Longitudinal Recovery of Cerebral Perfusion After Short-term Withdrawal in Alcohol Use Disorder and Its Molecular...

Alcohol use disorder (AUD) is associated with widespread cerebral perfusion abnormalities, but the extent to which these alterations change after abstinence and their underlying biological basis remain unclear. The present study adopted a longitudinal design to characterize the features of cerebral blood flow (CBF) alterations in patients with AUD following short-term withdrawal, analyze their correlations with improvements in cognitive function and emotional symptoms, and investigate the neurotransmitter and cellular molecular basis underlying CBF changes.

Forty male patients with AUD underwent ASL magnetic resonance imaging at baseline and again after approximately 1 month of standardized withdrawal treatment. Voxel-wise paired analyses were performed to identify withdrawal-related CBF changes. Following the primary longitudinal voxel-wise comparison of CBF, we conducted two sequential tiers of post-hoc exploratory analyses. The primary tier focused on elucidating the underlying molecular mechanisms, wherein cross-modal spatial correlation analyses were performed using the JuSpace toolbox to characterize the spatial associations between CBF-altered brain regions and normative neurotransmitter maps as well as cell surface marker atlases. The secondary tier aimed to explore the clinical relevance of these perfusion changes by examining the correlations between regional CBF alterations and participants' cognitive function as well as emotional symptoms.

Short-term withdrawal was associated with significant CBF increases in the left insula, right angular gyrus, bilateral precuneus, right inferior frontal gyrus, middle cingulate gyrus, and temporal-parietal regions. These perfusion increases were accompanied by improved cognitive performance and reduced anxiety and depressive symptoms. At the neurotransmitter level, CBF changes were significantly negatively correlated with receptors involved in the neuronal excitation-inhibition balance, while significantly positively correlated with markers of the monoaminergic and opioidergic neurotransmitter systems; at the brain metabolism and cellular level, CBF alterations were mainly significantly negatively correlated with neuronal energy metabolism-related markers, while mainly significantly positively correlated with neurovascular unit-associated cellular components.

These findings provide longitudinal evidence that short-term withdrawal can partially increase brain perfusion in patients with AUD. The observed associations between perfusion recovery, cognitive improvement, and spatial overlap with molecular/cellular architectures suggest that early abstinence-related brain changes may be associated with coordinated neurochemical and neurovascular adaptations.