Behavioral inhibition (BI) is an important early childhood marker of risk for later psychiatric problems. The current 20-year prospective, longitudinal study focused on individual differences in this early temperament and adolescent brain function. As adolescents, 83 participants initially identified in infancy with the temperament of BI were assessed using functional imaging to examine striatal responses to incentives. Five years later, as young adults, these participants provided self-report of their substance use. Our findings show that children's early temperament interacts with their striatal sensitivity to incentives in adolescence to predict their level of substance use in young adulthood. Those young adults who, as children, showed the highest levels of BI reported the greatest substance use if, as adolescents, they also exhibited striatal hypersensitivity to incentives. These longitudinal data delineate one developmental pathway involving early biology and brain mechanisms for substance use in young adulthood.

Social Reticence (SR) is a temperament construct identified in early childhood that is expressed as shy, anxiously avoidant behavior and, particularly when stable, robustly associated with risk for anxiety disorders. Threat circuit function may develop differently for children high on SR than low on SR. We compared brain function and behavior during extinction recall in a sample of 11-to-15-year-old children characterized in early childhood on a continuum of SR. Three weeks after undergoing fear conditioning and extinction, participants completed a functional magnetic resonance imaging extinction recall task assessing memory and threat differentiation for conditioned stimuli. Whereas self-report and psychophysiological measures of differential conditioning, extinction, and extinction recall were largely similar across participants, SR-related differences in brain function emerged during extinction recall. Specifically, childhood SR was associated with a distinct pattern of hemodynamic-autonomic covariation in the brain when recalling extinguished threat and safety cues. SR and attention focus impacted associations between trial-by-trial variation in autonomic responding and in brain activation. These interactions occurred in three main brain areas: the anterior insular cortex (AIC), the anterior subdivision of the medial cingulate cortex (aMCC), and the dorsolateral prefrontal cortex (dlPFC). This pattern of SCR-BOLD coupling may reflect selective difficulty tracking safety in a temperamentally at-risk population.