As [11C]ABP688 does not bind to the same site as glutamate on mGluR5, we and others have hypothesized that the presence of glutamate may alter [11C]ABP688 affinity for mGluR5.39, 40, 41 As magnetic resonance spectroscopy studies have reported higher levels of glutamate metabolites in the frontal cortex in depression (including late-life depression),44 this variability presents a potential confound for study results. The gene discussed is GRM5; the disease is depressive disorder.