The
cocaine analogue 2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (
beta-CIT) is a potent
ligand for both
dopamine- and
serotonin uptake sites which in its 123I labeled form can be used for single photon emission computerized tomography (SPECT). It was demonstrated previously by SPECT-studies in non-human primates that 123I-beta-CIT binds to
dopamine transporters in the striatum and to
serotonin transporters in hypothalamus and midbrain. The aim of the present study was to compare 123I-beta-CIT binding in the brain stem of normal controls and a group of subjects under treatment with the
selective serotonin reuptake inhibitor (SSRI)
citalopram. 123I-beta-CIT-SPECT was performed in 12 depressed patients under 20 mg (n = 5), 40 mg (n = 6) and 60 mg (n = 1)
citalopram daily, in one untreated depressed patient and in 11 controls at regular time intervals up till 24 hours p.inj. A highly significant reduction of
beta-CIT binding was found in an area including mesial thalamus, hypothalamus, midbrain and pons in patients under
citalopram compared to controls (44.1 +/- 14.4 vs. 82.3 +/- 18.6cpm's/mCi x kg
body weight; specific binding 4 hrs p.inj.; p = 0.0001). No differences were seen between the high and low dose group and no changes were found in the striatum. 123I-beta-CIT binding in the brain stem and striatum in one untreated depressed patient fell within the range of control values. To our knowledge this is the first report directly demonstrating the effect of a selective
serotonin uptake inhibitor in the brain in humans in vivo. SPECT measurements of
serotonin uptake sites in patients with depression and other
psychiatric disorders might provide better insights into the pathophysiology of these disorders and into mechanisms of
drug action.