| 91. |
- 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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| 92. |
- Plavén-Sigray, Pontus, et al.
(författare)
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Thalamic dopamine D2-receptor availability in schizophrenia : a study on antipsychotic-naive patients with first-episode psychosis and a meta-analysis.
- 2022
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 27:2, s. 1233-1240
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacological and genetic evidence support a role for an involvement of the dopamine D2-receptor (D2-R) in the pathophysiology of schizophrenia. Previous molecular imaging studies have suggested lower levels of D2-R in thalamus, but results are inconclusive. The objective of the present study was to use improved methodology to compare D2-R density in whole thalamus and thalamic subregions between first-episode psychosis patients and healthy controls. Differences in thalamocortical connectivity was explored based on the D2-R results. 19 antipsychotic-naive first-episode psychosis patients and 19 age- and sex-matched healthy controls were examined using high-resolution Positron Emission Tomography (PET) and the high-affinity D2-R radioligand [11C]FLB457. The main outcome was D2-R binding potential (BPND) in thalamus, and it was predicted that patients would have lower binding. Diffusion tensor imaging (DTI) was performed in a subgroup of 11 patients and 15 controls. D2-R binding in whole thalamus was lower in patients compared with controls (Cohen's dz = -0.479, p = 0.026, Bayes Factor (BF) > 4). Among subregions, lower BPND was observed in the ROI representing thalamic connectivity to the frontal cortex (Cohen's dz = -0.527, p = 0.017, BF > 6). A meta-analysis, including the sample of this study, confirmed significantly lower thalamic D2-R availability in patients. Exploratory analyses suggested that patients had lower fractional anisotropy values compared with controls (Cohen's d = -0.692, p = 0.036) in the inferior thalamic radiation. The findings support the hypothesis of a dysregulation of thalamic dopaminergic neurotransmission in schizophrenia, and it is hypothesized that this could underlie a disturbance of thalamocortical connectivity.
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| 93. |
- Rück, Christian, et al.
(författare)
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DN Debatt: "De utmattade måste få tillgång till rätt vård"
- 2022
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Ingår i: Dagens Nyheter. - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Nio forskare: Kunskapsbristerna som fanns vid införandet av diagnosen utmattningssyndrom är fortfarande lika stora. Nya kriterier håller nu på att tas fram utan att de först har utvärderats vetenskapligt.
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| 94. |
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| 95. |
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| 96. |
- Schalling, Martin, et al.
(författare)
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Nya rön om schizofreni kan ge ny diagnostik och behandling
- 2015
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Ingår i: Läkartidningen. - : Läkartidningen Förlag. - 0023-7205 .- 1652-7518. ; 112
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- Remarkable progress has been made in the understanding of schizophrenia in the past few years. A driving force has been genome wide association studies that have now led to the identification of over 100 vulnerability loci, implicating functions in the immune system, calcium signaling as well as dopamine and glutamate transmission. In coupling the genetic information to functional data sets from imaging and cognitive studies there is a promise of developing radically improved understanding of schizophrenia, and in some cases new therapies based on immune modulation. As we develop more knowledge and better therapies there will likely be a reduction in stigmatization that is a very real problem for those affected and their families.
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| 97. |
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| 98. |
- Sellgren, C. M., et al.
(författare)
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GRK3 deficiency elicits brain immune activation and psychosis
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 6820-6832
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Tidskriftsartikel (refereegranskat)abstract
- The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3(-/-) mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1 beta, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3(-/-) mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders.
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| 99. |
- Shang, Pei, et al.
(författare)
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Identification of cerebrospinal fluid and serum metabolomic biomarkers in first episode psychosis patients
- 2022
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Psychotic disorders are currently diagnosed by examining the patient's mental state and medical history. Identifying reliable diagnostic, monitoring, predictive, or prognostic biomarkers would be useful in clinical settings and help to understand the pathophysiology of schizophrenia. Here, we performed an untargeted metabolomics analysis using ultra-high pressure liquid chromatography coupled with time-of-flight mass spectroscopy on cerebrospinal fluid (CSF) and serum samples of 25 patients at their first-episode psychosis (FEP) manifestation (baseline) and after 18 months (follow-up). CSF and serum samples of 21 healthy control (HC) subjects were also analyzed. By comparing FEP and HC groups at baseline, we found eight CSF and 32 serum psychosis-associated metabolites with non-redundant identifications. Most remarkable was the finding of increased CSF serotonin (5-HT) levels. Most metabolites identified at baseline did not differ between groups at 18-month follow-up with significant improvement of positive symptoms and cognitive functions. Comparing FEP patients at baseline and 18-month follow-up, we identified 20 CSF metabolites and 90 serum metabolites that changed at follow-up. We further utilized Ingenuity Pathway Analysis (IPA) and identified candidate signaling pathways involved in psychosis pathogenesis and progression. In an extended cohort, we validated that CSF 5-HT levels were higher in FEP patients than in HC at baseline by reversed-phase high-pressure liquid chromatography. To conclude, these findings provide insights into the pathophysiology of psychosis and identify potential psychosis-associated biomarkers.
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| 100. |
- 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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