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The Nathan S. Kline Institute for Psychiatric Research

Schizophrenia Research

Kantrowitz Lab

Lab Name
#6f5091

Dr. Kantrowitz's Cognitive Psychopharmacology Program focuses on understanding the neural basis of novel pharmacological and sensory-based treatments for core neurocognitive dysfunction in schizophrenia, particularly glutamate-based and neuromodulation treatment approaches. MRI and EEG are utilized to understand the neurophysiology and functional target engagement of novel treatments.

Overview

Current treatments for schizophrenia, including both typical and atypical antipsychotics, function primarily by blocking dopamine (D2) receptors. While effective for treatment of positive symptoms, antipsychotics have limited efficacy against persistent negative symptoms or cognitive impairments, necessitating the development of alternative treatment approaches. Recent neurochemical models of persistent dysfunction focus on disturbances of brain glutamatergic (NMDAR) neurotransmission. Mechanisms by which NMDAR dysfunction leads to symptoms, however, remain relatively unexplored. As opposed to dopaminergic models, glutamatergic models specifically account for impairments not only in cognition, but also in the generation of neurophysiological measures, such as visual P1 or auditory mismatch (MMN). Such measures index local circuit dysfunction, and thus may be useful as translational biomarkers for translational drug development.

D-serine

Our lab focuses on D-serine, a naturally occurring endogenous modulator of NMDAR as a treatment for both chronic and early (prodromal) schizophrenia. Recent observations have shown that D-serine reverses MMN deficits in chronic schizophrenia, which in turn are tied to impaired functional connectivity (rsfMRI) within brain auditory/limbic networks.  In separate studies, investigators have observed that D-serine significantly reduces IL-6 levels in individuals at high clinical risk for schizophrenia, along with reduction in negative symptoms.  Most recently, we have investigated the impact of NMDAR dysfunction in underlying neuroplasticity deficits and, second, that repeated D-serine administration may enhance neuroplasticity in schizophrenia.

Current Investigations
  • Glutamatergic neurophysiology and treatment in schizophrenia and bipolar disorder.
  • Functional and neurophysiological consequences of early sensory processing deficits in schizophrenia.