REDUCED BRAIN-SEROTONIN TRANSPORTER AVAILABILITY IN MAJOR DEPRESSION AS MEASURED BY [I-123] 2-BETA-CARBOMETHOXY-3-BETA-(4-IODOPHENYL)TROPANE AND SINGLE-PHOTON EMISSION COMPUTED-TOMOGRAPHY

Background: Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post -mortem brain tissue of depressed patients. We sought to determine whe ther patients with unipolar major depression have diminished SERT avai lability as assessed by both brainstem [I-123]beta-CIT SPECT and plate let [H-3]paroxetine binding. Methods: Drug-free depressed and healthy subjects were injected with 211 +/- 22 MBq [I-123]beta-CIT mid imaged 24 +/- 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V-3'' = (brainstem-occipital)/occipital), a measure proportional to the binding potential (B-max/K-d), was used fo r all comparisons. Results: Results showed a statistically significant reduction in brainstem V-3'' values in depressed as compared to healt hy subjects (3.1 +/- .9 vs. 3.8 +/- .8, p = .02). Platelet [H-3]paroxe tine binding was nor altered (B-max = 2389 +/- 484 vs. 2415 +/- 538 fm ol/mg protein, p = .91) and was not significantly correlated with brai nstem [I-123]beta-CIT binding (r = -0.14, p = .48). Conclusions: These data are rite first to suggest reductions in the density of brain SER T binning sires in living depressed patients. These findings provide f urther support for a preeminent role for alterations in serotonergic n eurons in the pathophysiology of depression. (C) 1998 Society of Biolo gical Psychiatry.