Michael S Jacob1, Brian J Roach2, Holly K Hamilton1, Ricardo E Carrión3, Aysenil Belger4, Erica Duncan5, Jason Johannesen6, Matcheri Keshavan7, Sandra Loo8, Margaret Niznikiewicz7, Jean Addington9, Carrie E Bearden8, Kristin S Cadenhead10, Tyrone D Cannon11, Barbara A Cornblatt12, Thomas H McGlashan6, Diana O Perkins4, William Stone7, Ming Tsuang10, Elaine F Walker13, Scott W Woods6, Daniel H Mathalon14. 1. VA San Francisco Healthcare System, San Francisco, CA, USA; Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. 2. VA San Francisco Healthcare System, San Francisco, CA, USA. 3. Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA; Department of Psychiatry, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA. 4. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 5. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA; Atlanta Veterans Affairs Medical Center, Decatur, GA, USA. 6. Department of Psychiatry, Yale University, School of Medicine, New Haven, CT, USA. 7. Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston, MA, USA. 8. Semel Institute for Neuroscience and Human Behavior, Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA. 9. Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada. 10. Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. 11. Department of Psychiatry, Yale University, School of Medicine, New Haven, CT, USA; Department of Psychology, Yale University, School of Medicine, New Haven, CT, USA. 12. Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA; Department of Psychiatry, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA; Department of Molecular Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA. 13. Department of Psychology, Emory University, Atlanta, GA, USA. 14. VA San Francisco Healthcare System, San Francisco, CA, USA; Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. Electronic address: daniel.mathalon@ucsf.edu.
Abstract
BACKGROUND: Adolescence/early adulthood coincides with accelerated pruning of cortical synapses and the onset of schizophrenia. Cortical gray matter reduction and dysconnectivity in schizophrenia are hypothesized to result from impaired synaptic plasticity mechanisms, including long-term potentiation (LTP), since deficient LTP may result in too many weak synapses that are then subject to over-pruning. Deficient plasticity has already been observed in schizophrenia. Here, we assessed whether such deficits are present in the psychosis risk syndrome (PRS), particularly those who subsequently convert to full psychosis. METHODS: An interim analysis was performed on a sub-sample from the NAPLS-3 study, including 46 healthy controls (HC) and 246 PRS participants. All participants performed an LTP-like visual cortical plasticity paradigm involving assessment of visual evoked potentials (VEPs) elicited by vertical and horizontal line gratings before and after high frequency ("tetanizing") visual stimulation with one of the gratings to induce "input-specific" neuroplasticity (i.e., VEP changes specific to the tetanized stimulus). Non-parametric, cluster-based permutation testing was used to identify electrodes and timepoints that demonstrated input-specific plasticity effects. RESULTS: Input-specific pre-post VEP changes (i.e., increased negative voltage) were found in a single spatio-temporal cluster covering multiple occipital electrodes in a 126-223 ms time window. This plasticity effect was deficient in PRS individuals who subsequently converted to psychosis, relative to PRS non-converters and HC. CONCLUSIONS: Input-specific LTP-like visual plasticity can be measured from VEPs in adolescents and young adults. Interim analyses suggest that deficient visual cortical plasticity is evident in those PRS individuals at greatest risk for transition to psychosis. Published by Elsevier B.V.
BACKGROUND: Adolescence/early adulthood coincides with accelerated pruning of cortical synapses and the onset of schizophrenia. Cortical gray matter reduction and dysconnectivity in schizophrenia are hypothesized to result from impaired synaptic plasticity mechanisms, including long-term potentiation (LTP), since deficient LTP may result in too many weak synapses that are then subject to over-pruning. Deficient plasticity has already been observed in schizophrenia. Here, we assessed whether such deficits are present in the psychosis risk syndrome (PRS), particularly those who subsequently convert to full psychosis. METHODS: An interim analysis was performed on a sub-sample from the NAPLS-3 study, including 46 healthy controls (HC) and 246 PRS participants. All participants performed an LTP-like visual cortical plasticity paradigm involving assessment of visual evoked potentials (VEPs) elicited by vertical and horizontal line gratings before and after high frequency ("tetanizing") visual stimulation with one of the gratings to induce "input-specific" neuroplasticity (i.e., VEP changes specific to the tetanized stimulus). Non-parametric, cluster-based permutation testing was used to identify electrodes and timepoints that demonstrated input-specific plasticity effects. RESULTS: Input-specific pre-post VEP changes (i.e., increased negative voltage) were found in a single spatio-temporal cluster covering multiple occipital electrodes in a 126-223 ms time window. This plasticity effect was deficient in PRS individuals who subsequently converted to psychosis, relative to PRS non-converters and HC. CONCLUSIONS: Input-specific LTP-like visual plasticity can be measured from VEPs in adolescents and young adults. Interim analyses suggest that deficient visual cortical plasticity is evident in those PRS individuals at greatest risk for transition to psychosis. Published by Elsevier B.V.
Entities:
Keywords:
Clinical high risk; Plasticity; Psychosis; Schizophrenia; Visual evoked potentials
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