Dataset Information

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

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.

SUBMITTER: Narendran R

PROVIDER: S-EPMC4913897 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Narendran Rajesh R Tumuluru Divya D May Maureen A MA Chowdari Kodavali V KV Himes Michael L ML Fasenmyer Kelli K Frankle W Gordon WG Nimgaonkar Vishwajit L VL

PloS one 20160620 6

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 to ...[more]

PMID: 27322568

Similar Datasets

Project description:BackgroundDespite the widespread use of oral contraceptives (OCs), and the well-documented influence of estrogens, notably 17β-estradiol (E2), on cognition, research relating OCs to working memory is limited and mixed. Two factors may contribute to these mixed findings: 1) pharmacokinetics of oral contraceptives, which drive fluctuations in synthetic hormone levels; and 2) genetic polymorphisms related to dopamine degradation and working memory, which interact with E2. This research investigated whether the pharmacokinetics of oral contraceptives, in concert with the single nucleotide polymorphism (Val158Met; rs4680) of the catechol-o-methyltransferase gene (COMT), influence working memory performance.MethodsUniversity-age women taking and not taking OCs were tested for working memory and genotyped for COMT. If they were not taking OCs (n = 62), sessions occurred in the early follicular (low E2) and late follicular (high E2) phase. If they were taking OCs (n = 52), sessions occurred 1-2 hours after (high ethinyl estradiol, EE) and ~24 hours after (low EE) pill ingestion. Working memory was tested using the N-back, AX-CPT, Digit Span, and Digit Ordering Tasks. Data were analyzed using multilevel models with estrogen condition, COMT, and group as predictors, controlling for mood and practice effects.ResultsFor women taking OCs, time of pill ingestion did not influence performance. However, the subgroup with COMT val/val (low dopamine) were less accurate on 2-back lure trials than those with COMT met/met (high dopamine). For women not taking OCs, cycle phase moderated COMT's influence on lure accuracy. When compared, women taking OCs had higher AX-CPT proactive control indices than those not taking OCs.ConclusionThese findings suggest that oral contraceptives are not detrimental for young women's working memory and that they may increase proactive control. The more pronounced effects of COMT in women taking OCs suggests that, in women taking OCs, suppressed endogenous E2-not fluctuating EE levels-may be more relevant for working memory. Future studies are needed to differentiate effects of endogenous versus synthetic estrogens on working memory.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets