Addiction and the Role of Circadian Genes

In mammals, intimate interactions exist between the circadian system and other molecular systems, and mounting evidence is suggesting that these relationships may affect substance use disorders. Research in preclinical models supports the role of circadian genes as risk factors for addiction. Here, we explore the evidence and review human genetic studies testing the association between specific circadian genes and substance use disorders.

A literature search was conducted in PubMed for studies testing variants in eight circadian genes known to be central to the functioning of the master clock in the brain. The studies were primarily candidate gene studies, and although we considered all drugs of abuse, studies had tested mainly alcohol and opioid use disorders. Interestingly, several had examined gene-environment interactions on addiction.

Human genetic studies considered here do provide support for the role of specific variants in drug use disorders and additionally suggest a modifying role for environmental factors such as stress, sleep, and mood disorders. However, the number of studies is limited, and, in most instances, the research involved small sample sizes, which would have produced limited statistical power and thus influenced the results.

Despite the various caveats, circadian genes do appear to modulate drug use disorders; hence, molecules comprising the circadian system represent potential therapeutic agents, and we present a limited discussion of this interesting possibility. Future work using suitably powered large clinical samples in genome-wide association studies will identify additional molecules as well as functional pathways, and possibly new therapies.