Increases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics: evidence for glutamate hypothesis.

Strychnine-insensitive glycine binding sites, an absolute requirement of the responses mediated by N-methyl-D-aspartate (NMDA) receptors, were measured in the postmortem brains of 13 chronic schizophrenics and 10 controls, using a radiolabeled receptor assay. Specific [3H]glycine binding was significantly increased in six of the 16 areas of the cerebral cortex that were investigated. Scatchard analysis performed in these areas showed a significant increase in the maximum number of binding sites, with no change in the affinity of binding. Multiple regression analysis confirmed that the increase was not due to age at death or interval from death to freezing. The increase was also observed in the off-drug cases of schizophrenics who had not taken antipsychotics for more than 40 days before death. These results suggest that the increases in NMDA-associated glycine binding sites, possibly ascribed to the postsynaptic compensation for impaired glutamatergic neurotransmission, might be implicated in the pathophysiology of schizophrenia.