5-HTTLPR status predictive of neocortical 5-HT4 binding assessed with [11C]SB207145 PET in humans

Fisher, Patrick M.; Holst, Klaus K.; Mahon, Brenda Mc; Haahr, Mette E.; Madsen, Karine; Gillings, Nic; Baaré, William F.C.; Jensen, P.S.; Knudsen, Gitte M.

doi:10.1016/j.neuroimage.2012.05.013

Cited by 53 publications

(59 citation statements)

References 44 publications

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“…DNA was obtained from saliva using Oragene Kits (DNA Genotek, Ottawa, Canada) as detailed previously (42). 5-HTTLPR status was classified in a bivariate fashion as either LALA homozygous or S-or LG-allele carrier.…”

Section: Genotypingmentioning

confidence: 99%

Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study

Frøkjær

Pinborg

Holst³

et al. 2015

Biological Psychiatry

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Section: Genotypingmentioning

confidence: 99%

Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study

Frøkjær

Pinborg

Holst³

et al. 2015

Biological Psychiatry

119

124

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“…2) and established normative data for the 5-HTT , the 5-HT 2A (Adams et al, 2004) and the 5-HT 4 (Madsen et al, 2011b) receptors. A novel agonist radioligand for 5-HT 2A receptor PET studies, [11C]Cimbi-36, has also been developed and validated in humans (Ettrup et al, 2014) and 5-HT 4 receptor binding has been shown to be inversely related to 5-HT brain levels (Fisher et al, 2012;Haahr et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…fMRI has also been investigated in relation to genotype (Fisher et al, 2012) and bright light intervention . Diffusion tensor imaging data has also been related to personality traits associated with depression (Madsen et al, 2012c).…”

Section: Introductionmentioning

confidence: 99%

The Center for Integrated Molecular Brain Imaging (Cimbi) database

et al. 2016

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We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes. The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies. The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank.

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“…These data sets have been used in two other studies. However, one was a ROI-based analysis (Fisher et al, 2012) and the second focused on specific binding only within hippocampus (Haahr et al, 2012a). The protocol was approved by the Ethics Committee of Copenhagen and Frederiksberg, Denmark, and all subjects gave written informed consent.…”

Section: Methodsmentioning

confidence: 99%

Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data

et al. 2014

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Exploratory (i.e., voxelwise) spatial methods are commonly used in neuroimaging to identify areas that show an effect when a region-of-interest (ROI) analysis cannot be performed because no strong a priori anatomical hypothesis exists. However, noise at a single voxel is much higher than noise in a ROI making noise management critical to successful exploratory analysis. This work explores how preprocessing choices affect the bias and variability of voxelwise kinetic modeling analysis of brain positron emission tomography (PET) data. These choices include the use of volume- or cortical surface-based smoothing, level of smoothing, use of voxelwise partial volume correction (PVC), and PVC masking threshold. PVC was implemented using the Muller-Gartner method with the masking out of voxels with low gray matter (GM) partial volume fraction. Dynamic PET scans of an antagonist serotonin-4 receptor radioligand ([11C]SB2307145) were collected on sixteen healthy subjects using a Siemens HRRT PET scanner. Kinetic modeling was used to compute maps of non-displaceable binding potential (BPND) after preprocessing. The results showed a complicated interaction between smoothing, PVC, and masking on BPND estimates. Volume-based smoothing resulted in large bias and intersubject variance because it smears signal across tissue types. In some cases, PVC with volume smoothing paradoxically caused the estimated BPND to be less than when no PVC was used at all. When applied in the absence of PVC, cortical surface-based smoothing resulted in dramatically less bias and the least variance of the methods tested for smoothing levels 5mm and higher. When used in combination with PVC, surface-based smoothing minimized the bias without significantly increasing the variance. Surface-based smoothing resulted in 2-4 times less intersubject variance than when volume smoothing was used. This translates into more than 4 times fewer subjects needed in a group analysis to achieve similarly powered statistical tests. Surface-based smoothing has less bias and variance because it respects cortical geometry by smoothing the PET data only along the cortical ribbon and so does not contaminate the GM signal with that of white matter and cerebrospinal fluid. The use of surface-based analysis in PET should result in substantial improvements in the reliability and detectability of effects in exploratory PET analysis, with or without PVC.

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5-HTTLPR status predictive of neocortical 5-HT4 binding assessed with [11C]SB207145 PET in humans

Cited by 53 publications

References 44 publications

Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study

Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study

The Center for Integrated Molecular Brain Imaging (Cimbi) database

Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data

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