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

Neuropsychopharmacology volume 48, pages 1194–1200 (2023)Cite this article

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Abstract

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.

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Funding

Funding

This work was supported by the National Institute of Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (K23AA025111 awarded to SMG). The funding source had no role in the present manuscript.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, 370 W. 9th Avenue, Columbus, OH, 43210, USA

    Stephanie M. Gorka, Jagan Jimmy & Kayla A. Kreutzer

  2. Institute for Behavioral Medicine Research, The Ohio State University, 460 Medical Center Drive, Columbus, OH, 43210, USA

    Stephanie M. Gorka

  3. Yale Stress Center, Department of Psychiatry, Yale University School of Medicine, 2 Church St South, New Haven, CT, 06519, USA

    Milena Radoman

  4. Department of Psychology, University of South Florida, 3711 USF Citrus Drive, Tampa, FL, 33620, USA

    Charles Manzler

  5. Department of Biomedical Informatics, The Ohio State University Wexner Medical Center, 1800 Cannon Drive, Columbus, OH, 43210, USA

    Stacey Culp

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Contributions

SMG was the principal investigator of the study. SC performed the statistical analyses and aided in the interpretation of the data. SMG wrote the first draft of the manuscript. MR, JJ, KAK, and CM contributed significantly to the discussion and revision of this work, including analysis, interpretation of results, proofreading, edits and approval for submission.

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Correspondence to Stephanie M. Gorka.

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Gorka, S.M., Radoman, M., Jimmy, J. et al. Behavioral and brain reactivity to uncertain stress prospectively predicts binge drinking in youth. Neuropsychopharmacol. 48, 1194–1200 (2023). https://doi.org/10.1038/s41386-023-01571-x

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