An analysis of metabotropic glutamate receptors 2/3 and 5 in schizophrenia, major depression and bipolar disorder from the stanley neuropathology consortium
Purpose: Metabotropic glutamate receptors (mGluRs) are proposed novel therapeutic targets for a variety of brain disorders such as schizophrenia (SZ), bipolar disorder (BP) and major depression (MD). Despite their potential, the involvement of these receptors in these pathological processes is uncertain. This information is crucial to understand the efficiency of drugs that target these receptors. Methods: Using post-mortem human brains, mGluR2/3 and mGluR5 binding densities were measured in the anterior cingulate cortex of SZ, BP, MD and matched controls (CT) (n=15/group) by receptor autoradiography. Results: Whilst preliminary analyses indicated no diagnostic effect in mGluR2/3 or mGluR5 binding densities, mGluR2/3 binding negatively correlated with age at death in the CT (r=-0.695, p=0.004) and SZ (r=- 0.528, p=0.043) groups, but not MD or BP. Contrarily, mGluR5 displayed a borderline positive correlation with age at death in SZ (r=0.505, p=0.055) and MD (r=-0.453, p=0.090) subjects. Furthermore, mGluR2/3 and mGluR5 binding correlated in subjects with SZ (r=-0.516, p=0.049), but not BP, MD or CT groups. Conclusion: Targeting mGluRs may provide a therapeutic mechanism to modulate glutamatergic activity in psychiatric disorders. Our findings of unaltered levels of mGluRs in SZ, BD, and MD may be beneficial by potentially providing an unhindered therapeutic target. However the association between age and both mGluR2/3 and mGluR5 binding in SZ subjects may have age-dependant therapeutic implications for the use of these drugs in SZ patients. There are no published investigations examining mGluR function, which may be integral to interpreting absence of change in mGluR protein levels.