Training in genetic and neurobehavioral mechanisms of addiction

成瘾遗传和神经行为机制的培训

• 批准号: 10625300
• 负责人: Monica Luciana
• 金额: $ 34.81万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625300
• 关键词: Genetic; Training; addiction; neurobehavioral

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.

项目摘要 物质使用障碍越来越多地被描述为高度遗传和基于大脑的。临床前工作 建立了皮层下和额叶网络的偏差与从 强迫性的药物寻求，戒断和复发的循环。现款车型 强调遗传脆弱性对中间表型的重要性， 使用和依赖，包括行为去抑制的神经机制，奖励评价，负 强化，以及加剧退缩/渴望的负面影响。这些模型还强调， 机制可能会受到不同的影响，作为神经发育的功能。这些不同的机制， 他们的神经相关性和遗传基础，越来越多地被调查的背景下， 联盟的努力使用新的技术，如ABCD研究，人类连接组的各个分支， 项目，TOPMed，AllofUS和英国生物银行，仅举几例。然而，今天的学生不一定 准备好利用这些资源来推进这个领域。我们建议混合的博士前/博士后培训 计划，以神经行为措施为中心（例如，神经影像学），遗传信息 设计和尖端的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生物学研究的领导者。 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、药理学和神经成像技术以及定量建模。由共同PD Luciana领导 和Vrieze，并与生产下一代科学/学术领导人的目标，建议 培训计划将培养六名博士前和三名博士后学生，每年在定量方法， 成瘾的遗传学和/或神经行为机制。一个多样化的学员群体将被选中使用 严格的标准，从研究生池（博士前）以及国家（博士后）。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。每个受训者将获得为期两年的资助， 由具有专题和定量专业知识的科学家，并将追求教学培训，实验室， 研究所还举办了以专业发展为重点的讲习班、研讨会和研究伦理培训。 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 其中阐明了与具体研究方法培训和传播研究结果有关的里程碑。 因此，拟议中的计划将通过其重点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。

项目成果

Genetic correlation, pleiotropy, and causal associations between substance use and psychiatric disorder.

• DOI: 10.1017/s003329172000272x
• 发表时间: 2022-04
• 期刊: Psychological medicine
• 影响因子: 6.9
• 作者: Jang SK;Saunders G;Liu M;23andMe Research Team;Jiang Y;Liu DJ;Vrieze S
• 通讯作者: Vrieze S

Adolescent cortisol and DHEA responses to stress as prospective predictors of emotional and behavioral difficulties: A person-centered approach.

• DOI: 10.1016/j.psyneuen.2021.105365
• 发表时间: 2021-10
• 期刊: Psychoneuroendocrinology
• 影响因子: 3.7
• 作者: Bendezú JJ;Howland M;Thai M;Marceau K;Shirtcliff EA;Hastings PD;Zahn-Waxler C;Klimes-Dougan B
• 通讯作者: Klimes-Dougan B

Impacts of recreational cannabis legalization on cannabis use: a longitudinal discordant twin study.

• DOI: 10.1111/add.16016
• 发表时间: 2023-01
• 期刊: ADDICTION
• 影响因子: 6
• 作者: Zellers, Stephanie M.;Ross, J. Megan;Saunders, Gretchen R. B.;Ellingson, Jarrod M.;Anderson, Jacob E.;Corley, Robin P.;Iacono, William;Hewitt, John K.;Hopfer, Christian J.;McGue, Matt K.;Vrieze, Scott
• 通讯作者: Vrieze, Scott

Exploring joint HPA-inflammatory stress response profiles in adolescent girls: Implications for developmental models of neuroendocrine dysregulation.

• DOI: 10.1002/dev.22247
• 发表时间: 2022-03
• 期刊: Developmental psychobiology
• 影响因子: 2.2
• 作者: Bendezú JJ;Calhoun CD;Vinograd M;Patterson MW;Rudolph KD;Giletta M;Hastings P;Nock MK;Slavich GM;Prinstein MJ
• 通讯作者: Prinstein MJ

Mechanisms of parent-child transmission of tobacco and alcohol use with polygenic risk scores: Evidence for a genetic nurture effect.

• DOI: 10.1037/dev0001028
• 发表时间: 2021-05
• 期刊: Developmental psychology
• 影响因子: 4
• 作者: Saunders GRB;Liu M;Vrieze S;McGue M;Iacono WG;GWAS & Sequencing Consortium of Alcohol and Nicotine Use (GSCAN)
• 通讯作者: GWAS & Sequencing Consortium of Alcohol and Nicotine Use (GSCAN)