The dopamine system has been implicated in both substance use disorder (SUD) and schizophrenia. A recent meta-analysis suggests that A1 allele of the DRD2 gene imposes genetic risk for SUD, especially alcoholism and has been implicated in Reward Deficiency Syndrome (RDS). We hypothesize that dopamine D2 receptor (DRD2) gene Taq1 A2 allele is associated with a subtype of non-SUD schizophrenics and as such may act as a putative protective agent against the development of addiction to alcohol or other drugs of abuse. Schizophrenics with SUD may be carriers of the DRD2 Taq1 A1 allele, and/or other RDS reward polymorphisms and have hypodopaminergic reward function. One plausible mechanism for alcohol seeking in schizophrenics with SUD, based on previous research, may be a deficiency of gamma type endorphins that has been linked to schizophrenic type psychosis. We also propose that alcohol seeking behavior in schizophrenics, may serve as a physiological self-healing process linked to the increased function of the gamma endorphins, thereby reducing abnormal dopaminergic activity at the nucleus accumbens (NAc). These hypotheses warrant further investigation and cautious interpretation. We, therefore, encourage research involving neuroimaging, genome wide association studies (GWAS), and epigenetic investigation into the relationship between neurogenetics and systems biology to unravel the role of dopamine in psychiatric illness and SUD.
Bibliographical noteFunding Information:
Marlene Oscar-Berman is the recipient of grants from the National Institutes of Health, NIAAA RO1-AA07112 and K05-AA00219 and the Medical Research Service of the US Department of Veterans Affairs. Dr. Kenneth Blum is a recipients of a grant awarded to PATH Foundation NY from the Life Extension Foundation, Ft Lauderdale, Florida. The work of Dr Badgaiyan was partially supported by the National Institutes of Health grants 1R01NS073884 and 1R21MH073624 and the VA Merit Review Grants CX000479 and CX000780. We appreciate the expert editorial assistance of Margaret A. Madigan.