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Sökning: WFRF:(Farde L) > Medicin och hälsovetenskap

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1.
  • Schwarz, E, et al. (författare)
  • Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder
  • 2019
  • Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 12-
  • Tidskriftsartikel (refereegranskat)abstract
    • Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.
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2.
  • Elvsashagen, T, et al. (författare)
  • The genetic architecture of human brainstem structures and their involvement in common brain disorders
  • 2020
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4016-
  • Tidskriftsartikel (refereegranskat)abstract
    • Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson’s disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
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3.
  • Forsberg, A., et al. (författare)
  • The Immune Response of the Human Brain to Abdominal Surgery
  • 2017
  • Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 81:4, s. 572-582
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short-and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [C-11]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Results: Patients showed a global downregulation of gray matter [C-11]PBR28 binding of 26 +/- 26% (mean +/- standard deviation) at 3 to 4 days postoperatively compared to baseline (p=0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-a in blood displayed a reduction (41 +/- 39%) on the 3rd to 4th postoperative day, corresponding to changes in [C-11]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [C-11]PBR28 binding (p=0.027). Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function.
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4.
  • Malmqvist, Anna, et al. (författare)
  • Increased peripheral levels of TARC/CCL17 in first episode psychosis patients
  • 2019
  • Ingår i: Schizophrenia Research. - : ELSEVIER. - 0920-9964 .- 1573-2509. ; 210, s. 221-227
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evidence for a link between the pathophysiology of schizophrenia and the immune system is mounting. Altered levels of chemokines in plasma have previously been reported in patients with schizophrenia under antipsychotic medication. Here we aimed to study both peripheral and central chemokine levels in drugnaive or short-time medicated first episode psychosis (FEP) patients. Method: We analyzed nine chemokines in plasma and CSF from 41 FEP patients and 22 healthy controls using electrochemiluminescence assay. Results: In plasma four chemokines; TARC/CCL17, eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 and in CSF one chemokine; IP-10/CXCL10 showed reliable detection in N50% of the cases. FEP patients displayed increased levels of TARC/CCL17 in plasma compared to healthy controls, 89.6 (IQR 66.2-125.8) pg/mL compared to 48.6 (IQR 28.0-71.7) pg/mL (p = 0.001). The difference was not attributed to confounding factors. Plasma TARC/CCL17 was not associated with PANSS, CGI or GAF scores, neither with cognitive functions. The chemokines eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 in plasma and IP-10/CXCL10 in CSF did not differ between FEP patients and controls. Conclusion: In line with a previous study showing that chronic patients with schizophrenia display increased plasma TARC/CCL17 levels, we here found an elevation in FEP patients suggesting a role of TARC/CCL17 in early stages of schizophrenia. The exactmechanism of this involvement is still unknown and future longitudinal studies as well as studies of central and peripheral chemokine levels would be of great interest. (C) 2018 Elsevier B.V. All rights reserved.
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5.
  • Orhan, F., et al. (författare)
  • Increased number of monocytes and plasma levels of MCP-1 and YKL-40 in first-episode psychosis
  • 2018
  • Ingår i: Acta Psychiatrica Scandinavica. - : WILEY. - 0001-690X .- 1600-0447. ; 138:5, s. 432-440
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveMethodAccumulating evidence implicates immune activation in the development of schizophrenia. Here, monocyte numbers, monocyte chemoattractant protein-1 (MCP-1) and chitinase-3-like protein 1 (YKL-40) were investigated in plasma and cerebrospinal fluid (CSF) in first-episode psychosis (FEP) patients. CSF and blood were sampled from 42 first-episode psychosis (FEP) patients and 22 healthy controls. The levels of YKL-40 and MCP-1 were measured using electrochemiluminescence assay, and blood monocytes were counted using an XN-9000-hematology analyzer. ResultsConclusionWe found higher plasma levels of MCP-1 and YKL-40 in FEP patients compared with healthy controls, a condition that was unrelated to antipsychotic and/or anxiolytic medication. This was combined with an increased number of blood monocytes and a borderline significant increase in YKL-40 levels in the CSF of tobacco-free FEP patients. Plasma or CSF chemokines or blood monocytes did not correlate with the severity of symptoms or the level of functioning. These data demonstrate activation of monocytes in FEP and strengthens the idea of an immune dysfunction of psychotic disorders. Further studies are required to perceive a role of YKL-40 and MCP-1 in the initiation and progression of schizophrenia.
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6.
  • Collste, K., et al. (författare)
  • Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [C-11]PBR28
  • 2017
  • Ingår i: Molecular Psychiatry. - : NATURE PUBLISHING GROUP. - 1359-4184 .- 1476-5578. ; 22:6, s. 850-856
  • Tidskriftsartikel (refereegranskat)abstract
    • Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn. Here, we examined 16 drug-naive, first-episode psychosis patients and 16 healthy controls using PET and the TSPO radioligand [C-11]PBR28. Gray matter (GM) volume of distribution (V-T) derived from a two-tissue compartmental analysis with arterial input function was the main outcome measure. Statistical analyses were performed controlling for both TSPO genotype, which is known to affect [C-11]PBR28 binding, and gender. There was a significant reduction of [C-11]PBR28 V-T in patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM V-T and clinical or cognitive measures after correction for multiple comparisons. The observed decrease in TSPO binding suggests reduced numbers or altered function of immune cells in brain in early-stage schizophrenia.
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7.
  • Kaufmann, Tobias, et al. (författare)
  • Common brain disorders are associated with heritable patterns of apparent aging of the brain
  • 2019
  • Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
  • Tidskriftsartikel (refereegranskat)abstract
    • Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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8.
  • Talvik, M, et al. (författare)
  • A cross-validation study on the relationship between central D-2 receptor occupancy and serum perphenazine concentration
  • 2004
  • Ingår i: Psychopharmacology. - Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. Glostrup Univ Hosp, Dept Clin Biochem, Glostrup, Denmark. : SPRINGER. - 0033-3158 .- 1432-2072. ; 175:2, s. 148-153
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: There is a need for laboratory measures to guide clinical treatment with antipsychotic drugs. For serum concentration of the classical antipsychotic drug perphenzine an optimal therapeutic interval has been identified between 2 and 6 nmol/l. Positron emission tomography (PET) studies have suggested an optimal interval in central dopamine D-2 receptor occupancy of between 65 and 80%. Objectives: The aim of the present cross-validation study in clinically stable schizophrenic patients was to examine the relationship between the optimal interval in central D-2 receptor occupancy and the therapeutic window for serum perphenazine concentration. Methods: Six patients who had responded to maintenance treatment with perphenazine decanoate were examined with PET and [C-11]raclopride during steady-state conditions. Blood sampling was carried out for minimum serum perphenazine concentration and during the PET examination. Results: The serum perphenazine concentration was between 1.8 and 9 nmol/l and the D-2 receptor occupancy varied between 66 and 82%. The relationship between central receptor occupancy and serum drug concentration was curvilinear. Mild extrapyramidal symptoms were present in the patient with the highest D-2 receptor occupancy. Conclusions: The previously suggested therapeutic window in serum perphenazine concentration is in good agreement with the optimal interval suggested for central D-2 receptor occupancy. Serum concentrations at low dose levels may therefore serve as a useful tool in clinical monitoring of antipsychotic drug treatment.
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