Immune protein may drive alcoholism relapse

The anxiety that occurs during withdrawal from excessive alcohol use, and contributes to relapse, may be driven in part by the release of an immune protein in the brain, according to a new study from scientists at Scripps Research.

The discovery, reported online June 6, 2022, in Molecular Psychiatry, illuminates the molecular details of the brain’s response to alcohol withdrawal, and suggests that the immune protein, colony stimulating factor 1 (CSF1), could be a target of future treatments for alcohol use disorder (AUD).

“Alcohol withdrawal activates the stress system in the brain, which contributes to relapse, and in this study, we linked this stress response to CSF1, a neuroimmune mediator, opening up new opportunities for therapeutic intervention,” says study senior author Marisa Roberto, PhD, professor and Schimmel Family Chair in the Department of Molecular Medicine at Scripps Research.

The study’s first author, who performed many of the experiments, is Reesha R. Patel, PhD, a former postdoctoral researcher in the Roberto lab.

Alcohol is by far the most used and abused recreational drug. According to the 2019 National Survey on Drug Use and Health, nine million men and more than five million women in the United States have an alcohol use disorder (AUD), which is defined as an inability to control alcohol use despite its negative impact on the user’s health, social life and/or employment. Drug treatments, talk-therapy and support group-based treatments are available, but relapse is common, mainly due to the limited understanding of the brain-circuit dysfunctions underlying AUD.

Scientists know that relapse-promoting alcohol withdrawal symptoms include rising feelings of anxiety, caused at least in part by the release of stress molecules such as corticotropin-releasing factor (CRF) within the brain. CRF stimulates receptors on neurons in the prefrontal cortex, and in the limbic system, a set of more primitive brain structures that process emotions. If scientists could fully identify and characterize these CRF-sensitive neuronal populations, they could understand better how anxiety occurs during withdrawal and potentially devise effective treatments to block it.

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