Variations in [3H]imipramine and 5-HT2A but not [3H]paroxetine binding sites in suicide brains

Both the [H-3]imipramine and [H-3]paroxetine binding sites and the 5-HT2A receptor were simultaneously determined in frontal cortex, cingulate cortex, hippocampus and amygdala from 17 control subjects and 17 depressed suicide victims. A significant decrease in the maximum binding (B-max) of [H-3]imipramine was observed in the hippocampus of suicide victims as compared to control subjects (160 @ 25 vs. 328 @ 52 fmol/mg protein; P = 0.007) without changes in the apparent affinity constant (K-d). Furthermore, a significant decrease in the number of 5-HT2A binding sites, together with a significantly lower K-d, was also observed in the hippocampus of suicides as compared to control subjects (129 @ 18 vs. 225 @ 32 fmol/mg protein; P = 0.02 and 0.91 @ 0.07 vs. 1.38 @ 0.08 nM, respectively; P = 0.006). [H-3]Paroxetine binding did not display modifications between the two groups in either B-max or K-d from any of the brain regions studied. When all four brain regions were taken together, a down-regulation was noted between presynaptic [H-3]imipramine binding and the postsynaptic 5-HT2A, receptor (r = -0.40: P = 0.0013) in the control group. This correlation did not appear in the suicide group. No correlation was observed between [H-3]paroxetine binding and the 5-HT2A receptor in either control subjects or suicides. Taken together, these results suggest that the 5-HT uptake site measured with [H-3]imipramine and the 5-HT2A receptors are reliable markers of serotonergic dysfunction. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.