Striatal alcohol cue-reactivity is stronger in male than female problem drinkers

Abstract

Despite apparent sex differences in the development and treatment of alcohol use disorder, relatively little is known about the underlying neural mechanisms. In this study, we therefore investigated neural cue-reactivity in a sample of male (n = 28) and female (n = 27) problem drinkers (matched on age and alcohol use severity) with an average alcohol use disorder identification test score of 12 which is indicative of a likely alcohol use disorder. Neural cue-reactivity data were extracted from four regions of interest: the ventral and dorsal striatum and the ventral and dorsal anterior cingulate cortex, with a significance level set at p < 0.05. While the cue-reactivity paradigm induced similar levels of self-reported craving in men and women, visual alcohol cues induced significantly stronger striatal activation in men compared to drinkers. While sex differences in ventral striatal cue-reactivity were partly explained by sex differences in alcohol intake, cannabis use, negative affect and anxiety, this was not the case for sex differences in dorsal striatal cue-reactivity. These results suggest that alcohol cues are differentially processed by men and women and that the neurobiological mechanisms behind cue-reactivity differ between the sexes. Consequently, paradigms using alcohol-related pictures may not be optimal to induce cue-reactivity in female drinkers and may not be optimal to measure neurobiological markers of alcohol use severity and relapse. Future alcohol cue-reactivity studies should, in addition to including both men and women, include different types of cues (e.g., stressors and imagery in addition to pictures) to assess sex differences in alcohol cue-reactivity.

Keywords: alcohol cue-reactivity; alcohol use disorder; craving; nucleus accumbens; sex differences; striatum.

Figure 1

Sex by stimulus‐type interaction effect. There was a significant sex by stimulus‐type interaction effect in the dorsal and ventral striatum, but not in the dorsal or ventral ACC. More specifically, reactivity in the ventral and dorsal striatum in response to alcohol stimuli versus soda stimuli was significantly stronger in male compared to female problem drinkers. Values indicated with an asterisk (*) represent a significant sex by stimulus‐type interaction effect at p < 0.05.

Figure 2

Alcohol use severity by stimulus‐type interaction effect. There was a significant AUDIT (alcohol use severity) by stimulus‐type interaction effect in the ventral and dorsal striatum. More specifically, in individuals with the highest scores on alcohol use severity, the ventral and dorsal striatum responded stronger to alcohol stimuli compared to soda stimuli, whereas in individuals with the lowest scores on alcohol use severity, the ventral and dorsal striatum responded stronger to soda stimuli compared to alcohol stimuli. For visualization purposes, these data are plotted based on the median split of the AUDIT‐scores. Values indicated with an asterisk (*) represent a significant AUDIT by stimulus‐type interaction effect at p < 0.05