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Biol Psychiatry. 2008 Nov 1;64(9):803-9. doi: 10.1016/j.biopsych.2008.04.034. Epub 2008 Jun 30.

N-methyl-D-aspartate receptor and calbindin-containing neurons in the anterior cingulate cortex in schizophrenia and bipolar disorder.

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  • 1Program in Structural and Molecular Neuroscience, McLean Hospital, Belmont, Massachusetts 02478, USA. mail:



Glutamatergic modulation of gamma-aminobutyric acid (GABA) interneurons via the NR2A subunit of the N-methyl-D-aspartate (NMDA) receptor in the cerebral cortex contributes to the pathophysiology of schizophrenia and bipolar disorder. Previously, we found that, in the anterior cingulate cortex (ACCx), the number of GABA cells that expressed the messenger RNA (mRNA) for the NMDA NR2A subunit was significantly decreased in subjects with schizophrenia and bipolar disorder and that this decrease occurred most prominently in layer 2. In this study, we hypothesized that the subset of GABA interneurons that contained the calcium-binding protein calbindin (CB), by virtue of their preferential localization to layer 2, might be particularly affected.


We simultaneously labeled the mRNA for the NMDA NR2A subunit with [(35)S] and the mRNA for CB with digoxigenin with an immunoperoxidase procedure.


We found that, in the normal human ACCx, only approximately 10% of all CB-containing cells expressed NR2A mRNA. However, compared with the normal control subjects and subjects with bipolar disorder, the density of CB+/NR2A+ neurons in layer 2 was increased by 41% to 44 % in subjects with schizophrenia, whereas the amount of NR2A mRNA/CB+ neurons was unchanged.


These observations suggest that, in schizophrenia, a number of CB-containing cells that normally do not express NR2A might become NR2A-expressing or, perhaps not mutually exclusively, the number of CB-expressing cells might be increased and these cells express NR2A. The findings of this study highlight the notion that glutamatergic innervation of subsets of GABA cells might be differentially altered in schizophrenia and bipolar disorder.

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