Raising GABA Levels Might Undo Cognitive Defect in Schizophrenia

The neurotransmitter GABA is decreased in the brains of individuals with schizophrenia, researchers reported in the March 10 Journal of Neuroscience.

They used a technique called magnetic resonance spectroscopy to measure the levels of GABA in the visual cortex of 13 subjects with schizophrenia and 13 demographically matched control subjects. GABA concentration in the schizophrenia subjects was 10 percent less than in the control group.

Furthermore, the researchers found a highly significant link between the GABA deficiency in the visual cortex of the schizophrenia subjects and a particular cognitive defect—a visual perception problem already known to be present in individuals with schizophrenia. The problem is called orientation-specific surround suppression, a behavioral measure of visual inhibition thought to be dependent on GABA neurotransmission.

So it looks as if a GABA deficiency may be responsible for this cognitive defect in schizophrenia and perhaps for others as well, the researchers believe.

Or as Cameron Carter, M.D., senior author and a professor of psychiatry at the University of California, Davis, put it, “This work provides tremendous support for targeting the GABA system for treatment of cognitive decline in schizophrenia.”

Still another positive aspect of their study, Jong Yoon, M.D., lead investigator and an assistant professor of clinical psychiatry at the university, explained, is “that not only have we found that GABA is deficient in living [schizophrenia] subjects, but we have developed a model system with which we can evaluate GABA function and evaluate interventions targeting GABA function.” In other words, the hope is that a drug that acts on GABA might be found to correct some of the cognitive deficiencies that accompany schizophrenia, since antipsychotic medications currently on the market have a modest effect at best on cognition, he said.

There are already some indications that drugs that act on GABA might be of benefit in this regard. A small pilot study headed by David Lewis, M.D., a professor of psychiatry and neuroscience at the University of Pittsburgh, and published in the December 2008 American Journal of Psychiatry found that subjects with schizophrenia performed better on cognitive tests after being given a particular GABA agonist than after being given a placebo. And an Israeli company reported last year that subjects with schizophrenia who received an investigational drug that acts on GABA receptors experienced a significantly greater improvement in cognition than did subjects with schizophrenia who received a placebo (Psychiatric News, November 20, 2009).

The study was funded by NARSAD and the National Institute of Mental Health.

An abstract of “GABA Concentration Is Reduced in Visual Cortex in Schizophrenia and Correlates With Orientation-Specific Surround Suppression” is posted at <www.jneurosci.org/cgi/content/abstract/30/10/3777>.