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.
El Khoury
A
A
Department of Clinical Neuroscience and Karolinska Institute, St Göran's Hospital, Stockholm, Sweden. aram.el-khoury@spo.sll.se
Johnson
L
L
Aberg-Wistedt
A
A
Stain-Malmgren
R
R
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects*; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008238:Lysergic Acid Diethylamide / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000493:pharmacokinetics; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000097:blood; D050486:Serotonin Plasma Membrane Transport Proteins; D016896:Treatment Outcome
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018341:Receptors, Adrenergic, alpha-2; D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D016651:Lithium Carbonate; D012701:Serotonin; D017374:Paroxetine; D008238:Lysergic Acid Diethylamide