Genetic studies point to the genes encoding the NMDA 1, 2A and 2B subunits while neuropathological studies suggest a possible region specific decrease in the density of NMDA receptor and more consistently a reduced NMDA-mediated glutamatergic activity in patients with bipolar disorder in the frame of slower NMDA kinetics because of lower contribution of NR2A subunits.
These findings suggest that, in the PFC, glutamatergic regulation of PV-containing inhibitory neurons via NR2A-containing NMDA receptors does not appear to be altered in bipolar disorder.
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.
In addition, the density of the GAD67+/NR2A+ neurons was decreased by 57% and 49% in layers 3 and 4, respectively, in schizophrenia, but it was unchanged in bipolar disorder.
In the perirhinal cortex we detected decreased expression of GluR5 in all three diagnoses, of GluR1, GluR3, NR2B in both BD and MDD, and decreased NR1 and NR2A in BD and MDD, respectively.