GABA and Schizophrenia – Is There a Connection?

Schizophrenia is a mental disorder that has been misunderstood, misdiagnosed, and often mistreated.  Modern misconceptions about schizophrenia abound, even though major educational efforts have been underway for years. The diagnostic criteria for schizophrenia are ambiguous and unclear (and probably won’t be improved whenever the new Diagnostic and Statistical Manual of the American Psychiatric Association is released).  Treatment protocols have been uniformly unsuccessful, although there are a few medications that can alleviate some of the major symptoms.  One problem with drug treatment is the high rate of non-compliance.  Many patients discontinue drug therapy, often because the side-effects are hard to tolerate.

The prevailing view of the cause(s) of schizophrenia is some sort of chemical imbalance in the brain (a handy catch-all for most mental illness, even though there have been few, if any, chemical abnormalities actually demonstrated).  There also appears to be a genetic component, although the details of this piece of the puzzle are unclear at present.  Two neurotransmitters (serotonin and dopamine) have been implicated as contributing to the problems of schizophrenia.  Both neurotransmitters are believed to be elevated in patients with the disorder.  However, the data are conflicting and there have been few clear studies demonstrating increases of these materials in schizophrenic human brain.

Some interesting clues suggest that gamma-aminobutyric acid (GABA) might be decreased in humans with schizophrenia.  A drug that enhanced the ability of the brain to respond to GABA was shown to raise the cognitive skills in schizophrenic patients (1). A 2009 study (2) indicated that an experimental drug which acted on GABA receptors was effective in improving the cognitive abilities of schizophrenics.  Both studies involved small patient populations, but show promise in developing new treatments for this disorder.  A recent study (3) used high-field magnetic resonance spectroscopy to demonstrate an approximate 10% reduction in GABA levels in the visual cortex of schizophrenics as compared to a normal population.  The authors concluded that this GABA deficit could lead to impaired cortical inhibition and thus explain at least some of the behavioral issues in these individuals.

The search for neurotransmitter abnormalities in schizophrenia continues.  Present information suggests that a decrease in GABA levels in the brain could play a role in the etiology of schizophrenia.

1.  “Subunit-Selective Modulation of GABA Type A Receptor Neurotransmission and Cognition in Schizophrenia”, D.A. Lewis et al., American Journal of Psychiatry 165 (12), 1585-1593, (2008).
2. Psychiatric News, November 20, 2009
3. “GABA Concentration Is Reduced in Visual Cortex in Schizophrenia and Correlates with Orientation-Specific Surround Suppression”, J.H. Yoon et al., Journal of Neuroscience 30 (10), 3777-3781, (2010).

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