Why do some people struggle with drugs and alcohol abuse while others do not? This question has been studied extensively and researchers used to believe that drug abuse was a result of family history or the environment a person grew up in. The “nature versus nurture” issue with respect to substance abuse has been well-debated and well-researched, however, as research technologies and our knowledge of the human genome have drastically improved in recent years, a variety of studies have shown that substance addiction and abuse are complex processes involving both genetic (nature) and environmental (nurture) risk factors. It is still unclear if nature or nurture has more of an influence on the development of substance use disorders.
When evaluating the genetics of substance abuse, it is important to understand that genes associated with dependence on alcohol and other drugs do not directly cause substance abuse or dependence. In other words, there is not a single gene that codes for addiction, like there is for diseases like cystic fibrosis and sickle cell anemia. Gene variations at certain loci contribute to a person’s overall risk or protection from certain diseases, like addiction, because some gene variations can code for genetic predispositions leading to drug abuse or dependence.
Gene that have been identified to confer risk to alcohol and other drug dependence are involved in alcohol metabolism, modulation of nerve cell activity, and transmission of nerve cell signals. For example, the genes that encode for the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzymes that are involved in alcohol metabolism exist in several gene variants, some of which are associated with altered alcohol metabolism. Certain gene variations that code for ADH and ALDH lead to a higher or lower enzymatic activity, which impacts the metabolism of alcohol byproducts.
People with highly active ADH or less active ALDH can suffer from acetylaldehyde build up which is toxic and can lead to nausea, rapid heart rate and facial flushing, even with low alcohol consumption.
People, often those of East Asian descent, who possess this protective gene variant tend to drink less because they experience unpleasant physiological effects and are less likely to abuse alcohol (Dick & Agrawal, 2008). Therefore, the speed at which a person metabolizes alcohol, depending on their genes that encode for alcohol metabolic enzymes, can be a factor in a person’s susceptibility to developing alcohol use disorders. The heritability of genes that are associated with alcohol dependence ranges from 50-60% and heritability of genes associated with other drug abuse ranges from about 40-80%, demonstrating that family history and genes do matter in the development of addiction and substance use disorders (Dick & Agrawal, 2008).
Although genes may play a role in leading to addiction or abuse, people who have no apparent genetic predispositions for abuse disorders can develop a substance dependence. This shows that substance abuse is not purely genetic; One’s environment and experiences can influence their use of substances, which supports the nurture side of the debate. Some common risk factors for drug abuse include family structure, drug availability, cultural norms, and poverty. In lower income groups and communities, higher drug abuse rates are observed (Spooner & Hetherington, 2005).
Those who grow up around parents or peers who abuse drugs or alcohol are under the impression that substance abuse is typical and they are more likely to experiment and abuse drugs themselves. Children of smoker parents and siblings are twice as likely to become smokers because family members have a huge influence on their children’s actions. On the other hand, children of parents who disapprove of smoking are less likely to start smoking and tend to disapprove themselves (Jiloha, 2009). This supports the idea that children are highly impressionable and the actions of their parents and other family members greatly influence their own actions and their perceptions of right and wrong.
Another well-known risk factor for addiction initiation, relapse, and treatment failure is chronic stress. There is also evidence that adolescents who experience certain stressors early in life are more likely to show a decrease in executive functioning, increase in poor decision making, and higher amounts of impulsivity and deviant behavior, which leave them at risk for substance abuse. These vulnerability factors include adverse life events, chronic stressors, and trauma such as loss of a parent, isolation and abandonment, physical neglect, and sexual or physical abuse (Gordon, 2002). Certain regions of the corticostriatal-limbic pathways are highly susceptible to alternations by vulnerability factors that can induce stress and drug craving.
These pathways control cognition and behavior and regulate stress and are therefore associated with addiction risk, decision making, and impulsivity – all of which can be affected by high emotional stress. Stress-related vulnerability factors influence each other and increase the risk of alternations in the cortiocostriatal-limbic pathways which can result in maladaptive behaviors and stress responses such as an increase in craving, distress, and drug abuse (Sinha, 2008).
Specifically, the dysregulation of the norepinephrine (NE) and corticotropin-releasing factor (CRF) systems and their interactions with each other and the mesocorticolimbicstriatal dopamine pathways is the mechanism by which maladaptive stress responses can contribute and increase drug abuse risk. GABA and glutamate modulation of these pathways is also involved. Also, these pathways and their neuroadaptations due to chronic drug use increase stress-induced drug seeking and craving and relapse susceptibility (Sinha, 2008).
Considering the evidence for both sides of the argument and my knowledge of gene and environment interactions, I believe that genetic and environmental factors are both equally important in the development of substance abuse. In fact, substance abuse can be attributed to the relationship between genes and the environment, which is called epigenetics. Epigenetics is the study of changes in gene expression regulation due to environmental exposures, independent of gene sequences.
These changes in gene activity and expression can occur within an individual and do not alter DNA sequences, but instead determine which genes are transcribed, depending on the type of environmental stressors one experiences. There are certain epigenetic mechanisms involved in Behavioral addiction and neuronal plasticity that can occur in response to drug use and may trigger the development of chronic drug abuse. For example, chromatin remodeling may be a factor in cocaine addiction.
Through histone deacetylation, a form of chromatin remodeling, cocaine downregulates the expression of certain genes and transcription factors involved in mediating the initial response to the stimulant. Studies have shown that the gene expression changes during chronic cocaine exposure can lead to decreases in histone deacetylation (blocks transcription) and increases in acetylation (promotes transcription) of specific proteins in the nucleus accumbens, which contribute to an increase in reward response to the drug (Nielsen, Utrankar, Simons, & Kosten, 2012).
