Physiological Arousal During Alcohol Cue Exposure in Adult Drinkers: Sex Differences in Neural and Clinical Correlates : Alcohol Cue Exposure and Arousal
7 affiliations
- 1Department of Psychiatry Yale University School of Medicine New Haven Connecticut USA
- 2University College London London UK
- 3Department of Medicine VA Connecticut Healthcare System West Haven Connecticut USA
- 4Department of Medicine Yale University School of Medicine New Haven Connecticut USA
- 5Department of Neuroscience Yale University School of Medicine New Haven Connecticut USA
- 6Inter‐Department Neuroscience Program Yale University New Haven Connecticut USA
- 7Wu Tsai Institute Yale University New Haven Connecticut USA
Abstract
Cue exposure contributes to craving and reinforces alcohol misuse, potentially by altering interoceptive processing and physiological arousal. However, few studies have reported changes in physiological arousal or their neural underpinnings in response to alcohol cues. Here, we addressed these questions in 94 adult drinkers (39 females; age mean ± SD: 59.1 ± 19.1 years and range: 19–85 years) who underwent functional magnetic resonance imaging and skin conductance recording during alcohol and neutral cue exposures and completed clinical assessments including the Alcohol Use Disorder Identification Test (AUDIT; mean ± SD: 4.4 ± 5.5). Imaging data were processed with published routines and evaluated at a corrected threshold. The results showed significantly higher skin conductance response in ‘alcohol>neutral’ blocks (SCRAl‐Ne) in females than in males. However, SCRAl‐Ne was positively correlated with participants' AUDIT scores in males but not in females. SCRAl‐Ne was also positively correlated with global positive alcohol expectancy and novelty seeking scores in males but not in females. A voxel‐wise two sample test of the contrast ‘alcohol>neutral’ did not show any clusters with significant sex differences in cue reactivity. Whole‐brain regression of the same contrast on AUDIT scores identified a large cluster in the perigenual anterior cingulate cortex (pgACC), with the beta estimates showing a significant positive correlation with the SCRAl‐Ne, again in males only. These sex differences were all confirmed by slope tests. Thus, males with more drinking problems showed higher arousal as well as the pgACC response to alcohol cues in association with alcohol expectancy and novelty seeking. In chain mediation modelling, the pgACC response and alcohol expectancy interlinked SCRAl‐Ne and AUDIT scores in males. In contrast, we failed to observe any significant neural or psychological correlates of physiological arousal, despite higher SCRAl‐Ne, in females. With the caveat of a smaller sample size for females, these findings highlight sex and individual differences in physiological responses to alcohol cues and the neural and psychological underpinnings in male adult drinkers. Whether or how physiological arousal may play a role in the pathophysiology of alcohol misuse remains to be investigated for females.
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BibTeX
@article{chen2026physiological,
title = {{Physiological Arousal During Alcohol Cue Exposure in Adult Drinkers: Sex Differences in Neural and Clinical Correlates : Alcohol Cue Exposure and Arousal}},
author = {Yu Chen and Hak Kei Wong and Shefali Chaudhary and Herta H. Chao and Sheng Zhang and Chiang‐Shan R. Li},
journal = {Addiction biology},
year = {2026},
month = nov,
doi = {10.1111/adb.70197},
url = {https://europepmc.org/article/PMC/PMC13730815},
note = {CC BY},
}
RIS
TY - JOUR
TI - Physiological Arousal During Alcohol Cue Exposure in Adult Drinkers: Sex Differences in Neural and Clinical Correlates : Alcohol Cue Exposure and Arousal
AU - Yu Chen
AU - Hak Kei Wong
AU - Shefali Chaudhary
AU - Herta H. Chao
AU - Sheng Zhang
AU - Chiang‐Shan R. Li
PY - 2026
DA - 2026/11/01
JO - Addiction biology
DO - 10.1111/adb.70197
UR - https://europepmc.org/article/PMC/PMC13730815
AB - Cue exposure contributes to craving and reinforces alcohol misuse, potentially by altering interoceptive processing and physiological arousal. However, few studies have reported changes in physiological arousal or their neural underpinnings in response to alcohol cues. Here, we addressed these questions in 94 adult drinkers (39 females; age mean ± SD: 59.1 ± 19.1 years and range: 19–85 years) who underwent functional magnetic resonance imaging and skin conductance recording during alcohol and neutral cue exposures and completed clinical assessments including the Alcohol Use Disorder Identification Test (AUDIT; mean ± SD: 4.4 ± 5.5). Imaging data were processed with published routines and evaluated at a corrected threshold. The results showed significantly higher skin conductance response in ‘alcohol>neutral’ blocks (SCRAl‐Ne) in females than in males. However, SCRAl‐Ne was positively correlated with participants' AUDIT scores in males but not in females. SCRAl‐Ne was also positively correlated with global positive alcohol expectancy and novelty seeking scores in males but not in females. A voxel‐wise two sample test of the contrast ‘alcohol>neutral’ did not show any clusters with significant sex differences in cue reactivity. Whole‐brain regression of the same contrast on AUDIT scores identified a large cluster in the perigenual anterior cingulate cortex (pgACC), with the beta estimates showing a significant positive correlation with the SCRAl‐Ne, again in males only. These sex differences were all confirmed by slope tests. Thus, males with more drinking problems showed higher arousal as well as the pgACC response to alcohol cues in association with alcohol expectancy and novelty seeking. In chain mediation modelling, the pgACC response and alcohol expectancy interlinked SCRAl‐Ne and AUDIT scores in males. In contrast, we failed to observe any significant neural or psychological correlates of physiological arousal, despite higher SCRAl‐Ne, in females. With the caveat of a smaller sample size for females, these findings highlight sex and individual differences in physiological responses to alcohol cues and the neural and psychological underpinnings in male adult drinkers. Whether or how physiological arousal may play a role in the pathophysiology of alcohol misuse remains to be investigated for females.
SN - 1355-6215
SN - 1369-1600
ER -