Biomarkers to Measure Treatment Response for Alcohol Dependence

The goal of this study was to identify molecular mechanisms regulated by pharmacological and placebo effects of binge-drinking at a transcriptome-wide level. We performed RNA-seq on PBMC samples collected from healthy heavy social drinkers (N=18) enrolled in an upto 12-day in-patient, randomized, double-blind, cross-over human laboratory trial testing three alcohol doses: Placebo, medium (0.05g/kg (men), 0.04g/kg (women)), and binge (1g/kg (men), 0.9g/kg (women)), administered in three 4-day experiments, separated by minimum of 7-day washout periods. Effects of beverage doses on differential expression of genes (DEGs) within each experiment compared to its own baseline, across experimental sequences in which each beverage dose was administered, and responsiveness to regular alcohol compared to placebo assessing pharmacological effects of alcohol were analyzed. Overall design: Randomized, double-blind, cross-over human laboratory trial. Samples from baseline (D0) and final experimental day (D3) within each sequentially performed experiment were sequenced.

本研究旨在在全转录组层面，鉴定暴饮的药理效应与安慰剂效应所调控的分子机制。我们共纳入18名健康重度社交饮酒者，采集其外周血单个核细胞（PBMC）样本并开展RNA测序（RNA-seq）；这些受试者参与了一项最长为期12天的住院随机双盲交叉人体实验室试验，试验设置三种酒精给药剂量：安慰剂组、中等剂量组（男性0.05g/kg，女性0.04g/kg）与暴饮剂量组（男性1g/kg，女性0.9g/kg），试验分为三个为期4天的实验阶段，各阶段之间设置至少7天的洗脱期。我们针对以下内容进行了分析：各实验阶段内，给药剂量相较于各自基线的基因差异表达（DEGs）情况；各给药剂量对应的实验序列中的基因表达变化；以及常规酒精摄入相较于安慰剂的响应性，以此评估酒精的药理效应。总体实验设计：随机双盲交叉人体实验室试验。对每个连续开展的实验阶段内的基线样本（D0）与最终实验日样本（D3）进行了测序。