Imaging of serotonin transporters and its blockade by citalopram in patients with major depression using a novel SPECT ligand [123I]-ADAM

Herold, N.; Uebelhack, K.; Franke, L.; Amthauer, Holger; L, Luedemann; Bruhn, H.; Félix, R.; Uebelhack, Ralf; Plotkin, Michail

doi:10.1007/s00702-005-0429-7

Cited by 56 publications

(46 citation statements)

References 52 publications

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“…Our results confirm previous reports of similar SERT availability in the midbrain and diencephalon in MDD patients and healthy subjects [14][15][16][17][18]. Other studies have shown increased [19] or decreased [7][8][9][10][11][12][13] SERT availability in MDD patients compared with healthy subjects.…”

Section: Comparison With Previous Studiessupporting

confidence: 91%

“…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].…”

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confidence: 99%

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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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Section: Comparison With Previous Studiessupporting

confidence: 91%

mentioning

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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“…Neuroimaging investigations, sampling subjects with early onset MDD who are medication free for greater than 2 months, are non-smoking and do not have comorbid axis I disorders, and also apply better quality radiotracer technology, tend to find either no change in regional 5-HTT binding or an increase in regional 5-HTT binding (Cannon et al 2007;Herold et al 2006;Ichimiya et al 2002;Meyer et al 2004a). Investigations which include sampling of subjects with late onset MDD, Correlations between dysfunctional attitudes (DAS) and serotonin transporter binding potential (5-HTT BP) in some of the larger regions in depressed subjects.…”

Section: Dysfunctional Attitudes During Major Depressive Episodes Andmentioning

confidence: 99%

Neurochemical Imaging and Depressive Behaviours

Meyer

2012

Current Topics in Behavioral Neurosciences

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Neurochemical imaging is frequently applied to measure markers of pathological change so as to understand mechanisms that create symptoms of major depressive disorder. For example, indices of greater monoamine oxidase A(MAO-A) level, particularly in the prefrontal and anterior cingulate cortex, are associated with depressed mood states, and high-risk states for onset of major depressive episodes. MAO-A metabolises monoamines, and greater metabolism of monoamines occurs when MAO-A is elevated in brain. Lower extracellular serotonin is associated with greater pessimism in humans and chronic serotonin deficiency is associated with upregulation of 5-HT2A (serotonin2A) receptors in cortex. During major depressive episodes when pessimism is more severe, greater 5-HT2A BPND, an index of density occurs in prefrontal and anterior cingulate cortex. These results argue for a mechanism of lowering extracellular serotonin in the prefrontal and anterior cingulate cortex, consequent to elevated MAO-A level. The relationship between elevated 5-HTT BPND and greater pessimism during major depressive episodes suggests that greater 5-HTT density in the context of elevated MAO-A level further contributes to serotonin deficiency in these brain regions. A similar mechanism may explain the association between neuroimaging indices of greater dorsal striatal D2 density, DAT density and symptoms of motor retardation: Greater MAO-A level and relatively greater DAT density lower extracellular dopamine in the dorsal striatum, leading to motor retardation. Indices of greater 5-HT1A density, particularly in the cingulate cortex, have been associated with major depressive disorder, and well as anxiety disorders, suggesting that this abnormality is mechanistically related to presence of anxiety symptoms. To date, abnormalities of Glx a measure reflecting glutamate and glutamine levels have been most strongly associated with presence of major depressive episodes, with greater levels in occipital cortex, and reduced levels in prefrontal cortex. Ultimately, the future for neurochemical imaging is to better understand the mechanisms that predispose toward onset of MDE so as to create biologically informed, novel, methods of prevention, and superior, more symptom-targeted treatments.

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“…A recent DATSCAN study has revealed moderately reduced abundance of dopamine transporters in striatum of never-treated patients with schizophrenia (Mateos et al 2007 ) , which seems somewhat at odds with the fi nding of increased effects of amphetamine, noted above. The [ (Frokjaer et al 2008 ) ; SPECT studies with this tracer have revealed increased serotonin transporters in the brainstem of subjects with borderline personality disorder (Koch et al 2007 ) , and have shown the occupancy at serotonin transporters in depressed patients under treatment with citalopram (Herold et al 2006 ) . SPECT tracers for serotonin receptors, as opposed to presynaptic serotonin transporters, are not yet widely available.…”

Section: The Radiation Physics Of Molecular Imagingmentioning

confidence: 98%

Overview of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) Methodologies

Cumming

Böning

2011

Neural Metabolism in Vivo

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Molecular imaging with single photon emission computed tomography (SPECT) and positron emission tomography (PET) has revolutionized neuroscience. The external detection of radioactively labeled tracers allows the quantitative analysis of fundamental physiological processes in living brain of experimental animals, and human subjects. For molecular imaging, particular radioisotopes are incorporated into molecules (tracers) intended to serve as markers for cerebral blood fl ow, blood brain barrier physiology, energy metabolism, neurotransmitter synthesis, and neurotransmitter receptors. These tracers are administered to the subject by inhalation or intravenous injection, and swiftly delivered to brain in the arterial blood. During the processes of partitioning of the tracer across the blood brain barrier and its binding to specifi c molecular targets in brain, decay events are recorded by the tomograph and reconstructed into an image, or source map. After registration of the map to a brain template, the radioactivity concentration is assigned to specifi ed anatomic regions. Especially in PET, temporal changes in the brain concentration of radioactivity can be analyzed according to principles of compartmental analysis, so as to evaluate the step-wise processes of tracer uptake and entrapment in brain. The goal of this endeavour is to extract from the images physiological information about the relatively unperturbed brain, which can inform us about the processes underlying cognition, healthy aging, and diseases of the central nervous system. However the interpretation of PET and SPECT images is subject to caveats dictated by factors such as the limited spatial resolution of the instruments, and the validity of the kinetic analyses, which can only approximate the true complexity of biological processes.

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Imaging of serotonin transporters and its blockade by citalopram in patients with major depression using a novel SPECT ligand [123I]-ADAM

Cited by 56 publications

References 52 publications

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

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

Neurochemical Imaging and Depressive Behaviours

Overview of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) Methodologies

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