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Racial Disparities in Pediatric Psychiatric Emergencies: A Health Systems Approach. 儿科精神病突发事件中的种族差异:一种卫生系统方法。
Pub Date : 2020-01-01 Epub Date: 2020-04-13 DOI: 10.20900/jpbs.20200006
Abhery Das, Parvati Singh, Tim Bruckner

Less than half of African American youth with severe mental disorders receive psychiatric care. When they do receive care, African American youth use the Emergency Department at higher rates than whites. We examine whether rapid expansion of primary mental health care at Community Health Centers reduces Emergency Department visits for psychiatric care especially among African American youth. Through four studies, we examine (1) the impact of mental health service capacity on the disparity of psychiatric care among African American youth; (2) how Community Health Center mental health visits vary with repeat psychiatric emergency visits; (3) the county-level drivers of the expansion of Community Health Centers; and (4) how Community Health Center expansion affects overall psychiatric emergency care. Results indicate that increased continuity of mental health care at Community Health Centers corresponds with a reduction in racial disparities in youth psychiatric ED visits. In addition, an increase in Community Health Center capacity varies inversely with repeated psychiatric Emergency Department visits and inversely with psychiatric Emergency Department visits overall. And finally, results show an increase in Community Health Center mental health services among counties with greater poverty, lower physician availability, and higher percentage of uninsured. Our studies indicate that expansion of federally-funded primary mental health services affects the overall system of emergency psychiatric care. However, this expansion does not appear to dramatically reduce racial/ethnic disparities in psychiatric emergency department visits.

在患有严重精神障碍的非裔美国青年中,只有不到一半的人接受精神病治疗。当他们得到护理时,非裔美国青年使用急诊科的比率高于白人。我们研究了社区卫生中心初级精神卫生保健的快速扩张是否减少了急诊科对精神病护理的访问,尤其是在非裔美国青年中。通过四项研究,我们检验了(1)心理健康服务能力对非裔美国青年精神病护理差异的影响;(2) 社区卫生中心的心理健康就诊与重复的精神病急诊就诊有何不同;(3) 扩大社区卫生中心的县级驱动因素;以及(4)社区卫生中心的扩建如何影响整体精神病紧急护理。结果表明,社区卫生中心心理健康护理的连续性增加,与青年精神病ED就诊中种族差异的减少相对应。此外,社区卫生中心容量的增加与精神病急诊科的多次就诊呈反比,与精神病急救科的整体就诊呈反比。最后,研究结果显示,在贫困程度更高、医生可用性更低、未参保比例更高的县,社区卫生中心的心理健康服务有所增加。我们的研究表明,扩大联邦资助的初级精神卫生服务会影响整个紧急精神病护理系统。然而,这种扩大似乎并没有显著减少精神科急诊就诊中的种族/民族差异。
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引用次数: 4
Grant Report on d-Serine Augmentation of Neuroplasticity-Based Auditory Learning in Schizophrenia . d-丝氨酸增强精神分裂症患者基于神经可塑性的听觉学习的研究报告
Pub Date : 2020-01-01 Epub Date: 2020-08-06
Natalie de la Garrigue, Juliana Glasser, Pejman Sehatpour, Dan V Iosifescu, Elisa Dias, Marlene Carlson, Constance Shope, Tarek Sobeih, Tse-Hwei Choo, Melanie M Wall, Lawrence S Kegeles, James Gangwisch, Megan Mayer, Stephanie Brazis, Heloise M De Baun, Stephanie Wolfer, Dalton Bermudez, Molly Arnold, Danielle Rette, Amir M Meftah, Melissa Conant, Jeffrey A Lieberman, Joshua T Kantrowitz

We report on the rationale and design of an ongoing NIMH sponsored R61-R33 project in schizophrenia/schizoaffective disorder. This project studies augmenting the efficacy of auditory neuroplasticity cognitive remediation (AudRem) with d-serine, an N-methyl-d-aspartate-type glutamate receptor (NMDAR) glycine-site agonist. We operationalize improved (smaller) thresholds in pitch (frequency) between successive auditory stimuli after AudRem as improved plasticity, and mismatch negativity (MMN) and auditory θ as measures of functional target engagement of both NMDAR agonism and plasticity. Previous studies showed that AudRem alone produces significant, but small cognitive improvements, while d-serine alone improves symptoms and MMN. However, the strongest results for plasticity outcomes (improved pitch thresholds, auditory MMN and θ) were found when combining d-serine and AudRem. AudRem improvements correlated with reading and other auditory cognitive tasks, suggesting plasticity improvements are predictive of functionally relevant outcomes. While d-serine appears to be efficacious for acute AudRem enhancement, the optimal dose remains an open question, as does the ability of combined d-serine + AudRem to produce sustained improvement. In the ongoing R61, 45 schizophrenia patients will be randomized to receive three placebo-controlled, double-blind d-serine + AudRem sessions across three separate 15 subject dose cohorts (80/100/120 mg/kg). Successful completion of the R61 is defined by ≥moderate effect size changes in target engagement and correlation with function, without safety issues. During the three-year R33, we will assess the sustained effects of d-serine + AudRem. In addition to testing a potentially viable treatment, this project will develop a methodology to assess the efficacy of novel NMDAR modulators, using d-serine as a "gold-standard".

我们报告正在进行的NIMH赞助的精神分裂症/分裂情感性障碍R61-R33项目的基本原理和设计。本项目研究使用n -甲基-d-天冬氨酸型谷氨酸受体(NMDAR)甘氨酸位点激动剂d-丝氨酸增强听觉神经可塑性认知修复(AudRem)的疗效。我们将AudRem后连续听觉刺激之间音高(频率)阈值的改善(更小)作为改善的可塑性,并将失配负性(MMN)和听觉θ作为NMDAR激动作用和可塑性的功能目标参与的测量。先前的研究表明,单独使用AudRem可以显著但很小的改善认知能力,而单独使用d-丝氨酸可以改善症状和MMN。然而,当d-丝氨酸和AudRem结合使用时,可塑性结果(提高音调阈值,听觉MMN和θ)最强。AudRem的改善与阅读和其他听觉认知任务相关,这表明可塑性的改善可以预测功能相关的结果。虽然d-丝氨酸似乎对急性AudRem增强有效,但最佳剂量仍然是一个悬而未决的问题,d-丝氨酸+ AudRem联合使用是否能产生持续的改善也是一个悬而未决的问题。在正在进行的R61中,45名精神分裂症患者将被随机分为三个单独的15名受试者剂量队列(80/100/120 mg/kg),接受三个安慰剂对照,双盲d-丝氨酸+ AudRem疗程。R61的成功完成被定义为靶接触和功能相关性的效应大小变化≥中等,没有安全问题。在为期三年的R33中,我们将评估d-丝氨酸+ AudRem的持续效果。除了测试一种潜在可行的治疗方法外,该项目还将开发一种方法来评估新型NMDAR调节剂的功效,使用d-丝氨酸作为“金标准”。
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引用次数: 0
Progress Report on EMBED: A Pragmatic Trial of User-Centered Clinical Decision Support to Implement EMergency Department-Initiated BuprenorphinE for Opioid Use Disorder. EMBED 进展报告:以用户为中心的临床决策支持实用性试验,用于实施由急诊科发起的丁丙诺啡治疗阿片类药物使用障碍。
Pub Date : 2020-01-01 Epub Date: 2020-02-21 DOI: 10.20900/jpbs.20200003
Edward R Melnick, Bidisha Nath, Osama M Ahmed, Cynthia Brandt, David Chartash, James D Dziura, Erik P Hess, Wesley C Holland, Jason A Hoppe, Molly M Jeffery, Liliya Katsovich, Fangyong Li, Charles C Lu, Kaitlin Maciejewski, Matthew Maleska, Jodi A Mao, Shara Martel, Sean Michael, Hyung Paek, Mehul D Patel, Timothy F Platts-Mills, Haseena Rajeevan, Jessica M Ray, Rachel M Skains, William E Soares, Ashley Deutsch, Yauheni Solad, Gail D'Onofrio

Buprenorphine (BUP) can safely and effectively reduce craving, overdose, and mortality rates in people with opioid use disorder (OUD). However, adoption of ED-initiation of BUP has been slow partly due to physician perception this practice is too complex and disruptive. We report progress of the ongoing EMBED (EMergency department-initiated BuprenorphinE for opioid use Disorder) project. This project is a five-year collaboration across five healthcare systems with the goal to develop, integrate, study, and disseminate user-centered Clinical Decision Support (CDS) to promote the adoption of Emergency Department (ED)-initiation of buprenorphine/naloxone (BUP) into routine emergency care. Soon to enter its third year, the project has already completed multiple milestones to achieve its goals including (1) user-centered design of the CDS prototype, (2) integration of the CDS into an automated electronic health record (EHR) workflow, (3) data coordination including derivation and validation of an EHR-based computable phenotype, (4) meeting all ethical and regulatory requirements to achieve a waiver of informed consent, (5) pilot testing of the intervention at a single site, and (6) launching a parallel group-randomized 18-month pragmatic trial in 20 EDs across 5 healthcare systems. Pilot testing of the intervention in a single ED was associated with increased rates of ED-initiated BUP and naloxone prescribing and a doubling of the number of unique physicians adopting the practice. The ongoing multi-center pragmatic trial will assess the intervention's effectiveness, scalability, and generalizability with a goal to shift the emergency care paradigm for OUD towards early identification and treatment.

Trial registration: Clinicaltrials.gov # NCT03658642.

丁丙诺啡(BUP)可以安全有效地减少阿片类药物使用障碍(OUD)患者的渴求、用药过量和死亡率。然而,急诊室启动 BUP 的速度一直很慢,部分原因是医生认为这种做法过于复杂且具有破坏性。我们报告了正在进行的 EMBED(急诊科启动丁丙诺啡治疗阿片类药物使用障碍)项目的进展情况。该项目是一项为期五年的合作项目,涉及五个医疗保健系统,目标是开发、整合、研究和推广以用户为中心的临床决策支持(CDS),以促进在常规急诊护理中采用由急诊科(ED)启动的丁丙诺啡/纳洛酮(BUP)。该项目即将进入第三年,已经完成了多个里程碑式的目标,包括:(1) 以用户为中心设计 CDS 原型;(2) 将 CDS 集成到自动化电子病历 (EHR) 工作流程中;(3) 数据协调,包括推导和验证基于 EHR 的可计算表型、(4) 满足所有伦理和法规要求,获得豁免知情同意;(5) 在单个地点进行干预试点测试;(6) 在 5 个医疗系统的 20 个急诊室开展为期 18 个月的平行分组随机实用试验。在单个急诊室进行干预试点测试后,由急诊室发起的 BUP 和纳洛酮处方率有所提高,采用这种做法的医生人数也翻了一番。正在进行的多中心实用性试验将评估该干预措施的有效性、可扩展性和可推广性,目标是将 OUD 的急诊治疗模式转变为早期识别和治疗:试验注册:Clinicaltrials.gov # NCT03658642。
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引用次数: 0
Navigation Services to Avoid Rehospitalization among Medical/Surgical Patients with Comorbid Substance Use Disorder: Rationale and Design of a Randomized Controlled Trial. 导航服务避免内科/外科合并物质使用障碍患者再次住院:一项随机对照试验的基本原理和设计
Pub Date : 2020-01-01 Epub Date: 2020-06-12 DOI: 10.20900/jpbs.20200013
Courtney D Nordeck, Christopher Welsh, Robert P Schwartz, Shannon G Mitchell, Kevin E O'Grady, Laura Dunlap, Gary Zarkin, Stephen Orme, Jan Gryczynski

Substance use disorders (SUDs) are associated with significant morbidity and mortality and contribute to inefficient use of healthcare services. Hospitalized medical/surgical patients with comorbid SUD are at elevated risk of hospital readmission and poor outcomes. Thus, effective interventions are needed to help such patients during hospitalization and post-discharge. This article reports the rationale, methodological design, and progress to date on a randomized trial comparing the effectiveness of Navigation Services to Avoid Rehospitalization (NavSTAR) vs Treatmentas-Usual (TAU) for hospital medical/surgical patients with comorbid SUD (N = 400). Applying Andersen's theoretical model of health service utilization, NavSTAR employed Patient Navigation and motivational interventions to promote entry into SUD treatment, facilitate adherence to recommendations for medical follow-up and self-care, address basic needs, and prevent the recurrent use of hospital services. As part of the NavSTAR service model, Patient Navigators embedded within the SUD consultation service at a large urban hospital delivered patient-centered, proactive navigation and motivational services initiated during the hospital stay and continued for up to 3 months post-discharge. Participants randomized to TAU received usual care from the hospital and the SUD consultation service, which included referral to SUD treatment but no continued contact post-hospital discharge. Hospital service utilization will be determined via review of electronic health records and the regional Health Information Exchange. Participants were assessed at baseline and again at 3-, 6-, and 12-month follow-up on various measures of healthcare utilization, substance use, and functioning. The primary outcome of interest is time-to-rehospitalization through 12 months. In addition, a range of secondary outcomes spanning the medical and SUD service areas will be assessed. The study will include a health economic evaluation of NavSTAR. If NavSTAR proves to be effective and cost-effective in this high-risk patient group, it would have important implications for addressing the needs of hospital patients with comorbid SUD, designing hospital discharge planning services, informing cost containment initiatives, and improving public health.

物质使用障碍(sud)与显著的发病率和死亡率相关,并导致医疗保健服务的低效使用。合并SUD的住院内科/外科患者再次住院的风险较高,预后较差。因此,需要有效的干预措施来帮助这些患者在住院期间和出院后。本文报道了一项随机试验的基本原理、方法设计和迄今为止的进展,该试验比较了导航服务以避免再次住院(NavSTAR)和常规治疗(TAU)对住院内科/外科合并SUD患者(N = 400)的有效性。应用Andersen的卫生服务利用理论模型,NavSTAR采用患者导航和动机干预来促进进入SUD治疗,促进对医疗随访和自我保健建议的遵守,解决基本需求,并防止反复使用医院服务。作为NavSTAR服务模式的一部分,在一家大型城市医院的SUD咨询服务中嵌入了患者导航器,提供以患者为中心的主动导航和激励服务,从住院期间开始,并持续到出院后3个月。随机分配到TAU的参与者接受医院和SUD咨询服务的常规护理,包括转介到SUD治疗,但出院后没有继续联系。将通过审查电子健康记录和区域健康信息交换来确定医院服务的利用情况。在基线和3个月、6个月和12个月的随访中,对参与者的各种医疗保健利用、物质使用和功能进行评估。主要观察指标为12个月的再住院时间。此外,还将评估医疗和SUD服务领域的一系列次要成果。该研究将包括对NavSTAR的健康经济评估。如果NavSTAR在这一高危患者群体中被证明是有效且具有成本效益的,那么它将对解决合并SUD的住院患者的需求、设计出院计划服务、告知成本控制举措以及改善公共卫生具有重要意义。
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引用次数: 6
Perceptual Mechanisms of Visual Hallucinations and Illusions in Psychosis. 精神病患者视幻觉和错觉的感知机制。
Pub Date : 2020-01-01 Epub Date: 2020-08-21 DOI: 10.20900/jpbs.20200020
Samuel D Klein, Cheryl A Olman, Scott R Sponheim

Psychosis has been associated with neural anomalies across a number of brain regions and cortical networks. Nevertheless, the exact pathophysiology of the disorder remains unclear. Aberrant visual perceptions such as hallucinations are evident in psychosis, while the occurrence of visual distortions is elevated in individuals with genetic liability for psychosis. The overall goals of this project are to: (1) use psychophysical tasks and neuroimaging to characterize deficits in visual perception; (2) acquire a mechanistic understanding of these deficits through development and validation of a computational model; and (3) determine if said mechanisms mark genetic liability for psychosis. Visual tasks tapping both low- and high-level visual processing are being completed as individuals with psychotic disorders (IPD), first-degree biological siblings of IPDs (SibIPDs) and healthy controls (HCs) undergo 248-channel magneto-encephalography (MEG) recordings followed by 7 Tesla functional magnetic resonance imaging (MRI). By deriving cortical source signals from MEG and MRI data, we will characterize the timing, location and coordination of neural processes. We hypothesize that IPDs prone to visual hallucinations will exhibit deviant functions within early visual cortex, and that aberrant contextual influences on visual perception will involve higher-level visual cortical regions and be associated with visual hallucinations. SibIPDs who experience visual distortions-but not hallucinations-are hypothesized to exhibit deficits in higher-order visual processing reflected in abnormal inter-regional neural synchronization. We hope the results lead to the development of targeted interventions for psychotic disorders, as well as identify useful biomarkers for aberrant neural functions that give rise to psychosis.

精神病与多个大脑区域和皮层网络的神经异常有关。然而,这种疾病的确切病理生理学仍不清楚。幻觉等异常视觉感知在精神病中非常明显,而在具有精神病遗传倾向的个体中,视觉扭曲的发生率会升高。本项目的总体目标是(1)利用心理物理任务和神经影像学来描述视觉感知缺陷的特征;(2)通过开发和验证计算模型,从机制上理解这些缺陷;以及(3)确定上述机制是否标志着精神病的遗传责任。精神病患者(IPD)、IPD 患者的一级亲兄弟姐妹(SibIPDs)和健康对照组(HCs)在接受 248 通道脑磁图(MEG)记录和 7 特斯拉功能性磁共振成像(MRI)后,都要完成触及低级和高级视觉处理的视觉任务。通过从 MEG 和 MRI 数据中得出皮层源信号,我们将确定神经过程的时间、位置和协调特征。我们假设,容易产生视觉幻觉的 IPD 会在早期视觉皮层中表现出异常功能,而对视觉感知的异常环境影响将涉及更高级别的视觉皮层区域,并与视觉幻觉相关联。假设出现视觉失真但没有幻觉的西伯利亚综合症患者表现出高阶视觉处理缺陷,这反映在异常的区域间神经同步上。我们希望这些研究结果能为开发针对精神病的干预措施提供帮助,并为导致精神病的异常神经功能找到有用的生物标记物。
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引用次数: 0
Mobile Peer-Support for Opioid Use Disorders: Refinement of an Innovative Machine Learning Tool. 阿片类药物使用障碍的移动同伴支持:改进创新的机器学习工具。
Pub Date : 2020-01-01 Epub Date: 2020-02-03 DOI: 10.20900/jpbs.20200001
Caroline R Scherzer, Megan L Ranney, Shrenik Jain, Satya Prateek Bommaraju, John Patena, Kirsten Langdon, Evelyn Nimaja, Ernestine Jennings, Francesca L Beaudoin

Background: The majority of individuals with Opioid Use Disorder (OUD) do not receive any formal substance use treatment. Due to limited engagement and access to traditional treatment, there is increasing evidence that patients with OUDs turn to online social platforms to access peer support and obtain health-related information about addiction and recovery. Interacting with peers before and during recovery is a key component of many evidence-based addiction recovery programs, and may improve self-efficacy and treatment engagement as well as reduce relapse. Commonly-used online social platforms are limited in utility and scalability as an adjunct to addiction treatment; lack effective content moderation (e.g., misinformed advice, maliciousness or "trolling"); and lack common security and ethical safeguards inherent to clinical care.

Methods: This present study will develop a novel, artificial-intelligence (AI) enabled, mobile treatment delivery method that fulfills the need for a robust, secure, technology-based peer support platform to support patients with OUD. Forty adults receiving outpatient buprenorphine treatment for OUD will be asked to pilot a smartphone-based mobile peer support application, the "Marigold App", for a duration of six weeks. The program will use (1) a prospective cohort study to obtain text message content and feasibility metrics, and (2) qualitative interviews to evaluate usability and acceptability of the mobile platform.

Anticipated findings and future directions: The Marigold mobile platform will allow patients to access a tailored chat support group 24/7 as a complement to different forms of clinical OUD treatment. Marigold can keep groups safe and constructive by augmenting chats with AI tools capable of understanding the emotional sentiment in messages, automatically "flagging" critical or clinically relevant content. This project will demonstrate the robustness of these AI tools by adapting them to catch OUD-specific "flags" in peer messages while also examining the adoptability of the platform itself within OUD patients.

背景:大多数阿片类药物使用障碍(OUD)患者没有接受任何正式的药物使用治疗。由于参与和获得传统治疗的机会有限,越来越多的证据表明,oud患者转向在线社交平台获得同伴支持,并获得有关成瘾和康复的健康相关信息。在康复前和康复过程中与同伴互动是许多基于证据的成瘾康复计划的关键组成部分,可以提高自我效能和治疗参与度,并减少复发。作为成瘾治疗的辅助手段,常用的在线社交平台在实用性和可扩展性方面受到限制;缺乏有效的内容审核(例如,错误的建议、恶意或“拖钓”);缺乏临床护理所固有的共同安全和道德保障。方法:本研究将开发一种新颖的、人工智能(AI)支持的移动治疗交付方法,以满足对一个强大、安全、基于技术的同伴支持平台的需求,以支持OUD患者。40名因OUD接受丁丙诺啡门诊治疗的成年人将被要求试用一款基于智能手机的移动同伴支持应用程序,名为“金盏花应用程序”,为期六周。该项目将使用(1)前瞻性队列研究来获取短信内容和可行性指标,以及(2)定性访谈来评估移动平台的可用性和可接受性。预期结果和未来方向:Marigold移动平台将允许患者访问量身定制的聊天支持小组,作为不同形式的临床OUD治疗的补充。Marigold可以通过使用能够理解信息中的情绪、自动“标记”关键或临床相关内容的人工智能工具来增强聊天,从而保持群组的安全性和建设性。该项目将通过调整这些人工智能工具来捕捉同行消息中特定于OUD的“标志”,同时检查平台本身在OUD患者中的可接受性,从而证明这些人工智能工具的稳健性。
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引用次数: 6
Phenotypic Effects of Polygenic Risk for Schizophrenia: What Have We Learned So Far? 精神分裂症多基因风险的表型效应:到目前为止我们学到了什么?
Pub Date : 2019-12-19 DOI: 10.20900/jpbs.20190019
U. Heilbronner
The results of large genome-wide association studies of schizophrenia (SZ) can be used to calculate an individual’s polygenic risk for SZ (e.g., [1]). This polygenic risk score (PRS) is a weighted sum of SZ risk alleles, and thus holds promise to be used in clinical care someday, e.g., in prevention, diagnosis and treatment of mental disorders (e.g., [2]). It can be used to uncover other phenotypes, such as behavioral traits or disorders, that are influenced by SZ-PRS, and this issue of the Journal of Psychiatry and Brain Science aims to summarize some of the knowledge that has emerged to this regard. Three reviews and two original research articles are contained in this Virtual Special Issue. Schaupp, Schulze and Budde [3] provide an excellent summary of studies researching the associations of SZ-PRS and cognition. Their finding of inconsistent results, both in patients and the general population, albeit characteristic for a developing field, points to a need for larger sample sizes when studying the genetics of cognition, and highlights further methodological problems. Adorjan and Papiol [4] review the relationship of cannabis consumption, SZ, and the SZ-PRS, and discuss accumulating evidence that a high polygenic risk for SZ may be predisposing individuals to cannabis abuse. Thus, consumption of cannabis may not only be understood as an environmental risk factor for SZ, but also as a type of gene-environment correlation/interaction. The last review article of Bengesser and Reininghaus [5] highlights the interesting finding that the SZ-PRS may be used to delineate bipolar disorder patients that respond to lithium from those who do not [6], and can be understood to emphasize the need for biologically-based diagnosis of mental disorders. The original research article of Yasmeen, Papiol, Falkai, Schulze, & Bickeböller [7] researches effects of SZ-PRS in correlated target phenotypes, using both in-silico and empirical data of the PsyCourse study [8]. Results of empirical analyses show that the addition of SZ-PRS to statistical models explaining psychosocial functioning (the Global Assessment of Functioning score) improves model fit, which is further increased when current symptom status is additionally taken into account. Finally, the neuroimaging study of Eberle et al. [9] demonstrates that polygenic scores for SZ can be used to gain a more fundamental understanding of gene-environment interactions. In this study, the authors researched connectivity of the nucleus accumbens, a major component of the brain’s reward circuitry. In healthy individuals, polygenic risk for SZ was associated with a shift towards SZ-like Open Access
精神分裂症(SZ)的大型全基因组关联研究的结果可用于计算个体患SZ的多基因风险(例如,[1])。这种多基因风险评分(PRS)是SZ风险等位基因的加权和,因此有希望在将来的临床护理中使用,例如在精神障碍的预防、诊断和治疗中(例如[2])。它可以用来揭示受SZ-PRS影响的其他表型,如行为特征或疾病,本期《精神病学与脑科学杂志》旨在总结在这方面出现的一些知识。这期虚拟特刊包含三篇评论和两篇原创研究文章。Schaupp, Schulze和Budde等人对SZ-PRS与认知之间的关系进行了很好的总结。他们在患者和一般人群中发现了不一致的结果,尽管这是一个发展中的领域的特征,但这表明在研究认知遗传学时需要更大的样本量,并突出了进一步的方法问题。Adorjan和Papiol bbb回顾了大麻消费、SZ和SZ- prs之间的关系,并讨论了越来越多的证据表明SZ的高多基因风险可能使个体倾向于大麻滥用。因此,大麻消费不仅可以理解为SZ的环境风险因素,而且可以理解为一种基因-环境相关/相互作用。Bengesser和Reininghaus的最后一篇综述文章强调了一个有趣的发现,即SZ-PRS可用于描述对锂有反应的双相情感障碍患者和不对锂有反应的患者,并且可以理解为强调了基于生物学的精神障碍诊断的必要性。Yasmeen, Papiol, Falkai, Schulze, & Bickeböller[7]的原创研究文章使用PsyCourse研究[8]的计算机和实证数据研究了SZ-PRS对相关目标表型的影响。实证分析结果表明,将SZ-PRS添加到解释社会心理功能的统计模型(功能整体评估评分)中可以提高模型的拟合度,当额外考虑当前症状状态时,模型的拟合度进一步提高。最后,Eberle等人的神经影像学研究表明,SZ的多基因评分可用于更基本地了解基因与环境的相互作用。在这项研究中,作者研究了伏隔核的连通性,伏隔核是大脑奖励回路的主要组成部分。在健康个体中,SZ的多基因风险与向SZ样开放获取的转变有关
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引用次数: 0
Genetic Risk of Psychosis in Relation to Cannabis Use: Findings from Polygenic Risk Score Approaches 与大麻使用有关的精神病遗传风险:来自多基因风险评分方法的发现
Pub Date : 2019-12-11 DOI: 10.20900/jpbs.20190018
K. Adorjan, S. Papiol
A psychotic disorder is a multifactorial phenomenon in which not only environmental influences but also genetic factors play an important role. Evidence indicates that psychotic disorders are characterized by a complex mode of inheritance with high polygenicity, in which a large number of common genetic variants with small effects are relevant. One way to measure this polygenic risk is the calculation of polygenic risk scores (PRS). These reflect the complex multifactorial interaction of coding and regulatory DNA variants in the development of mental illness. It is known that the use of cannabis in patients with schizophrenia (SCZ) is much higher than in the general population. Although an exact clinical prognosis based on PRS is not possible at the present, the results found by PRS investigations so far are quite promising. Initial results suggest that people with SCZ and an increased polygenic risk of schizophrenia are more likely to use cannabis. According to these results, the connection between mental illnesses and cannabis use could therefore not simply be seen as an environmental risk, but rather explained as a gene-environment correlation.
精神障碍是一个多因素的现象,除了环境因素外,遗传因素也起着重要的作用。有证据表明,精神障碍具有复杂的遗传模式,具有高度的多基因性,其中大量的常见遗传变异与小影响有关。测量这种多基因风险的一种方法是计算多基因风险评分(PRS)。这些反映了编码和调控DNA变异在精神疾病发展中的复杂的多因素相互作用。众所周知,精神分裂症患者(SCZ)使用大麻的比例远高于一般人群。虽然目前基于PRS的确切临床预后是不可能的,但迄今为止PRS研究的结果是相当有希望的。初步结果表明,患有SCZ和精神分裂症多基因风险增加的人更有可能使用大麻。根据这些结果,精神疾病和大麻使用之间的联系因此不能简单地被视为一种环境风险,而是被解释为一种基因-环境相关性。
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引用次数: 1
An Historical Perspective on Psychiatric Genetics, the International Society of Psychiatric Genetics and the Role of Elliot Gershon 精神病学遗传学的历史观点,国际精神病学遗传学学会和艾略特·格尔森的作用
Pub Date : 2019-10-16 DOI: 10.20900/jpbs.20190015
L. DeLisi
Psychiatric Genetics is a relatively new field that was defined by groups of researchers interested in the familial aggregation of psychiatric disorders, and spurred on by the escalating new field of molecular genetics beginning in the 1980s. This manuscript contributes to a special issue honoring the career of Elliot S. Gershon, a true pioneer and critical thinker, who contributed substantially to the development of this field and also its stimulating meetings that brought colleagues together to discuss the latest research findings. It details the role Dr. Gershon played in establishing the precursor of the International Society of Psychiatric Genetics (ISPG) and how he remains in a leadership role on its Board of Directors and was honored with one of the ISPG Lifetime Achievement Awards.
精神病学遗传学是一个相对较新的领域,它是由对精神疾病家族聚集感兴趣的研究小组定义的,并受到20世纪80年代开始的分子遗传学新领域的推动。这份手稿为纪念艾略特·s·格尔森(Elliot S. Gershon)的职业生涯做出了贡献,他是一位真正的先驱和批判性思想家,他对这一领域的发展做出了重大贡献,也为同事们聚集在一起讨论最新研究成果而召开了鼓舞人心的会议。它详细介绍了Gershon博士在建立国际精神病学遗传学学会(ISPG)的前身中所扮演的角色,以及他如何在其董事会中担任领导角色,并荣获ISPG终身成就奖之一。
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引用次数: 1
Endophenotype Potential of Nucleus Accumbens Functional Connectivity: Effects of Polygenic Risk for Schizophrenia Interacting with Childhood Adversity 伏隔核功能连通性的内表型电位:精神分裂症多基因风险与童年逆境相互作用的影响
Pub Date : 2019-07-02 DOI: 10.20900/JPBS.20190011
C. Eberle, Y. Peterse, Filip Jukic, B. Müller-Myhsok, D. Czamara, Jade Martins, Vanessa Schmoll, M. Czisch, E. Binder, P. Sämann
Epidemiological and genetic studies suggest that schizophrenia (SCZ) is associated with both polygenic and environmental risk factors. Little is known if these factors project on common functional circuits relevant to the pathophysiology of SCZ. Here we focussed on resting state functional MRI (rsfMRI) as a biological measure to investigate if genetic and environmental factors for SCZ risk affect the same circuits in healthy controls as well as patients. For this, we compared the effects of a polygenic risk score for SCZ (PGRS), childhood adversity (CA) and their interaction on functional connectivity density (FCD) mapping and nucleus accumbens (NAcc) seed connectivity between 23 patients with SCZ or schizoaffective disorder and 253 healthy subjects. Patients demonstrated strong FCD increases compared with healthy controls mainly in subcortical nuclei including the NAcc, replicating previous reports. In healthy subjects, FCD of the NAcc was positively correlated with both the PGRS and the PGRS-CA-interaction. Both for high PGRS and PGRS-CA-interaction, fine-mapping revealed higher connectivity between the NAcc and visual association cortices. In conclusion, polygenic risk for SCZ shifted global and regionally specific connectivity of the NAcc in healthy subjects into the direction of the connectivity pattern observed in SCZ, and this shift was intensified by higher levels of CA.
流行病学和遗传学研究表明,精神分裂症(SCZ)与多基因和环境危险因素有关。这些因素是否在与SCZ病理生理相关的共同功能回路上发挥作用尚不清楚。本研究采用静息状态功能MRI (rsfMRI)作为生物学手段,研究SCZ风险的遗传和环境因素是否影响健康对照者和患者的相同回路。为此,我们比较了23名SCZ或分裂情感障碍患者和253名健康受试者的SCZ多基因风险评分(PGRS)、童年逆境(CA)及其相互作用对功能连接密度(FCD)定位和伏隔核(NAcc)种子连接的影响。与健康对照相比,患者表现出强烈的FCD增加,主要发生在皮质下核,包括NAcc,与先前的报道重复。在健康受试者中,NAcc的FCD与PGRS和PGRS- ca相互作用呈正相关。对于高PGRS和PGRS- ca相互作用,精细映射显示NAcc和视觉关联皮层之间的连通性更高。综上所述,SCZ的多基因风险将健康受试者的NAcc的整体和区域特异性连通性转向了SCZ中观察到的连通性模式,并且这种转变随着CA水平的提高而增强。
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引用次数: 3
期刊
Journal of psychiatry and brain science
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