Using a Genetic Approach to Understand Factors Influencing Resistance to Substance Use

使用遗传学方法了解影响药物使用耐药性的因素

• 批准号: 10677690
• 负责人: HERMINE H MAES
• 金额: $ 64.65万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677690
• 关键词: Accounting; Address; Adolescence; Adolescent; Adult; Age; Behavioral; Calibration; Childhood; Classification; Cohort Studies; Data; Data Collection; Detection; Development; Diagnosis; Disease; Drug user; Environment; Environmental Risk Factor; Face; Failure; Family Study; Genetic; Genotype; Goals; Health; Heritability; Illicit Drugs; Individual; Intervention; Life Cycle Stages; Measurement; Measures; Methods; Minnesota; Modeling; Outcome; Participant; Phenotype; Population; Prevalence; Prevention; Prevention strategy; Probability; Research; Resistance; Resistance development; Risk; Risk Factors; Sampling; Severities; Source; Substance Addiction; Symptoms; Testing; Translating; Twin Multiple Birth; Twin Studies; United States; Update; Variant; Virginia; addiction; addiction liability; aggregation factor; concept mapping; data mining; enhancing factor; genetic approach; genetic manipulation; high risk; indexing; model development; novel; population based; protective factors; psychologic; recruit; reduced substance use; resistance factors; response; substance use; substance use prevention; success; theories; trait; treatment strategy

PROJECT SUMMARY The goal of this project is to index individual resistance to psychoactive substance use (SU) during adolescence and use the indices to identify factors influencing resistance into early middle adulthood (30-40 years old), with a special focus on potentially modifiable factors. One possible cause for the limited success in reducing SU is a focus on factors that elevate risk for rather than resistance to SU. Although the risk and resistance aspects of liability to a disorder are symmetric, the respective factors are not. Factors enhancing resistance may more readily translate into prevention and treatment strategies. In addition, “environmental” variables, which are more likely to be modifiable than the genetic ones, may be confounded by the genetic influences. Failure to account for this confounding could hinder the detection of resistance factors. We address these limitations by measuring liability to SU/SUD in childhood/adolescence using previously collected and harmonizable data from the Virginia Twin Study of Adolescent and Behavioral Development (VTSABD; 1,214 twin pairs) and Minnesota Twin and Family Study (1,382 twin pairs), and assessing potential resistance factors. Long-term SU phenotype will be verified in a new wave of VTSABD data collection, where participants will be 30-50 years old. Aim 1. Develop continuous indices of resistance to SU and estimate genetic and environmental contributions to their variation. Two indices of SU resistance will be derived using a validated measure of childhood SU liability (Transmissible Liability Index) and SUD diagnosis in the same individuals as adults (verified in new Wave 7 SU data) to select psychological items measured in earlier waves. Two resistance indices will be generated via item response theory analysis: High Outset Resistance (based on items differentiating between low and average childhood SU liability) and High Realized Resistance (based on items distinguishing high and average childhood SU liability). Aim 2. Identify novel factors that have the highest probability of enhancing resistance to substance use. These factors will be sourced as most impactful on decisions related to substance use, using a Concept Mapping approach and existing data. Aim 3. Evaluate developmental trajectories of the resistance indices and SU outcomes while determining how these trajectories vary across levels of resistance factors. This will detail the influence of childhood/adolescent resistance on SU across the life course. This project will produce detail on potentially modifiable factors that can be targeted to reduce the likelihood of SU and addiction.

项目摘要 本项目的目标是在研究期间， 青春期，并使用指数来确定影响阻力的因素，进入早期中期成年（30-40 年龄），特别关注潜在的可修改因素。一个可能的原因是， 减少SU的重点是增加SU风险的因素，而不是对SU的耐药性。虽然风险和 抵抗方面的疾病的易感性是对称的，各自的因素不是。增强因素 抗药性可能更容易转化为预防和治疗战略。此外，“环境” 变量比遗传变量更容易改变，可能会被遗传变量混淆。 影响。如果不考虑这种混杂因素，可能会阻碍耐药因子的检测。我们解决 通过使用先前收集的数据测量儿童/青少年期SU/SUD的易患性， 来自弗吉尼亚州青少年和行为发展双胞胎研究（VTSABD; 1，214）的协调数据 双胞胎对）和明尼苏达州双胞胎和家庭研究（1,382双胞胎对），并评估潜在的阻力 因素长期SU表型将在新一波VTSABD数据收集中得到验证，其中参与者 将是30-50岁。目标1.制定持续的SU抗性指数，并估计遗传和 环境因素对它们的影响。将使用经过验证的方法推导出SU阻力的两个指数 儿童SU责任（传染责任指数）和SUD诊断的措施，在同一个人， 成年人（在新的第7波SU数据中得到验证）选择在早期波中测量的心理项目。两 将通过项目反应理论分析生成抵抗指数：高起始抵抗（基于 项目区分低和平均儿童SU负债）和高实现阻力（基于 区分高和平均儿童SU责任的项目）。目标二。确定新的因素， 提高对物质使用的抵抗力的可能性最高。这些因素将被视为最具影响力的因素 使用概念图方法和现有数据，对与物质使用有关的决定进行评估。目标3。评价 阻力指数和SU结果的发展轨迹，同时确定这些轨迹 不同级别的阻力因素不同。这将详细说明儿童/青少年抵抗对SU的影响 在整个生命过程中。该项目将详细说明可能修改的因素， 减少SU和成瘾的可能性。

项目成果

The Concept of Resistance to Substance Use and a Research Approach: The Resist! Project.

• DOI: 10.1017/thg.2023.8
• 发表时间: 2023-02
• 期刊: TWIN RESEARCH AND HUMAN GENETICS
• 影响因子: 0.9
• 作者: Vanyukov, Michael M.;Maes, Hermine H. M.;Iacono, William G.;Kirisci, Levent;Samek, Diana R.;Silberg, Judy L.;Zimmerman, Emily B.;Prom-Wormley, Elizabeth C.
• 通讯作者: Prom-Wormley, Elizabeth C.