There is a growing body of scientific evidence suggesting an alteration in Na+, Li+, and choline transport in erythrocytes, as well as membrane molecular dynamics in erythrocytes and lymphocytes from patients with affective illness. There are theoretical reasons, supported by experimental data, to suggest that the alterations in membrane molecular dynamics might provide the molecular basis for the alterations in cation transport. Alterations in membrane molecular dynamics might also result in a more generalized alteration in membrane cation permeability, including the permeability to divalent cations. The reported alterations in Na+, Li+ and choline transport might also result in alterations in cellular metabolic processes and the intracellular molecular mileau. In this grant application, a series of double-blind studies are proposed to be carried out on 50 bipolar depressed, 20 bipolar manic, 50 recurrent unipolar, and 50 control subjects. The proposed studies will be complimentary to and synergistic with previous studies by other investigators on membrane alterations (such as Na+, Li+, and choline transport) in affective illness. The membrane properties to be studied on intact erythrocytes are: 1) membrane molecular dynamics as assayed by fluorescence spectroscopy, and 2) membrane transport, intracellular, extracellular, and intramembranous concentration and atomic mobility of Na+ and Li+ as assayed by 23Na and 7Li NMR. The specific questions to be asked are: 1) Are there alterations in the measured membrane properties of erythrocytes from patients with affective illness (bipolar depressed, bipolar manic, recurrent unipolar) that distinguish them from normal control erythrocytes? 2) Are there alterations in the measured erythrocyte membrane properties that distinguish the 3 different clinical groups (bipolar depressed, bipolar manic, recurrent unipolar) from each other? 3) Do any identified membrane alterations appear to be primarily state or trait markers? and 4) Does medication appear to affect any of the observed membrane alterations?
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