2026 ECNP Congress

PS02-2003

Longitudinal associations between stress, craving, and alcohol use in individuals with alcohol use disorder, investigated using fMRI and EMA

Joscha Baessler — L. Roetzer, J. Zaiser, M. Kamyar, A. Bellem, L. Frischmann, D. Dogan, N. Schmitz, A. Buga, J. Nguyen, P. Bach, F. Kiefer · Zentralinstitut für Seelische Gesundheit, Klinik für Abhängiges Verhalten und Suchtmedizin, Mannheim, Germany

2026 ECNP Congress

Background

Stress reactivity is a key factor in both the development and persistence of alcohol use disorder (AUD), and it contributes to negative mood states following detoxification [1]. Among abstinent patients with AUD, stress-induced negative emotions frequently trigger a desire to consume alcohol. Both alcohol-related cues and stress, in particular psychosocial stress, are therefore established triggers off craving and subsequent relapse in AUD [2]. Rapid habituation to repeated stress is a well-documented characteristic of the HPA axis [3]. However, individuals vary considerably in their resilience to repeated stress [4]. It has been proposed that adaptive component of the stress response engage protective subsystems, thereby buffering against harmful effects and shaping overall stress reactivity [5].

Methods

This longitudinal experimental study (N=100 participants with AUD) consisting of two on-site assessment days and a follow-up period of 6 weeks aims to investigate the neurobiological mechanisms underlying AUD by examining individual variability in stress responses to repeated psychosocial stress and their associations with neural alcohol cue reactivity, alcohol craving and alcohol use. The primary endpoint of this study is the stress response to repeated psychosocial stress with cortisol levels as a physiological marker of HPA axis activity. Neural alcohol cue-reactivity will be assessed repeatedly using a validated fMRI-task, with neural activation patterns measured across two consecutive days. Prior to imaging participants are exposed to psychosocial stress and to their preferred alcoholic beverage in a controlled bar-like setting on both days. In addition to neuroimaging and EMA data, situation-specific cognitive appraisals are measured using the PASA scale, alongside assessments of cue-induced alcohol craving. Analyses of neural cue-reactivity will be testing group differences of groups of different stress reactivity using t-tets. Analyses of EMA data will be testing associations between stress exposure, craving and alcohol use using linear mixed models.

Results

To date, 96 of the planned 100 participants have been enrolled, with recruitment expected to be completed by the end of May 2026. Participants have a mean age of 39.92 years and meet an average of 4.47 AUD criteria. Saliva samples of N=70 participants have been analyzed. Of these, n=35 participants (50%) exhibited a sensitized cortisol response to repeated psychosocial stress on the second examination day, defined as an increase in maximal cortisol increase from baseline (baseline-to-peak) exceeding 1.5 nmol/l or 15.5% of the baseline value. The groups did not differ significantly in demographic characteristics, substance use patterns or AUD severity. No significant group differences in cortisol levels were observed on the first examination day. Participants showing a sensitized stress response showed significantly greater neural alcohol cue reactivity in areas of the bilateral middle occipital gyrus, right precuneus and left cuneus (pFWE<0.05).

Conclusions

These preliminary findings highlight substantial variability in stress responses and coping and their associations with neural alcohol cue reactivity, offering insights into real-life links between psychosocial stress, alcohol craving and alcohol use in AUD. The final analyses of the full sample along with results from the follow-up phase, are expected to further clarify the underlying mechanisms of AUD and highlight the importance of treatment approaches targeting stress reactivity.

References

  1. Breese, G. R., Chu, K., Dayas, C. V., Funk, D., Knapp, D. J., Koob, G. F., Lê, D. A., O’Dell, L. E., Overstreet, D. H., Roberts, A. J., Sinha, R., Valdez, G. R., & Weiss, F., 2005. Stress enhancement of craving during sobriety: A risk for relapse. Alcoholism, Clinical and Experimental Research, 29(2), 185–195.
  2. Adinoff, B., Junghanns, K., Kiefer, F., & Krishnan‐Sarin, S., 2005. Suppression of the HPA Axis Stress‐Response: Implications for Relapse. Alcoholism: Clinical and Experimental Research, 29(7), 1351–1355.
  3. Boyle, N. B., Lawton, C., Arkbåge, K., West, S. G., Thorell, L., Hofman, D., Weeks, A., Myrissa, K., Croden, F., & Dye, L., 2016. Stress responses to repeated exposure to a combined physical and social evaluative laboratory stressor in young healthy males. Psychoneuroendocrinology, 63, 119–127.
  4. Glier, S., Campbell, A., Corr, R., Pelletier‐Baldelli, A., Yefimov, M., Guerra, C., Scott, K., Murphy, L., Bizzell, J., & Belger, A., 2022. Coordination of autonomic and endocrine stress responses to the Trier Social Stress Test in adolescence. Psychophysiology, 59(9), e14056.
  5. Pulopulos, M. M., Baeken, C., & De Raedt, R., 2020. Cortisol response to stress: The role of expectancy and anticipatory stress regulation. Hormones and Behavior, 117, 104587, https://doi.org/10.1016/j.yhbeh.2019.104587.