Clinical and Basic
Neuroscience Research
Training Program in Psychiatry

Schizophrenia and Psychosis Research

A comprehensive clinical and preclinical program of research is dedicated to unraveling the neurobiological origins of psychotic disorders and their treatments. Two fascinating areas of study include:

• Brain Receptors/Neurotransmitters

One avenue of research is focusing on the role of excitatory amino acids, NMDA receptors, and cortical glutamatergic neuronal projections in the pathophysiology of psychosis. Pharmacological challenge studies in humans are evaluating the precise psychotomimetic properties of ketamine, an NMDA-receptor antagonist. In conjunction with these findings, functional (i.e., fast) magnetic resonance imaging (MRI) investigations are uncovering the corresponding neuroanatomical circuits correlated with ketamine's psychotomimetic effects. Moreover, clinical measures of brain glutamate levels are now possible through magnetic resonance spectroscopic (MRS) studies, providing direct in vivo measures of excitatory amino acid function in the brains of schizophrenic patients and controls.

• Medication

Few psychiatric discoveries have been as exciting and as promising as the introduction into clinical practice of the atypical neuroleptic medication, clozapine. A nation-wide, multicenter study of clozapine's efficacy in schizophrenic patients, coordinated by the West Haven VA National Center for Schizophrenia, is one example of ongoing research at the clinical level. In addition, ongoing trials of novel and recently developed atypicals, are also underway in the Schizophrenia Research Clinic at the Connecticut Mental Health Center. Simultaneously, basic research into clozapine's potentially unique effects on dopaminergic receptor subtypes (e.g., D4), dopamine-serotonin interactions, and the expression of immediate early gene transcription factors (e.g., c-fos, jun) and their target genes in critical brain regions are proceeding in parallel and are providing complementary insights into the brain basis of these important new pharmacotherapies and their mechanisms of action.

Faculty related to Schizophrenia Psychosis Research

D'Souza
Hoffman
Krystal
Mathalon

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