Evidence for an increase in functional platelet 5-HT2A receptors in depressed patients using the new ligand [I-125]-DOI

Abnormalities in the serotonergic system have been implicated in the pathop hysiology of depressive disorders. Human platelets possess serotonin-2A (5- HT2A) receptors, and previous research using LSD or ketanserin as ligands h ave indicated that their number is increased in depressed patients. Compare d to other ligands previously used in platelet studies, DOI is highly selec tive for the 5-HT2A receptor and binds to its high-affinity state, therefor e labeling only the receptors that are biologically coupled to the G-protei n. We determined the density (Bmax) and the affinity (Kd) of 5-HT2A recepto rs labeled by [I-125]-DOI in platelets from 21 untreated patients with majo r depression and 21 healthy volunteers. The density of the 5-HT2A binding s ites was found to be increased in platelets from female depressed patients as compared to controls. No changes were observed in the Kd. We did not fin d any relationship between the binding parameters and either the severity o f the depressive episode or the suicidal tendencies of the patients. Our re sults show that the number of coupled platelet 5-HT2A receptors is increase d in depressed patients, indicating that platelet 5-HT2A receptor function is enhanced in depression. (C) 1999 Editions scientifiques et medicales Els evier SAS.