PLATELET SEROTONERGIC INDEXES IN MAJOR DEPRESSION - UP-REGULATION OF 5-HT2A RECEPTORS UNCHANGED BY ANTIDEPRESSANT TREATMENT

This study examined, in the largest sample of major depressives report ed so far, platelet serotonergic parameters (5-HT uptake, [H-3]paroxet ine binding and 5-HT2A receptors measured by [H-3]LSD binding) in 60 a ntidepressant-free depressed patients and 40 age- and gender-matched c ontrol subject's before treatment, and in 45 major depression patients during treatment with antidepressants. We found that, at baseline, th e density (B-max) of 5-HT2A receptors was significantly higher (by 39% ) in depressed patients than in controls. Suicidal patients had signif icantly higher B-max values than controls or non-suicidal patients. Th e rate of serotonin uptake (V-max) but not the uptake at a single conc entration, was significantly higher in depressed patients, particularl y in females. There was no significant difference between the K-d or B -max of [H-3]paroxetine binding in control and depressed subjects. Tre atment 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 decr eased during treatment with antidepressants, particularly SSRIs. Suppr ession of 5-HT uptake correlated with decreases in Hamilton depression (HAMD) scores. Our data suggest that the increased density of platele t 5-HT2A receptors may be associated with untreated major depression i n antidepressant-free depressed patients, in particular those with sui cidal thoughts. The persistence after antidepressant treatment and cli nical 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 upt ake inhibition is a relevant factor in antidepressant drug effect and clinical improvement. (C) 1997 Elsevier Science Ireland Ltd.