In recent years, high-throughput genomic and proteomic approaches have been used extensively to provide clues about the molecular mechanisms underlying ARBD. Oligonucleotide and complementary DNA microarray studies of samples of human frontal cortex from individuals with alcoholism have identified alcohol-responsive genes relating to several broad categories, namely myelination, synaptic structure, mitochondria, signal transduction, intracellular metabolism, protein trafficking, apoptosis and transcriptional regulation.124–127 Moreover, samples of human temporal cortex from patients with alcoholism have exhibited changes in the expression of genes encoding proteins related to mitochondria, the ubiquitin system or signal transduction.128 Alcohol-responsive genes expressed in the nucleus accumbens and the ventral tegmental area are primarily associated with changes in neurotransmission and signal transduction, suggesting neuroplastic changes that may contribute to changes in reward response. The results of such genomic approaches suggest that multiple pathways may be involved in causing altered neuronal function and structural changes in ARBD, although changes in myelin-related genes seem particularly important. Indeed, altered expression levels of proteolipid protein and myelin basic protein, both of which are involved in stabilization and compaction of the myelin sheath,129,130 could explain the structural and functional changes in white matter in patients with alcoholism.131
