A postmortem study of glycine and its potential precursors in chronic schizophrenics.
We have measured the concentrations of glycine and its potential precursors, serine and threonine, in 20 areas of the postmortem brains of chronic schizophrenics and controls using high-performance liquid chromatography by pre-column derivatization with dimethyl-amino-azobenzene sulphonyl chloride. The regional distribution pattern of glycine in the postmortem brains with and without the disease was more similar to that of serine (r = 0.874, P < 0.0001) than to that of threonine (r = 0.476, P < 0.01). A multiple regression analysis with regressor variables including diagnosis, age at death and interval between death and freezing revealed that there is a significant difference between schizophrenics and controls in the contents of these amino acids in a number of brain areas. The level of glycine in the orbitofrontal cortex of schizophrenics was found to be significantly increased in schizophrenics, with a tendency to an increase in that of serine. The increase in glycine was also significantly high in the off-drug group of schizophrenics who had not taken antipsychotics more than 40 days before death. Prominent decreases in both glycine and serine were observed in the somesthetic cortex of the on-drug schizophrenics. Serine was found to be significantly decreased in the putamen of the off-drug schizophrenics. A marked decrease in threonine was also observed in the supramarginal cortex and posterior portion of the lateral occipitotemporal cortex of the off-drug group of schizophrenics and in the putamen of all schizophrenics. The highly similar distribution pattern of glycine and serine in the postmortem brains supports the close coupling of synthesis and metabolism between these chemicals in human brains. The increased content of glycine in the orbitofrontal cortex, the reduced level of serine in the putamen and the decrease in threonine in the cerebral cortices, which were prominent in the off-drug schizophrenics, may be involved in the pathophysiology of schizophrenia.
Kurumaji
A
A
Department of Neuropsychiatry, Tokyo Medical and Dental University School of Medicine, Japan.
Watanabe
A
A
Kumashiro
S
S
Semba
J
J
Toru
M
M
D000328:Adult; D000368:Aged; D001923:Brain Chemistry / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D005260:Female; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D012559:Schizophrenia / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D004124:p-Dimethylaminoazobenzene
D007202:Indicators and Reagents; D013912:Threonine; D012694:Serine; D004124:p-Dimethylaminoazobenzene; D005998:Glycine