A candidate-locus postmortem brain analysis showed that prodynorphin is downregulated in the dorsolateral prefrontal cortex of individuals with a diagnosis of AD or alcohol abuse when compared to controls149. The investigators hypothesized that prodynorphin down-regulation could lead to neurotransmission disinhibition, which could contribute to the formation of alcohol-related behaviour149. The cerebral cortex transcriptome-wide profile of AUD showed a lack of overlap with the gene expression changes observed in other psychiatric disorders (i.e., autism, schizophrenia, bipolar disorder, and depression)150. In nucleus accumbens, subjects with AD showed transcriptomic downregulation of gene modules enriched for neuronal-specific marker genes and upregulation of gene modules enriched for astrocyte and microglial specific marker genes151. The neuronal-specific modules were related to genes involved in oxidative phosphorylation, mitochondrial dysfunction, and MAPK signalling. The glial-specific modules were related to genes involved in the immune function151.
