Neurobehavioral mechanisms linking childhood social disadvantage with substance use trajectories in adolescence and adulthood

项目摘要 药物使用是一个主要的公共卫生问题，从社会经济方面对个人造成不成比例的影响。 弱势背景。我们提出了一个机械假说， 不利和社会不平等的其他方面导致神经行为偏差，在大脑中可测量 结构/功能和神经认知表现，增加了对有问题的物质使用的脆弱性。 重要的是，绝大多数研究都是横截面的，并且依赖于小的，动力不足的样本 中产阶级/上层阶级白色参与者。在这个二次数据分析提案中，我们利用现有的数据集 来自青少年大脑认知发展（ABCD）研究和明尼苏达州双胞胎和家庭中心 研究（MCTFR），在研究期间的多个时间点前瞻性评估的人群代表性样本 青春期（ABCD）和从青春期到成年期（MCTFR）。多式联运和可比 ABCD和MCTFR队列的结构/功能MRI评估使我们能够开发和验证 用于使用全脑生成多神经元风险分数索引自我调节能力的处理管道 关联研究（BWAS）。ABCD和MCTFR的纵向和全面评估 队列研究使我们能够检查这些多神经风险评分是否介导了儿童期与 青少年和成年期社会经济不利因素和药物使用轨迹，以及评估 在ABCD和MCTFR队列中，包括家庭和社区资源，家庭收入， 教育程度、职业、歧视和与COVID相关的压力因素，使我们能够研究 青少年和成年期社会不平等的更近距离经历影响物质使用轨迹 超越了童年社会经济劣势的影响。具有种族/族裔代表性的ABCD队列 允许我们进一步研究社会经济地位是否对种族/少数民族的影响较小 儿童比白色儿童-边缘化相关的收益递减现象。最后，独特的 ABCD和MCTFR队列中的双胞胎家庭样本允许进行双胞胎对照分析， 家族混杂因素，允许比单例样本更强的因果推断。理解 社会经济劣势和社会不平等的其他方面对药物使用轨迹的影响， 考虑到美国收入不平等的加剧和持续的COVID-19， 这一流行病严重影响社会经济处境不利的个人和家庭， 种族/少数民族背景。确定有问题的个人和家庭的最大风险 物质使用轨迹，并严格确定可能导致 因果风险，将告知最有针对性的发展，因此最有效，最具成本效益， 有效，预防和干预努力可能的物质滥用和使用障碍。

PROJECT SUMMARY Substance use is a major public health concern that disproportionately affects individuals from socioeconomically disadvantaged backgrounds. We propose the mechanistic hypothesis that childhood socioeconomic disadvantage and other aspects of social inequality leads to neurobehavioral deviations, measurable in brain structure/functioning and neurocognitive performance, that increases vulnerability to problematic substance use. Critically, the vast majority of research has been cross-sectional and relied upon small, underpowered samples of middle/upper-class White participants. In this secondary data analysis proposal, we leverage existing datasets from the Adolescent Brain Cognitive Development (ABCD) study and the Minnesota Center for Twin and Family Research (MCTFR), population-representative samples prospectively assessed at multiple time points during adolescence (ABCD) and from adolescence into adulthood (MCTFR). Multimodal and comparable structural/functional MRI assessments in both the ABCD and MCTFR cohorts allow us to develop and validate a processing pipeline for generating polyneuro risk scores indexing self-regulation abilities using whole-brain association studies (BWAS). Longitudinal and comprehensive assessments in both the ABCD and MCTFR cohorts allow us to examine whether these polyneuro risk scores mediate associations between childhood socioeconomic disadvantage and substance use trajectories in adolescence and adulthood, and assessments in both the ABCD and MCTFR cohorts, including family and community resources, household income, educational attainment, occupation, discrimination, and COVID-related stressors, allow us to examine whether more proximal experiences of social inequality in adolescence and adulthood affect substance use trajectories beyond effects of childhood socioeconomic disadvantage. The racially/ethnically representative ABCD cohort allows us to further examine whether socioeconomic status shows smaller effects for racial/ethnic minority children than White children—the marginalization-related diminished returns phenomenon. Finally, the unique twin family samples in both the ABCD and MCTFR cohorts allow co-twin control analyses that control for shared familial confounders, permitting stronger causal inference than possible in samples of singletons. Understanding effects of socioeconomic disadvantage and other aspects of social inequality on substance use trajectories is more important now than ever, given rising income inequality in the United States and the ongoing COVID-19 pandemic, which disproportionately affects individuals and families from socioeconomically disadvantaged and racial/ethnic minority backgrounds. Identifying individuals and families at the greatest risk for problematic substance use trajectories, and, critically, identifying the social and economic factors that potentially confer causal risk, will inform the development of the most targeted, and therefore most efficient, cost-effective, and efficacious, prevention and intervention efforts possible for substance misuse and use disorder.