Higher drinking frequency corresponds to lower synaptic density in people with alcohol use disorder

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 11CUCB-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 11CUCB-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 11CUCB-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 11CUCB-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.