Key faculty include Stephen I. Deutsch, M.D., Ph.D., Barbara L. Schwartz, Ph.D., Richard B. Rosse, M.D., and John Mastropaolo, Ph.D. Neuroscience research in Psychiatry at the VAMC spans many levels in the treatment of severe chronic mental illness. Research has addressed questions of etiology, characterization of cognitive disturbances, and pharmacological treatments in people with schizophrenia, Alzheimer's disease, traumatic brain injury, and substance abuse disorders. Faculty researchers have used animal models and experimental cognitive paradigms and eye scanning techniques, and novel pharmacological strategies in both healthy individuals and patient groups to address a variety of issues in psychiatry. A specific area of interest that has been pursued for more than a decade is the clinical and preclinical investigation of NMDA receptor hypofunction in neuropsychiatric disorders. This research has included investigation of NMDA receptor agonist interventions for schizophrenia, Alzheimer's disease and cognitive function in normal subjects, including healthy elderly adults.
Preclinical laboratory:
Drs. Stephen Deutsch, Richard B. Rosse, and John Mastropaolo have developed
functional behavioral outcome measures to assess both GABAA and NMDA receptor mediated
neurotransmission in the intact animal. These procedures showed that stress,
genetic strain differences, pharmacological and hormonal manipulations can alter
neurotransmission mediated by GABA and glutamate. Currently, the laboratory
utilizes three principal outcome measures: PCP-saline cue discrimination in
rats, MK-801 antagonism of electrically precipitated hindlimb extension in mice,
and MK-801 elicited popping behavior in mice.
Neurocognitive Laboratory:
Dr. Barbara Schwartz is an experimental neuropsychologist who has studied cognitive
function in schizophrenia and alcoholism. Her main interests lie in characterizing
preserved and impaired memory function in these disorders. She has also carried
out studies examining the effectiveness of novel pharmacological agents to improve
memory and language functions in healthy older adults, and patients with schizophrenia.
Clinical Trials:
Drs. Stephen Deutsch and Richard Rosse conducted early trials of pharmacological
interventions designed to facilitate NMDA mediated neural transmission at the
level of the strychnine-insensitive glycine binding site in patients with schizophrenia.
They examined the use of high dose glycine, milacemide (an acylated "prodrug"of
glycine that readily crosses the blood brain barrier and is converted to glycine
in the brain), and d-Cycloserine (a partial glycine agonist). Currently, they
are interested in examining the safety and efficacy of interventions designed
to address the "downstream" consequences of NMDA receptor hypofunction,
such as topiramate, AMPAKINES, and oral AMPA/Kainate receptor antagonists. Additionally,
they are among the first investigators to study a positive allosteric modulator
of nicotinic cholinergic neurotransmission in schizophrenia. They are very committed
to an exploration of selective a7 nicotinic cholinergic agonist interventions
for this disorder.
