Alcoholics are missing an important enzyme

Researchers have identified an enzyme whose production is turned off in nerve cells of the frontal lobe when alcohol dependence develops, leading to continued use of alcohol despite adverse consequences. Their study, which has been published in the Molecular Psychiatry, could mean new possibilities for treating alcoholism.

It has long been suspected that people with alcohol dependence have impaired function in the frontal lobes of the brain — the area responsible for impulse control — but the underlying biological mechanisms have not yet been known. Now, researchers from Linköping University in Sweden and Miami University in the US have discovered that the enzyme PRDM2 plays a central role in this molecular mechanism.

“We’ve worked hard for this,” said Professor Markus Heilig, head of the Center for Social and Affective Neuroscience (CSAN) at Linköping University, whose research group is linking research into alcoholism and other addictive illnesses with advanced brain research. “The enzyme, PRDM2, has previously been studied in cancer research, but we didn’t know that it has a function in the brain.”

The team’s work showed that alcohol dependence in rats leads to a downregulation of PRDM2 production, which in turn leads to disruption of impulse control. This is why the laboratory animals continued to consume alcohol, even when it was unpleasant. If they were subjected to stress, they also quickly relapsed into drinking alcohol.

“PRDM2 controls the expression of several genes that are necessary for effective signalling between nerve cells,” Professor Heilig said. “When too little enzyme is produced, no effective signals are sent from the cells that are supposed to stop the impulse.”

The researchers then went one step further, knocking out the production of PRDM2 in the frontal lobes of rats that were not dependent. They went on to observe the same behaviour in these rats — impulse control was disrupted.

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

“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.”