Biochemical and pharmacological studies on blood platelets and erythocytes in affective illness
This thesis describes various measurements made in blood platelets and erythrocytes from patients suffering from affective disorders, and the effect a variety of therapies have on these measures. No significant differences were detected in either platelet membrane ATPase or adenyl cyclase specific activity in any of the groups of patients studied, when compared to values obtained in control subjects. However, unipolar depressed and bipolar manic patients were shown to have a reduced erythrocyte membrane Na+ + K+- ATPase and Ca2++Mg2+-ATPase activity, respectively. It is suggested that membrane enzyme changes found in some peripheral cells in patients suffering from affective disorders, are not common to all peripheral cells, and may or may not reflect central nervous system changes. The decreased Na++ K+-ATPase activity in erythrocytes was found to be correlated with a reduction in the number of sodium pump sites. This reduction did not appear to be caused by a change in the phospholipid composition of the membrane. Neither amitripty1ine nor mianserin, in vivo or in vitro, affected platelet membrane ATPase activity. Lithium, in vitro, however, stimulated platelet Mg2+-ATPase activity. Both amitriptyline and mianserin therapy, and subsequent recovery, caused erythrocyte membrane Na++K+-ATPase activity in unipolar depressives to approach control values. In vitro neither drug affected the erythrocyte membrane. ECT did not affect the reduced Na++ K+-ATPase activity of erythrocyte membranes in unipolar depressed patients. After a course of treatment a slight increase in Ca2+-ATPase activity in erythrocyte membranes was observed. Although it is considered likely that an observed reduction in erythrocyte membrane Na++ K+-ATPase activity indicates a susceptibility to depression, increases in that Na++ K+-ATPase activity do not seem to be obligatory for clinical improvement to take place. A reduced Vmax for the 5"HT uptake process into platelets was observed in both unipolar and bipolar depressed patients, while Vmax values were found to be elevated in untreated unipolar well patients. Whole blood 5_HT levels in these patients were found to be normal. Lithium administration did not appear to affect platelet 5"HT uptake. Mianserin therapy and recovery caused a change towards normal Vmax values in unipolar depressed patients. Amitriptyline therapy and recovery caused reduced Vmax values to decrease further, Km values for the process to increase, and whole blood 5~HT levels to fall dramatically, in vitro, the two drugs acted in a similar manner, causing a decrease in Vmax and an increase in Km- As Vmax values appear to be independent of clinical condition in treated patients, a reduced Vmax for 5-HT uptake into platelets from untreated patients appears to represent at most a predisposition towards depression.