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| 2. |
- Svensson, Jonas E., et al.
(författare)
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Serotonin transporter availability increases in patients recovering from a depressive episode
- 2021
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Ingår i: Translational Psychiatry. - : Springer. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Molecular imaging studies have shown low cerebral concentration of serotonin transporter in patients suffering from depression, compared to healthy control subjects. Whether or not this difference also is present before disease onset and after remission (i.e. a trait), or only at the time of the depressive episode (i.e. a state) remains to be explored. We examined 17 patients with major depressive disorder with positron emission tomography using [C-11]MADAM, a radioligand that binds to the serotonin transporter, before and after treatment with internet-based cognitive behavioral therapy. In all, 17 matched healthy control subjects were examined once. Cerebellum was used as reference to calculate the binding potential. Differences before and after treatment, as well as between patients and controls, were assessed in a composite cerebral region and in the median raphe nuclei. All image analyses and confirmatory statistical tests were preregistered. Depression severity decreased following treatment (p<0.001). [C-11]MADAM binding in patients increased in the composite region after treatment (p=0.01), while no change was observed in the median raphe (p=0.51). No significant difference between patients at baseline and healthy controls were observed in the composite region (p=0.97) or the median raphe (p=0.95). Our main finding was that patients suffering from a depressive episode show an overall increase in cerebral serotonin transporter availability as symptoms are alleviated. Our results suggest that previously reported cross-sectional molecular imaging findings of the serotonin transporter in depression most likely reflect the depressive state, rather than a permanent trait. The finding adds new information on the pathophysiology of major depressive disorder.
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| 3. |
- Svensson, Jonas E., et al.
(författare)
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Validity and reliability of extrastriatal [C-11]raclopride binding quantification in the living human brain
- 2019
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Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 202
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Tidskriftsartikel (refereegranskat)abstract
- [C-11]raclopride is a well established PET tracer for the quantification of dopamine 2/3 receptors (D2/3R) in the striatum. Outside of the striatum the receptor density is up to two orders of magnitude lower. In contrast to striatal binding, the characteristics of extrastriatal [C-11]raclopride binding quantification has not been thoroughly described. Still, binding data for e.g., neocortex is frequently reported in the scientific literature. Here we evaluate the validity and reliability of extrastriatal [C-11]raclopride binding quantification. Two sets of healthy control subjects were examined with HRRT and [C-11]raclopride: (i) To assess the validity of extrastriatal [C-11]raclopride binding estimates, eleven subjects were examined at baseline and after dosing with quetiapine, a D2/3R antagonist. (ii) To assess test-retest repeatability, nine subjects were examined twice. Non displaceable binding potential (BPND) was quantified using the simplified reference tissue model with cerebellum as reference. Quetiapine dosing was associated with decrease in [C-11]raclopride BPND in temporal cortex (18 +/- 17% occupancy) and thalamus (20 +/- 17%), but not in frontal cortex. Extrastriatal occupancy was lower than in putamen (51 +/- 4%). The mean absolute variation was 4-7% in the striatal regions, 17% in thalamus, and 13-59% in cortical regions. Our data indicate that [C-11]raclopride PET, quantified using cerebellum as reference, is not a suitable tool to measure D2/3R in extrastriatal regions.
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| 4. |
- Tangen, Ämma, et al.
(författare)
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Associations between cognition and serotonin receptor 1B binding in patients with major depressive disorder : a pilot study
- 2017
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Ingår i: Psychiatry Research: Neuroimaging. - Stockholm : Karolinska Institutet, Dept of Clinical Neuroscience. - 0925-4927 .- 1872-7506.
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Tidskriftsartikel (refereegranskat)abstract
- The neurotransmitter serotonin has been widely implicated in the pathophysiology of major depressive disorder (MDD). In animal studies and human neuroimaging studies, involvement of the serotonin receptor 1B (5-HT1BR) in MDD and memory performance has been reported. However, the role of the 5-HT1BR in cognitive functions affected in MDD remains to be clarified. Ten patients with MDD diagnosis were examined with positron emission tomography (PET) and a battery of cognitive tests before and after Internet-based Cognitive Behavioral Therapy (ICBT). The results were compared to ten matched control subjects in order to investigate putative changes in 5-HT1BR availability and cognitive performance. Patients treated with ICBT showed statistically significant improvement relative to baseline in Verbal fluency, both letter and category production. Significant correlations were found between improvement in letter production and changes in 5-HT1BR availability in ventral striatum, between category production and amygdala, as well as between the improvement in Trailmaking test B and change in 5-HT1BR binding in dorsal brainstem, in amygdala and in hippocampus. The results suggest an association between 5-HT1BR binding and improvement in cognitive functioning. Replications in larger-scale studies are required to confirm these findings.
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| 6. |
- Veldman, Emma R, et al.
(författare)
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Serotonin 1B receptor density mapping of the human brainstem using positron emission tomography and autoradiography
- 2022
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 0271-678X .- 1559-7016. ; 42:4, s. 630-641
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Tidskriftsartikel (refereegranskat)abstract
- The serotonin 1B (5-HT1B) receptor has lately received considerable interest in relation to psychiatric and neurological diseases, partly due to findings based on quantification using Positron Emission Tomography (PET). Although the brainstem is an important structure in this regard, PET radioligand binding quantification in brainstem areas often shows poor reliability. This study aims to improve PET quantification of 5-HT1B receptor binding in the brainstem.Volumes of interest (VOIs) were selected based on a 3D [3H]AZ10419369 Autoradiography brainstem model, which visualized 5-HT1B receptor distribution in high resolution. Two previously developed VOI delineation methods were tested and compared to a conventional manual method. For a method based on template data, a [11C]AZ10419369 PET template was created by averaging parametric binding potential (BPND) images of 52 healthy subjects. VOIs were generated based on a predefined volume and BPND thresholding and subsequently applied to test-retest [11C]AZ10419369 parametric BPND images of 8 healthy subjects. For a method based on individual subject data, VOIs were generated directly on each individual parametric image.Both methods showed improved reliability compared to a conventional manual VOI. The VOIs created with [11C]AZ10419369 template data can be automatically applied to future PET studies measuring 5-HT1B receptor binding in the brainstem.
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