Physiological Arousal During Alcohol Cue Exposure in Adult Drinkers: Sex Differences in Neural and Clinical Correlates

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 (SCR _Al‐Ne ) in females than in males. However, SCR _Al‐Ne was positively correlated with participants' AUDIT scores in males but not in females. SCR _Al‐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 SCR _Al‐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 SCR _Al‐Ne and AUDIT scores in males. In contrast, we failed to observe any significant neural or psychological correlates of physiological arousal, despite higher SCR _Al‐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.