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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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.

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