Training in genetic and neurobehavioral mechanisms of addiction

项目概要 物质使用障碍越来越多地被描述为高度遗传性和基于大脑的疾病。临床前工作有 确定皮层下和额叶网络的偏差与从 用于强迫性吸毒、戒断和复发循环的实验。当前型号 强调遗传脆弱性对易产生物质的中间表型的重要性 使用和依赖，包括行为去抑制、奖励评估、消极的神经机制 强化，以及加剧退缩/渴望的负面影响。这些模型还强调了如何 作为神经发育的功能，机制可能会受到不同的影响。这些不同的机制， 它们的神经相关性和遗传基础，越来越多地在大背景下进行研究 使用ABCD研究、人类连接组的各个分支等新技术的联盟的努力 Project、TOPMed、AllofUS 和 UK Biobank 等等。然而现在的学生并不一定 准备利用这些资源来推进该领域的发展。我们建议混合博士前/博士后培训 计划，重点关注神经行为测量（例如神经影像学）、遗传信息 设计和尖端定量方法来揭示和表征神经行为机制 成瘾的发展。明尼苏达大学是行为和分子研究领域的领导者 成瘾的遗传学、药物滥用的神经行为机制及其通过使用 临床前、药理学和神经影像技术以及定量建模。由联合 PD 卢西亚娜 (Luciana) 领导 和 Vrieze，以培养下一代科学/学术领袖为目标，拟议的 培训计划每年将培养六名博士前学生和三名博士后学生进行定量方法和 成瘾的遗传学和/或神经行为机制。将使用以下方式选择不同的受训者群体： 来自研究生（博士前）以及全国（博士后）的严格标准。的 明尼苏达大学心理学系将在跨学科的支持下领导这项工作 除了 PD 之外，还有 19 名导师组成的团队。每位学员将获得为期两年的资助，并受到共同指导 由具有主题和定量专业知识的科学家组成，并将追求教学培训、实验室- 基于经验的讲习班、侧重于专业发展的研讨会以及研究伦理培训。 指导委员会将为每位学员制定个性化的发展计划并进行审查 具有与具体研究方法培训和研究结果传播相关的明确里程碑。 因此，拟议的计划将通过强调以下方面独特地推进成瘾科学： 与成瘾相关的遗传和神经行为因素的计算/定量建模。

Project Summary Substance use disorders are increasingly described as highly heritable and brain-based. Preclinical work has established that deviations in subcortical and frontal networks are associated with progression from experimentation to use to compulsive drug-seeking, to cycles of abstinence and relapse. Current models emphasize the importance of genetic vulnerabilities to intermediate phenotypes that predispose to substance use and dependence, including neural mechanisms of behavioral disinhibition, reward valuation, negative reinforcement, and negative affect that exacerbates withdrawal/craving. These models also emphasize how such mechanisms might be differentially impacted as a function of neurodevelopment. These various mechanisms, their neural correlates and genetic underpinnings, are increasingly being investigated in the context of large consortium efforts using novel technologies such as the ABCD study, various arms of the Human Connectome Project, TOPMed, AllofUS, and the UK Biobank, to name a few. However, today’s students are not necessarily prepared to leverage these resources to advance the field. We propose a mixed predoctoral/postdoctoral training program, with a central focus on neurobehavioral measures (e.g., neuroimaging), genetically informative designs, and cutting edge quantitative methods to uncover and characterize neurobehavioral mechanisms in the development of addiction. The University of Minnesota is a leader in the investigation of behavioral and molecular genetics of addiction, neurobehavioral mechanisms of substance abuse and its development through the use of preclinical, pharmacological, and neuroimaging techniques, and in quantitative modeling. Led by co-PDs Luciana and Vrieze and with the goal of producing the next generation of scientific/academic leaders, the proposed training program will train six predoctoral and three postdoctoral students each year in quantitative methods and the genetics and/or neurobehavioral mechanisms of addiction. A diverse group of trainees will be selected using stringent criteria from the pool of graduate students (predoctoral) as well as nationally (postdoctoral). The University of Minnesota’s Department of Psychology will lead this effort, with the support of an interdisciplinary team of 19 mentors in addition to the PDs. Each trainee will be funded for a two-year period, will be co-mentored by scientists with topical as well as quantitative expertise, and will pursue a combination of didactic training, lab- based experiences, workshops, seminars focused on professional development, and training in research ethics. For each trainee, individualized development plans will be developed and reviewed by a Steering Committee with articulated milestones related to training in specific research methods and the dissemination of findings. Accordingly, the proposed program will uniquely advance addiction science through its emphasis on computational/quantitative modeling of genetic and neurobehavioral factors relevant to addiction.