Dopamine-modulated aversive emotion processing fails in alcohol-dependent patients

Negative mood states after alco- hol detoxifi cation may enhance the relapse risk. As recently shown in healthy volunteers, dopamine storage capacity ( V d ) in the left amy- gdala was positively correlated with functional activation in the left amygdala and anterior cin- gulate cortex (ACC) during an emotional task; high functional connectivity between the amy- gdala and the ACC, a region important for emo- tion regulation, was associated with low trait anxiety. Based on these fi ndings, we now tested whether detoxifi ed alcohol-dependent patients have a disrupted modulation of the anterior cin- gulate cortex activation in response to aversive stimuli by amygdala dopamine. Furthermore, we asked whether disrupted functional coupling between amygdala and ACC during aversive processing is related to trait anxiety. Methods: We used combined 6-( 18 F)-fl uoro- L - DOPA positron emission tomography (PET), func- tional magnetic resonance imaging (fMRI) and Spielberger's state-trait anxiety questionnaire (STAI) in 11 male detoxifi ed alcohol-dependent patients compared to 13 matched healthy con- trols. Results: Unlike healthy controls, patients showed no signifi cant correlation between our PET metric for dopamine storage capacity (FDOPA V d ), in left amygdala and activation in left ACC. Moreover, the functional connectivity between amygdala and ACC during processing of aversive emotional stimuli was reduced in patients. Voxel- based morphometry did not reveal any discernible group diff erences in amygdala volume. Discussion: These results suggest that dopamine- modulated corticolimbic circuit function is impor- tant for responding to emotional information such that apparent functional defi cits in this neuromod- ulatory circuitry may contribute to trait anxiety in alcohol-dependent patients.