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

项目总结 物质使用是一个主要的公共卫生问题，它从社会经济角度对个人造成不成比例的影响 弱势群体背景。我们提出了一种机械假说，即童年时期的社会经济 劣势和社会不平等的其他方面会导致神经行为偏差，这在大脑中是可以测量到的 结构/功能和神经认知表现，这增加了对问题物质使用的脆弱性。 关键的是，绝大多数研究都是横截面的，依赖于小而有力的样本。 中上阶层的白人参与者。在这个辅助数据分析提案中，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)，在多个时间点对具有人口代表性的样本进行前瞻性评估 青春期(ABCD)和从青春期到成年期(MCTFR)。多式联运和可比性 ABCD和MCTFR队列中的结构/功能MRI评估使我们能够开发和验证 一种使用全脑生成自我调节能力索引的多神经元风险分数的处理流水线 联合研究(BWAS)。ABCD和MCTFR的纵向和全面评估 队列允许我们检查这些多神经风险评分是否在儿童与儿童之间的联系中起中介作用 青春期和成年期的社会经济劣势和物质使用轨迹，以及评估 在ABCD和MCTFR两个队列中，包括家庭和社区资源、家庭收入、 教育程度、职业、歧视和与COVID相关的压力源，使我们能够检查 青春期和成年期较近的社会不平等经历会影响物质使用轨迹 超越童年社会经济劣势的影响。具有种族/民族代表性的人 使我们能够进一步检查社会经济地位是否对种族/少数民族产生较小的影响 儿童多于白人儿童--与边缘化有关的回报递减现象。最后，独一无二的 ABCD和MCTFR队列中的双胞胎家族样本允许进行共同双胞胎对照分析，以控制共享 家族性混杂因素，允许比独生子女样本更强的因果推论。理解 社会经济劣势和社会不平等的其他方面对物质使用轨迹的影响是 考虑到美国日益加剧的收入不平等和正在进行的新冠肺炎倡议，现在比以往任何时候都更加重要 大流行，不成比例地影响到来自社会经济弱势群体和 种族/少数民族背景。确定有问题风险最大的个人和家庭 物质使用轨迹，关键是确定潜在的社会和经济因素 因果风险，将有助于制定最有针对性的、因此最有效率、最具成本效益的 对药物滥用和使用障碍采取有效的预防和干预措施。

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.