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 [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.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 [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.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.

Authors

Yasmin Zakiniaeiz, Nakul R. Raval, Will Riordan, Nabeel Nabulsi, Yiyun Huang, Brian Pittman, David Matuskey, Gustavo A. Angarita, Robin Bonomi, Sherry A. McKee, Ansel T. Hillmer, Kelly P. Cosgrove