Training in genetic and neurobehavioral mechanisms of addiction

项目摘要 物质使用障碍越来越多地被描述为高度遗传性和脑源性。临床前工作已经完成 证实皮质下和额叶网络的偏差与疾病进展有关 实验用于强迫性的药物寻觅、戒除和复发的循环。当前型号 强调遗传脆弱性对易受物质影响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，以及加剧戒断/渴求的负面影响。这些模型还强调了如何 这些机制可能因神经发育的不同而受到不同的影响。这些不同的机制， 它们的神经相关性和遗传基础，正越来越多地在大范围的 财团使用新技术的努力，如ABCD研究，人类连接组的各种分支 项目、TOPMed、AllfUS和英国生物库，仅举几例。然而，今天的学生并不一定 准备利用这些资源推动这一领域的发展。我们建议博士后/博士后混合培训 计划，以神经行为测量(例如，神经成像)为中心，遗传信息丰富 设计，和尖端的定量方法，以揭示和表征神经行为机制 成瘾的发展。明尼苏达大学在行为和分子研究方面处于领先地位 成瘾的遗传学、物质滥用的神经行为机制及其在应用中的发展 临床前、药理学和神经成像技术，以及定量建模。由联合警局的Luciana领导 和Vrieze，并以培养下一代科学/学术领袖为目标，拟议的 培训计划将每年培训6名博士后和3名博士后，掌握定量方法和 成瘾的遗传学和/或神经行为机制。不同的受训者群体将通过以下方式进行选择 研究生(博士后)和全国(博士后)的严格标准。这个 明尼苏达大学心理学系将领导这项工作，并得到一个跨学科的支持 除了PDS，还有19名导师组成的团队。每名实习生将获得为期两年的资助，并将共同指导 由具有专题和定量专业知识的科学家提出，并将结合教学培训、实验室- 以经验为基础，以专业发展和研究道德培训为重点的讲习班和研讨会。 指导委员会将为每个受训人员制定和审查个性化的发展计划 有明确的里程碑，涉及具体研究方法的培训和研究成果的传播。 因此，拟议的计划将通过强调以下方面独特地促进成瘾科学的发展 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.