| dc.description.abstract | 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. | en |
