Some Help Ahead for Those With Cognitive Impairment?

New research has traced elevated levels of a specific compound in the brain to problem-solving deficits in patients with schizophrenia.

The finding suggests that drugs used to suppress the compound, called kynurenic acid, might be an important supplement to antipsychotic medicines, as these adjuncts could be used to treat the disorder's most-resistant symptoms — cognitive impairments.

Though schizophrenia is commonly characterized by hallucinations and delusions, patients also have problems with what is known as cognitive flexibility or executive decision-making. Many patients can set a goal and plan one way to achieve it, but 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 John P. Bruno, professor of psychology, psychiatry and neuroscience at Ohio State University and principal investigator of the research.

He described the research at a recent gathering of the Society for Neuroscience meeting in Washington, D.C.

Bruno and colleagues have combined advanced animal modeling of schizophrenia-related chemical changes in the brain with the observation that the production of too much kynurenic acid is linked to troubled thinking that affects the research animals' behavior.

The compound is present in all human brains and has some useful functions. But, in excessive amounts, the researchers found, kynurenic acid interferes 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," said Bruno.

"Antipsychotics are particularly good at what we call positive symptoms, but these same drugs are very poor at treating the cognitive deficits.

"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," Bruno said.

The kynurenic acid essentially exacerbates a phenomenon already observed in patients with schizophrenia — the fact that two neurotransmitters in their brains are not as active as they need to be to allow for normal problem-solving capabilities.



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