beta-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo.
Neurological University Clinic, Vienna, Austria.Journal of Neural Transmission (Impact Factor: 2.4). 02/1995; 100(3):247-56.
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.
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- "Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant drugs in the USA (Grohol, 2010). They inhibit the action of the SERT to reduce reuptake of serotonin , and consequently they increase serotonin levels in the synaptic cleft (Pirker et al., 1995). Clinical trials have shown the benefit of SSRIs in treating MDD (Fournier et al., 2010), and their effects on emotional processing (Serrano-Blanco et al., 2006; Trivedi et al., 2006). "
ABSTRACT: Altered serotonin transporter levels have been reported in blood and brain of patients with major depressive disorders. However, the strength and consistency of the evidence for altered serotonin transporter availability in major depressive disorder is not clear. To address this, a comprehensive meta-analysis was conducted of all available in vivo neuroimaging and post mortem studies reporting serotonin transporter availability in patients with depression compared with healthy controls. The final sample consisted of fifty (n=27 in vivo and n=25 post mortem) studies including 877 patients with depression (mean age: 42.9 years) and 968 healthy controls (mean age: 42.7 years). In vivo neuroimaging studies indicated reduced serotonin transporter binding in the striatum (g=-0.39, p=0.01), the amygdala (g=-0.37, p=0.01) and the brainstem (g=-0.31, p=0.01), including the midbrain (g=-0.27, p=0.02), but no significant alteration in the thalamus or the hippocampus. The post mortem findings indicated no significant change in serotonin transporter binding in depression in the brainstem (p=0.64), the frontal cortex (p=0.75) and the hippocampus (p=0.32, corrected for publication bias). Although there were too few studies for a meta-analysis, the post mortem studies in the amygdala and striatum showed reduced SERT binding in MDD in absolute terms, consistent with the imaging findings. A number of potential factors might have biased the results of the present meta-analysis such as the imaging modality (post mortem or in vivo neuroimaging), partial volume effects, susceptibility of some radiotracers to synaptic serotonin levels or binding to other monoamine transporters. The results indicate that serotonin transporter availability in depressed patients is reduced in key regions of the limbic system. This provides direct support for the serotonin hypothesis of depression, and underlines the importance of the serotonin transporter as a target of pharmacological treatments. Copyright © 2015. Published by Elsevier B.V.
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- "Nevertheless, in vivo and in vitro receptor ligand occupancy studies strongly suggested that due to the different binding kinetics of [ 123 I]b-CIT to serotonin transporter rich brain areas and the striatum, the delayed state of binding equilibrium allows for almost exclusive quantification of striatal dopamine transporter binding. However, mild signal alterations potentially arising from serotonin transporter binding in the putamen cannot be entirely excluded (Staley et al., 1994; Pirker et al., 1995). It remains to be shown if the distribution of reduced striatal serotonin transporter availability follows that of dopamine transporter in right-handed patients with Parkinson's disease. "
ABSTRACT: The aim of this study was to investigate the distribution and the degree of asymmetric putaminal dopamine transporter availability in right-handed patients with Parkinson's disease and its association with the severity of lateralized motor signs. Asymmetry of motor symptoms was defined by the difference between right- and left-sided scores for lateralized items assessed by the Unified Parkinson's Disease Rating Scale Motor Score in a series of 68 patients with Parkinson's disease (disease duration 2.1 ± 1.5 years; Unified Parkinson's Disease Rating Scale Motor Score 22.7 ± 9). Putaminal dopamine transporter availability was measured with the radioligand [ 123I]β-carboxymethyoxy-3 -β-(4-iodophenyl) tropane ([ 123I]β-CIT) and single photon emission computed tomography. We found that in the right-handed Parkinson's disease cohort, the number of patients who had lower dopamine transporter uptake in the left posterior putamen was significantly greater compared with those with lower uptake in the right posterior putamen (Parkinson's disease-left group, n = 49; Parkinson's disease-right group, n = 19; P < 0.001). In addition, one-way analysis of variance revealed significant reductions of mean total putaminal [ 123I]β-CIT binding of the Parkinson's disease-right patients compared with Parkinson's disease-left patients (P < 0.05).The preponderance of reduced left putaminal dopamine transporter availability strengthens clinical observations of a greater proportion of right-handed patients with Parkinson's disease with predominantly right-sided motor signs and argues against a randomly distributed asymmetric vulnerability of substantia nigra dopaminergic neurons. The coexistence of a subgroup of right-handed patients with Parkinson's disease with more severe and predominant ipsilateral putaminal dopamine transporter decline suggests that asymmetry of dopaminergic denervation and motor dysfunction in Parkinson's disease cannot be fully explained by hemispheric dominance alone, but that other factors must be involved. © 2012 The Author (2012). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals. [email protected] /* */
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- "This would be consistent with the hypothesis that SSRI's increase striatal dopaminergic activity. A number of studies suggest that SSRI's are able to increase striatal DAT binding (Kugaya et al. 2003; De Win et al. 2005), although not all findings are consistent (Kim et al. 2007; Pirker et al. 1995). The nature of interaction of SSRI's and the dopaminergic system in the striatum is poorly understood and complex interactions appear to exist between the serotonergic and dopaminergic systems (Kapur and Remington 1996; Bonhomme and Esposito 1998). "
ABSTRACT: Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using (123)I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects' Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration.
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