Britta Hahn1, Carolyn H Reneski2, Ana Pocivavsek2, Robert Schwarcz2. 1. Maryland Psychiatric Research Center, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD, 21228, USA. bhahn@mprc.umaryland.edu. 2. Maryland Psychiatric Research Center, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD, 21228, USA.
Abstract
RATIONALE: Elevated brain kynurenic acid (KYNA) levels are implicated in the pathology and neurodevelopmental pathogenesis of schizophrenia. In rats, embryonic treatment with kynurenine (EKyn) causes elevated brain KYNA levels in adulthood and cognitive deficits reminiscent of schizophrenia. OBJECTIVES: Growing evidence suggests that people with schizophrenia have a narrowed attentional focus, and we aimed at establishing whether these abnormalities may be related to KYNA dysregulation. METHODS: To test whether EKyn rats display broad monitoring deficits, kynurenine was added to the chow of pregnant Wistar dams on embryonic days 15-22. As adults, 20 EKyn and 20 control rats were trained to stable performance on the five-choice serial reaction time task, requiring the localization of 1-s light stimuli presented randomly across five apertures horizontally arranged along a curved wall, equating the locomotor demands of reaching each hole. RESULTS: EKyn rats displayed elevated omission errors and reduced anticipatory responses relative to control rats, indicative of a lower response rate, and showed reduced locomotor activity. The ability to spread attention broadly was measured by parsing performance by stimulus location. Both groups displayed poorer stimulus detection with greater target location eccentricity, but this effect was significantly more pronounced in the EKyn group. Specifically, the groups differed in the spatial distribution of correct but not incorrect responses. This pattern cannot be explained by differences in response rate and is indicative of a narrowed attentional focus. CONCLUSIONS: The findings suggest a potential etiology of broad monitoring deficits in schizophrenia, which may constitute a core cognitive deficit.
RATIONALE: Elevated brain kynurenic acid (KYNA) levels are implicated in the pathology and neurodevelopmental pathogenesis of schizophrenia. In rats, embryonic treatment with kynurenine (EKyn) causes elevated brain KYNA levels in adulthood and cognitive deficits reminiscent of schizophrenia. OBJECTIVES: Growing evidence suggests that people with schizophrenia have a narrowed attentional focus, and we aimed at establishing whether these abnormalities may be related to KYNA dysregulation. METHODS: To test whether EKynrats display broad monitoring deficits, kynurenine was added to the chow of pregnant Wistar dams on embryonic days 15-22. As adults, 20 EKyn and 20 control rats were trained to stable performance on the five-choice serial reaction time task, requiring the localization of 1-s light stimuli presented randomly across five apertures horizontally arranged along a curved wall, equating the locomotor demands of reaching each hole. RESULTS:EKynrats displayed elevated omission errors and reduced anticipatory responses relative to control rats, indicative of a lower response rate, and showed reduced locomotor activity. The ability to spread attention broadly was measured by parsing performance by stimulus location. Both groups displayed poorer stimulus detection with greater target location eccentricity, but this effect was significantly more pronounced in the EKyn group. Specifically, the groups differed in the spatial distribution of correct but not incorrect responses. This pattern cannot be explained by differences in response rate and is indicative of a narrowed attentional focus. CONCLUSIONS: The findings suggest a potential etiology of broad monitoring deficits in schizophrenia, which may constitute a core cognitive deficit.
Authors: Ikwunga Wonodi; O Colin Stine; Korrapati V Sathyasaikumar; Rosalinda C Roberts; Braxton D Mitchell; L Elliot Hong; Yasushi Kajii; Gunvant K Thaker; Robert Schwarcz Journal: Arch Gen Psychiatry Date: 2011-07
Authors: Cynthia O Akagbosu; Gretchen C Evans; Danielle Gulick; Raymond F Suckow; David J Bucci Journal: Schizophr Bull Date: 2010-12-20 Impact factor: 9.306
Authors: Robert E Featherstone; Zoe Rizos; José N Nobrega; Shitij Kapur; Paul J Fletcher Journal: Neuropsychopharmacology Date: 2006-10-11 Impact factor: 7.853
Authors: Keith H Nuechterlein; Deanna M Barch; James M Gold; Terry E Goldberg; Michael F Green; Robert K Heaton Journal: Schizophr Res Date: 2004-12-15 Impact factor: 4.939
Authors: Courtney J Wright; Katherine M Rentschler; Nathan T J Wagner; Ashley M Lewis; Sarah Beggiato; Ana Pocivavsek Journal: Front Psychiatry Date: 2021-09-17 Impact factor: 4.157