Brain Chemical Linked to Cognitive Decline in Schizophrenia

(Ivanhoe Newswire) -- The delusions and hallucinations associated with schizophrenia may be linked to a deficit in a brain chemical. 

This may open an important avenue of inquiry for improving cognitive function in the more than 2 million Americans who suffer from schizophrenia, according to lead author Jong H. Yoon, assistant professor of psychiatry and behavioral sciences at University of California Davis Health System.

"We still know very little about the neurobiology of schizophrenia, particularly at the level of specific circuits and molecules and how their impairments affect behavior and cognition in the disease," Yoon was quoted as saying. "We need this level of specificity to guide targeted treatment development. This is one of the first studies to show that there is a strong association between cognitive deficits and a decrease in a particular neurotransmitter."

Schizophrenia is characterized by abnormalities in the perception or expression of reality. Sufferers may experience visual or auditory hallucinations and have paranoia, delusions and disorganized speech and thinking. They also experience profound cognitive difficulties that interfere with daily functioning.

Psychosis is treated with a variety of antipsychotic medications that dampen over-activity of the neurotransmitter dopamine, an acknowledged cause of psychotic behavior. But no medications are available to address cognitive deficits in schizophrenia because the source of the deficits has not been identified. Research involving animal models and post-mortem analyses of the neurotransmitter gamma-aminobutyric acid, or GABA, suggest that deficits in GABA may play a causal role in the cognitive difficulties experienced by people with schizophrenia.

"People think of schizophrenia as being related to psychosis. But patients' cognitive limitations can be even more debilitating for them," senior author Cameron Carter, professor of psychiatry and behavioral sciences and director of the Imaging Research Center was quoted as saying. "This study actually looked at brain chemistry in live patients in relation to cognitive performance to determine the underlying neurobiology of the cognitive deficits. Our ultimate goal is discovering ways to help patients lead more productive lives."

Yoon and his colleagues measured the levels of GABA in the visual cortexes of the brains of 13 study subjects with schizophrenia and 13 control subjects without the disorder. The measurements were conducted with high-field magnetic resonance spectroscopy, a technique that involves using a magnetic resonance imaging scanner to examine neurotransmitter activity. The schizophrenic patients were found to have a deficit in GABA of about 10 percent when compared with their non-schizophrenic counterparts.

The researchers then measured the visual perception of the subjects for whom GABA levels were assessed by showing them a well-known illusion in which the presence of a high-contrast surrounding region inhibits the ability to perceive information in the center of the visual field.
The researchers showed that this surround-suppression illusion had less of an effect on patients with schizophrenia, resulting in a highly unusual situation in which they outperformed healthy subjects. The researchers then found that the lower levels of GABA in patients were responsible for this behavioral abnormality.

"The link between changes in patients' brain chemistry and the cognitive impairments they experience never has been shown before in this way," Carter said. "This work provides tremendous support for targeting the GABA system for treatment of cognitive decline in schizophrenia."

SOURCE: Journal of Neuroscience, online, March 10, 2010