The neuronal pathology of schizophrenia: molecules and mechanisms.
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.
Reynolds
G P
GP
Division of Psychiatry and Neuroscience, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK.
Harte
M K
MK
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000172:deficiency; D001921:Brain / Q000473:pathology*; D003342:Corpus Striatum / Q000473:pathology; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000502:physiology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D009474:Neurons / Q000473:pathology*; D010622:Phencyclidine; D012559:Schizophrenia / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000172:deficiency / Q000502:physiology*
D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D010622:Phencyclidine