Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with [ 11 C]McN 5652

Kent, Justine; Coplan, Jeremy D.; Lombardo, Ilise; Hwang, Dah‐Ren; Huang, Yiyun; Mawlawi, Osama; Heertum, Ronald L. Van; Slifstein, Mark; Abi‐Dargham, Anissa; Gorman, Jack M.; Laruelle, Marc

doi:10.1007/s00213-002-1218-8

Cited by 68 publications

(51 citation statements)

References 20 publications

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“…There was, however, one subject in whom the cerebellar V T remained unchanged when the graphical analysis of reversible binding of the TAC was performed (Table 2, subject 1). The reductions of the cerebellar V T of this investigation are in line with previous reports by Parsey et al (2006a) who found in a [ 11 C]DASB study 33% occupancy in cerebellar grey matter of subjects after an acute treatment with sertraline or by Kent et al (2002) who reported from a [ 11 C]McN5652 study of five subjects with social phobia a reduction of the cerebellar V T of 23%±12% after paroxetine treatment. However, these reductions appear to be higher than expected from a blockade of the specific binding of the radioligand in the cerebellum given that the specific binding of [ 3 H]citalopram in autoradiographic studies of porcine brain has been reported as only 2.3 pmol/g tissue in the cerebellum in comparison with 26 pmol/g tissue in the amygdaloid area (Kretzschmar et al, 2003).…”

Section: Discussionsupporting

confidence: 91%

Effects of Citalopram Infusion on the Serotonin Transporter Binding of [¹¹C]DASB in Healthy Controls

Hinz

Selvaraj

Murthy

et al. 2008

J Cereb Blood Flow Metab

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The positron emission tomography (PET) ligand [ 11 C]DASB is currently the most widely used imaging agent for quantitative studies of the serotonin transporter (SERT) in human brain. The aim of this work was to assess the effects of an intravenous infusion of 10 mg citalopram, a selective serotonin reuptake inhibitor (SSRI), before the PET scan on the kinetics of [ 11 C]DASB in arterial plasma and in selected brain regions. Four healthy male volunteers underwent two PET scans with a mean of 523 MBq injected activity after either placebo or citalopram infusion in a randomised design. The citalopram infusion led to a substantial increase of the area under the curve of the metabolitecorrected arterial plasma input function. Total volumes of distribution V T were estimated applying the Logan plot to regional time-activity curves or by generating parametric maps with spectral analysis. A mean reduction of the cerebellar V T of 19% with Logan analysis and of 24% with spectral analysis was observed after citalopram infusion, which confirms previous findings of displaceable SERT ligand binding in cerebellar grey matter. The SERT occupancy for six target regions with moderate to high binding was 60% derived from BP ND and 69% derived from BP P .

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Section: Discussionsupporting

confidence: 91%

Effects of Citalopram Infusion on the Serotonin Transporter Binding of [¹¹C]DASB in Healthy Controls

Hinz

Selvaraj

Murthy

et al. 2008

J Cereb Blood Flow Metab

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“…This suggests a similar mode of action of these medication groups in serotonergic neurons. These findings are in line with results from PET studies on SERT occupancy using the selective ligands [ 11 C]DASB and [ 11 C]( + )McN5652 in major depression, social phobia and healthy volunteers showing similar degrees of SERT occupancy with SSRIs and clomipramine (Meyer et al, 2001;Kent et al, 2002;Suhara et al, 2003;Meyer et al, 2004). However, rates of SERT occupancy measured with these selective ligands are higher (about 80%) than those measured with b-CIT SPECT, which may be explained by the non-selectivity of b-CIT and contribution of dopamine and norepinephrine transporter binding to the signal measured in SERT-rich brain regions (for review see Meyer, 2007).…”

Section: Discussionsupporting

confidence: 87%

Changes in Thalamus–Hypothalamus Serotonin Transporter Availability during Clomipramine Administration in Patients with Obsessive–Compulsive Disorder

Zitterl

Aigner

Stompe

et al. 2008

Neuropsychopharmacol

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To the authors' knowledge there is as of yet no study demonstrating in vivo alterations in human serotonin transporters (SERT) during clomipramine treatment in patients with obsessive-compulsive disorder. The only study in which SERT binding has been investigated in obsessive-compulsive disorder (OCD) patients before and after treatment is a small pilot study by Stengler-Wenzke et al (2006), who treated five OCD patients with citalopram. In the study at hand, we measured transporter availability in the thalamus-hypothalamus with [ 123 I] b-CIT single photon emission computed tomography (SPECT) in 24 patients with DSM-IV OCD. All patients displayed prominent behavioral checking compulsions (OC-checkers). At baseline and upon medication after 12 weeks of treatment with clomipramine (150 mg daily) 24 non-depressed OC-checkers underwent a SPECT measurement of brain SERT availability using [ 123 I]-2b-carbomethoxy-3b-(4-iodophenyl)tropane. For quantification of brain serotonin transporter availability, a ratio of specific to nondisplaceable [ 123 I] b-CIT brain binding was used (BP ND ¼ (thalamus and hypothalamusÀcerebellum)/cerebellum). The SERT availability was compared between baseline and after treatment and correlated with severity of OC symptomatology and treatment response as assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). After treatment with clomipramine patients showed a 48% reduced brain serotonin transporter availability in the thalamus-hypothalamus, as compared with values at baseline (0.72±0.12 vs 1.39±0.18, po0.001). Correlations between brain SERT availability and OC symptomatology (Y-BOCS scores) revealed significantly negative associations both at baseline and after treatment (r ¼ À0.46; po0.05 and r ¼ À0.53; po0.01 respectively). These data suggest that the SERT availability values could be considered a biological indicator of disease severity. Moreover, in search of predictors we found that higher pretreatment SERT availability significantly predicted better treatment response 12 weeks later (B ¼ 14.145 ± 4.514; t ¼ 3.133; p ¼ 0.005). These results provide further support for an important role of alterations in serotonergic neurons in the pathophysiology of OCD.

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“…The cerebellum (especially the vermis) contains small amounts of SERT [43,44], which could result in an underestimation of BP ND in patients and healthy controls, expected to be 7% at most [45]. [ 123 I]β-CIT binds in vivo to SERT, DAT and norepinephrine transporters.…”

Section: Methodological Explanations For Inconsistent Findingsmentioning

confidence: 99%

Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Ruhé

Booij

Reitsma

et al. 2009

Eur J Nucl Med Mol Imaging

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Purpose The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls. Methods We included 49 depressed outpatients (mean±SD 42.3±8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for ≥4 weeks, and 49 healthy controls matched for age (±2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [ 123 I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BP ND ) in the midbrain and diencephalon with cerebellar binding as a reference. Results In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosis×gender interaction; p=0.048). In the diencephalon we found a comparable diagnosis×gender interaction (p=0.002) and an additional smoking×gender (p=0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p=0.018) with higher SERT availability in winter. Conclusion Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosis×gender and gender×smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.

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Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with [ 11 C]McN 5652

Abstract: The results of this study in an anxiety disorder sample are consistent with previously reported results in a depressed sample and suggest that paroxetine at therapeutic doses achieves very high occupancy levels of the SERT.

Cited by 68 publications

References 20 publications

Effects of Citalopram Infusion on the Serotonin Transporter Binding of [¹¹C]DASB in Healthy Controls

Effects of Citalopram Infusion on the Serotonin Transporter Binding of [¹¹C]DASB in Healthy Controls

Changes in Thalamus–Hypothalamus Serotonin Transporter Availability during Clomipramine Administration in Patients with Obsessive–Compulsive Disorder

Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

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Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with [ 11 C]McN 5652

Abstract: The results of this study in an anxiety disorder sample are consistent with previously reported results in a depressed sample and suggest that paroxetine at therapeutic doses achieves very high occupancy levels of the SERT.

Cited by 68 publications

References 20 publications

Effects of Citalopram Infusion on the Serotonin Transporter Binding of [11C]DASB in Healthy Controls

Effects of Citalopram Infusion on the Serotonin Transporter Binding of [11C]DASB in Healthy Controls

Changes in Thalamus–Hypothalamus Serotonin Transporter Availability during Clomipramine Administration in Patients with Obsessive–Compulsive Disorder

Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

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Effects of Citalopram Infusion on the Serotonin Transporter Binding of [¹¹C]DASB in Healthy Controls

Effects of Citalopram Infusion on the Serotonin Transporter Binding of [¹¹C]DASB in Healthy Controls