A POSTMORTEM STUDY OF GLYCINE AND ITS POTENTIAL PRECURSORS IN CHRONIC-SCHIZOPHRENICS

We have measured the concentrations of glycine and its potential precu rsors, serine and threonine, in 20 areas of the postmortem brains of c hronic schizophrenics and controls using high-performance liquid chrom atography by pre-column derivatization with dimethyl-amino-azobenzene sulphonyl chloride. The regional distribution pattern of glycine in th e postmortem brains with and without the disease was more similar to t hat 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 variabl es including diagnosis, age at death and interval between death and fr eezing revealed that there is a significant difference between schizop hrenics and controls in the contents of these amino acids in a number of brain areas. The level of glycine in the orbitofrontal cortex of sc hizophrenics was found to be significantly increased in schizophrenics , with a tendency to an increase in that of serine. The increase in gl ycine was also significantly high in the off-drug group of schizophren ics who had not taken antipsychotics more than 40 days before death. P rominent decreases in both glycine and serine were observed in the som esthetic 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 o f the off-drug group of schizophrenics and in the putamen of all schiz ophrenics. The highly similar distribution pattern of glycine and seri ne in the postmortem brains supports the close coupling of synthesis a nd metabolism between these chemicals in human brains. The increased c ontent of glycine in the orbito-frontal cortex, the reduced level of s erine in the putamen and the decrease in threonine in the cerebral cor tices, which were prominent in the off-drug schizophrenics, may be inv olved in the pathophysiology of schizophrenia. Copyright (C) 1996 Else vier Science Ltd.