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

Narendran, R and Tumuluru, D and May, MA and Chowdari, KV and Himes, ML and Fasenmyer, K and Frankle, WG and Nimgaonkar, VL (2016) Cortical Dopamine Transmission as Measured with the [11C]FLB 457 - Amphetamine PET Imaging Paradigm Is Not Influenced by COMT Genotype. PloS one, 11 (6). e0157867 - ?.

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Abstract

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 D1 and D2/3 receptor binding potential (BP), and interpreted them in terms of dopaminergic tone. The use of baseline dopamine D1 and D2/3 receptor binding potential (BPND) 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 [11C]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 D2/3 receptor BPND.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Narendran, Rran29@pitt.eduRAN29
Tumuluru, D
May, MA
Chowdari, KV
Himes, ML
Fasenmyer, K
Frankle, WG
Nimgaonkar, VLnimga@pitt.eduNIMGA
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorHerholz, KarlUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 January 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PloS one
Volume: 11
Number: 6
Page Range: e0157867 - ?
DOI or Unique Handle: 10.1371/journal.pone.0157867
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Human Genetics
School of Medicine > Psychiatry
School of Medicine > Radiology
Refereed: Yes
Date Deposited: 23 Aug 2016 15:12
Last Modified: 02 Feb 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/28289

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