Genetic Predisposition – How Addictions Affect our Genes

Shagun Nikke Churasia, Guru Nanak Dev University

Introduction

Genes, the functional units of DNA that compose the human genome and play a vital role in various aspects of an individual’s life. From a person’s behavior to physical characteristics, genetics are responsible for nearly every human trait a person has. The behavioral trait that can be passed down through genetics is a predisposition towards alcohol abuse and addiction.
A recent survey stated that nearly 80 percent of people who are observed to be suffering from addiction are unable to recover mainly due to lacking willpower. But often weakness and willpower have very little to do with the process of addiction. Sometimes, addicts might have a pre-existing chronic disease and thus may require enormous medical help along the road to recovery.
The phenomenon where certain parentally inherited genetic variations influence potential phenotypic development(s) of disease(s) in an individual organism, is known as a genetic predisposition. And it often enhances the chance that the person might develop a certain disease based on his/her genetic makeup. Such diseases can be identified by studying the persons’ family history, or genetic alterations.

Major Causes of Predisposition

Studies have compared brain-imaging scans of non-addicts and addicts and demonstrated that genetics indeed plays a significant role in the development of one’s addiction(s), rather than other external factors. Individuals who are already genetically predisposed to potentially addictive behaviors can be easily influenced by certain external factors.

The manifestation of addiction has been directly linked to the functioning of multiple genetic factors. Individuals with familial history of addicts are far more prone to the condition than people with no history of addiction in previous generations. It has also been noticed that there are people who are genetically predisposed to metabolize drugs uniquely, and thus are also at an increased risk of drug use and related disorder. For instance, it has been observed time and again that the chances of becoming an alcoholic are significantly more for those who primarily experience pleasurable effects or stay unaffected after consumption, than for those who experience adverse effects from alcohol consumption.

Correlation between Environment and Genes

The famous saying “nature or nurture” might be better suited as “nature and nurture”. This is because studies have shown that a person’s health is the result of dynamic interactions between his/her genes and environmental factors. Therefore, environmental factors play an important role in determining whether or not a person will develop an addiction-induced disease/disorder. Environmental factors that can increase the chances of addiction include:

1. Early exposure to drugs 
2. Lack of resources 
3. Aggressive or violent behavior as a child 
4. Little or no parental supervision
5. Easy access to alcohol 
6. Peer pressure       
7. Child abuse or trauma

Oftentimes environmental factors are considered to be the final determinant of whether a person with a genetic predisposition will ultimately become an addict or not. It has been noticed that people who are genetically predisposed for tolerance of certain drugs or similar compounds are more likely to have an environmental factor trigger them into actually becoming addicts. Thus, the development of their addiction is in that case directly dependent on that trigger from whatever that external factor may be. It may also be the case that the environmental factors that can trigger the addiction are more than one (a combination of many factors). Such cases are called “multifactorial“. And naturally, the chances of developing the same addiction(s) are then much higher. It is also possible that a person’s predisposition from a healthier lifestyle choice might ultimately help prevent the manifestation of addiction, despite him/her having inherited genetics for the addiction from his/her parents.

The connection Between Drugs and Genes

It is now clear that the combination of both genetic and environmental factors controls the initiation of the use of addictive substances. And the probability of developing an addiction due to genetic inheritance alone is moderate to high.

The risk of developing an addiction tends to be proportional to the degree of genetic relationships to an addicted relative or family member. This was proven by studies on the topic and considered family, adoption, and twins to study the inheritance pattern of genetic predispositions. Possibilities of inheriting addictive disorders range from 0.39 for hallucinogens to 0.72 for cocaine. Exposure to these drugs can affect specific histones, modifying gene expressions in localized brain regions.

Substance-use disorders can be treated by manipulating histone-modifying enzymes and their binding proteins. Currently, a major research has been supported by The National Institute on Drug Abuse (NIDA), to identify gene variations that make a person vulnerable to drug addiction. The study involves examining the DNA of subjects, as that is what directs the development of every human cell and its components. Scientists isolate gene sequences for mapping DNA sequences in drug addicts. The sequences are studied to reveal whether or not the person is at a greater risk of becoming addicted to drugs. Gene sequences encode instructions for producing specific proteins, which ultimately perform almost all life functions. The indicator of how susceptible a person is to drug addiction depends on the expression and way in which these proteins function.

A major discovery about the genetics of drug addiction was reported in 2004 by an analyst at the Howard Hughes Medical Institute at Duke University Medical Center. The researchers had recognized a specific protein- PSD-95, that showed relationships for both drug addictions as well as for learning and memory. Mice with lower levels of PSD-95’s took more time to learn their way around a maze and they were much more sensitive to drugs like Cocaine.

It has been speculated by researchers that mice with normal amounts of PSD-95 were more likely to learn their way around the maze (better learning/memory) and were less likely to become addicted to Cocaine. Drugs like Cocaine increase the concentration of dopamine (neurotransmitter), which is responsible for feelings of pleasure, otherwise colloquially referred to as being “high” (an informal term affiliated with behavioral patterns showcased by drugged individuals). But the use of such hard drugs has also been shown to cause memory loss. PSD-95 was likely involved in other types of addictions as well. According to Marc G. Caron, Ph.D., an investigator who was also a part of the research team, suggested that PSD-95 likely plays a role in the addiction of other drugs viz. nicotine, alcohol, morphine, and heroin, because like cocaine, they all exert effects through dopamine increase.

Addictions can be Inherited Genetically and Epigenetically

Genetics and heredity are often inseparable. However, multiple factors govern how or to what degree the inheritance of various genes takes place. Someone may inherit a mutated gene responsible for a hereditary disease from his/her parents but it may or may not manifest depending on the person’s genetic predisposition (genetic inheritance).

People whose parents have a history of addictions of any kind are 2-4 times more susceptible to have the same addiction themselves. This could imply that people with close family members with addictive habits are at a higher risk of acquiring the genetic transformation that causes the same addiction. And it was indeed the case that individuals who had an alcohol addiction more often than not grew up in an alcohol-centric environment in their homes or families. This is known as epigenetic inheritance.

Several precautionary measures can be taken to reduce the risk of developing addictions:

1. Informing the younger generations about the illegality of various addictive substances, how they work, and how they can ruin lives.
2. If there are behavioral markers of addiction then being understanding and taking action accordingly instead of backlash may help deal with situations effectively. Immediate medical help and psychological guidance are also equally important in severe cases.
3. Maintaining or encouraging a healthy-balanced diet and inculcating exercise helps improve the functioning of various organs of the body, ultimately leading to better productivity and overall temperament. This goes a long way in helping realize how important it is to be healthy and often helps one to stay away from unnecessary addictions.
4. Develop coping strategies to effectively deal with stress and adverse situations by figuring out self-management and stress management.
5. A healthier lifestyle improves overall mental strength or willpower. It is easier to not get influenced into doing addictive practices when the quality of life is already good.

Conclusion

Helping addicts who are struggling with disorders by supporting them with appropriate treatment is an important decision that should be taken as soon as possible. Many people are unable to overcome an addiction to drugs without formal treatment. Inpatient programs have proven to be the most successful treatment option for such patients. The medical personnel needs to treat such patients with sensitivity and have unbiased opinions. And for treatment to be more effective, doctors must study such patients for both genetic and epigenetic causes.

Also read: PhyloFisher- A software package for phylogenomic analysis

References:

1. Blazer, D. G., & Hernandez, L. M. (Eds.). (2006). Genes, behavior, and the social environment: Moving beyond the nature/nurture debate. https://www.ncbi.nlm.nih.gov/books/NBK19932/.
2. Abuse, National Institute on Drug. “Genetics and Epigenetics of Addiction DrugFacts.” National Institute on Drug Abuse, 5 Aug. 2019, https://www.drugabuse.gov/publications/drugfacts/genetics-epigenetics-addiction.
3. Genetic Predisposition – an Overview | ScienceDirect Topics. https://www.sciencedirect.com/topics/nursing-and-health-professions/genetic-predisposition.

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