Transcriptomic markers of psychoactive substance addiction in peripheral blood

Abstract

The regular use of psychoactive substances, resulting in substance use disorders, represents a significant public health concern globally. Due to genetic variability and the substantial impact of environmental factors, identifying specific genes associated with predisposition to addictive behaviors presents a significant challenge. Regular exposure to psychoactive substances is known to change gene expression levels in the brain regions for reward and motivation. These changes affect the dopaminergic, glutamatergic, and cannabinoid systems of the brain. The existing data on cellular gene expression in the central nervous system has been predominantly derived from postmortem brain samples or animal models, which limits their clinical applicability. Therefore, analyzing gene expression levels in peripheral blood may provide considerable advantages for clinical practice. In this study, we conducted a differential gene expression analysis followed by a pathway analysis in individuals with long-term substance use disorders, such as opiates, psychostimulants, and cannabinoids. Our results revealed a significant number of genes exhibiting differential expression in peripheral blood. The pathway analysis suggested that the metabolic changes associated with regular substance use primarily impact energy catabolism, toxin metabolism, anabolic processes, and cell signaling pathways. The examination of peripheral blood transcriptome profiles provided valuable insights into the overall health status of individuals with substance use disorders related to various classes of psychoactive substances. Transcriptome analysis has the potential to significantly enhance the diagnosis of substance use disorders.