An Examination of The Genetic Risk Factors in Drug Addiction

Drug addiction is a widely misunderstood condition. The timeless nature versus nurture debate is often brought up when discussing drug dependence. Is addiction a mental illness or a consequence of poor lifestyle choices? Are some people more susceptible to becoming addicts than others? The answers to these questions boils down to the analysis of genes and whether their roles influence drug addiction. Research from the National Institute on Drug Abuse in 2013 shows that most drug addictions begin under eighteen years of age, and drug use is highest among those in their late teens or early twenties. As a young adult, these statistics are frightening. Understanding more about the science behind addiction can help researchers and healthcare providers develop the tools they need to prevent drug addiction and rehabilitate those who are suffering everyday. A 2017 study published in Scientific Reports titled, “Association of the PLCB1 Gene with Drug Dependence” explores the genetic risk factors behind addiction.

The article begins by introducing the idea that the scientific community understands that addiction has some level of heritability, but the specific genetic risk factors involved remain unknown. They also mention the findings of other relevant studies, including the importance of microRNAs (miRNAs) in psychological disorders like drug dependence. MiRNAs, as described in the article, are noncoding RNA molecules in the central nervous system that modify gene expression by binding to mRNAs and causing mRNA degradation. The studies mentioned essentially show that individuals with some level of drug dependence either have up-regulated or altered miRNAs in the frontal lobe, the part of the brain responsible for cognitive processes and decision-making. Other studies mentioned discuss single nucleotide polymorphisms (SNPs) and their role in altering the binding process between miRNA and mRNA. Based on this prior research, the scientists began their examination of the role of miRNA and SNPs in drug addiction. Their main hypothesis was that certain SNPs alter the gene expression produced by miRNA and mRNA binding, and influences an individual’s susceptibility to drug addiction.

The subjects for the experiment were patients from a psychiatric hospital in Barcelona who have been diagnosed with substance dependence, 73.5% of which were addicted to cocaine. Controls were recruited as well, giving them a total of 735 patients and 739 controls to work with. They started by isolating DNA samples from all subjects. Then, they located SNPs in target genes that they predicted would alter miRNA and mRNA binding, using Kompetitive Allele Specific PCR (KASP) technology. Additionally, they decided to test the effect of cocaine usage on the expression of the PLCB1 gene by examining gene expression of cocaine users with quantitative PCR.

They ended up finding significant associations in gene frequencies of seven different genes associated with these SNPs. They ran the same test again with another sample of individuals, and found that two of the seven genes once again had SNPs that were significantly associated. However, upon analyzing both the patient samples and control samples, only one SNP on the PLCB1 gene was found to be significantly associated with drug dependence. Any associations they found were tested with statistical analysis, including nonparametric tests and comparison to Hardy-Weinberg Equilibrium, to ensure statistically significant p values of <0.05. Additionally, they discovered that the PLCB1 gene was up-regulated in cocaine users.The PLCB1 gene is expressed in the brain and influences cognition and emotion. Their research shows that a particular SNP on the PLCB1 gene is associated with drug dependence, and that this gene exhibits a higher level of expression when the individual is using cocaine, further proving that the gene is linked to addiction. However, they were unsuccessful in proving that this particular SNP played a part in miRNA and mRNA binding, which was their original prediction.

There is no reason to reject these findings since all data is credible and ethically obtained. The researchers explicitly state their methods of data collection and provide statistical analysis for every claim made. Any background information or data used from other studies is accurately cited and an ethics statement is provided.

As mentioned in the discussion section of the study, this is the first time the role of SNPs in miRNA and mRNA binding and its association with drug dependence was ever experimentally tested. Although they couldn’t prove this association, they did confirm that the PLCB1 gene plays a significant role in drug addiction. Studies like these are incredibly important in understanding the mechanisms behind addiction. Although they couldn’t prove the original hypothesis, their research provides evidence against a possible genetic cause of drug dependence. They also succeeded in narrowing down a single gene variation present in individuals diagnosed with drug dependence, confirming previous studies. The knowledge in regards to genetics and drug dependence is constantly changing, and any information is beneficial in compiling a bigger picture of addiction. If a comprehensive record of genes and gene variants associated with addiction is collected, treatments can be created to potentially modify the activity of these genes.

This information not only impacts the scientific community, but contributes to the societal effort to understand and treat addiction. Addiction is complex with a large variety of causes. Because of this, scientists will never be able to find a single “addiction gene”. An individual may have multiple genes that are associated with addiction, but never become an addict. On top of genetic influence, it is well-known that drug use and addiction is strongly regulated by environmental factors. The complicated nature of this condition is what makes it so difficult to pinpoint any single cause or combination of factors that could lead a person to being dependent on drugs. However, when scientific research like this study is published, the public has access to getting a more complete picture of addiction. This allows people to make informed claims and could potentially de-stigmatize addiction. If society can clearly comprehend the multi-faceted nature of addiction, efforts to prevent and treat it may be more successful. Studies like this provide more insight to the genetic components of drug dependence so that personalized preventative medicine and/or treatments can be developed.