Abstract
BACKGROUNDChronic alcohol use leads to synaptic dysfunction in preclinical studies. However, whether in vivo synaptic density deficits are found in people with alcohol use disorder (AUD) remains unclear.METHODSThirty-two people with AUD (n = 17 women; n = 15 men) and 29 control participants (n = 17 women; n = 12 men)completed 1 PET brain imaging scan with the radiotracer [11C]UCB-J, which binds to SV2A, a marker of synaptic density. The levels of synaptic density were quantified by estimating the nondisplaceable binding potential (BPND) across 4 regions of interest: frontal cortex, striatum, hippocampus, and cerebellum.RESULTSPeople with AUD were, on average (±SD), 43 ± 13 years of age, and most met the criteria for having mild or moderate AUD. The control participants were 37 ± 12 years of age. People with AUD had, on average, a 11% lower [11C]UCB-J BPND than did controls in the frontal cortex [F(1,62) = 13.074, P < 0.001], striatum [F(1,60) = 10.283, P = 0.002], and hippocampus [F(1,60) = 5.964, P = 0.018], trending in the same direction in the cerebellum [F(1,50) = 3.438, P = 0.070]. Among people with AUD, lower [11C]UCB-J BPND was significantly related to more drinks per drinking day, in the frontal cortex (P = 0.022) and striatum (P = 0.026). People with AUD performed worse on executive function than did controls (P = 0.020), but this was not related to [11C]UCB-J BPND.CONCLUSIONSynaptic density deficits were evident, even in people with mild-to-moderate AUD, with larger deficits observed in those with greater drinking severity. These findings underscore the potential of synaptic restoration as a therapeutic target for AUD.FUNDINGNIH (U54AA027989, P01AA02747307, K01AA029706, and K24AA031345); UCB Pharma SA.