Kynurenic Acid may be Behind Problem-solving Deficits in Schizophrenia Patients

by Hannah Punitha on Nov 21 2008 6:49 PM

A research team in the United States says that the inability to solve problems among patients with schizophrenia may be due to elevated levels of a specific compound, called kynurenic acid, in their brains.

Professor John P. Bruno, who led the study at Ohio State University, says that drugs used to suppress this compound may be an important supplement to anti-psychotic medicines, as these adjuncts could be used to treat the disorder's most resistant symptoms - cognitive impairments.

Apart from hallucinations and delusions, schizophrenia patients also have problems with what is known as cognitive flexibility or executive decision-making.

While some of them set their goals and plan ways to achieve them, they cannot adjust their thinking if circumstances force them to consider alternative strategies.

"We've got this core cluster of symptoms that is the Achilles heel for these individuals, and we're not really doing a good job of treating them," said Bruno, who teaches Psychology, Psychiatry, and Neuroscience at the university.

Bruno said that kynurenic acid is present in all human brains and has some useful functions, but excessive amounts of this compound may interfere with other chemical processes that govern the ability to pay attention and think strategically under changing conditions.

"If we try to make predictions about how disabled patients with schizophrenia will be and how likely are they to be integrated into the social fabric, it's the severity of the cognitive deficits that are most predictive. Anti-psychotics are particularly good at what we call positive symptoms, but these same drugs are very poor at treating the cognitive deficits," he said.

"There are a lot of therapeutic strategies for dealing with schizophrenia, but one which has not been explored, and which we think has a great deal of promise, has to do with regulating production of kynurenic acid," he added.

While making a presentation at the Society for Neuroscience meeting in Washington, D.C., on Tuesday, Bruno said that he and his colleagues tested kynurenic acid's effects on cognitive abilities in rats.

The researcher revealed that seven rats were given a compound that stimulated excess production of the molecule in their brains, while a control group of rats received no such stimulation.

All of the rats were tested to gauge their ability to change response strategies based on changing contingencies-in a quest to find food in the present case.

The researchers observed that only 28 percent of the rats with elevated kynurenic acid were able to solve problems to receive a food reward, compared to 100 percent of the control animals. Before the intervention, all of the animals were equally able to find the food under changing circumstances.

The team highlighted the fact that two neurotransmitters called acetylcholine and glutamate, which are critical to normal critical to normal cognition, are already at abnormally low levels in schizophrenics, most likely because of genetic mutations.

They further point out that the activity of the two neurotransmitters are partially regulated by what are called alpha-7 receptors, a class of proteins involved in the brain's chemical communication system.

According to them, excess levels of kynurenic acid inhibit the work of the alpha-7 receptors, which suggests that they suppress the release of such neurotransmitters even more.

"So we've already got problems with these neurotransmitters, and then to make matters worse, we've got all this extra kynurenic acid antagonizing the alpha-7 receptors, which just throws gasoline onto the fire. If we can design drugs that are able to inhibit the enzymes that are responsible for overproducing kynurenic acid, we may improve cognitive performance in these patients," Bruno said.