in humans show fewer activated microglia in alcohol-dependent subjects compared with age-matched healthy controls (Hillmer et al., 2017). Cultured monocytes from these alcohol-dependent individuals also indicate blunted pro-inflammatory responses following an LPS challenge. Similarly, alcohol-dependent patients who had undergone recent detoxification show decrease TSPO expression in the hippocampus (Kalk et al., 2017). Hippocampal TSPO is also positively correlated with verbal memory performance in a combined group of healthy control subjects and recently detoxified alcohol-dependent individuals. However, limitations of the TSPO labeling technique (e.g., individual differences in radioligand binding affinity, lack of specificity, and difficulty in quantifying subtle changes in neuroinflammation) hamper interpretation of findings in relation to alcohol dependence (Vivash and OBrien, 2016). Chemically diverse radioligands with variable TSPO binding affinity between individuals and species may also contribute to incongruous results across studies (Sakata et al., 2017). A recent study proposes that decreases in TSPO binding in AUD patients could be due to increased levels of the endogenous TSPO ligand cholesterol, and suggests a relationship between cholesterol levels and TSPO binding in humans, an effect largely driven by inverse correlation in the AUD population (Kim et al., 2018). Discovery of more selective and sensitive biomarkers for brain microglia activation will
