Gene expression profiling in the human alcoholic brain

•An integrated perspective on alcohol-responsive transcriptional changes contributing to alcohol dependence in the human brain is outlined.•Human postmortem studies require high quality RNA from established brain banks such as the New South Wales Tissue Resource Center.•Alcohol alters DNA methylation and expression of individual genes.•Distinct noncoding RNA regulatory mechanisms in brain are thought to influence the development and progression of psychiatric disorders.

Long-term alcohol use causes widespread changes in gene expression in the human brain. Aberrant gene expression changes likely contribute to the progression from occasional alcohol use to alcohol use disorder (including alcohol dependence). Transcriptome studies have identified individual gene candidates that are linked to alcohol-dependence phenotypes. The use of bioinformatics techniques to examine expression datasets has provided novel systems-level approaches to transcriptome profiling in human postmortem brain. These analytical advances, along with recent developments in next-generation sequencing technology, have been instrumental in detecting both known and novel coding and non-coding RNAs, alternative splicing events, and cell-type specific changes that may contribute to alcohol-related pathologies. This review offers an integrated perspective on alcohol-responsive transcriptional changes in the human brain underlying the regulatory gene networks that contribute to alcohol dependence.This article is part of the Special Issue entitled “Alcoholism”.