Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo.
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.
Do
K Q
KQ
Brain Research Institute, University of Zurich and Centre for Research in Psychiatric Neuroscience, University of Lausanne, Route de Cery, CH-1008 Prilly-Lausanne, Switzerland. Kim.Do@inst.hospvd.ch
Trabesinger
A H
AH
Kirsten-Krüger
M
M
Lauer
C J
CJ
Dydak
U
U
Hell
D
D
Holsboer
F
F
Boesiger
P
P
Cuénod
M
M
D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D005978:Glutathione / Q000134:cerebrospinal fluid* / Q000172:deficiency*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012559:Schizophrenia / Q000134:cerebrospinal fluid* / Q000473:pathology / Q000503:physiopathology*
D017382:Reactive Oxygen Species; D005978:Glutathione; D004298:Dopamine