Evidence map›Paper›PMID 21727251›Full record

ArticleArchives of general psychiatry2011

Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes.

Ikwunga Wonodi, O Colin Stine, Korrapati V Sathyasaikumar, Rosalinda C Roberts, Braxton D Mitchell, L Elliot Hong, Yasushi Kajii, Gunvant K Thaker, Robert Schwarcz

Open access · bronzeAbstract read
In one paragraph

Article in Archives of general psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 3 pooled it
4.7field-weighted citation impact, top 4% of its field
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

93 citing papers in PubMed, 3 syntheses or guidelines pooled it, 158 citations in OpenAlex.

  1. Pooled it
  2. BrainFrontiers in immunology · 2021
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33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Ikwunga WonodiDepartment of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228. iwonodi@mprc.umaryland.edu
O Colin Stine
Korrapati V Sathyasaikumar
Rosalinda C Roberts
Braxton D Mitchell
L Elliot Hong
Yasushi Kajii
Gunvant K Thaker
Robert Schwarcz
University of Maryland, Baltimore · USUniversity of Alabama · US

Funding

Zonulin Antibodies in Intestinal Permeabilitiy in IDDMM01RR016500 · NCRR · UNIVERSITY OF MARYLAND BALTIMORE · PI OSWALD, LYNN M · 2002 to 2009
$20.2M
Clinical Research Career Development (RMI)K12RR023250 · NCRR · UNIVERSITY OF MARYLAND BALTIMORE · PI SHULDINER, ALAN R. · 2005 to 2009
$13.3M
CORE--RESEARCH NETWORK DEVELOPMENT COREP30MH068580 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI CARPENTER, WILLIAM T. · 2003 to 2007
$7.9M
FAMILIAL SCHIZOPHRENIA SPECTRUM PERSONALITY DISORDERSR01MH049826 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI THAKER, GUNVANT K · 1993 to 2007
$2.9M
Shared Neural Circuitry in Comorbid Schizophrenia and Nicotine AddictionR01DA027680 · NIDA · UNIVERSITY OF MARYLAND BALTIMORE · PI HONG, L ELLIOT ELLIOT · 2010 to 2014
$2.4M
Neural Oscillatory Biomarkers for Genetics and Animal Models of SchizophreniaR01MH085646 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI HONG, L ELLIOT ELLIOT · 2010 to 2013
$2.2M
Motion Perception in SchizophreniaR01MH067014 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI THAKER, GUNVANT K · 2003 to 2007
$1.0M
Identifying molecular path of behavioural phenotype in schizophreniaR21MH079172 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI HONG, L ELLIOT ELLIOT · 2007 to 2008
$384k
Genetic Polymorphism of a Schizophrenia EndophenotypeR03MH075101 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI WONODI, IKWUNGA · 2006 to 2007
$146k
NCRR NIH HHS K12 RR023250NCRR NIH HHS M01 RR016500NCRR NIH HHS M01RR16500NIDA NIH HHS R01 DA027680NIMH NIH HHS MH075101NIMH NIH HHS MH079172NIMH NIH HHS MH49826NIMH NIH HHS MH67014NIMH NIH HHS MH68580NIMH NIH HHS MH-K12RR023250NIMH NIH HHS P30 MH068580NIMH NIH HHS R01 MH049826NIMH NIH HHS R01 MH067014NIMH NIH HHS R01 MH085646NIMH NIH HHS R03 MH075101NIMH NIH HHS R21 MH079172
6 · The paper itself

Abstract

contextKynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, is an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors and modulates glutamate, dopamine, and acetylcholine signaling. Cortical kynurenic acid concentrations are elevated in the brain and cerebrospinal fluid of schizophrenia patients. The proximal cause may be an impairment of kynurenine 3-monooxygenase (KMO), a rate-limiting enzyme at the branching point of the kynurenine pathway.

objectivesTo examine KMO messenger RNA expression and KMO enzyme activity in postmortem tissue from the frontal eye field (FEF; Brodmann area 6) obtained from schizophrenia individuals compared with healthy control individuals and to explore the relationship between KMO single-nucleotide polymorphisms and schizophrenia oculomotor endophenotypes.

designCase-control postmortem and clinical study.

settingMaryland Brain Collection, outpatient clinics.

participantsPostmortem specimens from schizophrenia patients (n = 32) and control donors (n = 32) and a clinical sample of schizophrenia patients (n = 248) and healthy controls (n = 228).

main outcome measuresComparison of quantitative KMO messenger RNA expression and KMO enzyme activity in postmortem FEF tissue between schizophrenia patients and controls and association of KMO single-nucleotide polymorphisms with messenger RNA expression in postmortem FEF and schizophrenia and oculomotor endophenotypes (ie, smooth pursuit eye movements and oculomotor delayed response).

resultsIn postmortem tissue, we found a significant and correlated reduction in KMO gene expression and KMO enzyme activity in the FEF in schizophrenia patients. In the clinical sample, KMO rs2275163 was not associated with a diagnosis of schizophrenia but showed modest effects on predictive pursuit and visuospatial working memory endophenotypes.

conclusionOur results provide converging lines of evidence implicating reduced KMO activity in the etiopathophysiology of schizophrenia and related neurocognitive deficits.

Indexed as

AdultBrain ChemistryCase-Control StudiesDown-RegulationFemaleGene Expression Regulation, EnzymologicGenetic Association StudiesGenotypeHumansKynurenic AcidKynurenine 3-MonooxygenaseMaleMiddle AgedOculomotor MusclesPolymerase Chain ReactionPolymorphism, Single NucleotideKynurenic AcidKynurenine 3-MonooxygenaseRNA, Messenger

Identifiers

PMID21727251
PMCPMC3855543
OpenAlexW2022349991

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Registered trials

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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.