Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo

Eur J Neurosci. 2000 Oct;12(10):3721-8. doi: 10.1046/j.1460-9568.2000.00229.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Chromatography, High Pressure Liquid
  • Dopamine / metabolism
  • Glutathione / cerebrospinal fluid*
  • Glutathione / deficiency*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / pathology
  • Prefrontal Cortex / physiopathology
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / pathology
  • Reactive Oxygen Species / metabolism
  • Schizophrenia / cerebrospinal fluid*
  • Schizophrenia / pathology
  • Schizophrenia / physiopathology*


  • Reactive Oxygen Species
  • Glutathione
  • Dopamine