Neural correlates of altered loss aversion in alcohol use disorder: preliminary evidence of sex-related differences from 18F-FDG-PET imaging.

Previous findings suggest that the altered punishment sensitivity displayed by individuals with Alcohol Use Disorder (AUD) might reflect lower levels of loss aversion (LA), i.e., the tendency to overweigh negative relative to positive choice consequences. However, whether lower LA represents a core facet of abnormal decision-making in AUD, rather than a secondary consequence of defective executive functioning, remains debated. We used a gambling task to compare LA across 22 AUD patients and 19 age-, sex-, and education-matched healthy controls, and 18F-FDG-PET to investigate its neural correlates in the AUD sample, using 42 age/sex-matched PET healthy controls as the reference group for analyses on brain metabolism. Although AUD patients displayed both significantly lower LA and a hypometabolic pattern in the anterior cingulate and anterior insular nodes of the salience network, the behavioral finding was not explained by altered attentional or executive skills. Instead, we observed a negative relationship with left anterior insular metabolism and LA, possibly reflecting altered regulation of emotions associated with interoceptive processing. Within the AUD sample, lower LA was associated with a steeper negative relationship with frontomedial metabolism in males than in females, suggesting sex-related modulation of its neural correlates. While providing novel insights into the hypometabolic brain pattern associated with lower LA in AUD, these findings unveil sex-specific effects calling for tailored intervention approaches both in research and clinical practice.