Behavioral and brain reactivity to uncertain stress prospectively predicts binge drinking in youth

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 48; no. 8; pp. 1194 - 1200
• Main Authors: Gorka, Stephanie M, Radoman, Milena, Jimmy, Jagan, Kreutzer, Kayla A, Manzler, Charles, Culp, Stacey
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-07-2023; Springer International Publishing
• Subjects: Adolescent; Alcohol Drinking; Alcohol use; Alcoholism; Binge Drinking; Brain - diagnostic imaging; Cortex (cingulate); Drinking behavior; Humans; Risk factors; Uncertainty; Young Adult; Young adults
• ISSN: 0893-133X; 1740-634X; 1740-634X
• DOI: 10.1038/s41386-023-01571-x

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.