Prior studies show that individuals with alcohol use disorder exhibit exaggerated behavioral and brain reactivity to uncertain threats (U-threat). It is posited this brain-based factor emerges early in life and contributes to the onset and escalation of alcohol problems. However, no study to date has tested this theory using a longitudinal within-subjects design. Ninety-five young adults, ages 17-19, with minimal alcohol exposure and established risk factors for alcohol use disorder participated in this multi-session study with a 1-year tracking period. Startle eyeblink potentiation and brain activation were collected at separate baseline sessions during the well-validated No-Predictable-Unpredictable (NPU) threat-of-shock task designed to probe reactivity to U-threat and predictable threat (P-threat). Participants self-reported their drinking behavior over the past 90 days at baseline and one-year later. We fit a series of multilevel hurdle models to model the binary outcome of whether binge drinking occurred and the continuous outcome of number of binge drinking episodes. Zero-inflated binary submodels revealed that greater baseline startle reactivity, bilateral anterior insula (AIC) reactivity, and dorsal anterior cingulate cortex (dACC) reactivity to U-threat were associated with increased probability of binge drinking. There were no other associations between reactivity to U- and P-threat and probability of binge drinking and number of binging episodes. These results demonstrate that exaggerated reactivity to U-threat is a brain-based individual difference factor that connotes risk for problem drinking. These findings also add to a growing literature implicating AIC and dACC dysfunction in the pathophysiology of alcohol use disorder.
© 2023. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.