From the outset, the use of these therapies might indicate a hyperglutamatergic state or specific NMDAR hyperfunction in depression, suggesting that the mGluR5 reduction seen in patients with depression represents an endogenous compensatory response, and that the use of mGluR5 NAMs may act to further assist this mGluR5 downregulation. Here, GRM5 is linked to depressive symptom measurement.