Baseline brain and behavioral factors distinguish adolescent substance initiators and non-initiators at follow-up

Abstract

Background: Earlier substance use (SU) initiation is associated with greater risk for the development of SU disorders (SUDs), while delays in SU initiation are associated with a diminished risk for SUDs. Thus, identifying brain and behavioral factors that are markers of enhanced risk for earlier SU has major public health import. Heightened reward-sensitivity and risk-taking are two factors that confer risk for earlier SU.

Materials and methods: We characterized neural and behavioral factors associated with reward-sensitivity and risk-taking in substance-naïve adolescents (N = 70; 11.1-14.0 years), examining whether these factors differed as a function of subsequent SU initiation at 18- and 36-months follow-up. Adolescents completed a reward-related decision-making task while undergoing functional MRI. Measures of reward sensitivity (Behavioral Inhibition System-Behavioral Approach System; BIS-BAS), impulsive decision-making (delay discounting task), and SUD risk [Drug Use Screening Inventory, Revised (DUSI-R)] were collected. These metrics were compared for youth who did [Substance Initiators (SI); n = 27] and did not [Substance Non-initiators (SN); n = 43] initiate SU at follow-up.

Results: While SI and SN youth showed similar task-based risk-taking behavior, SI youth showed more variable patterns of activation in left insular cortex during high-risk selections, and left anterior cingulate cortex in response to rewarded outcomes. Groups displayed similar discounting behavior. SI participants scored higher on the DUSI-R and the BAS sub-scale.

Conclusion: Activation patterns in the insula and anterior cingulate cortex may serve as a biomarker for earlier SU initiation. Importantly, these brain regions are implicated in the development and experience of SUDs, suggesting differences in these regions prior to substance exposure.

Keywords: adolescence; anterior cingulate (ACC); decision making; insula; reward; risk-taking; substance use.

FIGURE 1

Wheel of Fortune (WOF) task. (A) Task stimuli illustrating two trial types (90/10 and 70/30), and highlighting high-reward/risk selections for each of these trial types. (B) Example trial timing. Pressing the left button, corresponding to the smaller, magenta portion of the wheel, represents selection of the high-reward/risk option (10% chance of receiving $9), over the low-reward/risk option depicted in blue (90% chance of receiving $1). Analyses reported examined Selection and Feedback phases of the task.

FIGURE 2

Between-group results for which substance non-initiators (SN) participants demonstrate increased activation relative to Substance Initiators (SI) adolescents. Interaction charts depict mean parameter estimates (error bars represent standard errors) for (A) High-reward/risk > Low-reward/risk, left insula; and (B) Win > Lose, left anterior cingulate cortex (ACC). FSIQ as covariate of no interest. Initial cluster defining threshold = p < 0.001, k = 10 voxels. Results survive FWE cluster-correction at p < 0.05.