Schizophrenia GABAergic neurons

Beasley CL, Zhang ZJ, Patten I, Reynolds GP. 2002b. Selective deficits in prefrontal cortical GABAergic neurons in schizophrenia defined by the presence of calcium-binding proteins. Biol Psychiatry 52 708-715. 

Cabungcal JH, Nicolas D, Kraftsik R, Cuenod M, Do KQ, et al. 2006. Glutathione deficit during development induces anomalies in the rat anterior cingulate GABAergic neurons Relevance to schizophrenia. Neurobiol Dis 22 624-637. 

Lewis, D. A. (2000) GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia. Brain Res. Rev. 31,270-276. 

Thus there is evidence, albeit circumstantial, of a disturbance of glutamate systems in the disease. In addition there is evidence of GABAergic deficits. Adding to the relevance of these hypotheses of amino acid transmitter dysfunction is the opportunity to relate neurochemical changes directly to a neuronal pathology and, with some further extrapolation, to the aetiology of schizophrenia. 

While these proposals provide useful and testable hypotheses, they are based on slim evidence from post mortem neurochemistry of schizophrenia. Since the deficits in GABAergic markers may be interpreted as demonstrating neuronal hypofunction rather than cell loss, they could equally be ascribed to a consequence of, rather than a cause of, glutamatergic abnormalities. It would be valuable to identify temporal changes in neurochemistry over the disease course, rather than end-stage information that most post-mortem studies inevitably provide, as well as more information from individuals at risk for schizophrenia. 

Is there any evidence for deficits in subsets of hippocampal neurons Here, we will briefly review the evidence for an abnormality of the GABAergic and glutamatergic neurons in the hippocampus in schizophrenia (reviewed by others (Benes, 1999 Arnold, 2000 Benes and Berretta, 2001 Harrison and Eastwood, 2001 Harrison, 2004) and in this volume (Kristiansen et al.)). 

The NMDA hypothesis, called the glutamatergic dysfunction hypothesis, of schizophrenia is based on the action of glutamate on NMDA receptors on GABAergic, serotonergic, and noradrenergic neurons that inhibit two major excitatory pathways in the retrosplenial cortical neurons. (Coyle, 1996). 

Davis and Lewis (1995) found a selective increase in the density of a subpopulation of GABAergic local circuit neurons in the prefrontal cortex of patients with schizophrenia. 

Kalus etal. (1997) showed an increase in a subpopulation of GABAergic local circuit neurons in the layers Va and Vb of the anterior cingulate cortex of patients with schizophrenia. The authors suggest this may indicate an increased inhibition of projection neurons, thus altering the neuronal output pattern of the anterior cingulate cortex in schizophrenia. Other authors could not replicate these findings (Woo et al.l997). 

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