Lack of key enzyme may cause alcohol dependence: study

Scientists have found that the deficiency of a key enzyme may lead to alcohol dependence, a breakthrough that could lead to new treatments for alcoholism.
Researchers identified the enzyme PRDM2 whose production is turned off in nerve cells of the frontal lobe when alcohol dependence develops.
The deficiency in this enzyme leads to continued use of alcohol despite adverse consequences, researchers said.
"We have worked hard for this. The enzyme, PRDM2, has previously been studied in cancer research, but we did not know that it has a function in the brain," said Markus Heilig, professor of psychiatry at Linkoping University in Sweden.

It has long been suspected that people with alcohol dependence have impaired function in the frontal lobes of the brain, but the underlying biological mechanisms have not been known.
The team, which includes researchers from Linkoping and University of Miami in the US, is the first to identify this molecular mechanism.

If frontal function is impaired, it is difficult for us to control our impulses, researchers said.
"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," Heilig said.

The research has shown that alcohol dependence in rats leads to a down-regulation of PRDM2 production, which in turn leads to disruption of impulse control.
This is why the laboratory animals continue to consume alcohol, even when it is unpleasant. If they are subjected to stress, they also quickly relapse into drinking alcohol.
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 see how a single molecular manipulation gives rise to important characteristics of an addictive illness. Now that we are beginning to understand what is happening, we hope we will also be able to intervene," 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," he said.
The research was published in the journal Molecular Psychiatry.