This is an application for a new Conte Center for Schizophrenia Research based at the New York University School of Medicine (NYUSoM) and the affiliated Nathan Kline Institute for Psychiatric Research (NKI). Schizophrenia (SZ) is associated with sensory processing deficits that represent a core, but understudied, connponent of the disorder. In the auditory system, patients show deficits in basic processes such as tone matching and auditory mismatch negativity (MMN) generation. In the visual system, patients show deficits in processes such as contrast gain and integration that contribute to higher order impairments in processes such as object recognition and face recognition. Sensory deficits may relate specifically to impairments in Nmethyl- D-aspartate (NMDA) receptor-mediated neurotransmission, and are especially amenable to translational investigation using human and animal models. The Center consists of 6 projects and 3 cores, which build from pre-existing collaborations among Center investigators. Projects 1, 2 and 4 are based at NKI/NYSoM and utilize human (Javitt) and primate (Schroeder) neurophysiological, and human postmortem/laser capture microscopy/gene array (Ginsberg/Smiley) approaches to the study of sensory cortical dysfunction and impaired functional connectivity in SZ. Project 3 (Hlllyard) is based at UCSD and investigates modulatory processes underlying normal visual function. Project 5 (Cornblatt) is based at Zucker Hillside Hospital and investigates sensory processing dysfunction within the SZ prodrome. Finally, Project 6 (Weiser) is based at Sheba Hospital/Tel Aviv University and evaluates effectiveness of sarcosine (N-methylglycine), a naturally occurring NMDA agonist not currently available in the US. Cores are devoted to administration (Javitt), patient recruitment/assessment (Butler) and data management/biostatistics (Robinson/Petkova). Although traditional models of SZ focus on dopamine, more recent models focus on underlying glutamatergic dysfunction, and have received support from neurogenetic, imaging, and treatment studies, as well as challenge studies with putative NMDA antagonists. The overall goal of the Center is to develop new assessment and intervention approaches for schizophrenia based upon glutamatergic models
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