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• W2022349991 endingPage "665" @default.
• W2022349991 startingPage "665" @default.
• W2022349991 abstract "<h3>Context</h3> Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, is an antagonist at<i>N</i>-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. <h3>Objectives</h3> To examine<i>KMO</i>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<i>KMO</i>single-nucleotide polymorphisms and schizophrenia oculomotor endophenotypes. <h3>Design</h3> Case-control postmortem and clinical study. <h3>Setting</h3> Maryland Brain Collection, outpatient clinics. <h3>Participants</h3> Postmortem 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). <h3>Main Outcome Measures</h3> Comparison of quantitative<i>KMO</i>messenger RNA expression and KMO enzyme activity in postmortem FEF tissue between schizophrenia patients and controls and association of<i>KMO</i>single-nucleotide polymorphisms with messenger RNA expression in postmortem FEF and schizophrenia and oculomotor endophenotypes (ie, smooth pursuit eye movements and oculomotor delayed response). <h3>Results</h3> In postmortem tissue, we found a significant and correlated reduction in<i>KMO</i>gene expression and KMO enzyme activity in the FEF in schizophrenia patients. In the clinical sample,<i>KMO</i>rs2275163 was not associated with a diagnosis of schizophrenia but showed modest effects on predictive pursuit and visuospatial working memory endophenotypes. <h3>Conclusion</h3> Our results provide converging lines of evidence implicating reduced KMO activity in the etiopathophysiology of schizophrenia and related neurocognitive deficits." @default.
• W2022349991 created "2016-06-24" @default.
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• W2022349991 date "2011-07-01" @default.
• W2022349991 modified "2023-09-29" @default.
• W2022349991 title "Downregulated Kynurenine 3-Monooxygenase Gene Expression and Enzyme Activity in Schizophrenia and Genetic Association With Schizophrenia Endophenotypes" @default.
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• W2022349991 doi "https://doi.org/10.1001/archgenpsychiatry.2011.71" @default.
• W2022349991 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3855543" @default.
• W2022349991 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21727251" @default.

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