This Project represents an innovative integration of two theoretical approaches that have great potential for improving prediction of schizophrenia and for helping to clarify the neural mechanisms involved in the onset of psychosis. Although late adolescence/eariy adulthood is the period when onset typically occurs, few prospective prodromal studies have focused on the changes in brain function that occur during this period. Information about the neural processes leading to illness during this eariy phase of development could both improve accurate prediction and potentially lead to novel interventions targeting the specific abnormalities identified. The proposed Project combines the expertise of two established investigators (Cornblatt and Javitt) who currently collaborate on studies of D-serine effects on symptoms in the SZ prodrome, and will provide the funding and resources to introduce Dr. Javitt's biological approach into Dr. Cornblatt's prospective, longitudinal prodromal study. Dr. Cornblatt has conducted research concerned with identifying neurocognitive, behavioral and clinical risk factors of schizophrenia for over 20 years. Since 1998, she has been the director of the Recognition and Prevention (RAP) program, a prospective study of adolescents between the ages of 12-22 who are at clinical risk (i.e., prodromal) for schizophrenia at Zucker Hillside Hospital (ZHH). She will serve as PI for this project. The project will incorporate event-related potential (ERP) and behavioral measures of sensory processing dysfunction to enhance existing neurocognitive batteries.
Specific aims of the project are 1. to introduce a sensory processing battery (behavioral measures/ERP procedures) to the existing RAP baseline procedures and assess the extent to which sensory deficits are present in the prodromal stage of illness;2. to evaluate short-term changes in sensory processing and ERPs at six months in subjects who are medication free as compared to those stabilized on medication, and 3. to assess long-term change in processing associated with a two-year retest. We have elected to follow all participants for two years, since previous findings indicate that conversions peak during this time period, and can be expected to be about 35%. Primary ERP support for this Project will be provided by Core B. ERP measures will be compared across Project 1, 5 and 6 to assess deficits in chronic, prodromal and first episode cohorts, respectively. This project integrates as well with database component of Project 6, and will receive database and statistical support from Core C.

Public Health Relevance

Schizophrenia is a major mental disorder. Neurocognitive dysfunction is a core component of schizophrenia and a major determinant of poor long-term outcome. This project is part of a Center application to determine brain mechanisms underiying neurocognitive dysfunction in schizophrenia with particular emphasis on sensory processing dysfunction. This project will evaluate deficits in sensory processing in patients showing prodi^omal symptoms of schizophrenia , in collaboration with other projects and core programs, as a way to improve eariy detection and intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH086385-04
Application #
8380056
Study Section
Special Emphasis Panel (ZMH1-ERB-F)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$164,721
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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Lee, Migyung; Balla, Andrea; Sershen, Henry et al. (2018) Rodent Mismatch Negativity/theta Neuro-Oscillatory Response as a Translational Neurophysiological Biomarker for N-Methyl-D-Aspartate Receptor-Based New Treatment Development in Schizophrenia. Neuropsychopharmacology 43:571-582
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Kantrowitz, Joshua T; Epstein, Michael L; Lee, Migyung et al. (2018) Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: Correlation with symptoms. Schizophr Res 191:70-79
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Lee, M; Sehatpour, P; Hoptman, M J et al. (2017) Neural mechanisms of mismatch negativity dysfunction in schizophrenia. Mol Psychiatry 22:1585-1593
Potvin, Olivier; Dieumegarde, Louis; Duchesne, Simon et al. (2017) Freesurfer cortical normative data for adults using Desikan-Killiany-Tourville and ex vivo protocols. Neuroimage 156:43-64
Brucato, G; Masucci, M D; Arndt, L Y et al. (2017) Baseline demographics, clinical features and predictors of conversion among 200 individuals in a longitudinal prospective psychosis-risk cohort. Psychol Med 47:1923-1935
Potvin, Olivier; Dieumegarde, Louis; Duchesne, Simon et al. (2017) Normative morphometric data for cerebral cortical areas over the lifetime of the adult human brain. Neuroimage 156:315-339
Poe, Sarah-Lucy; Brucato, Gary; Bruno, Nicolina et al. (2017) Sleep disturbances in individuals at clinical high risk for psychosis. Psychiatry Res 249:240-243

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