There is an accumulation of evidence for abnormalities in
schizophrenia of both the major
neurotransmitter systems of the brain - those of
GABA (
gamma-aminobutyric acid) and
glutamate. Initial studies have found deficits in the putative neuronal marker,
N-acetylaspartate, in a number of brain regions in
schizophrenia. The animal models have provided some interesting correlates and discrepancies with these findings. The deficit in inhibitory interneurons within structures implicated in schizophrenic symptomatology may well have direct functional relevance, and can be induced by animal models of the disease such as subchronic
phencyclidine administration or social isolation. Their association with these animal models suggests an environmental involvement. A loss of glutamatergic function in
schizophrenia is supported by decreases in markers for the neuronal
glutamate transporter in striatal structures that receive cortical glutamatergic projections. Deficits in the VGluT1 (
vesicular glutamate transporter-1) in both striatal and hippocampal regions support this observation, and the association of VGluT1 density with a genetic risk factor for
schizophrenia points to genetic influences on these glutamatergic deficits. Further studies differentiating neuronal loss from diminished activity and improved models allowing us to determine the temporal and causal relationships between GABAergic and glutamatergic deficits will lead to a better understanding of the processes underlying the neuronal pathology of
schizophrenia.