Alterations in serum microRNA in humans with alcohol use disorders impact cell proliferation and cell death pathways and predict structural and functional changes in brain

Background There is currently a lack of reliable, minimally invasive biomarkers that could predict the extent of alcoholism-induced CNS damage. Developing such biomarkers may prove useful in reducing the prevalence of alcohol use disorders (AUDs). Extracellular microRNAs (miRNAs) can be informative molecular indicators of changes in neuronal gene expression. In this study, we performed a global analysis of extracellular miRNAs to identify robust biomarkers of early CNS damage in humans diagnosed with DSM-IV AUDs. We recruited a relatively young set of 20 AUD subjects and 10 age-matched controls. They were subjected to comprehensive medical, neuropsychological and neuroimaging tests, followed by comparison of miRNA levels found in peripheral blood serum. Employing a conservative strategy to identify candidate biomarkers, miRNAs were quantified using two independent high-throughput methods: microarray and next-generation RNA-sequencing. This improved our capacity to discover and validate relevant miRNAs.