Genetic signature might be shared across multiple substance use disorders, new study reveals

By Sarah MooreMar 22 2023Reviewed by Emily Henderson, B.Sc.

A new study has revealed a common genetic signature that seems to underlie multiple substance use disorders. The study, conducted by researchers at Washington University School of Medicine, St Louis, might lead to the development of novel treatments for substance use disorders, particularly those where a person is addicted to more than one substance.

Potential new treatments could be revolutionary for people living with substance use disorders, which claim the lives of millions every year globally and for which relapse rates after entering recovery are still high.

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Prevalence and impact of substance use disorders. Current therapies and relapses

According to recent National Survey on Drug Use and Health statistics, over 46 million people worldwide have a substance use disorder, translating to 16.5% of the population. The prevalence of substance use disorders has unfortunately increased in recent years, and it is vital that we expand our understanding of them so that we can develop effective treatments.

Currently, relapse rates for those with substance use disorders are high. Recent studies show that as many as 40-60% of individuals who enter recovery from drug or alcohol use relapse within 30 days of completing treatment. During the first year after inpatient treatment, around 85% of people will relapse. Around the globe, drug and alcohol use claims the lives of millions each year.

Gaining a deeper understanding of the role of dopamine in addiction

The research, led by Alexander Hatoum, PhD, at Washington University School of Medicine, was published on March 22 in the journal Nature Mental Health. The study drew together 150 researchers from institutions across the globe to access a wide data pool. Its findings are the result of an analysis of this huge pool of genomic data collected from over 1 million people with European ancestry and a smaller population of people of African descent (over 92,000).

A genetic signature emerged in the data analysis that seems to underpin substance use disorders of numerous kinds. The signature encompasses variations in numerous genes that play a role in dopamine signaling regulation. Dopamine has long been understood to play a fundamental role in the brain’s reward system. Specifically, dopamine is known as the “feel-good” hormone, and it is responsible for the sense of pleasure we feel when participating in an activity. As part of the brain’s reward system, it motivates us to act. Studies have shown that when repeatedly exposed to addictive substances, the brain’s reward system is rewired, resulting in desensitization to the substance - where more of it is required to achieve the same amount of reward previously experienced.

While dopamine’s role in addiction has previously been studied, this research focuses on an area often neglected by looking at addiction to more than one substance. The findings of this research give us a more in-depth look into the mechanisms of action that underly addiction.

"We can implicate more specific mechanisms by which the brain regulates response to dopamine across different substances, and ultimately find processes that could reverse maladaptive regulation that leads to addiction.” 

Hatoum

Repurposing pharmaceutical drugs to treat substance use disorders

Armed with this new information on the genetic underpinnings of substance use disorders, the researchers developed a list of currently approved pharmaceutical drugs that can potentially target the effects of the genetic signature. The resultant list includes more than 100 drugs that can be researched in future clinical trials to investigate their efficacy in treating substance use disorders, which could potentially lead to much-needed novel therapies in this disease area. “There is a tremendous need for treatments that target addiction generally, given patterns of the use of multiple substances, lifetime substance use, and severity seen in clinic”, Hatoum states.

The future

Co-senior author Arpana Agrawal believes the study “represents a major advance in understanding how genetic factors predispose people to substance use disorders.” Overall, 19 single-letter differences in the DNA code were found that were associated with general risk, and a further 47 were found to be linked to specific substance use disorders. This information will likely be key to developing novel treatments and potential preventative strategies.

Sources:

• [Multiple substance use disorders may share inherited genetic signature] - please add once published
• Lee, Y.K., Gold, M.S. and Fuehrlein, B.S. (2022) “Looking beyond the opioid receptor: A desperate need for new treatments for opioid use disorder,” Journal of the Neurological Sciences, 432, p. 120094. Available at: https://doi.org/10.1016/j.jns.2021.120094.
• SAMHSA Announces National Survey on Drug Use and Health (NSDUH) Results Detailing Mental Illness and Substance Use Levels in 2021 [online]. US Department of Health and Human Services. Available at: https://www.hhs.gov/about/news/2023/01/04/samhsa-announces-national-survey-drug-use-health-results-detailing-mental-illness-substance-use-levels-2021.html (Accessed March 2023)
• Volkow, N.D. et al. (2007) “Dopamine in drug abuse and addiction,” Archives of Neurology, 64(11), p. 1575. Available at: https://doi.org/10.1001/archneur.64.11.1575.
• Witkiewitz, K., Litten, R.Z. and Leggio, L. (2019) “Advances in the science and treatment of alcohol use disorder,” Science Advances, 5(9). Available at: https://doi.org/10.1126/sciadv.aax4043.