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
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.