Administrative Core

行政核心

• 批准号: 8278009
• 负责人: ANDREW C. HEATH
• 金额: $ 21.9万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8278009
• 关键词: ARHGEF5 gene; Achievement; Acute; Address; Adolescence; Adolescent; Adult Children; Affect; Affective; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholism; Alcohols; Behavioral; Behavioral Genetics; Biological Models; Borderline Personality Disorder; Budgets; CCL7 gene; Child; Childhood; Chromosome Mapping; Communication; Communities; Comorbidity; Consumption; Data; Data Analyses; Data Collection; Dependence; Developmental Gene; Developmental Process; Disease; Education; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiology; Etiology; Evaluation; Faculty; Family; Forcible intercourse; Funding; Funding Mechanisms; Generations; Genes; Genetic; Genetic Predisposition to Disease; Genetic Research; Goals; Heavy Drinking; Human; Impulsivity; Individual; Journals; Lead; Measures; Mental disorders; Mentors; Minority; Modeling; Molecular Epidemiology; National Institute on Alcohol Abuse and Alcoholism; Palm-Top Computers; Patients; Pattern; Personal Digital Assistant; Physicians; Pilot Projects; Play; Productivity; Progress Reports; Prospective Studies; Recording of previous events; Regulation; Research; Research Personnel; Research Priority; Research Project Grants; Resources; Risk; Role; Running; Sampling; Science; Scientist; Self-control as a personality trait; Series; Smoking; Smoking Behavior; Structure; Students; TNFRSF5 gene; Training; Training Programs; Trauma; Twin Multiple Birth; Update; alcohol effect; alcohol research; alcohol use disorder; base; career; career development; cognitive neuroscience; cost; design; dissemination research; early adolescence; executive function; follow-up; gene discovery; gene environment interaction; genome wide association study; graduate student; improved; innovation; meetings; offspring; operation; outreach; parental alcoholism; post-doctoral training; pre-doctoral; programs; prospective; psychosocial; research study; skills; success; symposium; young adult

In this competing application, we have changed the funding mechanism by which we seek support, from P50 to P60, requiring a strengthening and closer evaluation for achievement of our Outreach efforts. We retain our focus on the etiology of alcoholism, including its course and psychiatric comorbidity, with a particular emphasis on the period of young adulthood, with a major (though not exclusive) emphasis on etiologic mechanisms - whether genetic or environmental - that frequently unfold within the family, whether in terms of (a) the emergence of heavy drinking or alcohol problems in adolescent or young adult offspring, or (b) the environmental risk exposures correlated with parental alcoholism that may interact with offspring genetic vulnerabilities, or (c) consequences of partner alcoholism. Our research continues to be guided by its consideration of (i) behavioral undercontrol, (ii) affect regulation, and (iii) pharmacologic vulnerability as three meta-models (not mutually exclusive) for integrating our research findings. The scientific goals and hypotheses of the Center, and its administrative functions, are closely interconnected. Because of the limited resources of a P60, and the high costs of etiologic research on alcoholism, the success of the Center depends critically upon not only the coordination of the Center-based research projects, but also the coordination of these efforts with a larger R01-supported portfolio (see Introduction, Table A.1). In this coordination the Admin Core and Scientific Resource Core (SRC) play critical roles, with the Pilot Project Core ("Pilots") playing an important supporting function, in furthering the career development of our large pool of talented junior faculty investigators, and the "Outreach" Core providing a new focus for, and expansion of, our Outreach efforts. In the Admin Core ("Admin"), we present an overview of the conceptual structure of the Center, the research priorities that guide its activities, and the administrative structure designed to meet these scientific needs. We outline the research projects of the Center and their interactions with each other and with our associated R01 portfolio that are facilitated through Admin, as well as the role of Admin in oversight and coordination of the operations of the Science Resource, Pilots and Outreach Cores. During the first 4 Vz years of its history (our original Center received funding in June of 1999, but ran through December 2003), our Center had a more traditional behavioral genetic focus in its approach. We greatly broadened our Center focus at the last competing continuation, reflecting in particular recognition of the rapid advances in discovery of genes associated with differences in alcoholism risk through projects such as COGA. This competing continuation is again being submitted after approximately 3.5 years of funding: we encountered delays in NIAAA funding for the first renewal of our Center, with a funding gap until May 2004. With the first generation of Genomewide Association Studies of Alcoholism (including our own GWAS using 4000 informative individuals identified through Australian Twin Register coordinated gene-mapping studies) in progress, we continue this broadened focus, with Center-supported projects that seek to better characterize some of the varied risk-mechanisms, including developmental processes and gene-environment interactions, that may ultimately lead to differences in alcohol dependence risk. These include (i) a series of alcohol challenge experiments focused on clarifying the acute effects of alcohol on executive functioning, thereby introducing a cognitive neuroscience perspective to our Center's integrative behavioral undercontrol and pharmacologic vulnerability themes (project eight); (ii) a follow-up data collection on our GWAS sample, to obtain more detailed retrospective characterization of certain early environmental exposures (e.g. childhood assaultive trauma such as rape) and more proximal environmental measures that may be important modifiers of effects on the course of alcohol consumption and abuse/dependence, as well as updated assessments of persistence versus desistance of alcohol problems and comorbid conditions, and of quantitative measures of heaviness of consumption, to permit more comprehensive analyses of gene-environment interplay, albeit in retrospective data (project seven); (iii) a continuation and extension of project five, adding a molecular epidemiology component to ongoing prospective studies that have followed samples from early adolescence (Chassin and Bucholz studies, Heath study in part) or late adolescence (Sher and Anokhin studies, Heath study in part) through young adulthood, and with assessments that span the domains of behavioral undercontrol and negative affect, to allow prospective characterization of gene-environment interplay effects on risk; and a narrower focusing of our palm-top computer based project (project six), using Ecological Momentary Assessment (EMA) to investigate alcohol consumption patterns associated with affect-regulation in a patient group characterized by severe affective instability and self-control deficits and increased risks of alcohol dependence, smoking and other substance involvement (borderline patient series) compared to controls (continuation of project six) - using borderline personality disorder, which is characterized by both high negative affect and high impulsivity, as a model system in which to examine the relationship between affect dysregulation, alcohol use, and comorbid smoking behavior. Project four (Children-of-Twins project) will seek R01 funding to continue data-collection; its goals are no longer a good fit with the immediate focus of our Center-based projects: a progress report is included as an appendix. Project three was not funded

在此竞争应用中，我们改变了我们寻求支持的资金机制 P50至P60，需要加强和更深入的评估来实现我们的外展工作。我们保留 我们专注于酒精中毒的病因，包括其课程和精神病合并症，特定 强调年轻成年时期，重点（尽管不是排他性）对病因的重视 无论是遗传还是环境的机制 - 家庭内经常出现 （a）青少年或年轻人后代的大量饮酒或酒精问题的出现，或（b） 环境风险暴露与可能与后代遗传相互作用的父母酒精中毒相关 脆弱性，或（c）伴侣酒精中毒的后果。我们的研究继续受到其的指导 考虑（i）行为不足，（ii）影响调节和（iii）药物脆弱性为三个 元模型（不是相互排斥的）用于整合我们的研究发现。科学目标和 中心的假设及其行政职能密切相互联系。因为有限 P60的资源以及对酒精中毒的病因学研究的高昂成本，中心的成功取决于 不仅要对中心研究项目的协调进行批判性，而且对 通过较大的R01支持的投资组合进行了这些努力（请参阅简介，表A.1）。在这个协调中 核心和科学资源核心（SRC）扮演关键角色，飞行员项目核心（“飞行员”）扮演 重要的支持功能，进一步发展我们大量才华横溢的初级教师的职业发展 调查人员和“外展”核心为我们的外展工作提供了新的重点和扩展。 在管理员核心（“ admin”）中，我们概述了中心的概念结构， 指导其活动的研究优先级以及旨在满足这些科学的行政结构 需要。我们概述了中心的研究项目及其彼此之间的互动以及与我们的互动 通过管理员促进的相关R01投资组合以及管理员在监督和 协调科学资源，飞行员和外展核心的运营。在最初的4 Vz年中 它的历史（我们的原始中心于1999年6月获得资金，但持续到2003年12月），我们 中心在其方法中具有更传统的行为遗传重点。我们大大拓宽了中心 专注于最后一个竞争的延续，特别反映了发现快速进步 通过COGA等项目与酒精中毒风险差异相关的基因。这个竞争 经过大约3。5年的资金，延续再次提交：我们遇到了延误 NIAAA资助我们中心的第一个续约，并有资金差距，直到2004年5月。 全基因组的酒精中毒研究（包括我们自己的GWAS使用4000条信息 通过澳大利亚双胞胎登记协调基因映射研究确定的个人，我们正在进行中，我们 继续这一广泛的重点，由中心支持的项目寻求更好地描述一些 各种风险机理，包括发展过程和基因环境相互作用，可能 最终导致酒精依赖风险差异。其中包括（i）一系列酒精挑战 实验着重于阐明酒精对执行功能的急性影响，从而引入了 认知神经科学的观点，表明我们中心的综合行为不足和药理学 脆弱性主题（项目八）； （ii）我们的GWAS样本上的后续数据收集，以获取更多 某些早期环境暴露的详细回顾性表征（例如，儿童攻击 创伤（例如强奸）和更近端的环境措施可能是重要的效果修饰符 关于饮酒和滥用/依赖的过程，以及对持久性的更新评估 与酒精问题和合并状况的避免，以及重重的定量措施 消费，允许对基因环境相互作用进行更全面的分析，尽管回顾性 数据（项目7）； （iii）项目五的延续和扩展，增加了分子流行病学 正在进行的前瞻性研究的组成部分，这些研究遵循青春期早期的样本（Chassin和Chassin和 Bucholz的研究，Heath研究部分或青春期晚期（Sher和Anokhin研究，Heath研究部分研究） 整个成年期，以及跨越行为范围内部控制领域的评估和 负面影响，以使基因环境相互作用对风险的前瞻性表征；和 使用生态瞬间，缩小集中于我们基于棕榈的计算机项目（第六个项目） 评估（EMA）调查与患者情感调节相关的饮酒模式 以严重的情感不稳定和自我控制缺陷和饮酒风险增加为特征的群体 与对照组相比 （第六项目的延续） - 使用边缘性人格障碍，其特征在于高 负面影响和高冲动性，作为一个模型系统，在其中检查影响之间的关系 失调，饮酒和合并吸烟行为。第四项目（孤岛儿童项目）将寻求 R01资金继续数据收集；它的目标不再适合我们的直接重点 基于中心的项目：将进度报告作为附录包括在内。第三项目没有资助