Vulnerability to Substance Use: Transitions and Trajectories in ABCD Youth with Validation Using Longitudinal Twin Family Samples - Adolescence is a key developmental stage during which many youth experiment with substances (e.g., alcohol, nicotine, cannabis). Some experimenters progress to regular use, potentially leading to substance use disorders. Whether and how early youth initiate substance use (SU) and how quickly they transition to heavier use is influenced by demographic, environmental and genetic factors. Internalizing (INT) and externalizing (EXT) behaviors, sensitivity to reward, and cognitive control/impulsivity have all been associated with SU trajectories. However, questions remain about whether these associations are causal or reflect shared risk factors, whether INT behaviors are risk or protective factors, and whether EXT/INT are independent, redundant, incremental or interactive. Changes in reward sensitivity and development of cognitive control across adolescence further impact SU trajectories and may moderate the role of EXT/INT on SU. Data from longitudinal twin studies also suggest a change in the relative importance of environmental and genetic factors in both SU and behavioral correlates, with family environment more critical in early adolescence and genetic factors increasing in importance with age. However, few studies have large enough samples that are reflective of the US population and genetically informative, with assessments of key domains across this critical developmental period. The nationwide epidemiologically informed Adolescent Brain Cognitive Development (ABCD) Study, which assesses youth (N=11k+) from age 9-10 until young adulthood, provides a unique opportunity to investigate the role of demographic, environmental and psychological factors in the rate of transition from substance initiation to regular and/or heavy use, controlling for potential confounding by genetic factors. We propose to perform secondary data analyses of the risk and protective roles of behavioral correlates in SU trajectories across adolescence and to inform when prevention might be most successful. The ABCD sample was enriched with >1000 twin pairs, primarily collected at four sites with long histories of twin research (Minnesota, Colorado, Missouri, & Virginia), and includes siblings and twins at other sites. This unique genetically informative subsample, and the remaining population-based sample on whom genomic data and a rich set of demographic and environmental variables are available, affords great opportunities. We have assembled investigators from the four twin sites, who each bring unique expertise and rigor in assessment and genetic epidemiological methods. Their skills are relevant to the study of SU trajectories and the simultaneous changes in INT/EXT behavior and reward sensitivity/cognitive control. In addition, each site has existing data from longitudinal assessments of SU and its correlates, which provide preliminary data to serve as validation samples to test assumptions and validate conclusions drawn from ABCD analyses. The combination of investment and involvement of the team in ABCD data collection, methodological and substantive expertise, and decades of experience analyzing twin data from large longitudinal samples puts us in an ideal position to study vulnerability to SU.
