Cortical Dopamine Transmission as Measured with the [(11)C]FLB 457 – Amphetamine PET Imaging Paradigm Is Not Influenced by COMT Genotype

Basic investigations link a Val158Met polymorphism (rs4680) in the catechol-O-methyltransferase (COMT) gene to not only its enzymatic activity, but also to its dopaminergic tone in the prefrontal cortex. Previous PET studies have documented the relationship between COMT Val158Met polymorphism and D(1) and D(2/3) receptor binding potential (BP), and interpreted them in terms of dopaminergic tone. The use of baseline dopamine D(1) and D(2/3) receptor binding potential (BP(ND)) as a proxy for dopaminergic tone is problematic because they reflect both endogenous dopamine levels (a change in radiotracer's apparent affinity) and receptor density. In this analysis of 31 healthy controls genotyped for the Val158Met polymorphism (Val/Val, Val/Met, and Met/Met), we used amphetamine-induced displacement of [(11)C]FLB 457 as a direct measure of dopamine release. Our analysis failed to show a relationship between COMT genotype status and prefrontal cortical dopamine release. COMT genotype was also not predictive of baseline dopamine D(2/3) receptor BP(ND).