Epidemiology, Genetics, and Neurobiology of Substance Use and Disorders

Abstract

This chapter reviews the epidemiology, genetic and epigenetic influences, and involved neuroanatomy and circuitry in substance use disorders (SUD), providing a broad overview. The spectrum of unhealthy substance use and its morbidity is introduced, alongside prevalence data for specific substances and trends in patterns of use in the United States. Effects of age, gender, culture, immigration, and psychiatric comorbidity are reviewed, as well as the markedly low rate of engagement in treatment for those with SUD (i.e., the treatment gap). Genetic influences on risk of developing SUD are heuristically organized by their functional effects on substance metabolism or SUD-related neurocircuitry. Gene-by-environment interactions and epigenetic mechanisms (including DNA methylation, histone modification, and microRNA regulation) are reviewed. Clinically relevant effects of genetic heterogeneity in SUD populations (e.g., polymorphisms in genes important for hepatic metabolism of methadone) are also highlighted. Finally, major neuroanatomical structures and circuits involved in the three-stage model of the addiction cycle are presented, with associated neurotransmitter systems and the differential effects of individual substances on these systems.