Biomarkers of Systemic Inflammation in Alcohol Use Disorder
2022 Award: $98,500
Studies of post-mortem brains of people who suffered from Alcohol Use Disorders show abnormal activation of inflammatory immune signals that are proposed to underlie addiction to alcohol. We propose to determine if serum levels of inflammatory markers are biomarkers of excessive alcohol drinking. Such a biomarker could provide a useful diagnostic tool and indicate if patients might respond to novel treatments that inhibit the same inflammatory pathways. We will test this idea in men and women who meet criteria for AUD in hopes of discovering a biomarker of AUD drinking severity and to facilitate study of new ways to treat alcohol use disorders.
Need/Problem: The burden of alcohol use disorders (AUDs) in our society is greater than any other addictive drug, but, there is no reliable diagnostic biomarker of heavy drinking or AUD severity.
Grant Summary: We will develop a biomarker assay of innate inflammation in macrophages of non-treatment seeking heavy drinkers who meet AUD criteria compared to light drinkers and determine if allopregnanolone can inhibit the inflammatory signals or sensitivity to pathogens in macrophages from these subjects.
Goals and Projected Outcomes: We predict that markers of inflammatory signaling will be present in blood plasma of AUD+ heavy drinkers, but not in light drinkers. We further predict the inflammatory signals in the blood will be inhibited by allopregnanolone ex vivo and there will be a negative correlation between the presence of inflammatory markers and allopregnanolone in blood of all subjects. These results may establish novel biomarkers of AUD severity that could potentially be used to identify patients who would respond to anti-inflammatory medications, including allopregnanolone.