| 1. |
- Caravaggio, Fernando, et al.
(författare)
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Trait impulsivity is not related to post-commissural putamen volumes : A replication study in healthy men
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- High levels of trait impulsivity are considered a risk factor for substance abuse and drug addiction. We recently found that non-planning trait impulsivity was negatively correlated with post-commissural putamen volumes in men, but not women, using the Karolinska Scales of Personality (KSP). Here, we attempted to replicate this finding in an independent sample using an updated version of the KSP: the Swedish Universities Scales of Personality (SSP). Data from 88 healthy male participants (Mean Age: 28.16 +/- 3.34), who provided structural T1-weighted magnetic resonance images (MRIs) and self-reported SSP impulsivity scores, were analyzed. Striatal sub-region volumes were acquired using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Contrary to our previous findings trait impulsivity measured using SSP was not a significant predictor of post-commissural putamen volumes (beta = .14, df = 84, p = .94). A replication Bayes Factors analysis strongly supported this null result. Consistent with our previous findings, secondary exploratory analyses found no relationship between ventral striatum volumes and SSP trait impulsivity (beta = -.05, df = 84, p = .28). An exploratory analysis of the other striatal compartments showed that there were no significant associations with trait impulsivity. While we could not replicate our previous findings in the current sample, we believe this work will aide future studies aimed at establishing meaningful brain biomarkers for addiction vulnerability in healthy humans.
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| 2. |
- Farde, Lars, et al.
(författare)
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Brain neuroreceptor density and personality traits : towards dimensional biomarkers for psychiatric disorders.
- 2018
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Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 373:1744
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Forskningsöversikt (refereegranskat)abstract
- Positron emission tomography has, for 30 years, been used in numerous case-control studies searching for hypothesized differences in the density of neuroreceptor or transporter proteins in psychiatric disorders such as schizophrenia and depression. In most cases, the results have not been conclusive. One reason could be the sizeable interindividual variability in biochemical markers, which in twin studies have shown to emanate from both environmental and genetic factors, leading to low statistical power for the detection of group effects. On the other hand, the same interindividual variability has served as an opportunity for correlative studies on the biological underpinning of behaviour. Using this approach, a series of studies has linked markers for the dopamine and serotonin system to personality traits associated with psychiatric conditions. Based on increasing evidence for the view that many psychopathological states represent extremes of a continuum rather than distinct categories, this research strategy may lead to new biological insights about the vulnerability to and pathophysiology of major psychiatric disorders.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.
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| 3. |
- Plaven-Sigray, Pontus, et al.
(författare)
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Is dopamine D1 receptor availability related to social behavior? : A positron emission tomography replication study
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Associations between dopamine receptor levels and pro- and antisocial behavior have previously been demonstrated in human subjects using positron emission tomography (PET) and self-rated measures of personality traits. So far, only one study has focused on the dopamine D1-receptor (D-1-R), finding a positive correlation with the trait social desirability, which is characterized by low dominant and high affiliative behavior, while physical aggression showed a negative correlation. The aim of the present study was to replicate these previous findings using a new independent sample of subjects.Materials and methods Twenty-six healthy males were examined with the radioligand [C-11]SCH-23390, and completed the Swedish universities Scales of Personality (SSP) which includes measures of social desirability and physical trait aggression. The simplified reference tissue model with cerebellum as reference region was used to calculate BPND values in the whole striatum and limbic striatum. The two regions were selected since they showed strong association between D-I-R availability and personality scores in the previous study. Pearson's correlation coefficients and replication Bayes factors were then employed to assess the replicability and robustness of previous results.Results There were no significant correlations (all p values >0.3) between regional BPND values and personality scale scores. Replication Bayes factors showed strong to moderate evidence in favor no relationship between Dl-receptor availability and social desirability (striatum BF01 = 12.4; limbic striatum BF01 = 7.2) or physical aggression scale scores (limbic striatum BF01 = 3.3), compared to the original correlations.Discussion We could not replicate the previous findings of associations between D1-R availability and either pro- or antisocial behavior as measured using the SSP. Rather, there was evidence in favor of failed replications of associations between BPND and scale scores. Potential reasons for these results are restrictive variance in both PET and personality outcomes due to high sample homogeneity, or that the previous findings were false positives.
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| 4. |
- Plavén-Sigray, Pontus
(författare)
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Positron emission tomography : development, evaluation and application of quantification methods
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Positron Emission Tomography (PET) is an imaging technique that allows for in vivo quantification of biochemical and physiological processes in the brain. Examples of targets in the brain that can be imaged using PET are dopamine receptors and the translocator protein 18kDa (TSPO). Following intravenous injection of a radio-labeled ligand and the ensuing PET examination of a subject, kinetic models are often used to estimate parameters of interest. Example of such parameters are binding potential or distribution volume, which are estimates of the availability of receptors in a specific region or volume-element of the brain. These parameters can then be inserted into statistical models to infer e.g. differences in target availability between patients and controls or relationships to behavioral traits. In order to detect effects of interest, it is important that the estimation of these parameters is precise, reliable and valid. The aim of this thesis was to evaluate different methods for estimating such parameters, and apply them on clinical data. The thesis consists of two different themes. The focus of theme I was the quantification of dopamine receptor in striatum and the cortex, and their relationship to normal and dysfunctional social behavior. Study I and Study II examined the relationship between dopamine D1 receptor availability and self-rated pro and anti-social behavior in healthy subjects. Study I found a positive correlation between striatal D1 receptor availability and Social Desirability, and a negative correlation to Trait Aggression. Study II did however fail to replicate these results. In Study III, dopamine D2 receptor availability in limbic and cortical regions in patients with social anxiety disorder and healthy controls were compared. Exploratory analyses suggested that patients had higher D2 receptor availability in the lateral and orbitofrontal cortex, although the results warrant replication in a larger sample. The focus of theme II was the quantification of TSPO in patients with psychosis and healthy subjects. The level of TSPO in the brain has been hypothesized to function as an index of microglial cell activity, which in turn is believed to be a proxy for immune activation in the central nervous system. In Study IV, [11C]PBR28 binding in the whole grey-matter in patients with first-episode psychosis and healthy controls were compared. Contrary to the hypothesis of elevated microglia activity, patients were found to have lower TSPO levels. Study V evaluated the test-retest reliability and convergent validity of different methods to measure TSPO levels using [11C]PBR28. Distribution volume ratios and standardized uptakes value ratios, derived using pseudo-reference regions, showed both poor reliability and convergent validity. Study VI carried out a meta-analysis of TSPO in patients with schizophrenia and psychotic disorders compared to healthy controls. Again, contrary to the hypothesis of higher microglia activity, strong evidence was found in favor of patients having lower TSPO levels in both cortical and subcortical regions. In Study VII, the test-retest reliability and convergent validity of different methods to estimate TSPO levels using (R)-[11C]PK11195 were evaluated. Outcomes derived using pseudo-reference region approaches were unreliable and showed no convergent validity to outcomes derived using arterial input function. Finally, Study VIII evaluated the reliability and accuracy of a new modeling method, applied to [11C]PBR28 data, in order to estimate specific binding without requiring a reference region. Simulations, a pharmacological challenge and test-retest analysis showed that non-displaceable distribution volume, and ensuing specific distribution volume values, derived using this method were accurate, precise and reliable. Taken together, the results of the studies illustrate the importance of evaluating quantification methods prior to applying them on clinical data. The thesis also shows how robust kinetic and statistical modeling, and the use of direct replications or multi-center collaborations, can yield more trustworthy and reliable findings in PET.
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| 5. |
- Plaven-Sigray, Pontus, et al.
(författare)
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Positron Emission Tomography Studies of the Glial Cell Marker Translocator Protein in Patients With Psychosis : A Meta-analysis Using Individual Participant Data
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 84:6, s. 433-442
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Accumulating evidence suggests that the immune system may be an important target for new treatment approaches in schizophrenia. Positron emission tomography and radioligands binding to the translocator protein (TSPO), which is expressed in glial cells in the brain including immune cells, represents a potential method for patient stratification and treatment monitoring. This study examined whether patients with first-episode psychosis and schizophrenia had altered TSPO levels compared with healthy control subjects.METHODS: PubMed was searched for studies comparing patients with psychosis with healthy control subjects using second-generation TSPO radioligands. The outcome measure was total distribution volume (V-T), an index of TSPO levels, in frontal cortex, temporal cortex, and hippocampus. Bayes factors (BFs) were applied to examine the relative support for higher, lower, or no difference in patients' TSPO levels compared with healthy control subjects.RESULTS: Five studies, with 75 participants with first-episode psychosis or schizophrenia and 77 healthy control subjects, were included. BFs showed strong support for lower VT in patients relative to no difference (all BFs > 32), or relative to higher V-T (all BFs > 422), in all brain regions. From the posterior distributions, mean patient-control differences in standardized V-T values were -0.48 for frontal cortex (95% credible interval [CredInt] = -0.88 to 0.09), -0.47 for temporal cortex (CredInt = -0.87 to -0.07), and -0.63 for hippocampus (CredInt = -1.00 to -0.25).CONCLUSIONS: The lower levels of TSPO observed in patients may correspond to altered function or lower density of brain immune cells. Future studies should focus on investigating the underlying biological mechanisms and their relevance for treatment.
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| 6. |
- Plaven-Sigray, Pontus, et al.
(författare)
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Test-retest reliability and convergent validity of (R)-[11C]PK11195 outcome measures without arterial input function
- 2018
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Ingår i: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The PET radioligand (R)-[C-11]PK11195 is used to quantify the 18-kDa translocator protein (TSPO), a marker for glial activation. Since there is no brain region devoid of TSPO, an arterial input function (AIF) is ideally required for quantification of binding. However, obtaining an AIF is experimentally demanding, is sometimes uncomfortable for participants, and can introduce additional measurement error during quantification. The objective of this study was to perform an evaluation of the test-retest reliability and convergent validity of techniques used for quantifying (R)-[C-11]PK11195 binding without an AIF in clinical studies.Methods: Data from six healthy individuals who participated in two PET examinations, 6weeks apart, were analyzed. Regional non-displaceable binding potential (BPND) values were calculated using the simplified reference tissue model, with either cerebellum as reference region or a reference input derived using supervised cluster analysis (SVCA). Standardized uptake values (SUVs) were estimated for the time interval of 40-60min.Results: Test-retest reliability for BPND estimates were poor (80% of ICCs <0.5). BPND estimates derived without an AIF were not correlated with BPND, total or specific distribution volume from the 2TCM using an AIF (all R-2<12%). SUVs showed moderate reliability but no correlation to any other outcome measure.Conclusions: Caution is warranted when interpreting patient-control comparisons employing (R)-[C-11]PK11195 outcome measures obtained without an AIF.
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| 7. |
- Stenkrona, Per, et al.
(författare)
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[11C]SCH23390 binding to the D-1-dopamine receptor in the human brain : a comparison of manual and automated methods for image analysis
- 2018
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Ingår i: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The D-1-dopamine receptor radioligand [C-11] SCH23390 has been frequently used in PET studies. In drug-naive patients with schizophrenia, the findings have been inconsistent, with decreases, increases, and no change in the frontal cortex D-1-dopamine receptors. While these discrepancies are likely primarily due to a lack of statistical power in these studies, we speculated that an additional explanation may be the differences due to methods of image analysis between studies, affecting reliability as well as bias between groups. Methods: Fifteen healthy subjects underwent two PET measurements with [C-11] SCH23390 on the same day. The binding potential (BPND) was compared using a 95% confidence interval following manual and automated delineation of a region of interest (ROI) as well as with and without frame-by-frame realignment. Results: Automated target region delineation produced lower BPND values, while automated delineation of the reference region yielded higher BPND values. However, no significant differences were observed for repeatability using automated and manual delineation methods. Frame-by-frame realignment generated higher BPND values and improved repeatability. Conclusions: The results suggest that the choice of ROI delineation method is not an important factor for reliability, whereas the improved results following movement correction confirm its importance in PET image analysis. Realignment is therefore especially important for measurements in patient populations such as schizophrenia or Parkinson's disease, where motion artifacts may be more prevalent.
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