Density of Glutamic Acid Decarboxylase 67 Messenger RNA–Containing Neurons That Express the N-Methyl-D-Aspartate Receptor Subunit NR2A in the Anterior Cingulate Cortex in Schizophrenia and Bipolar Disorder

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Disturbances of γ-aminobutyric acid interneurons in the cerebral cortex contribute to the pathophysiology of schizophrenia and bipolar disorder. The activity of these neurons is, in turn, modulated by glutamatergic inputs furnished by pyramidal neurons.


To test the hypothesis that glutamatergic inputs onto γ-aminobutyric acid interneurons via the N-methyl-D-aspartate (NMDA) receptor are altered in the anterior cingulate cortex in schizophrenia and bipolar disorder.


A double in situ hybridization technique was used to simultaneously label the messenger RNA (mRNA) for the NMDA NR2A subunit with 35sulfur and the mRNA for the 67-kDa isoform of the γ-aminobutyric acid synthesizing enzyme glutamic acid decarboxylase (GAD67) with digoxigenin.


Postmortem human brain studies.


We studied 17 subjects with schizophrenia, 17 subjects with bipolar disorder, and 17 normal control subjects.


The density of all GAD67 mRNA–containing neurons was decreased by 53% and 28%, in layers 2 and 5, respectively, in subjects with schizophrenia, whereas in subjects with bipolar disorder there was a 35% reduction in layer 2 only. For GAD67 mRNA–containing neurons that co-expressed NR2AmRNA, their numerical density was decreased by 73% and 52%, in layers 2 and 5, respectively, in subjects with schizophrenia and by 60% in layer 2 in those with bipolar disorder. In the schizophrenia group, the density of the GAD67mRNA–containing neurons that did not co-express NR2AmRNA was also decreased by 42% in layer 2. In both disease groups, the expression level of NR2AmRNA in GAD67 mRNA–containing cells was unaltered.


The density of γ-aminobutyric acid interneurons that express the NMDA NR2Asubunit appears to be decreased in schizophrenia and bipolar disorder. Future studies will address whether subpopulations of these neurons may be differentially affected in the 2 conditions.

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