Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics.
Recent investigations of postmortem brain from schizophrenic patients have revealed reduced numbers of neurons in several different corticolimbic brain regions. In the prefrontal and anterior cingulate cortices, more specific decreases in the numbers of interneurons, but not pyramidal cells, have been reported to occur preferentially in layer II. Based on this latter finding, a loss of inhibitory basket cells leading to a compensatory upregulation of the GABAA receptor has been hypothesized to occur in schizophrenic patients and to be a contributory factor in the pathophysiology of this disorder. We now report the results of a high-resolution quantitation of GABAA receptor binding in anterior cingulate cortex of postmortem specimens from normal and schizophrenic cases. The results indicate a preferential increase in bicuculline-sensitive 3H-muscimol binding on neuronal cell bodies of layers II and III, but not layers V and VI, of the schizophrenic cases. There was no difference in the size of neurons in any of the layers examined when the control and schizophrenic groups were compared. The neuropil of layer I also showed significantly greater GABAA binding in schizophrenics. The differences seen in the schizophrenic group did not appear to be the result of exposure to antipsychotic medication because one patient who was medication naive and a second who had received minimal exposure to antipsychotic drugs also showed elevated GABAA receptor binding. Since information processing depends on corticocortical integration in outer layers I-III, a disturbance of inhibitory activity in these superficial layers of limbic cortex may contribute to the defective associative function seen in schizophrenia.
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115.
F M
FM
Benes
S L
SL
Vincent
G
G
Alsterberg
E D
ED
Bird
J P
JP
SanGiovanni
D000328:Adult; D000368:Aged; D001345:Autoradiography; D001640:Bicuculline / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D009118:Muscimol / Q000378:metabolism; D010640:Phenothiazines; D011963:Receptors, GABA-A / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*; D013194:Staining and Labeling
D010640:Phenothiazines; D011963:Receptors, GABA-A; D009118:Muscimol; C009469:thionine; D001640:Bicuculline