Platelet serotonergic indices in major depression: up-regulation of 5-HT 2A receptors unchanged by antidepressant treatment

Abstract

This study examined, in the largest sample of major depressives reported so far, platelet serotonergic parameters (5-HT uptake, [ 3H]paroxetine binding and 5-HT 2A receptors measured by [ 3H]LSD binding) in 60 antidepressant-free depressed patients and 40 age- and gender-matched control subjects before treatment, and in 45 major depression patients during treatment with antidepressants. We found that, at baseline, the density ( B max) of 5-HT 2A 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 maxof [ 3H]paroxetine binding in control and depressed subjects. Treatment with antidepressant drugs of different pharmacological profile had no significant effect on the density of 5-HT 2A receptors, nor did the receptor number predict the response to treatment. The affinity of serotonin uptake site for 5-HT and [ 3H]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-HT 2A receptors may be associated with untreated major depression in antidepressantfree depressed patients, in particular those with suicidal thoughts. The persistence after antidepressant treatment and clinical improvement would suggest that up-regulation of 5-HT 2A receptors is a trait rather than state phenomenon. Correlation of 5-HT uptake suppression with decreases in HAMD scores suggests that serotonin uptake inhibition is a relevant factor in antidepressant drug effect and clinical improvement.