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.
|Noponen, M; Sanfilipo, M; Samanich, K et al. (1993) Elevated PLA2 activity in schizophrenics and other psychiatric patients. Biol Psychiatry 34:641-9|
|Qian, Y; Hitzemann, B; Hitzemann, R (1992) D1 and D2 dopamine receptor distribution in the neuroleptic nonresponsive and neuroleptic responsive lines of mice, a quantitative receptor autoradiographic study. J Pharmacol Exp Ther 261:341-8|
|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|