Evidence map›Paper›PMID 22364739›Full record

Trial reportBiological psychiatry2012

COMT Val(158)Met genotype determines the direction of cognitive effects produced by catechol-O-methyltransferase inhibition.

Sarah M Farrell, Elizabeth M Tunbridge, Sven Braeutigam, Paul J Harrison

Erratum issuedAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Biological psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed.

  1. Trial
  2. Effects of pharmacological and genetic regulation of COMT activity in alcohol use disorder: a randomized, placebo-controlled trial of tolcapone.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022
    Trial
  3. Cortical dopamine reduces the impact of motivational biases governing automated behaviour.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022
    Trial
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Effects of COMT genotype and tolcapone on lapses of sustained attention after sleep deprivation in healthy young men.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018
    Trial
  9. Tolcapone-Enhanced Neurocognition in Healthy Adults: Neural Basis and Predictors.The international journal of neuropsychopharmacology · 2017
    Trial
  10. Trial
  11. Trial
  12. Amphetamine modulates brain signal variability and working memory in younger and older adults.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Review
  19. Hydroethanolic Extract ofTheScientificWorldJournal · 2025
    Article
  20. Review

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
  • Erratum issued
5 · Who and what money

Authors and funding

4 authors.

Sarah M FarrellDepartment of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom.
Elizabeth M Tunbridge
Sven Braeutigam
Paul J Harrison

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundCatechol-O-methyltransferase (COMT) metabolizes dopamine. The COMT Val(158)Met polymorphism influences its activity, and multiple neural correlates of this genotype on dopaminergic phenotypes, especially working memory, have been reported. COMT activity can also be regulated pharmacologically by COMT inhibitors. The inverted-U relationship between cortical dopamine signaling and working memory predicts that the effects of COMT inhibition will differ according to COMT genotype.

methodsThirty-four COMT Met(158)Met (Met-COMT) and 33 COMT Val(158)Val (Val-COMT) men were given a single 200-mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a randomized, double-blind, between-subjects design. They completed the N-back task of working memory and a gambling task.

resultsIn the placebo group, Met-COMT subjects outperformed Val-COMT subjects on the 2- back, and they were more risk averse. Tolcapone had opposite effects in the two genotype groups: it worsened N-back performance in Met-COMT subjects but enhanced it in Val-COMT subjects. Tolcapone made Met-COMT subjects less risk averse but Val-COMT subjects more so. In both tasks, tolcapone reversed the baseline genotype differences.

conclusionsDepending on genotype, COMT inhibition can enhance or impair working memory and increase or decrease risky decision making. To our knowledge, the data are the clearest demonstration to date that the direction of effect of a drug can be influenced by a polymorphism in its target gene. The results support the inverted-U model of dopamine function. The findings are of translational relevance, because COMT inhibitors are used in the adjunctive treatment of Parkinson's disease and are under evaluation in schizophrenia and other disorders.

Indexed as

Catechol O-Methyltransferase InhibitorsCognitionMemory, Short-TermAdolescentAdultBenzophenonesCatechol O-MethyltransferaseDouble-Blind MethodGamblingHumansMaleMethionineMiddle AgedNeural InhibitionNeuropsychological TestsNitrophenolsBenzophenonesCatechol O-MethyltransferaseCatechol O-Methyltransferase InhibitorsMethionineNitrophenolsTolcaponeValine

Identifiers

PMID22364739
PMCPMC3314969

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.