Impaired Kynurenine Pathway Metabolism in The Prefrontal Cortex of Individuals With Schizophrenia
Korrapati V. Sathyasaikumar,Erin K. Stachowski,Ikwunga Wonodi,Rosalinda C. Roberts,Rosalinda C. Roberts,Arash Rassoulpour,Robert P. McMahon,Robert Schwarcz +7 more
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TLDR
The present results further support the hypothesis that the normalization of cortical KP metabolism may constitute an effective new treatment strategy in SZ.Abstract:
The levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the branched kynurenine pathway (KP) of tryptophan degradation and antagonist of α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors, are elevated in the prefrontal cortex (PFC) of individuals with schizophrenia (SZ). Because endogenous KYNA modulates extracellular glutamate and acetylcholine levels in the PFC, these increases may be pathophysiologically significant. Using brain tissue from SZ patients and matched controls, we now measured the activity of several KP enzymes (kynurenine 3-monooxygenase [KMO], kynureninase, 3-hydroxyanthranilic acid dioxygenase [3-HAO], quinolinic acid phosphoribosyltransferase [QPRT], and kynurenine aminotransferase II [KAT II]) in the PFC, ie, Brodmann areas (BA) 9 and 10. Compared with controls, the activities of KMO (in BA 9 and 10) and 3-HAO (in BA 9) were significantly reduced in SZ, though there were no significant differences between patients and controls in kynureninase, QPRT, and KAT II. In the same samples, we also confirmed the increase in the tissue levels of KYNA in SZ. As examined in rats treated chronically with the antipsychotic drug risperidone, the observed biochemical changes were not secondary to medication. A persistent reduction in KMO activity may have a particular bearing on pathology because it may signify a shift of KP metabolism toward enhanced KYNA synthesis. The present results further support the hypothesis that the normalization of cortical KP metabolism may constitute an effective new treatment strategy in SZ.read more
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Imbalanced Kynurenine Pathway in Schizophrenia
Magdalena E. Kegel,Maria Bhat,Elisabeth Skogh,Martin Samuelsson,Kristina Lundberg,Marja-Liisa Dahl,Carl M. Sellgren,Lilly Schwieler,Göran Engberg,Ina Schuppe-Koistinen,Sophie Erhardt +10 more
TL;DR: Support is offered for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia, and the CSF QUIN/KYNA ratio was lower in patients than in controls.
Journal ArticleDOI
Toxoplasma gondii Immunoglobulin G Antibodies and Nonfatal Suicidal Self-Directed Violence
Yuanfen Zhang,Lil Träskman-Bendz,Shorena Janelidze,Patricia Langenberg,Ahmed S.M. Saleh,Ahmed S.M. Saleh,Niel T. Constantine,Olaoluwa O. Okusaga,Cecilie Bay-Richter,Lena Brundin,Lena Brundin,Teodor T. Postolache,Teodor T. Postolache +12 more
TL;DR: Seropositivity of T gondii was associated with higher SUAS-S scores, a relationship significant for the whole sample, but not for suicide attempters only, and this results are consistent with previous reports on the association between T Gondii infection and nonfatal suicidal self-directed violence.
Journal ArticleDOI
The KMO allele encoding Arg 452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression
Catharina Lavebratt,Sara K. Olsson,Lena Backlund,Louise Frisén,Carl M. Sellgren,Lutz Priebe,Pernilla Nikamo,Lil Träskman-Bendz,Sven Cichon,Marquis P. Vawter,Urban Ösby,Göran Engberg,Mikael Landén,Sophie Erhardt,Martin Schalling,Martin Schalling +15 more
TL;DR: Findings from five independent cohorts suggest that genetic variation in KMO influences the risk for psychotic features in mania of bipolar disorder patients, providing a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association betweenKYNA levels and number of manic episodes.
Journal ArticleDOI
Kynurenine 3-monooxygenase: an influential mediator of neuropathology
TL;DR: The influence of KMO on brain kynurenine metabolism and the current understanding of molecular mechanisms by which altered KMO activity may contribute to neurodevelopment, neurodegenerative, and neuropsychiatric diseases are discussed.
Journal ArticleDOI
Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia.
Francesco Fazio,Luana Lionetto,Martina Curto,Luisa Iacovelli,Michele Cavallari,Cristina Zappulla,Martina Ulivieri,Flavia Napoletano,Matilde Capi,Valentina Corigliano,Sergio Scaccianoce,Alessandra Caruso,Jessica Miele,Antonio De Fusco,Luisa Di Menna,Anna Comparelli,Antonella De Carolis,Roberto Gradini,Robert Nisticò,Antonio De Blasi,Paolo Girardi,Valeria Bruno,Giuseppe Battaglia,Ferdinando Nicoletti,Maurizio Simmaco +24 more
TL;DR: Serum XA levels were largely reduced in a large cohort of patients affected by schizophrenia, and, in patients with first-episode schizophrenia, levels remained low after 12 months of antipsychotic medication, suggesting that lowered serumXA levels might represent a novel trait marker for schizophrenia.
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