Reduced brain serotonin transporter availability in major depression as measured by [123I]-2β-carbomethoxy-3β-(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 whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [I-123]beta-CIT SPECT and platelet [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 for all comparisons. Results: Results showed a statistically significant reduction in brainstem V-3" values in depressed as compared to healthy subjects (3.1 +/- .9 vs. 3.8 +/- .8, p = .02). Platelet [H-3]paroxetine binding was nor altered (B-max = 2389 +/- 484 vs. 2415 +/- 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [I-123]beta-CIT binding (r = -0.14, p = .48). Conclusions: These data are rite first to suggest reductions in the density of brain SERT binning sires in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression. (C) 1998 Society of Biological Psychiatry.