GRM1 and mood disorder: In particular, glutamate has been implicated in the pathophysiology and treatment of mood disorders, particularly with respect to altered transmission in limbic–thalamocortical circuits.30 Rs2268666 in GRM1 was shown to be associated with unipolar depression (UPD) phenotype in a discovery cohort of 350 patients and 370 matched controls (P=7.0 × 10−5 in allelic test and P=0.0002 in genotypic test with T being the risk allele, both passing multiple testing correction threshold), and was partially replicated in an independent cohort of 904 patients and 1012 controls (genotypic test P=0.