Substance Abuse Disorders May Share a Common Genetic Signature

Substance use disorders (SUDs), including alcohol, tobacco, cannabis, or opioids, appear to share a common genetic signature, suggest new findings that researchers say could eventually lead to universal therapies to treat multiple and comorbid addictions.

“Genetics play a key role in determining health throughout our lives, but they are not destiny. Our hope with genomic studies is to further illuminate factors that may protect or predispose a person to substance use disorders — knowledge that can be used to expand preventative services and empower individuals to make informed decisions about drug use,” Nora Volkow, MD, director of the National Institute on Drug Abuse (NIDA), said in news release.

“A better understanding of genetics also brings us one step closer to developing personalized interventions that are tailored to an individual’s unique biology, environment, and lived experience in order to provide the most benefits,” Volkow added.

The research was published online March 22 in Nature Mental Health.

Global Research

Led by a team at the University of Washington School of Medicine in St. Louis, the study included more than 150 collaborating investigators from around the world.

The risk of developing SUDs is influenced by a complex interplay between genetics and environmental factors. In a genome-wide association study (GWAS), the investigators looked for variations in the genome that were closely associated with SUDs in more than 1 million people of European ancestry and 92,630 people of African ancestry.

Among the European ancestry sample, they discovered 19 single nucleotide polymorphisms (SNPs) that were significantly associated with general addiction risk and 47 genetic variants linked to specific SUDs — nine for alcohol, 32 for tobacco, five for cannabis, and one for opioids.

The strongest gene signals consistent across the various SUDs mapped to areas in the genome involved in dopamine signaling regulation, which reinforces the role of the dopamine system in addiction.

The genomic pattern also predicted higher risk of mental and physical illness, including psychiatric disorders, suicidal behavior, respiratory disease, heart disease, and chronic pain conditions. In children aged 9 or 10 years, presumably without any SUD, these genes correlated with parental substance use and externalizing behavior.

“Substance use disorders and mental disorders often co-occur, and we know that the most effective treatments help people address both issues at the same time. The shared genetic mechanisms between substance use and mental disorders revealed in this study underscore the importance of thinking about these disorders in tandem,” Joshua A. Gordon, MD, PhD, director of the National Institute of Mental Health (NIMH), said in a news release.

Repurpose Existing Drugs for SUDs?

Separately, the genomic analysis of individuals of African ancestry showed only one genetic variation associated with general addiction risk and one substance-specific variation for risk of alcohol use disorder. The smaller sample size may be one reason for the more limited findings in this population.

“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 the clinic,” lead researcher Alexander Hatoum, PhD, at Washington University, St. Louis, said in a news release.

“Our study opens the door to identifying medications that may be leveraged to treat addiction broadly, which may be especially useful for treating more severe forms, including addiction to multiple substances,” Hatoum added.

As part of the study, the researchers compiled a list of approved and investigational pharmaceutical drugs that could potentially be repurposed to treat SUDs.

The list includes more than 100 drugs to investigate in future clinical trials, including those that can influence regulation of dopamine signaling.

This research was supported by the National Institute on Drug Abuse (NIDA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Mental Health (NIMH), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute on Aging (NIA). A complete list of author disclosures is available with the original article.

Nat Mental Health. Published online March 22, 2023. Full text.

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