People with clinical alcohol use disorder (AUD) may experience more damage to their brains the more they drink, according to a new Yale study.
The findings, published in the Journal of Clinical Investigation, are among the first to show the effect of alcohol use on synapses—the places where brain cells communicate with each other—in humans.
“Many studies have examined the effect of alcohol use on synaptic density in animals and post-mortem tissue, but there was an urgent need to translate this to the living human brain. And that’s exactly what we did,” says Yasmin Zakiniaeiz, PhD, assistant professor of psychiatry and the paper’s first author.
Researchers used positron emission tomography (PET) brain imaging on 32 people with AUD and 29 controls. They found 11% lower synaptic density in the frontal cortex, striatum, and hippocampus of people with AUD compared with controls.
Among people with AUD, lower synaptic density in the frontal cortex and striatum was related to a greater number of drinks per drinking day and trended in the same direction for alcohol drinking quantity and alcohol use severity.
Taken together, these findings suggest that chronic alcohol use contributes to dose-dependent synaptic loss, and that synaptic restoration—the process of repairing or rebuilding lost or damaged brain connections—may be a promising treatment strategy for AUD.
“The findings show the profound effects of alcohol drinking on synapses in the brain. These deficits are evident, even in people with mild-to-moderate AUD,” Zakiniaeiz says. “Further, it shows that among people with AUD, the more you drink, the greater the deficit in synapse loss.”
The study adds to the literature showing that alcohol has detrimental effects on synaptic transmission, synaptic function, synaptic plasticity, and overall behavior by altering neurotransmitter release, receptor signaling, and gene expression in the brain. The researchers say it fills a crucial gap in the understanding of how excessive drinking can impact the brains of people living with AUD.
Other Yale contributors include Nakul R. Raval, PhD; Will Riordan; Nabeel Nabulsi, PhD; Yiyun Huang, PhD; Brian Pittman, MS; David Matuskey, MD; Gustavo A. Angarita, MD; Robin Bonomi, MD, PhD; Sherry A. McKee, PhD; Ansel T. Hillmer, PhD; and Kelly P. Cosgrove, PhD.