Platelet serotonergic indices in major depression: Up-regulation of 5-HT2A receptors unchanged by antidepressant treatment

This study examined, in the largest sample of major depressives reported so far, platelet serotonergic parameters (5-HT uptake, [H-3]paroxetine binding and 5-HT2A receptors measured by [H-3]LSD binding) in 60 antidepressant-free depressed patients and 40 age- and gender-matched control subject's before treatment, and in 45 major depression patients during treatment with antidepressants. We found that, at baseline, the density (B-max) of 5-HT2A receptors was significantly higher (by 39%) in depressed patients than in controls. Suicidal patients had significantly higher B-max values than controls or non-suicidal patients. The rate of serotonin uptake (V-max) but not the uptake at a single concentration, was significantly higher in depressed patients, particularly in females. There was no significant difference between the K-d or B-max of [H-3]paroxetine binding in control and depressed subjects. Treatment with antidepressant drugs of different pharmacological profile had no significant effect on the density of 5-HT2A receptors, nor did the receptor number predict the response to treatment. The affinity of serotonin uptake site for 5-HT and [H-3]paroxetine significantly decreased during treatment with antidepressants, particularly SSRIs. Suppression of 5-HT uptake correlated with decreases in Hamilton depression (HAMD) scores. Our data suggest that the increased density of platelet 5-HT2A receptors may be associated with untreated major depression in antidepressant-free depressed patients, in particular those with suicidal thoughts. The persistence after antidepressant treatment and clinical improvement would suggest that up-regulation of 5-HT2A receptors is a trait rather than state phenomenon. Correlation of 5-HT2A uptake suppression with decreases in HAMD scores suggests that serotonin uptake inhibition is a relevant factor in antidepressant drug effect and clinical improvement. (C) 1997 Elsevier Science Ireland Ltd.