The Center for Schizophrenia Research will test the primary hypothesis that NMDA dysfunction leads to early sensory and higher cognitive level deficits. Our hypothesis reaches beyond the limitations of the traditional model of schizophrenia as a disorder of dopaminergic neurotransmission, and explores the promising new model of schizophrenia as a disorder of NMDA receptor-mediated glutamatergic neurotransmission.
Our hypothesis is driven by evidence supporting the role of NMDA dysfunction in schizophrenia:
- NMDA receptor agonists reproduce core symptoms of schizophrenia.
- A dependency upon a confluence of events characterizes both current flow through NMDA receptor channels and responses to sensory stimuli that are dysfunctional in schzophrenia.
- Deficits in NMDA function have been linked to abnormal generation of sensory event-related potentials (ERPs), including auditory mismatch negativity (MMN), N1, and visual P1, particularly in response to magnocellular-based stimuli.
- Primate work conducted by investigators in this Center has delineated basic concepts of cortical organization, including hierarchical information processing networks that may depend on underlying NMDA function.
Project 1: Multimodal assessment of sensory processing dysfunction in schizophrenia
Project 2: Neuro-oscillations, sensation and neurocognition
Project 3: Multimodal assessment of visual function and attention
Project 4: Neuronal basis of sensory processing dysfunction in schizophrenia
Project 5: Sensory processing deficits in the schizophrenia prodrome
Project 6: The impact of NMDA receptor hypofunction on schizophrenia-relevant sensory neurophysiological function
The studies conducted within these projects in both humans and non-human primates will improve conceptualizations of schizophrenia, improve biomarkers for diagnosis and evaluation of the disorder, and improve treatments, leading to improved functional and psychosocial outcomes. The projects are carried out at Columbia University, the Nathan Kline Institute, the University of California - San Diego, and Zucker Hillside Hospital.