Abstract & Overview
Schizophrenia, a major psychiatric disease, affects individuals in the centre of their personality.Its aetiology is not clearly established.In this review, we will present evidence that patients suffering of schizophrenia present a brain deficit in glutathione, a major endogenous redox regulator and antioxidant.We will also show that, in experimental models, a decrease in glutathione, particularly during development, induces morphological, electrophysiological and behavioural anomalies consistent with those observed in the disease.In the cerebrospinal fluid of drug-naive schizophrenics, glutathione level was decreased by 27% and its direct metabolite of glutathione by 16%.Glutathione level in prefrontal cortex of patients, measured by magnetic resonance spectroscopy, was 52% lower than in controls.Patients' fibroblasts reveal a decrease in mRNA levels of the two glutathione synthesising enzymes, glutamatecysteine ligase modulatory subunit (GCLM) and glutathione synthetase.GCLM expression level in fibroblasts correlates negatively with symptoms severity.Glutathione is an important endogenous redox regulator and neuroactive substance.It is protecting cells from damage by reactive oxygen species generated, among others, by dopamine metabolism.A glutathione deficit-induced oxidative stress would lead to lipid peroxidation and micro-lesions at the level of dendritic spines, a synaptic damage responsible for abnormal nervous connections or