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

Abstract 

Platelet [¹⁴C]serotonin uptake, the density of serotonin transporters and 5HT₂ receptors, and 5HT₂ and alpha₂ 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-HT₂ 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-HT₂ receptors.

Keywords: Depression, Lithium, Serotonin, Platelets