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Addiction


People with harmful drinking habits will likely experience withdrawal symptoms once they remove alcohol from their diets. Some individuals face much more intense — and sometimes dangerous — withdrawal symptoms than others, but why? A recent Yale-led investigation may have found the answer.
person with alcohol use disorder
A new study identifies the genetic predictors of severe alcohol withdrawal symptoms.

Alcohol use disorder affects an estimated 16 million people in the United States alone, both adults and adolescents, and it has a strong negative impact on a person’s overall state of health and quality of life.

Existing research has linked alcohol use disorder with inherited genetic traits, saying that genetic makeup is “responsible for about half of the risk” of developing alcohol use disorder.

But do genes also influence how a former heavy alcohol user will react to the detox process once they stop drinking for good?

Alcohol withdrawal syndrome is characterized by symptoms such as nausea, headaches, agitation, tremors, hypertension, and — in some particularly severe cases — even seizures.

Some people experience much more severe alcohol withdrawal symptoms than others, and researchers have suggested that genetic makeup may have a role to play in this outcome.

A team of specialists — from the Yale School of Medicine at Yale University in New Haven, CT, alongside colleagues from Aarhus University in Denmark, and from other international institutions — has taken this idea further.

In a new study, the researchers have found a set of gene variants that may explain why some individuals experience intense alcohol withdrawal symptoms.

The study paper — published in Alcoholism: Clinical and Experimental Research — also outlines which populations are most at risk of carrying these gene variants and which groups are not.

The gene variants that impact outcomes

“Alcohol takes more lives in the [U.S.] every year than opioids, but there are few effective treatments to help people who have an alcohol use disorder,” notes the study’s lead author, Andrew H. Smith.

“For people who experience intense withdrawal symptoms, that’s one more barrier they have to face while trying to reduce unhealthy alcohol use,” he adds.

So, Smith and colleagues decided to try and identify any genetic variants that might predispose people to severe alcohol withdrawal symptoms. Having a better understanding of potential genetic risk factors may help specialists devise better strategies for treating alcohol use disorder further down the line.

The current study was a genome-wide association study, a type of research that analyzes complete DNA sets across various populations in order to determine which specific gene variants correspond to the risk of particular diseases or health outcomes.

Through their investigation, the researchers revealed that certain variants in the SORCS2 gene are good predictors of how severe withdrawal symptoms will be for a person.

SORCS2 variants, Smith and colleagues explain in the study paper, may ultimately disrupt stress-regulatory mechanisms in the hippocampus, a brain region involved in the reward system, which also mediates addiction.

The activity of these gene variants may, more specifically, hinder the central nervous system’s ability to adapt to the sudden cessation of alcohol intake.

However, not all populations seem to be exposed to the risks determined by the SORCS2 variants. People of European descent are affected, the researchers say, as approximately 1 in 10 of them carry these variants.

Those of African-American heritage, however, do not appear to carry these genetic predictors of severe alcohol withdrawal symptoms.

The study’s senior author, Prof. Joel Gelernter, notes that the current findings may eventually lead to the development of more effective, safer therapies for alcohol use disorder.

Better understanding of the many genes likely to be involved in withdrawal symptoms could ultimately lead to new medications that moderate these symptoms, which could help with the discontinuation of habitual alcohol use.”

Senior author, Prof. Joel Gelernter

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