Reduced midbrain serotonin transporter availability in drug-naïve patients with depression measured by SERT-specific [123I] nor-β-CIT SPECT imaging

Joensuu, Mikko; Tolmunen, Tommi; Saarinen, Pirjo; Tiihonen, Jari; Kuikka, Jyrki T.; Ahola, Pasi; Vanninen, Ritva; Lehtonen, Johannes

doi:10.1016/j.pscychresns.2006.08.001

Cited by 66 publications

(49 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We performed measurements on healthy subjects. Because several medical conditions can influence brain SERT (e.g., Parkinson disease and Lewy bodies dementia (5,6), panic disorder (19), and depression (22,23)), it is unknown at present whether peak extrastriatal SERT binding of 123 I-FP-CIT is similar in subjects with any of these diseases. This topic also needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with ¹²³I-FP-CIT SPECT in Healthy, Male Subjects

Koopman

Fleur²,

Fliers³

et al. 2012

J Nucl Med

View full text Add to dashboard Cite

123 I-N-v-fluoropropyl-2b-carboxymethoxy-3b-(4-iodophenyl) nortropane ( 123 I-FP-CIT) is commonly used to assess the dopamine transporter in the striatum. However, recent studies suggest that this tracer may be used also to assess binding to monoamine transporters in the midbrain or diencephalon, which may reflect predominantly serotonin transporter (SERT) binding. However, it is still unclear at what time point after injection SPECT should be performed for optimal assessment of SERT with 123 I-FP-CIT. Therefore, we examined the time course of extrastriatal 123 I-FP-CIT binding. Methods: Nineteen healthy, male subjects were included, and SPECT images were acquired up to 3 h after 123 I-FP-CIT injection. Region-of-interest analysis was performed, and specific-to-nonspecific binding ratios were calculated. Results: Specific-to-nonspecific 123 I-FP-CIT binding ratios in the midbrain and diencephalon were significantly higher 2 h after injection than 1 h after injection and remained stable between 2 and 3 h after injection. Conclusion: The optimal time frame for assessing 123 I-FP-CIT binding to extrastriatal SERT is between 2 and 3 h after injection of the tracer. In 2000, the radiotracer 123 I-N-v-fluoropropyl-2b-carboxymethoxy-3b-(4-iodophenyl)nortropane ( 123 I-FP-CIT) was registered in Europe to assess striatal dopamine transporter (DAT) binding, and it is now commonly used to study the integrity of nigrostriatal dopaminergic neurons in vivo (1). Recently, the same tracer was licensed in the United States. The optimal time point for measuring striatal DAT is between 3 and 6 h after bolus injection of 123 I-FP-CIT (2).In vitro studies showed a high affinity of 123 I-FP-CIT for the DAT. However, this tracer also has a moderate affinity for the serotonin transporter (SERT) (3). Indeed, in healthy controls we showed that, after administration of the selective serotonin reuptake inhibitor paroxetine, 123 I-FP-CIT binding was significantly blocked in the SERT-rich midbrain and diencephalon (4). Likewise, another recent study showed that thalamic binding of 123 I-FP-CIT could be blocked by the selective serotonin reuptake inhibitor citalopram (5). The relative anatomic segregation between striatal DAT and extrastriatal SERT binding sets the condition for 123 I-FP-CIT SPECT studies to examine also SERT in vivo. Interestingly, recent clinical FP-CIT SPECT studies showed not only loss of striatal DAT but also loss of midbrain SERT binding in dementia with Lewy bodies and in Parkinson patients with depression (6,7). In these 2 studies, 123 I-FP-CIT binding in SERT-rich areas was measured 3 h after injection, but it is not known whether this time point is optimal for assessing FP-CIT binding to SERT.Abi-Dargham et al. studied 4 healthy controls and showed that peak specific 123 I-FP-CIT binding in the midbrain occurred at 72 6 37 min after injection, followed by slow washout (3). In a previous study, we measured SERT binding in the midbrain and diencephalon only at 1 and 3 h after injection of 123 I-FP-CIT (4). These preli...

show abstract

Section: Discussionmentioning

confidence: 99%

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with ¹²³I-FP-CIT SPECT in Healthy, Male Subjects

Koopman

Fleur²,

Fliers³

et al. 2012

J Nucl Med

View full text Add to dashboard Cite

show abstract

“…Thus, we recruited severely affected and often melancholic patients who were drug-free, with 69% of the patients being drug-naive. Three studies [7,13,31] included larger proportions of drug-naive patients. Like Parsey et al [10], we observed (nonsignificant −15%) lower midbrain SERT availability in drug-naive patients (results available on request).…”

Section: Methodological Explanations For Inconsistent Findingsmentioning

confidence: 99%

“…Other studies have shown increased [19] or decreased [7][8][9][10][11][12][13] SERT availability in MDD patients compared with healthy subjects. However, none of these studies except two [11,13] investigated the effect of gender, and none of the study corrected for season. Furthermore, we confirmed a significant contribution of season of scanning on midbrain BP ND [24].…”

Section: Comparison With Previous Studiesmentioning

confidence: 99%

“…Studies comparing depressed patients with healthy subjects have shown decreased [7][8][9][10][11][12][13], unchanged [14][15][16][17][18] or increased [19] SERT availability in MDD patients. A negative correlation between SERT availability and the severity of depression, measured in terms of Hamilton depression rating scale (HDRS) scores, has been reported in patients with primary MDD [9] or Wilson's disease [20].…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

“…Estudos de tomografia computadorizada em pacientes com diagnóstico de depressão que não estavam recebendo nenhuma medicação antidepressiva, observaram reduções na densidade de 5-HTT no mesencéfalo (Malison et al, 1998;Joensuu et al, 2007).…”

Section: Mesencéfalounclassified

Administração prolongada do ácido 13-cis-retinóico (isotretinoína) em camundongos machos adolescentes: comportamentos emocionais e quantificação de transcritos de componentes do sistema serotoninérgico central.

Ofuchi¹

View full text Add to dashboard Cite

Reduced midbrain serotonin transporter availability in drug-naïve patients with depression measured by SERT-specific [123I] nor-β-CIT SPECT imaging

Cited by 66 publications

References 39 publications

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with ¹²³I-FP-CIT SPECT in Healthy, Male Subjects

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with ¹²³I-FP-CIT SPECT in Healthy, Male Subjects

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

Administração prolongada do ácido 13-cis-retinóico (isotretinoína) em camundongos machos adolescentes: comportamentos emocionais e quantificação de transcritos de componentes do sistema serotoninérgico central.

Contact Info

Product

Resources

About

Reduced midbrain serotonin transporter availability in drug-naïve patients with depression measured by SERT-specific [123I] nor-β-CIT SPECT imaging

Cited by 66 publications

References 39 publications

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with 123I-FP-CIT SPECT in Healthy, Male Subjects

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with 123I-FP-CIT SPECT in Healthy, Male Subjects

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

Administração prolongada do ácido 13-cis-retinóico (isotretinoína) em camundongos machos adolescentes: comportamentos emocionais e quantificação de transcritos de componentes do sistema serotoninérgico central.

Contact Info

Product

Resources

About

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with ¹²³I-FP-CIT SPECT in Healthy, Male Subjects

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with ¹²³I-FP-CIT SPECT in Healthy, Male Subjects