Effects of long-term lithium treatment on monoaminergic functions in major depression

Platelet [ 14C]serotonin uptake, the density of serotonin transporters and 5HT 2 receptors, and 5HT 2 and alpha 2 receptor function in platelets were investigated in 29 outpatients (15 women and 14 men) diagnosed as having a major affective disorder (21 bipolar and 8 unipolar). The data were compared with data for 26 healthy volunteers matched for age, sex and season. No differences were found in the mean values for the uptake velocity ( V max) and the affinity ( K m) of the transport carrier for serotonin between patients and controls. However, female patients had lower V max compared to male patients and female control subjects. A positive correlation between plasma lithium and V max and a tendency toward a negative correlation between plasma lithium and K m was observed. Furthermore, there were no differences in platelet B max and K d for [ 3H]paroxetine binding and K d for [ 3H]LSD binding between patients and controls. However, there was an increased number of platelet 5-HT 2 receptors and a difference in serotonin-mediated potentiation of platelet ATP secretion between patients compared to controls, especially in women. The findings in the present study suggest that lithium has a net ameliorating impact on serotonin uptake which may render it resistant to change. They also postulate that the effect of lithium may be attained by a dual influence on postsynaptic serotonergic structures, as it increases both the density and the sensitivity of 5-HT 2 receptors.