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

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Abstract
BACKGROUND: Chronic 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. METHODS: Thirty-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 [ 11 C]UCB-J, which binds to SV2A, a marker of synaptic density. The levels of synaptic density were quantified by estimating the nondisplaceable binding potential ( BP ND ) across 4 regions of interest: frontal cortex, striatum, hippocampus, and cerebellum. RESULTS: People 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 [ 11 C]UCB-J BP ND 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 [ 11 C]UCB-J BP ND 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 [ 11 C]UCB-J BP ND . CONCLUSION: Synaptic 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. FUNDING: NIH (U54AA027989, P01AA02747307, K01AA029706, and K24AA031345); UCB Pharma SA.
Funding Information
  • Foundation for the National Institutes of Health (U54AA027989,P01AA02747307,K01AA029706,K24AA031345)
  • UCB Pharma (UCB Pharma SA)

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