There is now a significant body of evidence to support the view that the underlying pathology of the psychoses results, at least in part, from abnormalities in membrane dynamics. Psychotic patients have functional membrane abnormalities in such diverse activities as ion transport, phospholipid methylation, hormone- stimulated adenyl cyclase and drug and neurotransmitter receptor binding. Such abnormalities may result from defects in specific receptor binding. Such abnormalities may result from defects in specific systems and/or from more general abnormalities in membrane dynamics and may be sufficiently generalized to be detected in a wide variety of tissues including formed blood elements. Several recent studies have begun to evaluate such general membrane defects characterized by changes in membrane phospholipids or phospholipid metabolism in psychotic patients. The goals of the present study are to document the type and extent of erythrocyte membrane phospholipid abnormalities in diagnostically well-characterized schizophrenic patients and control groups. Our central working hypotheses are: 1. Schizophrenia is associated with a membrane disorder characterized by changes in phospholipid ratios; 2. This membrane disorder is associated with functional changes in membrane characteristics; 3. This membrane disorder is associated with schizophrenia per se, as opposed to psychoses that are not schizophrenia-like 4. This membrane disorder is not a result of chronic neuroleptic treatment.
The specific aims of this study are to examine RBC membranes from patients and controls with respect to (a) phospholipid content and ratios, (b) measures of membrane fluidity, (c) phospholipid methylation, and (d) lithium transport.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH043385-03
Application #
3382888
Study Section
Special Emphasis Panel (SRCM (19))
Project Start
1988-08-01
Project End
1992-07-31
Budget Start
1990-09-01
Budget End
1992-07-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
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Hirschowitz, J; Hitzemann, R; Burr, G et al. (1991) A new approach to dose reduction in chronic schizophrenia. Neuropsychopharmacology 5:103-13
Rubinstein, J E; Hitzemann, R J (1990) Further evidence against the coupling of dopamine receptors to phosphoinositide hydrolysis in rat striatum. Biochem Pharmacol 39:1965-70