The NR1 subunit of the glutamate/NMDA receptor in the superior temporal cortex in schizophrenia and affective disorders

The NMDA receptor has been implicated in the pathophysiology of several diseases including schizophrenia and affective disorders. We have investigated the NR1 subunit of the NMDA receptor in a well-defined series of psychiatric cases using radioligand binding and quantitative immunoblotting techniques. Saturable radioligand binding of [H-3]L-689,560 to the glycine site on this subunit of the NMDA receptor was undertaken in superior temporal cortex of patients with schizophrenia, bipolar disorder, depression and matched control subjects. A tendency towards an increased receptor density was found in schizophrenia. A significant decrease in NMDA receptor density below control value was found in both bipolar and depressive disorders. The immunoblotting technique was used to identify NR1 protein in the same series of cases of which two bands were identified consistent with NR1 splice variants. A tendency to a decrease in the density of the NR1 upper band below control values was found in bipolar and depressed patients, but not schizophrenics. Consistent with this observation, the ratio between the upper and lower NR1-immunoreactive bands showed a significant decrease in bipolar disorder, although the ratio in depression did not reach significance. No significant difference was found in the NR1 lower band in any patient group compared with control. The finding of an increase NMDA receptor density in schizophrenia is consistent with the previous reports, with a possible compensatory response to glutamatergic deficits in superior temporal cortex in schizophrenia. The findings in affective disorders are interesting in respect of reports of cortical NMDA receptor deficits in suicide victims, although antidepressant drug treatment may contribute to these changes. (C) 2004 Elsevier Ireland Ltd. All rights reserved.