Hypothesizing Major Depression as a Subset of Reward Deficiency Syndrome (RDS) Linked to Polymorphic Reward Genes: Considerations for Translational Medicine Approaches for Future Drug Development

We hypothesize that major depressive disorder (MDD), especially anhedonia, (excluding bipolar) should be included as a subtype of Reward Deficiency Syndrome (RDS) following more extensive genetic and molecular neurobiological research. RDS, first coined by Blum in 1995, is a failure of the reward system that usually confers satisfaction, resulting in behaviors such as overeating, heavy cigarette smoking, drug and alcohol abuse (substance use disorder [SUD]), hoarding, internet addiction, gambling, and hyperactivity. RDS is caused by hypodopaminergia. We suggest that the inclusion of MDD within RDS will assist in more appropriate treatment in the addiction recovery community, whereby the goal of achieving dopamine stabilization or homeostasis will result in better clinical outcomes. One therapeutic technique to achieve this laudable goal is via epigenetic induction involving the administration of gene expression modulators that may have a positive impact on reversing hypodopaminergia, SUD, and anhedonia. We hereby encourage further research into dopaminergic homeostasis in SUD with MDD that will guide future drug development programs.