Project: Research project

Project Details


Recent data, obtained by magnetic resonance imaging (MRI), positron
emission tomography (PET), electrophysiological methods, and post-mortem
examination, suggest that there may be an abnormality in the anterior
hippocampal region (including amygdala) in schizophrenia. Hippocampal
involvement in schizophrenia is supported by findings indicating that
lesions in or stimulation of the hippocampal region can cause symptoms
typical of schizophrenia. There is evidence that antipsychotic agents,
such as remoxipride and clozapine, may act upon the mesolimbic dopamine
system and this lends support to the notion that a functional hippocampal
defect in patients with schizophrenia may be a causative factor in the
typical symptoms of schizophrenia. Also, myelination of
cortico-hippocampal relays occurs during late adolescence, generally the
earliest time of onset of psychotic symptoms in patients with
schizophrenia. Prefrontal decrease in regional cerebral metabolic rate of
glucose (rCMRglc) measured by PET has been noted in some studies of
chronic, medication-free patients. This could be related to a defect in
the hippocampal region. This project will use the high-resolution (2.6 mm) 600-crystal PET
(PET-600) and the tracer [F-18]-2-fluoro-2-deoxyglucose (FDG) for the
measurement of rCMRglc in schizophrenia. We will correlate rCMRglc in the
hippocampal region with typical symptoms of schizophrenia, in order to test
the hypothesis that the hippocampal function is involved in producing these
symptoms. We will also study the effects of two different anti-psychotic
agents, remoxipride and haloperidol, on hippocampal, limbic, and striatal
glucose metabolism in schizophrenia. An important strength of the proposed research is the use of a PET system
with sufficient spatial resolution to quantitate activity in the
hippocampal region. Blurring (lower recovery coefficients) seen in lower
resolution systems results in a reduction of the apparent metabolic rate.
High resolution of the scanner, however, increases the need for accuracy of
positioning. We achieve this accuracy by the use of high resolution
emission and transmission images obtained with the same instrument, as well
as with magnetic resonance imaging (MRI). A total of 24 normal subjects and 24 patients with schizophrenia will be
studied over a 4 year period. Twelve of the patients will be studied after
a two week medication-free period and again after six weeks of treatment
with remoxipride. The remaining twelve patients will be studied after two
weeks free of medication and again after six weeks of treatment with
haloperidol. This project is focused on the investigation of hippocampal metabolism in
schizophrenia seeking to localize functional abnormalities. The
relationship between anterior hippocampal region (including amygdala) and
striatal region rCMRglc with psychotic and motor symptoms of schizophrenia
will be studied.
Effective start/end date9/1/918/31/96


  • National Institutes of Health


  • Medicine(all)


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