A Systematic Review and Meta-analysis on the Transcriptomic Signatures in Alcohol Use Disorder – a Translational Approach

Abstract

AbstractAlcohol Use Disorder (AUD) is a complex mental disease with a large treatment need. However, the clinically available therapeutic approaches are limited and thus new treatment targets are warranted. One approach to discover new treatment targets is transcriptomic profiling of key brain regions of the addiction neurocircuitry in animal models of AUD and/or in post-mortem brain tissue from deceased AUD patients. Unfortunately, those studies suffer from large heterogeneity and low sample sizes. Here we used a cross-species meta-analysis that integrates the entire literature on this topic to make more robust conclusions on transcriptomic changes in AUD. Here, we report on differentially expressed genes (DEGs) in 108 rat brain and 380 human brain samples, respectively in one of the key regions of AUD – the prefrontal cortex. We found 50 differentially expressed genes (DEGs) in rat brain, which were mainly associated with pro-oncogenic molecules, signal transduction as well as oxidative stress and inflammation. When we compared these findings with the meta-analytic results in human post-mortem PFC, we found that across species Hsd11b1 is significantly down-regulated. This finding is also confirmed by our cross-species data integrational approach. In summary, our data suggests that down-regulation of Hsd11b1 enzyme and stress-related pathways is a conserved mechanism for the alcohol dependent phenotype across different species, which might explain increased cortisol levels in AUD and therefore serves as a new treatment target.