12 Mar Genetics and Addiction
Addictions or substance abuse disorders are a diverse set of common, complex diseases that affect millions of people worldwide. The environmental factors that predispose to substance abuse are well known, but the question is whether genetics plays a role as well. It is becoming evident that there are shared genetic and environmental etiological factors at play. Genetic studies and other analyses are clarifying the origins of addiction and the role genes play in their development. This knowledge of genetic factors in etiology and treatment response can bolster the personalized treatment of these disorders and even prevent them.
Addictions are chronic and often relapsing psychiatric disorders with maladaptive and destructive outcomes that affect not only the individual, but also one’s family, community, and society. Just talking about alcohol alone, around 2 billion people consume alcoholic beverages and 76.3 million of these have an alcohol use disorder. The second most abused drug is tobacco, with 1.3 billion users worldwide. Approximately, up to 200 million people worldwide consume illicit drugs.
Addiction is characterized by three phenomena, regardless of the type of agent of abuse: craving (preoccupation/anticipation), binge/intoxication, and withdrawal/negative effect. The initial stages are dominated by impulsivity and positive reinforcement that drive drug-seeking behavior. These are replaced by compulsivity and negative reinforcement in the later stages of the addiction cycle. Addictive drugs have been found to induce adaptive changes in gene expression in brain reward regions, leading to tolerance and habit formation. These processes are implicated in the development of relapse as well.
Genetics supposedly plays an important role in determining which treatment modalities are effective in these patients. This can induce a paradigm shift in substance abuse disorder therapy as currently, the clinical options are untargeted and only partially effective. Inherited variation is thought to affect the initiation and maintenance of drug use, and new therapies and preventive strategies could be developed and better targeted to individuals.
Addictions have been found to be moderate to highly heritable. Family, adoption, and twin studies reveal that an individual’s risk for substance abuse disorder tends to be proportional to the degree of genetic relationship to an addicted relative. These heritabilities are not the same across the board – it is 0.39 for hallucinogens, and 0.72 for cocaine. An important study (Virginia Twin Study) revealed that while familial and social factors play a stronger role in the initiation and use of nicotine, alcohol, and cannabis in adolescence, there is an increasingly greater role of genetics in the same as one grows older.
It must be noted that the underlying pathogenesis of these substance use disorders is complex, and while there has been some progress in unraveling the genetic factors that are linked to their development and to one’s response to therapy, there is still a lot that we don’t know about how genetic factors interact with environmental factors in the natural history of these conditions. But it is encouraging to see that this knowledge has the potential to guide prevention and management practice in this field.