Transcriptional correlates of human substance use.

Abstract

Drugs of abuse produce both acute and chronic changes in brain function, each of which is reflected in altered gene expression patterns. A number of large-scale gene expression studies have employed microarray analysis of human postmortem brain to identify transcriptional correlates of antemortem substance use. These studies have identified changes in transcripts encoding proteins functionally involved in neuronal function and synaptic plasticity, oligodendrocyte function and myelination, lipid and energy metabolism, mitochondrial function, oxidative phosphorylation, and cytoskeleton-related signal transduction. Overall, different types of substance use appear to share some of these effects, but there are more differences than similarities in gene expression for different types of substance use. Moreover, data suggest that transcriptional subtypes within a diagnostic classification of substance use may occur. These transcriptional subtypes, or "endophenotypes," may reflect complex patterns of substance use and co-morbid neuropsychiatric disorders or other diseases, which may interact with substance use to differentially affect gene expression. A broader understanding of the manner in which substance abuse causes long-term changes in brain function may be obtained from studies replicating and expanding the present gene expression data. In particular, cross-referencing comprehensive transcriptional data on regional and/or substance use-specific changes with genetic and proteomic data may further aid in identifying candidate biomarkers of altered brain function in substance-use disorders.