The phenomics and genetics of addictive and affective comorbidity in opioid use disorder

Opioid use disorder (OUD) creates significant public health and economic burdens worldwide. Therefore, understanding the risk factors that lead to the development of OUD is fundamental to reducing both its prevalence and its impact. Significant sources of OUD risk include co-occurring lifetime and current diagnoses of both psychiatric disorders, primarily mood disorders, and other substance use disorders, and unique and shared genetic factors. Although there appears to be pleiotropy between OUD and both mood and substance use disorders, this aspect of OUD risk is poorly understood. In this review, we describe the prevalence and clinical significance of addictive and affective comorbidities as risk factors for OUD development as a basis for rational opioid prescribing and OUD treatment and to improve efforts to prevent the disorder. We also review the genetic variants that have been associated with OUD and other addictive and affective disorders to highlight targets for future study and risk assessment protocols.