Criterion validity of the genetic addiction risk severity (GARS) as a marker of reward deficiency in polydrug addiction: a multi-center study

Aim : This study evaluated the Genetic Addiction Risk Severity (GARS) panel, which assesses genetic predisposition to addictive disorders by examining eleven polymorphisms in ten genes associated with dopaminergic reward system functioning. Methods : The GARS registered mark instead panel includes six single-nucleotide polymorphisms [DRD1, DRD2, DRD3, DRD4, OPRM1, and catechol-O-methyltransferase (COMT )], four simple sequence repeats (5HTT, DAT1, DRD4, and MAOA ), and one dinucleotide repeat (GABRA3 ). Criterion validity was tested in 393 polydrug abusers by correlating GARS scores with Addiction Severity Index-Multimedia Version (ASI-MV) alcohol and drug severity scores. Results : We identified a significant correlation between GARS and the ASI-MV alcohol severity score. While individuals with elevated drug severity also exhibited increased GARS, the relationship did not follow a strictly linear pattern. Variations in multiple genes involved in dopaminergic signaling contributed to risk in an additive manner, with age serving as a significant covariate. A greater number (≥ 7) of reward gene polymorphisms associated with moderate reductions in dopamine signaling demonstrated a significant association with higher ASI-MV alcohol severity scores. In contrast, individuals possessing four or more reward gene polymorphisms associated with moderate reductions in dopamine signaling exhibited significantly elevated ASI-MV drug severity scores. Conclusion: Our findings align with previous research implicating dopaminergic pathways in the progression of alcoholism and substance abuse. Additionally, they build upon prior work by identifying a potential pre-existing polygenic risk factor, as defined by the GARS panel, that may be influenced by age-related physiological changes and environmental factors. Further research is warranted to explore associated endophenotypes, with particular emphasis on the role of Reward Deficiency Syndrome linked to dysfunction within the dopaminergic reward system.