Abstract
The prevalence of risky behavior such as substance use increases during adolescence; however, the neurobiological precursors to adolescent substance use remain unclear. Predictive modeling may complement previous work observing associations with known risk factors or substance use outcomes by developing generalizable models that predict early susceptibility. The aims of the current study were to identify and characterize behavioral and brain models of vulnerability to future substance use. Principal components analysis (PCA) of behavioral risk factors were used together with connectome-based predictive modeling (CPM) during rest and task-based functional imaging to generate predictive models in a large cohort of nine- and ten-year-olds enrolled in the Adolescent Brain & Cognitive Development (ABCD) study (NDA release 2.0.1). Dimensionality reduction (n = 9,437) of behavioral measures associated with substance use identified two latent dimensions that explained the largest amount of variance: risk-seeking (PC1; e.g., curiosity to try substances) and familial factors (PC2; e.g., family history of substance use disorder). Using cross-validated regularized regression in a subset of data (Year 1 Fast Track data; n>1,500), functional connectivity during rest and task conditions (resting-state; monetary incentive delay task; stop signal task; emotional n-back task) significantly predicted individual differences in risk-seeking (PC1) in held-out participants (partial correlations between predicted and observed scores controlling for motion and number of frames [rp]: 0.07-0.21). By contrast, functional connectivity was a weak predictor of familial risk factors associated with substance use (PC2) (rp: 0.03-0.06). These results demonstrate a novel approach to understanding substance use vulnerability, which—together with mechanistic perspectives—may inform strategies aimed at early identification of risk for addiction.
Highlights
Adolescents are prone to a variety of risky behaviors, experimentation and use of substances are common amongst youth—with nearly a quarter of 8th graders and half of 12th graders reporting experimentation with illicit substances (Johnston et al, 2018)
Using a combination of data-driven and hypothesis-driven approaches, we show that functional connectivity in the developing brain predicts vulnerability to substance use in children prior to initiation
Participants in the current study are enrolled in the ongoing Adolescent Brain Cognitive Development (ABCD) Study—a 10-year longitudinal study that aims to further our understanding of the environmental and genetic influences on brain development and their roles in substance use and other health outcomes (Garavan et al, 2018)
Summary
Adolescents are prone to a variety of risky behaviors, experimentation and use of substances are common amongst youth—with nearly a quarter of 8th graders and half of 12th graders reporting experimentation with illicit substances (Johnston et al, 2018). Functional connectivity during cognitive challenges has been shown to improve behavioral predictions when compared to functional connectivity during rest (Greene et al, 2018; Rosenberg et al, 2016a; Yoo et al, 2018) This distinction may point towards the usefulness of in-scanner tasks for assessing circuitry associated with substance use, such as circuits involved in reward and inhibitory control processing (Balodis & Potenza, 2015; Bjork et al, 2004; Whelan et al, 2012; Yau et al, 2012) as well as general cognitive function (Squeglia et al, 2012). Using a combination of data-driven and hypothesis-driven approaches, we show that functional connectivity in the developing brain predicts vulnerability to substance use in children prior to initiation
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