Genetic Bases of Addictive Behaviors

Addiction is not a medical term, and the range of disorders included varies according to the beliefs of the beholder. Nonetheless, its lay usage and dictionary definitions reflect the common belief that at its core is surrender to habitual, self-destructive behavior. Like most psychiatric disorders, attempts to define diagnostic criteria must use terms and constructs from entirely different languages, descriptions of biological factors and descriptions of intrapsychic events whose basis is unknown. The term addiction does not appear in the Diagnostic and Statistical Manual-IV, but in that manual, " substance use disorders " would be on nearly everyone's list of addictions, while such disorders as Bulemia Nervosa, Pathological Gambling, etc. would make the list for many [1]. This review will focus on drug addiction for several reasons. Most data on genetic contributions to addictive behaviors relates to drug dependence. Neurobiological insights have been derived almost entirely from rat and mouse studies employing genetic models of addiction. This is because drugs, given systematically in an experimentally controlled setting to genetically defined subjects, exert their effects in increasingly well-understood pharmacological pathways, often via specific neurotransmitter receptors. Many pharmacological agonist and antagonist drugs and genetic manipulations are available to the experimenter. Once the global boundaries of the addictions have been agreed on, to ascertain genetic contributions will require, as for any complex trait, that specific diagnostic heterogeneities and comorbidities be selectively measured. The ultimate goal of genetic studies is to identify specific genes, and for these complex traits there are many genes conferring only a small degree of risk for or protection against diagnosis. Finding any such gene presents a large signal-to-noise problem because of the small effect it has, but also because genes interact with each other. For example, a gene possessed by an individual whose risk is being assessed might itself be nearly Philibin, Wiren & Crabbe-Page 3 irrelevant to diagnosis, yet could potentiate the risk conferred by a specific other gene (i.e., two risk-promoting genes might increase risk 10-fold). Thus, the drug addiction phenotype might consist of individuals from a very heterogeneous population. Even within the substance abuse and dependence diagnoses, the path is not clear. The National Institute on Alcohol Abuse and Alcoholism defines alcoholism as synonymous with alcohol dependence, and as including four symptoms: craving, loss of control, physical dependence, and tolerance. These symptoms include both physical sequelae of chronic drug use and internal feelings and thoughts about …