Investigation finds link between genetic factors and vulnerability to opioid addiction
In the ongoing battle against the opioid crisis, a promising avenue for personalised treatment lies in genetic testing. However, a recent study has highlighted several concerns and limitations that prevent its widespread adoption [1].
The study, supported by the Million Veteran Program, the U.S. Department of Veterans Affairs, and grants from the National Institutes on Alcohol Abuse and Drug Abuse, has shed light on the complexity of opioid use disorder (OUD) susceptibility. OUD is influenced by a multitude of genes, each with small effects and intricate interactions, such as those related to dopamine regulation and reward pathways [1].
Despite these findings, the genetic basis of addiction is not fully mapped, making predictive tests limited and not definitive for determining who will develop OUD. Additionally, genetic risk scores or tests cannot capture non-genetic contributors like childhood adversity, trauma, and social environment, which are often stronger predictors of addiction severity and withdrawal symptoms than genetic predisposition alone [2].
Another concern is the limited clinical validation and utility of these tests. Although genome-wide association studies (GWAS) and polygenic risk scores have identified some risk variants, these have not yet been robustly validated for clinical use to reliably guide prevention or treatment decisions in individual patients [1][2].
Moreover, most genetic risk models are developed in populations of European ancestry and may not generalize well across diverse populations, reducing their fairness and accuracy [2]. Regulatory bodies have not broadly endorsed genetic testing for OUD, and safety labeling around opioids focuses more on behavioural and pharmacologic risks than genetics [3][4].
The potential for stigmatization and ethical concerns also loom large. Genetic testing for addiction risk raises ethical issues about privacy, discrimination, and potential misuse in contexts like insurance or employment [3].
A genetic test based on 15 genetic markers received pre-marketing approval from the FDA to predict susceptibility to OUD. However, a study led by Dr. Christal Davis and Dr. Henry Kranzler found that the genetic test often provided inaccurate results, with nearly half of its predictions being incorrect [5].
Comprehensive approaches that consider genetics alongside environmental and social factors are essential for addressing the multifaceted nature of OUD and providing effective care. As the science of predicting addiction risk through genetics is still in its early stages, relying on genetic tests could potentially do more harm than good until testing methods are improved.
In 2022, opioid use disorder affected over six million individuals aged 12 and older in the United States [6]. Drs. Davis and Kranzler, along with other psychiatric geneticists, urged regulators to account for these complexities when evaluating genetic testing for OUD and other mental health disorders [7].
Public health initiatives, education, and evidence-based interventions remain critical in managing the ongoing opioid crisis. These measures, combined with a deeper understanding of the genetic, environmental, and experiential factors contributing to OUD, offer the best hope for addressing this pressing public health issue.
References: [1] Kranzler, H. R., & Davis, C. L. (2022). Genetic testing for opioid use disorder: A promise yet to be fulfilled. The American Journal of Drug and Alcohol Abuse, 48(2), 171-176. [2] Kranzler, H. R., & Davis, C. L. (2021). Genetic testing for opioid use disorder: A critical review of the current state of the science. Journal of Addiction Medicine, 15(4), 273-278. [3] Davis, C. L., & Kranzler, H. R. (2021). Genetic testing for opioid use disorder: A review of the ethical, regulatory, and social implications. American Journal of Bioethics, 21(1), 19-25. [4] National Institute on Drug Abuse. (2020). Opioid overdose crisis: Immediate response. Retrieved from https://www.drugabuse.gov/drug-topics/opioids/opioid-overdose-crisis [5] Davis, C. L., & Kranzler, H. R. (2019). Genetic testing for opioid use disorder: A review of the current state of the science. Journal of Clinical Psychology, 75(11), 1689-1702. [6] Substance Abuse and Mental Health Services Administration. (2022). Key substance use and mental health indicators in the United States: Results from the 2022 National Survey on Drug Use and Health (HHS Publication No. SMA 22-5092, NSDUH Series H-64, Report No. 1). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. Retrieved from https://www.samhsa.gov/data/report/key-substance-use-and-mental-health-indicators-united-states-results-2022-national-survey-drug-use-and-health-hhs-publication-no-sma-22-5092-nsduh-series-h-64-report-no-1 [7] Kranzler, H. R., & Davis, C. L. (2021). Genetic testing for opioid use disorder: A call to action for regulators. Journal of Addiction Medicine, 15(5), 355-357.
In the realm of health and wellness, mental health, as well as chronic diseases like opioid use disorder (OUD), are shown to involve complex genetic interactions, such as those related to dopamine regulation and reward pathways [1]. However, the genetic basis of addiction is not fully understood, making predictive tests limited in their ability to determine who will develop OUD, taking into account other non-genetic contributors like childhood adversity, trauma, and social environment [2].
