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

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.