Addictive behavior is a major global health concern. Addiction is commonly defined as the repetitive use of substances or a repetitive pattern of behaviors that are harmful. It is believed that addiction is a brain disorder, meaning that it is caused by the impact of drugs or other addictive substances/influences on the brain and it can be modified by different environmental factors.

The presence of specific variants of some genes may promote or decrease the chances of developing an addiction. According to scientists, genetic factors may play an important role in determining both the vulnerability to addiction and the response to treatments aimed to cure addiction.

The Brain and Genetics in Addictive Behavior

One group of researchers demonstrated that polymorphisms in the genes encoding for opioid receptors and opioid ligands, and more specifically the MOPR gene (OPRM1), is associated with drug addiction. It has been found that one variant of this gene contributes to alcoholism and heroin addiction.

Another study has found that carriers of the same gene variant experience a more pronounced sensitivity to pain and decreased analgesic response to opioids, which means that they require higher doses of morphine in the management of pain, such as pain associated with cancer.

Heroin and Opioids

Some authors underlined that addiction to MOPR agonists, including heroin, has become epidemic in the 21^st century. According to the same authors, the endogenous opioid system interacts with other neurotransmitter systems in the brain. More precisely, opioid receptors regulate the release of dopamine and serotonin, neurotransmitters with important roles in mood.

Additionally, the opioid system seems to interact with noradrenergic, GABAergic, and glutamatergic pathways, as well as with neural growth factors. Furthermore, these studies indicate that chronic exposure to opiates alters gene expression in the brain, and this causes long-term changes in neuronal networks.

Activation of opioid receptors leads to changes in the expression of genes in the above-mentioned neurotransmitter pathways. Variations in the genes of those pathways may determine whether someone is more prone to the development of opiate addiction.

Cocaine

One very recent study published this year revealed that the use of cocaine and cocaine addiction are associated with certain variants of the glucocorticoid receptor gene, along with lower expression of this gene.

More specifically, the authors of the study compared the expression level of this gene in chronic cocaine users and healthy controls. Apart from significantly lower gene expression in the cocaine users, the carriers of some gene variants were at increased risk of cocaine addiction. In addition, they scored higher on depression scales.

Dopamine

It seems that the major challenge in understanding and treating addictive disorders is understanding why some individuals develop addiction while others do not. According to research findings, whether or not a person will become addicted depends largely on genetic factors, which contribute ~50% of the risk for addiction.

The processes in our brain are also important. It is well established that the rewarding effects of drugs and addictive substances, in general, are based on their ability to increase the level of dopamine in the brain. Accordingly, imaging studies have shown that individual variations in brain circuits modulated by dopamine, including circuits involved in the mechanisms of reward, contribute to the inter-individual variability in the vulnerability to addiction. Thus, it seems that the roles of genetic factors and brain pathways in the addiction may be intertwined via dopamine.

Alcohol and tobacco

Apart from drug addiction, addiction to alcohol seems to depend on genetics and is influenced by heritage. A recent study has investigated the effects of parental drinking on the use of alcohol in young adults. More than 3500 adolescents and their parents have been included in this prospective research. As results have indicated, young adults whose parents are moderate or high alcohol consumers are more prone to alcohol consumption than those young adults whose parents don’t consume alcohol or consume it in low quantities.

Alcohol and tobacco use represent leading global health risks, which are responsible for 3.3 and 6 million premature deaths per year respectively, according to the World Health Organization. Genetic factors were estimated to contribute 40-60% and 40-85% to the development of alcohol and tobacco addictions respectively.

Finding out which genetic variants are associated with alcohol and tobacco addictions would be an important step in understanding their underlying mechanisms and developing the effective therapies. Over the last years, Genome-Wide Association Studies (GWAS) have been performed in order to elucidate the role of certain genes and their variants in alcohol and tobacco use. These studies have recognized that single nucleotide polymorphisms (SNP, i.e., gene variants with a difference in a single nucleotide) are important for developing these addictions.

For alcohol addiction, SNPs include polymorphisms in the KLB gene, as well as in the alcohol dehydrogenase gene cluster. In the latter, different variations of genes differently influence the metabolism of alcohol. In the case of tobacco use, the most evident variations have been detected in the nicotinic acetylcholine receptor subunit genes cluster.

However, only a small number of common genetic variants have been studied, and they account for a modest proportion of alcohol and nicotine addiction heritability. Thus, further investigation into the role of low frequency and rare genetic variants is required in order to fully understand the heritability of both alcohol and tobacco use.

In Sum

Considering all of these facts together, it seems that genetics does indeed play an important role in the development of addiction to substances such as opioids, alcohol, and tobacco. Some of these factors include differences in gene expression and gene variants in brain neurotransmitter pathways. Further research is needed in order to develop working strategies for treating heritable addictions.

References

Kreek, M.J., Levran, O., Reed, B., Schlussman, S.D., Zhou, Y., Butelman, E.R. (2012). Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics. Journal of Clinical Investigation. 122(10): 3387-3393. DOI: 10.1172/JCI60390

Shi, Q., Cleeland, C.S., Klepstad, P., Miaskowski, C., Pedersen, N.L. (2010). Biological pathways and genetic variables involved in pain. Quality of Life Research. 19(10): 1407–1417. doi: 10.1007/s11136-010-9738-x

Reed, B., Butelman, E.R., Yuferov, V., Randesi, M., Kreek, M.J. (2014). Genetics of opiate addiction. Current Psychiatry Reports. 16(11): 504. doi: 10.1007/s11920-014-0504-6

Schote, A.B., Jäger, K., Kroll, S.L., et al. (2018). Glucocorticoid receptor gene variants and lower expression of NR3C1 are associated with cocaine use. Addiction Biology. doi: 10.1111/adb.12632

Volkow, N.D., Wang, G.J., Fowler, J.S., Tomasi. D. (2012). Addiction circuitry in the human brain. Annual Review of Pharmacology and Toxicology. 52: 321-336. DOI: 10.1146/annurev-pharmtox-010611-134625

Mahedy, L., MacArthur, G.J., Hammerton, G., et al. (2018). The effect of parental drinking on alcohol use in young adults: the mediating role of parental monitoring and peer deviance. Addiction. doi: 10.1111/add.14280

Marees, A.T., Hammerschlag, A.R., Bastarache, L., et al. (2018). Exploring the role of low-frequency and rare exonic variants in alcohol and tobacco use. Drug and Alcohol Dependence. 188: 94-101. doi: 10.1016/j.drugalcdep.2018.03.026

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