Greater Neuroimmune System Deficit in Women Than Men With Alcohol Use Disorder.

Abstract

Background: Women who drink are more vulnerable than men to many of the consequences of alcohol use, including alcohol-related cancers, cardiovascular disease, liver cirrhosis, and immune system dysfunction. Acute alcohol triggers neuroimmune cells including microglia-the brain's resident immune cells. Excessive activation can contribute to neuronal dysfunction and alcohol-induced neurodegeneration. Women have a greater vulnerability to alcohol-induced neurodegeneration; thus, there is a critical need to examine sex differences in neuroimmune mechanisms that underlie alcohol use disorder (AUD) to inform novel treatment strategies for women.

Methods: A total of 41 individuals with mild-to-moderate AUD (20 women) and 37 sex-matched control individuals completed a positron emission tomography brain imaging scan with the radiotracer [¹¹C]PBR28, which binds to the 18-kDa TSPO, a microglial marker. Volume of distribution was estimated regionally in the cerebellum, hippocampus, striatum, and frontal cortex as a measure of TSPO availability. Neurocognitive function was also assessed.

Results: People with versus without AUD had significantly lower TSPO availability in all brain regions. Women (but not men) with AUD had significantly lower TSPO availability (average of 21%) in all 4 regions (p = .022) compared with sex-matched control participants. Women with versus without AUD performed worse on executive function (p = .020). Lower hippocampal (p = .059) and cerebellar (p = .097) TSPO availability were trendingly related to more errors on the executive function task in women with AUD.

Conclusions: This study showed lower TSPO levels in people with mild-to-moderate AUD versus control participants and demonstrated that the deficit was significantly greater in women than men with AUD. This suggests that women with AUD may particularly benefit from novel neuroimmune-modulating treatments for AUD.