scholarly journals Serotonin 5-HT1A receptor binding and self-transcendence in healthy control subjects—a replication study using Bayesian hypothesis testing

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5790
Author(s):  
Gina Griffioen ◽  
Granville J. Matheson ◽  
Simon Cervenka ◽  
Lars Farde ◽  
Jacqueline Borg
Keyword(s):  
Hypothesis Testing ◽  
Receptor Binding ◽  
Binding Potential ◽  
Imaging Data ◽  
Reference Tissue ◽  
Bayesian Hypothesis Testing ◽  
Control Subjects ◽  
Serotonin System ◽  
Healthy Control ◽  
Self Transcendence

Objective A putative relationship between markers for the serotonin system and the personality scale self-transcendence (ST) and its subscale spiritual acceptance (SA) has been demonstrated in a previous PET study of 5-HT1A receptor binding in healthy control subjects. The results could however not be replicated in a subsequent PET study at an independent centre. In this study, we performed a replication of our original study in a larger sample using Bayesian hypothesis testing to evaluate relative evidence both for and against this hypothesis. Methods Regional 5-HT1A receptor binding potential (BPND) was examined in 50 healthy male subjects using PET with the radioligand [11C]WAY100635. 5-HT1Aavailability was calculated using the simplified reference tissue model (SRTM) yielding regional BPND. ST and SA were measured using the Temperament and Character Inventory (TCI) questionnaire. Correlations between ST/SA scores and 5-HT1ABPND in frontal cortex, hippocampus and raphe nuclei were examined by calculation of default correlation Bayes factors (BFs) and replication BFs. Results There were no significant correlations between 5-HT1A receptor binding and ST/SA scores. Rather, five of six replication BFs provided moderate to strong evidence for no association between 5-HT1A availability and ST/SA, while the remaining BF provided only weak evidence. Conclusion We could not replicate our previous findings of an association between 5-HT1A availability and the personality trait ST/SA. Rather, the Bayesian analysis provided evidence for a lack of correlation. Further research should focus on whether other components of the serotonin system may be related to ST or SA. This study also illustrates how Bayesian hypothesis testing allows for greater flexibility and more informative conclusions than traditional p-values, suggesting that this approach may be advantageous for analysis of molecular imaging data.

scholarly journals Serotonin 5-HT1A receptor binding and self-transcendence in healthy control subjects - a replication study using Bayesian hypothesis testing

2017 ◽  
Author(s):  
Gina Griffioen ◽  
Granville James Matheson ◽  
Simon Cervenka ◽  
Lars Farde ◽  
Jacqueline Borg
Keyword(s):  
Hypothesis Testing ◽  
Receptor Binding ◽  
Binding Potential ◽  
Imaging Data ◽  
Reference Tissue ◽  
Bayesian Hypothesis Testing ◽  
Control Subjects ◽  
Serotonin System ◽  
Healthy Control ◽  
Self Transcendence

AbstractObjectiveA putative relationship between markers for the serotonin system and the personality scale self-transcendence (ST) and its subscale spiritual acceptance (SA) has been demonstrated in a previous PET study of 5-HT1A receptor binding in healthy control subjects. The results could however not be replicated in a subsequent PET study at an independent centre. In this study, we performed a replication of our original study in a larger sample using Bayesian hypothesis testing to evaluate relative evidence both for and against this hypothesis.MethodsRegional 5-HT1A receptor binding potential (BPND) was examined in 50 healthy male subjects using PET with the radioligand [11C]WAY100635. 5-HT1A availability was calculated using the simplified reference tissue model (SRTM) yielding regional BPND. ST and SA were measured using the Temperament and Character Inventory (TCI) questionnaire. Correlations between ST/SA scores and 5-HT1A BPND in frontal cortex, hippocampus and raphe nuclei were examined by calculation of default correlation Bayes factors (BFs) and replication BFs.ResultsThere were no significant correlations between 5-HT1A receptor binding and ST/SA scores. Rather, five of six replication BFs provided moderate to strong evidence for no association between 5-HT1A availability and ST/SA, while the remaining BF provided only weak evidence.ConclusionWe could not replicate our previous findings of an association between 5-HT1A availability and the personality trait ST/SA. Rather, the Bayesian analysis provided evidence for a lack of correlation. Further research should focus on whether other components of the serotonin system may be related to ST or SA. This study also illustrates how Bayesian hypothesis testing allows for greater flexibility and more informative conclusions than traditional p-values, suggesting that this approach may be advantageous for analysis of molecular imaging data.

scholarly journals Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Thomas A. Johnson ◽  
Ville Paakinaho ◽  
Sohyoung Kim ◽  
Gordon L. Hager ◽  
Diego M. Presman
Keyword(s):  
Receptor Binding ◽  
Site Response ◽  
Physiological Role ◽  
Binding Potential ◽  
Open Chromatin ◽  
Imaging Data ◽  
Response Elements ◽  
Genome Wide ◽  
Genomic Studies

AbstractA widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.

scholarly journals Correction: Bayesian hypothesis testing and experimental design for two-photon imaging data

2019 ◽  
Vol 15 (10) ◽  
pp. e1007473
Author(s):  
Luke E. Rogerson ◽  
Zhijian Zhao ◽  
Katrin Franke ◽  
Thomas Euler ◽  
Philipp Berens
Keyword(s):  
Experimental Design ◽  
Hypothesis Testing ◽  
Imaging Data ◽  
Two Photon ◽  
Bayesian Hypothesis Testing ◽  
Photon Imaging ◽  
Two Photon Imaging

scholarly journals Validity and reliability of extrastriatal [11C]raclopride binding quantification in the living human brain

2019 ◽  
Author(s):  
Jonas E Svensson ◽  
Martin Schain ◽  
Pontus Plavén-Sigray ◽  
Simon Cervenka ◽  
Mikael Tiger ◽  
...  
Keyword(s):  
Temporal Cortex ◽  
Binding Potential ◽  
Validity And Reliability ◽  
Reference Tissue ◽  
Pet Tracer ◽  
Binding Data ◽  
Healthy Control ◽  
The Mean ◽  
Cortical Regions ◽  
Simplified Reference Tissue Model

Abstract[11C]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 [11C]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 [11C]raclopride binding quantification. Two sets of healthy control subjects were examined with HRRT and [11C]raclopride: i) To assess the validity of extrastriatal [11C]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. Quetiapine dosing was associated with decrease in [11C]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 [11C]raclopride PET is not a suitable tool for D2/3R binding quantification in extrastriatal regions.

scholarly journals Bayesian hypothesis testing and experimental design for two-photon imaging data

2019 ◽  
Vol 15 (8) ◽  
pp. e1007205 ◽  
Author(s):  
Luke E. Rogerson ◽  
Zhijian Zhao ◽  
Katrin Franke ◽  
Thomas Euler ◽  
Philipp Berens
Keyword(s):  
Experimental Design ◽  
Hypothesis Testing ◽  
Imaging Data ◽  
Two Photon ◽  
Bayesian Hypothesis Testing ◽  
Photon Imaging ◽  
Two Photon Imaging

scholarly journals Reproducibility of Striatal and Thalamic Dopamine D2 Receptor Binding Using [11C]raclopride with High-Resolution Positron Emission Tomography

2010 ◽  
Vol 31 (1) ◽  
pp. 155-165 ◽  
Author(s):  
Kati Alakurtti ◽  
Sargo Aalto ◽  
Jarkko J Johansson ◽  
Kjell Någren ◽  
Terhi Tuokkola ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
High Resolution ◽  
Spatial Resolution ◽  
Receptor Binding ◽  
Dopamine D2 Receptor ◽  
Intraclass Correlation ◽  
Emission Tomography ◽  
Binding Potential ◽  
Reference Tissue ◽  
Positron Emission

Positron emission tomography (PET) imaging of small striatal brain structures such as the ventral striatum (VST) has been hampered by low spatial resolution causing partial-volume effects. The high-resolution research tomograph (HRRT) is a brain-dedicated PET scanner that has considerably better spatial resolution than its predecessors. However, its superior spatial resolution is associated with a lower signal-to-noise ratio. We evaluated the test–retest reliability of the striatal and thalamic dopamine D2 receptor binding using the HRRT scanner. Seven healthy male volunteers underwent two [11C]raclopride PET scans with a 2.5-hour interval. Dopamine D2 receptor availability was quantified as binding potential (BPND) using the simplified reference tissue model. To evaluate the reproducibility of repeated BPND estimations, absolute variability (VAR) and intraclass correlation coefficients (ICCs) were calculated. VAR values indicated fairly good reproducibility and were 3.6% to 4.5% for the caudate nucleus and putamen and 4.5% to 6.4% for the lateral and medial part of the thalamus. In the VST, the VAR value was 5.8% when the definition was made in the coronal plane. However, the ICC values were only moderate, in the range of 0.34 to 0.66, for all regions except the putamen (0.87). Experimental signal processing methods improved neither ICC nor VAR values significantly.

Sign in / Sign up

Export Citation Format

Share Document