Altered physiological, affective, and functional connectivity responses to acute stress in patients with alcohol use disorder

Background There is evidence that the processing of acute stress is altered in alcohol use disorder (AUD), but little is known about how this is manifested simultaneously across different stress parameters and which neural processes are involved. The present study examined physiological and affective responses to stress and functional connectivity in AUD. Methods Salivary cortisol samples, pulse rate, and affect ratings were collected on two days from 34 individuals with moderate or severe AUD and 34 controls. On one day, stress was induced, and on the other day, a non-stressful control task was performed. Following the intervention, participants underwent fMRI to assess functional connectivity, focusing on cortical and subcortical seed regions previously reported to be involved in AUD and/or stress. Results For pulse rate and cortisol, stress responses were blunted in AUD, whereas negative affect was increased. Furthermore, stress-related changes in pulse rate, cortisol, and affect were only correlated in healthy controls. Neuroimaging analyses revealed stress-related group differences in functional connectivity, involving the connectivity of striatal seeds with the posterior DMN, cerebellum and midcingulate cortex, and of the posterior DMN seed with the striatum and thalamus. Conclusions The results suggest a dissociation between subjective experienced distress and the physiological stress response in AUD as well as stress-related alterations in functional connectivity. These findings highlight the complex interplay between chronic alcohol use and acute stress regulation, offering valuable considerations for the development of therapeutic strategies. ### Competing Interest Statement The authors have declared no competing interest.