Alcoholics Lack Key Enzyme That Helps Control Impulses, Study Finds

Scientists hope the discovery could pave the way for new treatment.

People who struggle with alcohol addiction lack an important enzyme which makes it harder for them to control impulses, new research suggests. 

Researchers from Linköping University and Miami University found the production of enzyme PRDM2 is turned off in nerve cells in the frontal lobe of the brain when alcohol dependence develops.

The found that deficiency of this enzyme leads to continued use of alcohol despite adverse consequences. 

The researchers said they are hopeful their discovery may help end stigma around alcohol addiction and pave the way for new treatments.

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Andrei Spirache via Getty Images

It has long been suspected that people with alcohol dependence have impaired function in the frontal lobes of the brain - making it harder to control impulses - but the underlying biological mechanisms have not been known.

The researchers conducted experiments involving rats over several years before identifying the changing nature of the enzyme.

They found that when rats were made alcohol dependent, they experienced a reduced production of PRDM2, which in turn caused disruption of impulse control.

They noted that the laboratory animals continued to consume alcohol, even when it was unpleasant. If they were subjected to stress, the rats also quickly relapsed into drinking alcohol.

In the next step, the researchers knocked out the production of PRDM2 in the frontal lobes of rats that were not dependent, and they observed the same behaviour - impulse control was disrupted.

“We’ve worked hard for this. The enzyme, PRDM2, has previously been studied in cancer research, but we didn’t know that it has a function in the brain,” lead author Professor Markus Heilig said. 

The researchers explained that a person with intact impulse control can walk past a bar on a warm day and think “a beer would be nice, but I can’t have one now because I have to get back to work”.

An alcoholic, on the other hand, does not have sufficient impulse control to refrain, thinking: “It’s hot and I’m thirsty.”

Professor Heilig added: “PRDM2 controls the expression of several genes that are necessary for effective signalling between nerve cells.

“When too little enzyme is produced, no effective signals are sent from the cells that are supposed to stop the impulse.”

Professor Heilig and his team noted that more research is needed, but said they are hopeful their findings will pave the way for new treatment and understanding around alcohol dependency.  

“We see how a single molecular manipulation gives rise to important characteristics of an addictive illness. Now that we’re beginning to understand what’s happening, we hope we’ll also be able to intervene,” Professor Heilig said.

“Over the long term, we want to contribute to developing effective medicines, but over the short term the important thing, perhaps, is to do away with the stigmatisation of alcoholism.”

The research is published in the journal Molecular Psychiatry from the Nature Publishing Group.

Signs Of Alcoholism
Abuse: Not Meeting Responsibilities(01 of20)
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Abuse, the regular use of a substance that leads to serious psychological and/or physical disability, is shown by one or more of these symptoms during the same year:Repeated substance use to the point of not being able to meet responsibilities -- not performing well at work, being suspended from school, being repeatedly late or absent from required duties, or neglecting household tasks. (credit:Shutterstock)
Abuse: Involving Risk(02 of20)
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Abuse, the regular use of a substance that leads to serious psychological and/or physical disability, is shown by one or more of these symptoms during the same year:Repeated substance use when there is risk involved, like operating equipment or driving a car while under the influence. (credit:Shutterstock)
Abuse: Difficulties With The Law(03 of20)
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Abuse, the regular use of a substance that leads to serious psychological and/or physical disability, is shown by one or more of these symptoms during the same year:Repeated difficulties with the law related to substance use -- being arrested for physical aggression or drunk driving, for instance. (credit:Shutterstock)
Abuse: Personal Or Social Difficulties(04 of20)
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Abuse, the regular use of a substance that leads to serious psychological and/or physical disability, is shown by one or more of these symptoms during the same year:Insisting on using the substance regardless of continued or repeated personal or social difficulties because of it, verbal or physical aggression with a loved one, or frequent arguments about the substance use. (credit:Shutterstock)
Dependence: Needing Great Amounts(05 of20)
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Symptoms of alcohol dependence, a physical need to drink, are identified as three or more of the following within the same year:Needing greater amounts of alcohol to satisfy cravings. (credit:Shutterstock)
Dependence: An Inability To Reduce Use(06 of20)
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Symptoms of alcohol dependence, a physical need to drink, are identified as three or more of the following within the same year:Using the substance longer than planned or more frequently and in greater amounts.An inability to reduce use, despite a sincere wish to do so. (credit:Shutterstock)
Dependence: Going Through Withdrawal(07 of20)
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Symptoms of alcohol dependence, a physical need to drink, are identified as three or more of the following within the same year:Going through withdrawal when not using alcohol, with symptoms such as tremors, restlessness, and agitation. (credit:Shutterstock)
Dependence: Avoiding Withdrawal(08 of20)
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Symptoms of alcohol dependence, a physical need to drink, are identified as three or more of the following within the same year:Taking a substance or a similar one to avoid the effects of withdrawal. (credit:Shutterstock)
Dependence: Spending Time On Alcohol(09 of20)
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Symptoms of alcohol dependence, a physical need to drink, are identified as three or more of the following within the same year:Spending a significant amount of time trying to acquire the substance.Spending less time at work or on other activities because of substance use; a person may completely abandon previously enjoyable activities. (credit:Shutterstock)
Dependence: Drinking In The Face Of Difficulty(10 of20)
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Symptoms of alcohol dependence, a physical need to drink, are identified as three or more of the following within the same year:Continuing to drink despite being aware that alcohol is causing psychological or physical difficulties. (credit:Shutterstock)
Addiction: Saying Inappropriate Things(11 of20)
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Stephen Gilman, MD, an addiction specialist in New York City, helps determine the severity of alcohol addiction by asking the following questions:Does he/she frequently say inappropriate things? (credit:Shutterstock)
Addiction: Slurred Speech(12 of20)
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Stephen Gilman, MD, an addiction specialist in New York City, helps determine the severity of alcohol addiction by asking the following questions:Does his/her speech slurred? (credit:Shutterstock)
Addiction: Missing Work(13 of20)
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Stephen Gilman, MD, an addiction specialist in New York City, helps determine the severity of alcohol addiction by asking the following questions:Does he/she miss work? (credit:Shutterstock)
Addiction: Off Balance(14 of20)
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Stephen Gilman, MD, an addiction specialist in New York City, helps determine the severity of alcohol addiction by asking the following questions:Is his/her balance off when they walk? (credit:Shutterstock)
Addiction: Trouble With The Law(15 of20)
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Stephen Gilman, MD, an addiction specialist in New York City, helps determine the severity of alcohol addiction by asking the following questions:Has he/she gotten in trouble with the law, for example, with drinking and driving? (credit:Shutterstock)
Addiction: Health Problems(16 of20)
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Stephen Gilman, MD, an addiction specialist in New York City, helps determine the severity of alcohol addiction by asking the following questions:Is he having health issues related to alcohol addiction, such as heartburn, liver problems, high blood pressure, or insomnia? (credit:Shutterstock)
Question To Ask: Should I Cut Down?(17 of20)
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Take the CAGE questionnaire -- if the answer to two or more of the four CAGE questions is yes, it is likely you have a problem.C stands for cut-down: Do you ever feel that you should cut down on your drinking? (credit:Shutterstock)
Question To Ask: People Getting Annoyed?(18 of20)
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Take the CAGE questionnaire -- if the answer to two or more of the four CAGE questions is yes, it is likely you have a problem.A stands for annoyed: Have people annoyed you by criticizing your drinking? (credit:Shutterstock)
Question To Ask: Ever Felt Guilty?(19 of20)
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Take the CAGE questionnaire -- if the answer to two or more of the four CAGE questions is yes, it is likely you have a problem.G stands for guilty: Have you ever felt guilty about your drinking? (credit:Shutterstock)
Question To Ask: Drinking To 'Recover'?(20 of20)
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Take the CAGE questionnaire -- if the answer to two or more of the four CAGE questions is yes, it is likely you have a problem.E stands for eye-opener: Have you ever had to drink as soon as you wake up to steady your nerves or get over a hangover? (credit:Shutterstock)

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