Stress-Induced Sensitization of Insula Activation Predicts Alcohol Craving and Alcohol Use in Alcohol Use Disorder

Patrick Bach; Judith Zaiser; Sina Zimmermann; Tatjana Gessner; Sabine Hoffmann; Sarah Gerhardt; Oksana Berhe; Nina Kim Bekier; Martin Abel; Philipp Radler; Jens Langejürgen; Heike Tost; Bernd Lenz; Sabine Vollstädt-Klein; Jan Stallkamp; Clemens Kirschbaum; Falk Kiefer

doi:10.1016/j.biopsych.2023.08.024

Stress-Induced Sensitization of Insula Activation Predicts Alcohol Craving and Alcohol Use in Alcohol Use Disorder

Biol Psychiatry. 2024 Feb 1;95(3):245-255. doi: 10.1016/j.biopsych.2023.08.024. Epub 2023 Sep 9.

Authors

Patrick Bach¹, Judith Zaiser², Sina Zimmermann², Tatjana Gessner², Sabine Hoffmann³, Sarah Gerhardt², Oksana Berhe⁴, Nina Kim Bekier², Martin Abel², Philipp Radler⁵, Jens Langejürgen⁵, Heike Tost⁴, Bernd Lenz², Sabine Vollstädt-Klein⁶, Jan Stallkamp⁷, Clemens Kirschbaum⁸, Falk Kiefer⁹

Affiliations

¹ Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany; Feuerlein Center on Translational Addiction Medicine, University of Heidelberg, Heidelberg, Germany. Electronic address: patrick.bach@zi-mannheim.de.
² Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany.
³ Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany; Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁴ Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
⁵ Fraunhofer Institute for Manufacturing Engineering and Automation Institute for Production Technology and Automation, Mannheim, Germany.
⁶ Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany; Mannheim Center for Translational Neurosciences, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany.
⁷ Mannheim Institute for Intelligent Systems in Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
⁸ Department of Psychology, Technical University Dresden, Dresden, Germany.
⁹ Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim. Heidelberg University, Heidelberg, Germany; Feuerlein Center on Translational Addiction Medicine, University of Heidelberg, Heidelberg, Germany; Mannheim Center for Translational Neurosciences, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany.

PMID: 37678541
DOI: 10.1016/j.biopsych.2023.08.024

Abstract

Background: Stress and alcohol cues trigger alcohol consumption and relapse in alcohol use disorder. However, the neurobiological processes underlying their interaction are not well understood. Thus, we conducted a randomized, controlled neuroimaging study to investigate the effects of psychosocial stress on neural cue reactivity and addictive behaviors.

Methods: Neural alcohol cue reactivity was assessed in 91 individuals with alcohol use disorder using a validated functional magnetic resonance imaging (fMRI) task. Activation patterns were measured twice, at baseline and during a second fMRI session, prior to which participants were assigned to psychosocial stress (experimental condition) or a matched control condition or physical exercise (control conditions). Together with fMRI data, alcohol craving and cortisol levels were assessed, and alcohol use data were collected during a 12-month follow-up. Analyses tested the effects of psychosocial stress on neural cue reactivity and associations with cortisol levels, craving, and alcohol use.

Results: Compared with both control conditions, psychosocial stress elicited higher alcohol cue-induced activation in the left anterior insula (familywise error-corrected p < .05) and a stress- and cue-specific dynamic increase in insula activation over time (F_22,968 = 2.143, p = .007), which was predicted by higher cortisol levels during the experimental intervention (r = 0.310, false discovery rate-corrected p = .016). Cue-induced insula activation was positively correlated with alcohol craving during fMRI (r = 0.262, false discovery rate-corrected p = .032) and alcohol use during follow-up (r = 0.218, false discovery rate-corrected p = .046).

Conclusions: Results indicate a stress-induced sensitization of cue-induced activation in the left insula as a neurobiological correlate of the effects of psychosocial stress on alcohol craving and alcohol use in alcohol use disorder, which likely reflects changes in salience attribution and goal-directed behavior.

Keywords: Alcohol use disorder; Cortisol; Craving; Cue reactivity; Stress; fMRI.

Publication types

Randomized Controlled Trial

MeSH terms

Alcohol Drinking
Alcoholism*
Behavior, Addictive*
Craving
Cues
Ethanol / pharmacology
Humans
Hydrocortisone
Magnetic Resonance Imaging

Substances

Hydrocortisone
Ethanol