Benzodiazepine receptors increase in post-mortem brain of chronic schizophrenics

Abstract

[³H]-Flunitrazepam (FNT) binding was measured in the post-mortem brains of 13 chronic schizophrenics and 10 controls whose mean ages and death-to-freezing intervals were the same in each group. The specific binding of [³H]-FNT to the medial frontal cortex, orbitofrontal cortex, orbital cortex, medial and inferior temporal gyri, superior temporal gyrus, cornu Ammonis 1–3 and putamen was significantly higher in schizophrenics than in controls. Specific binding to the eye movement area (frontal eye field), motor cortex, lateral occipitotemporal gyrus, dentate gyrus of the hippocampus and secondary and tertiary visual cortex did not differ in the two groups. Type 1 benzodiazepine (BZ) binding sites in the superior temporal gyrus of schizophrenics, determined from the displacement of [³H]-FNT binding using a triazolopyridazine, CL 218,872 (200nM), were significantly higher than in the control group. The increase in type 2 BZ binding sites was not significant. Antipsychotic or benzodiazepine medication did not appear to affect the results. There were significant correlations between specific [³H]-FNT binding and concentration of GABA (positive) and of glutamic acid (negative), specific [³H]-kainic acid binding (positive), activity of tyrosine hydroxylase (positive), and substance P-like immunoreactivity (positive) in many areas of the brain. The B_max of [³H]-spiperone binding in the putamen was also correlated positively with specific [³H]-FNT binding. These data suggest that dysfunction of BZ receptors may be involved in the pathogenesis and some symptoms of chronic schizophrenia.