Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo
Abstract
Schizophrenia is a major psychiatric disease, which affects the centre of the personality, with severe problems of perception, cognition as well as affective and social behaviour. In cerebrospinal fluid of drug-free schizophrenic patients, a significant decrease in the level of total glutathione (GSH) by 27% (P<0.05) was observed as compared to controls, in keeping with the reported reduced level of its metabolite gamma-glutamylglutamine. With a new non-invasive proton magnetic resonance spectroscopy methodology, GSH level in medial prefrontal cortex of schizophrenic patients was found to be 52% (P = 0.0012) lower than in controls. GSH plays a fundamental role in protecting cells from damage by reactive oxygen species generated among others by the metabolism of dopamine. A deficit in GSH would lead to degenerative processes in the surrounding of dopaminergic terminals resulting in loss of connectivity. GSH also potentiates the N-methyl-D-aspartate (NMDA) receptor response to glutamate, an effect presumably reduced by a GSH deficit, leading to a situation similar to the application of phencyclidine (PCP). Thus, a GSH hypothesis might integrate many established biological aspects of schizophrenia.
References
Quantitative 1H MRS of the human brain in vivo based on the stimulation phantom calibration strategy
Citations
Dopamine-induced oxidative stress in neurons with glutathione deficit: implication for schizophrenia
Omega-3 prevents behavior response and brain oxidative damage in the ketamine model of schizophrenia
Glutathione depletion in the brain disrupts short-term spatial memory in the Y-maze in rats and mice
Cognitive impairment is related to oxidative stress and chemokine levels in first psychotic episodes
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