How do genes influence addiction?
Doctors who are treating addicted people often find a big variability to how patients respond to the same treatment. This variability can in many cases be explained by genetics.
Genes consist of DNA. One gene is the code that the cell reads to know how to construct a specific protein in the cell. Proteins are molecules that perform a lot of different activities in the cell, and depending on where the cell is located in the body, different sets of activities need to take place. Example of such activities are 1) Execution of chemical reactions (for example making sure food is broken down into molecules that can be converted into energy), 2) Sending signals throughout the body (like hormones released from the brain that travel to their destination organ to give a message), 3) Antibodies, that attack invaders like bacteria or virus, 4) Transportation of molecules in or out from cells (for example, to absorb digested food in the intestine). All cells in the body contain the same genes, and all genes exist in two copies – one from your mother and one from you father. Even though all cells have the same genes, some genes are active only in certain cells and some in others (for example is the gene coding for eye color only active in certain cells in the eye). In addition, depending on the different gene variants you get from your mother and father respectively, the expression of the genes will differ.
Genes influence, for example, how we respond to different medications and to different kind of addictive substances. The more we will learn about the role of genetics, medical treatments will probably become more personally adjusted to achieve maximal results with minimal side effects.
Why are there genes for addiction?
From the evolutionary point of view there is an advantage to associate eating something good with pleasure. It makes the animal (or human) search for this food again in the future, and therefore it gives a survival advantage to be able to find the right food. This is the how addictive behavior once arose and why it has been allowed to further develop during evolution. Most of you know the feeling of having eaten too much of something you like even though you know it is not that good for you.
How is it possible to identify genes involved in addiction?
When scientists look for genes involved in addiction, what they are really looking for are biological differences that may make someone more or less vulnerable to addiction. It may, for example, be harder for people with certain genes to quit an addictive substance once they have started. Or they may experience more severe withdrawal symptoms if they decide to try to quit. Factors that make it harder to become addicted may also be genetic. For example, someone may feel sick from a drug that makes other people feel good.
How do scientists actually do to find specific genes involved in addiction? As is often the case in science, animals are used to find genes involved in different conditions. This is a very good first step, as it is both cheaper, faster and more ethical than doing such tests on humans. Animals can be used as models since all organisms share a big number of genes that are crucial for life. Examples of animals used in identification of addiction genes are fruit flies (60% genes similar to humans) and mice (75% genes similar to humans). One might think that fruit flies are too different from us, but not only do they share many of our genes, but also several of our behaviors. Fruit flies are easy to manipulate genetically, and they have a short generation time, which helps obtaining results faster. There are methods to use to introduce mutations randomly in flies. This will lead to a mix of flies that have different genetic variants. These flies can then be further tested in addiction experiments.
By genetically analyzing flies showing increased addictive behavior in such experiments, candidate genes can be identified.
When a gene has been identified in an animal, the DNA sequence of that gene can be compared to the human genome, and hence a similar gene can be found. By further comparing the DNA of a group of people with an addiction to a group of non addicts it can be confirmed (or rejected) that a variant of this gene actually does have a role in addiction.
A new method to find new candidate genes for addiction, that do not involve animal testing, is Genome Wide Association Studies (GWAS). This is a new technique that has become possible firstly due to the completion of the human genome sequencing project, and secondly due to the development of faster and cheaper techniques for sequencing genes. The method covers all our genes, and normally compares two groups as described above (one group with the diagnosed addiction, the second group without addiction as a control). The samples are scanned to find small variations in the DNA called Single Nucleotide Polymorphisms (SNP), which are places where individuals differ in just one single letter of the genetic code. If such a variation is found more frequently in a group of tested addicts than in a control group, it is believed to be located close to a gene that can influence the development of addiction.
This method has, for example, been used to show that a certain variation in the gene for a nicotine receptor doubled the risk for nicotine addiction in smokers (1). Using GWAS for studying addiction is relatively new and will likely identify more interesting genes in the future.
Which are the genes involved in addiction?
The following image summarizes genes that have been shown to be involved in addiction (2,3).
The three groups of genes that can be seen in the bottom of the above image (which are all resulting in increased risk of addiction), are genes participating in signaling happiness, reward and appetite in the brain. Changes in these signals can have a destabilizing effect and therefore increase the probability to become addicted.
How can Genetics help?
One goal of genetic research is to help develop and improve treatments. Each new identified addiction gene becomes a potential drug target. That is, researchers can focus on one gene product and develop a drug that modifies its activity. In doing so, signals can be modified or stabilized to restore proper brain function.
Understanding the role of genetic variation in addiction genes can also help when choosing treatments. The effectiveness of medications varies from person to person, depending on their genetic make-up. In the future, as more genetic risk variants for addiction are discovered and personalized genotyping and sequencing becomes widespread, there will be further possibilities to use genetic risk scores to predict vulnerability to addiction. As individual genetic sequencing will become both faster and cheaper, these test can be performed on patients and it will be possible to adapt to a treatment more likely to be effective for that specific patient.
What role does the environment play in addiction – is it nature or nurture?
The gene (Nature) versus environment (Nurture) debate is complicated since genetic and environmental factors interact in complex ways. They are said to be linked when the effect of exposure to an environmental factor is modified by a genotype. For example, stress occurring early in life is known to be a risk factor for developing addictions, as well as conditions such as antisocial personality disorder (ASPD), borderline, personality disorder, and anxiety disorders. Nevertheless, not all people exposed to such early traumas develop addiction.
There are several studies that have shown that addiction is due 50% to genetics and 50% to environmental reasons. These studies compare identical twin pairs to non-identical twin pairs, and shows that for identical twins the second twin has an increased probability to become addicted, if the first twin is already addicted, which is not true for non-identical twins. Based on a study of 861 identical twin pairs, and 653 non-identical twin pairs, it was concluded that 50-60% of addiction is due to genetic factors (4). These results have been further confirmed in other studies (5). By comparing one group diagnosed with drug or alcohol addiction to another group without any addiction, analyzing first-degree relatives (parents, siblings or children), it was further shown that children of addicts have eight times higher risk of developing an addiction (6). Although one may argue, that children growing up with addicted parents also live in an environment that favors this behavior.
In another study of twins it was shown that the influence of genetics and environment respectively, change during life span. It was, for example, shown that the genetic effect on addiction was low in early adolescence but that the importance gradually grew in adulthood. In contrast, the effect of family environment declined from childhood to adulthood. A possible explanation is that, as they mature, people have increasing freedom to shape their own choices and social environments, therefore the relative importance of genotype increases. Another explanation could be that some genetic factors are important only after repetitive exposure to the addictive agent, or that some genes are only active in adults (7).
To conclude, the old saying “nature or nurture?” might be better phrased “nature and nurture,” because research shows that individual health is the result of dynamic interactions between genes and environmental conditions. For example, susceptibility to high blood pressure is influenced by both genetics and lifestyle, including diet, stress, and exercise. Environmental influences, such as exposure to drugs or stress, can alter both gene expression and gene function. In some cases, these effects may persist throughout a person’s life. Research suggests that genes can also influence how a person responds to his or her environment, placing some individuals at higher risk than others.
What is important to remember is that the genetic makeup will never doom anyone to inevitably become an addict – your genes are not your destiny! The 50% of addiction that is caused by environment is where you can make a difference. Lots of people have come from addicted families but managed to overcome their family history and live happy lives.
(1) Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K, Madden PA, Breslau N, Johnson EO, Hatsukami D, Pomerleau O, Swan GE, Goate AM, Rutter J, Bertelsen S, Fox L, Fugman D, Martin NG, Montgomery GW, Wang JC, Ballinger DG, Rice JP, Bierut LJ. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs.Hum Mol Genet. 2007 Jan 1;16(1):36-49.
(2) Francesca Ducci and David Goldman,The Genetic Basis of Addictive DisordersPsychiatr Clin North Am. 2012 June ; 35(2): 495–519.
(3) Clarke TK, Weiss AR, Ferarro TN, Kampman KM, Dackis CA, Pettinati HM, O’brien CP, Oslin DW, Lohoff FW, Berrettini WH. The dopamine receptor D2 (DRD2) SNP rs1076560 is associated with opioid addiction. Ann Hum Genet. 2014 Jan;78(1):33-9.
(4) Prescott CA, Kendler KS. Genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. American Journal Psychiatry. 1999 Jan;156(1):34-40.
(5) Enoch MA, Goldman D. The genetics of alcoholism and alcohol abuse. Current Psychiatry Reports. 2001 Apr;3(2):144-51.
(6) Merikangas KR, Stolar M, Stevens DE, Goulet J, Preisig MA, Fenton B, Zhang H, O’Malley SS, Rounsaville BJ. Familial transmission of substance use disorders. Archives General Psychiatry. 1998 Nov;55(11):973-9
(7) Kendler KS, Schmitt E, Aggen SH, et al. Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood. Arch Gen Psychiatry. 2008; 65(6):674–82.
My interests are wide-ranging, and include computer games, online culture and addictions. Most of all, I’m interested in exploring why people act in a certain way; what makes them tick. I publish articles on several sites, and if you’d like to get to know me better, feel free to visit my Google+ profile below.
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