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

项目总结 该项目的目标是将个体对精神活性物质使用(SU)的抵抗力指标化 青春期，并使用这些指数来确定影响中年早期(30-40岁)抵抗力的因素 岁)，特别关注潜在的可修改因素。其中一个可能的原因是 降低SU的重点是增加SU风险的因素，而不是抵抗SU的因素。尽管风险和 抵抗力方面对一种疾病的易感性是对称的，而各自的因素不是。增强因素 耐药性可能更容易转化为预防和治疗策略。此外，“环境” 与遗传变量相比，更有可能改变的变量可能会被遗传因素混淆 影响。如果不能解释这种混淆，可能会阻碍对耐药性因素的检测。我们致力于 这些限制是通过使用以前收集的和 来自弗吉尼亚青少年和行为发展双胞胎研究(VTSABD；1214)的可协调数据 双胞胎)和明尼苏达州双胞胎和家庭研究(1,382对双胞胎)，并评估潜在的抗性 各种因素。长期的SU表型将在新一波VTSABD数据收集中得到验证，参与者 年龄在30-50岁之间。目的1.开发连续的抗病指数，并估计遗传和 环境对它们的变异有贡献。SU抗性的两个指数将使用经过验证的 儿童SU责任的测量(可传染责任指数)和相同个体的SU诊断 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。二 阻力指数将通过项目反应理论分析生成：高起点阻力(基于 区分儿童低水平和平均水平的SU负债)和高实现阻力(基于 区分儿童SU责任高和中等的条目)。目标2.找出新的因素 增强对物质使用的抵抗力的可能性最高。这些因素将被认为是最有影响力的 关于与物质使用有关的决定，使用概念图方法和现有数据。目标3.评估 阻力指数和SU结果的发展轨迹，同时确定这些轨迹如何 阻力因素的不同程度不同。这将详细说明儿童/青少年抵抗对SU的影响 横跨整个人生历程。该项目将产生关于潜在的可修改因素的细节，可以针对 减少SU和成瘾的可能性。

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.