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Chronic Drinking Linked to Lower Brain Synaptic Density

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

Summary

Question
This study examined whether individuals with alcohol use disorder (AUD) exhibit lower synaptic density—a measure of the connections between nerve cells in the brain—compared to healthy individuals. The researchers also investigated whether synaptic density was associated with drinking behavior and cognitive performance in people with AUD.
Why it Matters
Alcohol use disorder is a significant public health issue, affecting millions worldwide and contributing to various health problems. Chronic alcohol use is known to damage brain function, but the underlying mechanisms, particularly in living humans, remain unclear. Understanding synaptic density deficits in AUD could provide insights into how alcohol damages the brain and inform new treatments aimed at restoring brain health and improving recovery outcomes for individuals with AUD.
Methods
The study included 32 adults with AUD and 29 healthy control participants. All participants underwent a positron emission tomography (PET) brain scan using a tracer called [11C]UCB-J, which binds to SV2A, a protein found in synapses. This allowed the researchers to measure synaptic density in specific brain regions, including the frontal cortex (responsible for decision-making), striatum (linked to reward processing), hippocampus (involved in memory), and cerebellum (important for motor control).
Key Findings
The researchers found that individuals with AUD had, on average, 11% lower synaptic density in the frontal cortex, striatum, and hippocampus compared to healthy controls, with a similar trend in the cerebellum. Among people with AUD, lower synaptic density in the frontal cortex and striatum was associated with consuming more drinks per drinking day. However, synaptic density was not linked to cognitive performance, such as executive function or memory, in this study.
Implications
These findings suggest that chronic alcohol use leads to significant loss of synapses in key brain regions, even in individuals with mild-to-moderate AUD. This synaptic loss could contribute to the progression of AUD and related brain dysfunction. Targeting synaptic restoration, possibly through emerging therapies like psychedelic compounds, may represent a promising approach for treating AUD and improving brain health.
Next Steps
Future research should explore whether synaptic density can recover with sustained abstinence from alcohol and examine the potential sex differences in synaptic deficits. Additionally, studies could investigate the effectiveness of treatments aimed at restoring synaptic density in mitigating the effects of AUD.
Funding Information
This research was supported by the National Institutes of Health (awards U54AA027989, P01AA02747307, K01AA029706, and K24AA031345). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional funding was provided by UCB Pharma SA.

Full Citation

Zakiniaeiz Y, Raval N, Riordan W, Nabulsi N, Huang Y, Pittman B, Matuskey D, Angarita G, Bonomi R, McKee S, Hillmer A, Cosgrove K. Higher drinking frequency corresponds to lower synaptic density in people with alcohol use disorder. Journal Of Clinical Investigation 2026, 136: e199989. PMID: 41528802, PMCID: PMC13038192, DOI: 10.1172/jci199989.
This AI-assisted summary has been reviewed and approved by at least one of the study's authors to ensure it accurately reflects the research.

Authors

  • Yasmin Zakiniaeiz, PhD

    First Author
    Yale School of Medicine

    Assistant Professor of Psychiatry

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  • Kelly Cosgrove, PhD

    Last Author
    Yale School of Medicine

    Charles B.G. Murphy Professor of Psychiatry and of Neuroscience and of Radiology and Biomedical Imaging

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Additional Yale School of Medicine Authors

Other Authors

  • Will Riordan;
  • Robin Bonomi

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