophrenia Network on Intermediate Phenotypes studies 1 and 2 across 6 sites. Participants included healthy controls; patients with schizophrenia, schizoaffective disorder, or bipolar I disorder with psychosis; and relatives of patients. Predictive modeling was performed using extreme gradient boosting regression to train a composite cognitive score prediction model with nested cross-validation. Shapley additive explanations values were used to examine the relationship between exposures and cognitive function.</p><p><strong>Exposure: </strong>Exposures were chosen based on associations with cognition previously identified: age, sex, race and ethnicity, childhood adversity, education, parental education, parental socioeconomic status, parental age at birth, substance use, antipsychotic dose, and diagnosis.</p><p><strong>Main outcomes and measures: </strong>Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia.</p><p><strong>Results: </strong>A total of 3370 participants were included: 840 healthy controls, 709 patients with schizophrenia, 541 with schizoaffective disorder, 457 with bipolar I disorder with psychosis, and 823 relatives of patients. The mean (SD) age was 37.9 (13.3) years; 1887 were female (56%) and 1483 male (44%). The model predicted cognitive scores with high accuracy: out-of-sample Pearson correlation between predicted and observed cognitive composite score was r = 0.72 (SD = 0.03). Individuals with schizophrenia (z = -1.4), schizoaffective disorder (z = -1.2), and bipolar I disorder with psychosis (z = -0.5) all had significantly worse cognitive composite scores than controls. Factors other than diagnosis and medication accounted for much of this impairment (schizophrenia z = -0.73, schizoaffective disorder z = -0.64, bipolar I disorder with psychosis z = -0.13). Diagnosis accounted for a lesser proportion of this deficit (schizophrenia z = -0.29, schizoaffective disorder z = -0.15, bipolar I disorder with psychosis z = -0.13), and antipsychotic use accounted for a similar deficit across diagnostic groups (schizophrenia z = -0.37, schizoaffective disorder z = -0.33, bipolar I disorder with psychosis z = -0.26).</p><p><strong>Conclusions and relevance: </strong>This study found that transdiagnostic factors accounted for a meaningful share of the variance in cognitive fu
重要性:认知功能与年龄、性别、教育程度和童年逆境等多种因素有关,精神病患者的认知功能也会受损。除了精神障碍的特殊影响外,认知功能障碍还可能反映出患者更多地暴露于导致认知功能低下的一般风险因素:目的:确定精神病患者的认知障碍在多大程度上反映了所暴露的风险因素:这项横断面研究利用双相情感障碍-精神分裂症中间表型网络研究 1 和研究 2 在 6 个地点获得的数据,研究了暴露因素与认知功能之间的关系。参与者包括健康对照组;精神分裂症、分裂情感障碍或伴有精神病的双相情感障碍 I 型患者;以及患者亲属。预测建模采用极端梯度提升回归法,通过嵌套交叉验证训练综合认知分数预测模型。沙普利加法解释值用于检验暴露与认知功能之间的关系。暴露:暴露的选择基于之前确定的与认知相关的因素:年龄、性别、种族和民族、童年逆境、教育、父母教育、父母的社会经济地位、父母的出生年龄、药物使用、抗精神病药物剂量和诊断:认知能力采用精神分裂症认知能力简要评估进行评估:结果:共纳入 3370 名参与者:结果:共纳入了 3370 名参与者:840 名健康对照者、709 名精神分裂症患者、541 名分裂情感障碍患者、457 名躁狂 I 型精神障碍患者以及 823 名患者亲属。平均(标清)年龄为 37.9 (13.3) 岁;1887 名女性(占 56%),1483 名男性(占 44%)。该模型预测认知分数的准确性很高:预测认知综合分数与观察认知综合分数之间的样本外皮尔逊相关性为 r = 0.72(标度 = 0.03)。精神分裂症(z =-1.4)、分裂情感障碍(z =-1.2)和伴有精神病的双相情感障碍 I(z =-0.5)患者的认知综合评分均明显低于对照组。除诊断和药物治疗外,其他因素也是造成认知障碍的主要原因(精神分裂症 z = -0.73,分裂情感障碍 z = -0.64,伴有精神病的双相 I 型障碍 z = -0.13)。诊断在这一缺陷中所占比例较小(精神分裂症 z = -0.29,分裂情感性障碍 z = -0.15,Ⅰ型双相情感障碍伴有精神病 z =-0.13),而抗精神病药物的使用在各诊断组中造成的缺陷相似(精神分裂症 z = -0.37,分裂情感性障碍 z = -0.33,Ⅰ型双相情感障碍伴有精神病 z =-0.26):本研究发现,跨诊断因素在精神病认知功能的变异中占了相当大的比例。很大一部分精神病患者的认知功能障碍可能反映了与普通人群认知功能相关的因素。因此,在考虑干预措施时,以诊断为导向、以症状为目标的方法可能是合适的。
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引用次数: 0
Racial and Ethnic Disparities in Fentanyl and Polysubstance Overdose Deaths. 芬太尼和多种药物过量致死的种族和民族差异。
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2025-01-01 DOI: 10.1001/jamapsychiatry.2024.3435
David T Zhu
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引用次数: 0
Ending Unequal Treatment for People With Behavioral Health Conditions. 结束行为健康患者的不平等待遇。
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2025-01-01 DOI: 10.1001/jamapsychiatry.2024.3596
Ruth S Shim, Margarita Alegría
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引用次数: 0
Slowing Cognitive Decline in Major Depressive Disorder and Mild Cognitive Impairment: A Randomized Clinical Trial. 减缓重度抑郁症和轻度认知障碍患者的认知能力衰退:随机临床试验
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2025-01-01 DOI: 10.1001/jamapsychiatry.2024.3241
Tarek K Rajji, Christopher R Bowie, Nathan Herrmann, Bruce G Pollock, Krista L Lanctôt, Sanjeev Kumar, Alastair J Flint, Linda Mah, Corinne E Fischer, Meryl A Butters, Marom Bikson, James L Kennedy, Daniel M Blumberger, Zafiris J Daskalakis, Damien Gallagher, Mark J Rapoport, Nicolaas P L G Paul Verhoeff, Angela C Golas, Ariel Graff-Guerrero, Erica Vieira, Aristotle N Voineskos, Heather Brooks, Ashley Melichercik, Kevin E Thorpe, Benoit H Mulsant

Importance: Older adults with major depressive disorder (MDD) or mild cognitive impairment (MCI) are at high risk for cognitive decline.

Objective: To assess the efficacy of cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) targeting the prefrontal cortex in slowing cognitive decline, acutely improving cognition, and reducing progression to MCI or dementia in older adults with remitted MDD (rMDD), MCI, or both.

Design, setting, and participants: This randomized clinical trial was conducted at 5 academic hospitals in Toronto, Ontario, Canada. Participants were older adults who had rMDD (with or without MCI, age ≥65 y) or MCI without rMDD (age ≥60 y). Assessments were made at baseline, month 2, and yearly from baseline for 3 to 7 years.

Interventions: CR plus tDCS (hereafter, active) or sham plus sham 5 days a week for 8 weeks followed by twice-a-year 5-day boosters and daily at-home CR or sham CR.

Main outcomes and measures: The primary outcome was change in global composite cognitive score. Secondary outcomes included changes in 6 cognitive domains, moderating effect of the diagnosis, moderating effect of APOE ε4 status, change in composite score at month 2, and progression to MCI or dementia over time.

Results: Of 486 older adults who provided consent, 375 (with rMDD, MCI, or both) received at least 1 intervention session (mean [SD] age, 72.2 [6.4] years; 232 women [62%] and 143 men [38%]). Over a median follow-up of 48.3 months (range, 2.1-85.9), CR and tDCS slowed cognitive decline in older adults with rMDD or MCI (adjusted z score difference [active - sham] at month 60, 0.21; 95% CI, 0.07 to 0.35; likelihood ratio test [LRT] P = .006). In the preplanned primary analysis, CR and tDCS did not improve cognition acutely (adjusted z score difference [active - sham] at month 2, 0.06, 95% CI, -0.006 to 0.12). Similarly, the effect of CR and tDCS on delaying progression from normal cognition to MCI or MCI to dementia was weak and not significant (hazard ratio, 0.66; 95% CI, 0.40 to 1.08; P = .10). Preplanned analyses showed treatment effects for executive function (LRT P = .04) and verbal memory (LRT P = .02) and interactions with diagnosis (P = .01) and APOE ε4 (P < .001) demonstrating a larger effect among those with rMDD and in noncarriers of APOE ε4.

Conclusions and relevance: The study showed that CR and tDCS, both targeting the prefrontal cortex, is efficacious in slowing cognitive decline in older adults at risk of cognitive decline, particularly those with rMDD (with or without MCI) and in those at low genetic risk for Alzheimer disease.

Trial registration: ClinicalTrials.gov Identifier: NCT02386670.

重要性:患有重度抑郁症(MDD)或轻度认知障碍(MCI)的老年人是认知能力下降的高危人群:目的:评估针对前额叶皮质的认知矫正(CR)加经颅直流电刺激(tDCS)在减缓认知能力下降、急性改善认知能力以及减少MCI或痴呆进展方面的疗效:这项随机临床试验在加拿大安大略省多伦多市的 5 家学术医院进行。参与者为患有rMDD(伴有或不伴有MCI,年龄≥65岁)或不伴有rMDD的MCI(年龄≥60岁)的老年人。在基线期、第2个月和从基线期开始的3至7年内每年进行一次评估:干预措施:CR加tDCS(以下简称为活性)或假CR加假CR,每周5天,为期8周,之后每年两次,每次5天,每天在家进行CR或假CR:主要结果和测量指标:主要结果是总体综合认知评分的变化。次要结果包括 6 个认知领域的变化、诊断的调节作用、APOE ε4 状态的调节作用、第 2 个月时综合得分的变化以及随着时间的推移发展为 MCI 或痴呆:在征得同意的 486 名老年人中,有 375 人(rMDD、MCI 或两者兼有)接受了至少一次干预治疗(平均 [SD] 年龄 72.2 [6.4] 岁;232 名女性 [62%] 和 143 名男性 [38%])。在48.3个月的中位随访期间(范围为2.1-85.9),CR和tDCS减缓了患有rMDD或MCI的老年人的认知能力下降(第60个月时调整后的z评分差异[活动-假]为0.21;95% CI为0.07-0.35;似然比检验[LRT] P = .006)。在预先计划的主要分析中,CR 和 tDCS 并未改善急性期的认知能力(第 2 个月时调整后的 z 评分差异[活动-假],0.06;95% CI,-0.006 至 0.12)。同样,CR 和 tDCS 对延缓认知功能从正常发展为 MCI 或 MCI 发展为痴呆症的效果也很弱,且不显著(危险比为 0.66;95% CI 为 0.40 至 1.08;P = .10)。预先计划的分析显示,执行功能(LRT P = .04)和言语记忆(LRT P = .02)的治疗效果以及与诊断(P = .01)和 APOE ε4(P 结论和相关性)的交互作用:该研究表明,CR 和 tDCS(均以前额叶皮层为靶点)对减缓有认知能力下降风险的老年人的认知能力下降具有疗效,尤其是那些患有 rMDD(伴有或不伴有 MCI)以及阿尔茨海默病遗传风险较低的老年人:试验注册:ClinicalTrials.gov Identifier:试验注册:ClinicalTrials.gov Identifier:NCT02386670。
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引用次数: 0
TikTok Challenges-Unintentional Injuries vs Suicide Attempts. TikTok 挑战--意外伤害与自杀未遂。
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2025-01-01 DOI: 10.1001/jamapsychiatry.2024.3522
Onomeasike Ataga, Valerie K Arnold
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引用次数: 0
Sexual Trauma, Polygenic Scores, and Mental Health Diagnoses and Outcomes. 性创伤、多基因评分以及心理健康诊断和结果。
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2025-01-01 DOI: 10.1001/jamapsychiatry.2024.3426
Allison M Lake, Yu Zhou, Bo Wang, Ky'Era V Actkins, Yingzhe Zhang, John P Shelley, Anindita Rajamani, Michael Steigman, Chris J Kennedy, Jordan W Smoller, Karmel W Choi, Nikhil K Khankari, Lea K Davis
<p><strong>Importance: </strong>Leveraging real-world clinical biobanks to investigate the associations between genetic and environmental risk factors for mental illness may help direct clinical screening efforts and evaluate the portability of polygenic scores across environmental contexts.</p><p><strong>Objective: </strong>To examine the associations between sexual trauma, polygenic liability to mental health outcomes, and clinical diagnoses of schizophrenia, bipolar disorder, and major depressive disorder in a clinical biobank setting.</p><p><strong>Design, setting, and participants: </strong>This genetic association study was conducted using clinical and genotyping data from 96 002 participants across hospital-linked biobanks located at Vanderbilt University Medical Center (VUMC), Nashville, Tennessee (including 58 262 individuals with high genetic similarity to the 1000 Genomes Project [1KG] Northern European from Utah reference population [1KG-EU-clustered] and 11 047 with high genetic similarity to the 1KG African-ancestry reference population of Yoruba in Ibadan, Nigeria [1KG-YRI-clustered]), and Mass General Brigham (MGB), Boston, Massachusetts (26 693 individuals with high genetic similarity to the combined European-ancestry superpopulation [1KG-EU-clustered]). Clinical data analyzed included diagnostic billing codes and clinical notes spanning from 1976 to 2023. Data analysis was performed from 2022 to 2024.</p><p><strong>Exposures: </strong>Clinically documented sexual trauma disclosures and polygenic scores for schizophrenia, bipolar disorder, and major depressive disorder.</p><p><strong>Main outcomes and measures: </strong>Diagnoses of schizophrenia, bipolar disorder, and major depressive disorder, determined by aggregating related diagnostic billing codes, were the dependent variables in logistic regression models including sexual trauma disclosure status, polygenic scores, and their interactions as the independent variables.</p><p><strong>Results: </strong>Across the VUMC and MGB biobanks, 96 002 individuals were included in analyses (VUMC 1KG-EU-clustered: 33 011 [56.7%] female; median [range] age, 56.8 [10.0 to >89] years; MGB 1KG-EU-clustered: 14 647 [54.9%] female; median [range] age, 58.0 [10.0 to >89] years; VUMC 1KG-YRI-clustered: 6961 [63.0%] female; median [range] age, 44.6 [10.1 to >89] years). Sexual trauma history was associated with all mental health conditions across institutions (ORs ranged from 8.83 [95% CI, 5.50-14.18] for schizophrenia in the VUMC 1KG-YRI-clustered cohort to 17.65 [95% CI, 12.77-24.40] for schizophrenia in the VUMC 1KG-EU-clustered cohort). Sexual trauma history and polygenic scores jointly explained 3.8% to 8.8% of mental health phenotypic variance. Schizophrenia and bipolar disorder polygenic scores had greater associations with mental health outcomes in individuals with no documented disclosures of sexual trauma (schizophrenia interaction: OR, 0.70 [95% CI, 0.56-0.88]; bipolar disorder interac
重要性:利用真实世界的临床生物库来研究精神疾病的遗传和环境风险因素之间的关联,可能有助于指导临床筛查工作并评估多基因评分在不同环境中的可移植性:目的:在临床生物库中研究性创伤、精神健康结果的多基因责任以及精神分裂症、双相情感障碍和重度抑郁障碍的临床诊断之间的关联:这项遗传关联研究使用了田纳西州纳什维尔范德比尔特大学医学中心(VUMC)与医院相连的生物库中 96 002 名参与者的临床和基因分型数据(包括 58 262 名与 1000 基因组计划[1KG]犹他州北欧参考人群[1KG-EU-clustered]具有高度遗传相似性的个体,以及 11 047 名与 1KG 尼日利亚伊巴丹约鲁巴非洲裔参考人群[1KG-YRI-clustered]具有高度遗传相似性的个体)、1KG-YRI 聚类]),以及马萨诸塞州波士顿的 Mass General Brigham (MGB)(26 693 人与欧洲-非洲裔联合超级人口[1KG-EU 聚类]具有高度遗传相似性)。分析的临床数据包括 1976 年至 2023 年的诊断账单代码和临床笔记。数据分析时间为 2022 年至 2024 年:临床记录的性创伤披露以及精神分裂症、双相情感障碍和重度抑郁障碍的多基因评分:在逻辑回归模型中,精神分裂症、双相情感障碍和重度抑郁障碍的诊断是因变量,这些诊断是通过汇总相关诊断账单代码确定的,包括性创伤披露情况、多基因评分以及它们之间的交互作用作为自变量:在VUMC和MGB生物库中,96 002人被纳入分析(VUMC 1KG-EU聚类:33 011人[56.7%],MGB 1KG-EU聚类:2 011人[56.7%]):33 011名[56.7%]女性;年龄中位数[范围]为56.8[10.0至>89]岁;MGB 1KG-EU分组:14 647名[54.9%]女性;年龄中位数[范围]为58.0[10.0至>89]岁;VUMC 1KG-YRI分组:6 961名[63.0%]女性;年龄中位数[范围]为44.6[10.1至>89]岁)。性创伤史与各机构的所有精神健康状况都有关联(ORs 从 VUMC 1KG-YRI 聚类队列中精神分裂症的 8.83 [95% CI, 5.50-14.18] 到 VUMC 1KG-EU 聚类队列中精神分裂症的 17.65 [95% CI, 12.77-24.40])。性创伤史和多基因评分共同解释了3.8%至8.8%的精神健康表型变异。OR,0.70 [95% CI,0.56-0.88];双相情感障碍交互作用:结论及相关性:在一个大型、多样化的医院生物库人群中,性创伤和精神健康多基因评分虽然相互关联,但却是严重精神疾病的独立和联合风险因素。此外,精神分裂症和双相情感障碍的多基因评分与各自诊断的相关性在没有披露的人群中更大,这表明通过多基因评分衡量的精神疾病遗传易感性在存在这种严重环境风险因素的情况下可能影响较小。
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引用次数: 0
Building Resilient Relationships. 建立有韧性的关系
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2025-01-01 DOI: 10.1001/jamapsychiatry.2024.3400
Manasi Kumar, Jennifer Mootz, Myrna Weissman
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引用次数: 0
期刊
JAMA Psychiatry
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