Substance dependence: distinct transcriptomic patterns and neuroimmune system involvement in addiction pathogenesis and progression

Background It is well-established that consistent exposure to psychoactive substances can alter gene expression within the brain’s reward and motivation centers. These lasting changes in neuronal gene expression, including those driven by transcriptional mechanisms, can lead to a persistent craving for these substances, resulting in a definitive loss of behavioral control over consumption. Examining transcriptome alterations in individuals with established addiction may provide valuable insight into the mechanisms underlying addiction; however, research remains limited. Utilizing peripheral blood samples rather than solely postmortem brain tissues to evaluate gene expression changes may offer significant clinical benefits. Materials and methods We examined data from a cohort of patients addicted to alcohol and other psychoactive substances, including their drug use histories, psychometric status, and personality traits. We performed differential gene expression analysis to identify general and addiction-specific changes in peripheral blood transcriptomes in participants with different types of addiction. Results We detected patterns of expression changes in peripheral blood characteristic of addictions to psychoactive substances. Some of the changes were reflective of the overall pathological processes occurring in individuals with chronic substance use disorders. However, other changes, such as the hyperexpression of genes and dysregulation of functional pathways associated with the immune-inflammatory responses, may be indicative of the development of neuroinflammation and may illuminate its role in addiction development. Conclusion Changes in specific RNA levels could explain pathological processes occurring during chronic substance use. The identified candidate molecular markers of addiction in peripheral blood could contribute to enhanced diagnostic capabilities and facilitate the development of personalized treatment strategies. However, these peripheral blood findings lack functional or causal verification, representing candidate transcriptomic associations rather than confirmed molecular markers.