MAR 17, 2016 07:30 AM PDT

Special Lecturer - NMDAR dysfunction in schizophrenia: Implications for pathophysiology and basic neuroscience

Presented At Neuroscience
  • Director, Division of Experimental Therapeutics, Director, Columbia Conte Center for Schizophrenia Research, Professor of Psychiatry and Neuroscience, Columbia University College of Physician
      Daniel C Javitt, MD, PhD, is Professor of Psychiatry and Neuroscience at Columbia University College of Physicians and Surgeons, where he directs the Division of Experimental Therapeutics as well as the Columbia Conte Center for Schizophrenia Research in New York City. Additionally, Dr Javitt serves as Director of Schizophrenia Research at Nathan Kline Institute for Psychiatric Research, a New York State Office of Mental Health-supported research facility. He received his MD and PhD degrees from Albert Einstein College of Medicine. His research focuses on mechanisms underlying negative symptoms and cognitive deficits in schizophrenia and other serious mental disorders, with particular emphasis on NMDA receptors and neurophysiological assessment, and on new treatment development using both pharmacological and brain stimulation approaches. Dr Javitt has published over 250 articles on issues related to normal brain function, NMDA receptors and schizophrenia. He has received awards for his research from numerous organizations, including the Penwalt Resident Research Award from the American Psychiatric Association; The Kempf Fund Award for Research Development in Psychobiological Psychiatry from the American Psychiatric Association; the A.E. Bennett Basic Science Award from the Society for Biological Psychiatry; the Joel Elkes Research Award from the American College of Neuropsychopharmacology; and a MERIT award from the National Institutes of Mental Health. Dr Javitt serves on the editorial board of several prestigious journals including Schizophrenia Bulletin, Schizophrenia Research, and American Journal of Psychiatry. He is a Fellow of the American College of Neuropsychopharmacology and an advisory board member for the Brain and Behavior Research Foundation.


    Schizophrenia (Sz) is a major mental disorder that affects ~1% of the population.  Although traditional models of Sz focused on dopaminergic dysfunction, newer models increasingly implicate glutamatergic systems, particularly N-methyl-D-aspartate receptors (NMDAR).    NMDAR models are supported by the ability of NMDAR antagonists (e.g. PCP, ketamine) to induce symptoms and neurocognitive deficits closely resembling those of Sz and by genetic and auto-immune findings. One key deficit related to NMDAR dysfunction in Sz is a failure in the generation of mismatch negativity (MMN).  Deficit in MMN generation have been extensively replicated in Sz and shown to predict functional outcome.  At the physiological level, MMN impairments are related to impaired theta (4-7 Hz) generation within somatomotor networks.  At the cognitive level, deficits in basic auditory processing contribute to impairments in phonological reading and auditory emotion recognition which, in turn, contribute to poor psychosocial function.In the visual system, NMDAR play a preferential role in non-linear gain which, in turn, particularly affects functioning of the magnocellular visual system.  Thus, consistent impairments are observed in ERP (e.g. visual P1) and fMRI response to magnocellular-biased visual static and motion stimuli, while responses to parvocellular-biased stimuli remain relatively intact.  Deficits in magnocellular function in turn lead to impairments in higher order visual information processing, including ability to detect and process facial expression.  As with auditory deficits, basic visual deficits contribute directly to social dysfunction and impaired functional outcome.  Overall patterns of dysfunction in Sz highlight the role played by NMDAR in information processing at the ensemble and network levels. 
    Learning objectives:

    1.  Understand the role played by NMDAR in basic auditory processing and implications for schizophrenia.
    2. Understand the role played by NMDAR in basic visual processing and implications for schizophrenia

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