RNA biomarkers for alcohol use disorder

Abstract

Alcohol use disorder (AUD) is highly prevalent and one of the leading causes of disability in the US and around the world. There are some molecular biomarkers of heavy alcohol use and liver damage which can suggest AUD, but these are lacking in sensitivity and specificity. AUD treatment involves psychosocial interventions and medications for managing alcohol withdrawal, assisting in abstinence and reduced drinking (naltrexone, acamprosate, disulfiram, and some off-label medications), and treating comorbid psychiatric conditions (e.g., depression and anxiety). It has been suggested that various patient groups within the heterogeneous AUD population would respond more favorably to specific treatment approaches. For example, there is some evidence that so-called reward-drinkers respond better to naltrexone than acamprosate. However, there are currently no objective molecular markers to separate patients into optimal treatment groups or any markers of treatment response. Objective molecular biomarkers could aid in AUD diagnosis and patient stratification, which could personalize treatment and improve outcomes through more targeted interventions. Biomarkers of treatment response could also improve AUD management and treatment development. Systems biology considers complex diseases and emergent behaviors as the outcome of interactions and crosstalk between biomolecular networks. A systems approach that uses transcriptomic (or other -omic data, e.g., methylome, proteome, metabolome) can capture genetic and environmental factors associated with AUD and potentially provide sensitive, specific, and objective biomarkers to guide patient stratification, prognosis of treatment response or relapse, and predict optimal treatments. This Review describes and highlights state-of-the-art research on employing transcriptomic data and artificial intelligence (AI) methods to serve as molecular biomarkers with the goal of improving the clinical management of AUD. Considerations about future directions are also discussed.

Keywords: RNA seq; alcohol dependence; alcoholism; biomarker; microarray; transcriptome.

FIGURE 1

Dysregulated gene expression could lead to improper cellular function, circuit function, and eventually contribute to abnormal behavior observed in alcohol use disorder (AUD). Created with BioRender.com.

FIGURE 2

(Top) PubMed was searched (inception through 2 July 2022) for relevant literature using a Boolean search strategy. The articles were evaluated for the following inclusion characteristics: English language, full text availability, related to alcohol use disorder (the search results contained many studies related to liver diseases and carcinomas which were excluded), non-targeted study with multiple biomarkers evaluated, some metric of biomarker utility (e.g., accuracy, area under the receiver operating characteristic curve). References from articles in the search were also considered for inclusion in the Review. The resulting information from these searches was reviewed to provide an overview of the current knowledge regarding RNA based biomarkers in alcohol use disorder (AUD). (Bottom) Overview of the RNA biomarker studies identified in the literature search. The seventeen studies identified were classified by the following attributes: performance metric, RNA type, tissue sampled, and species.