Dean_2019_J.Affect.Disord_244_80

BACKGROUND: We previously reported that, compared to controls, there are lower levels of [(3)H]LY341495 binding to metabotropic 2/3 receptors (GRM2/3) in Brodmann's area (BA) 24, but not 17 or 46, from subjects with major depressive disorders (MDD) but not bipolar disorders (BD) or schizophrenia. To be able to better interpret these data we have now measured levels of GRM2 in two of these cortical regions. METHODS: Using a rabbit anti-metabotropic GRM2 monoclonal antibody with Western blotting we measured levels of GRM2 in BA 24 and 46 from subjects with MDD, BD, schizophrenia and controls (n=15 per group). RESULTS: Compared to controls, levels of GRM2, normalised to beta-actin, did not differ in BA 24 or 46 from subjects with MDD, BD or schizophrenia (p from 0.36 to 0.79). Levels of GRM2 in BA 46, but not BA 24, were significantly higher in males compared to females (p<0.01) and in suicide completers (p<0.01) compare to death by other causes. LIMITATIONS: Our cohort sizes, whilst being comparable to many postmortem CNS studies, are relatively low. CONCLUSIONS: Our data suggests levels of GRM2 are not altered in two cortical regions from subjects with mood disorders or schizophrenia. Given we have found lower levels of [(3)H]LY341495 binding to GRM2/3 in BA 24 from subjects with MDD, our new data argues the lower levels of radioligand binding was due to lower levels of GRM3. Our data also suggests that glutamatergic activity through GRM2 in BA 46 may differ with gender and suicide ideation.