Altered [H-3]imipramine and 5-HT2 but not [H-3]paroxetine binding sites inplatelets from depressed patients

Background: Serotonergic system alterations were studied in 51 depressed pa tients classified according to DSM-III-R criteria for major depression with melancholia compared to 31 healthy controls. Method: [H-3]Imipramine and [ H-3]paroxetine binding sites and the 5HT2 receptor were simultaneously dete rmined in blood platelet membranes. Results: A significantly lower maximum binding in [H-3]imipramine binding was observed in depressed patients compa red to controls (1134 +/- 74 vs. 1712 +/- 106 fmol/mg protein, P < 0.0001) without changes in the equilibrium dissociation constant (1.10 +/- 0.05 vs. 1.25 +/- 0.09 nM). [H-3]Paroxetine binding did not differ between the two groups (B-max, 1441 +/- 55 vs. 1280 +/- 81 fmol/mg protein; K-d, 0.060 +/- 0.002 vs. 0.062 +/- 0.002 nM). The K-d value of 5HT2 binding was lower in d epressed patients than controls (0.95 +/- 0.04 vs. 1.15 +/- 0.09 nM, P < 0. 039) without changes in maximum binding (140 +/- 11 vs. 127 +/- 14 fmol/mg protein). Conclusions: Taken together, these results suggest that [H-3]imip ramine and 5HT2 receptors may be good biological markers for serotonergic d ysfunction in depressive disorders. (C) 1999 Elsevier Science B.V. All righ ts reserved.