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Sökning: WFRF:(Landen M) > (2015-2019) > (2019)

  • Resultat 21-29 av 29
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21.
  • Sellgren, C. M., et al. (författare)
  • Peripheral and central levels of kynurenic acid in bipolar disorder subjects and healthy controls
  • 2019
  • Ingår i: Translational Psychiatry. - 2158-3188. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolites of the kynurenine pathway of tryptophan degradation, in particular, the N-Methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA), are increasingly recognized as primary pathophysiological promoters in several psychiatric diseases. Studies analyzing central KYNA levels from subjects with psychotic disorders have reported increased levels. However, sample sizes are limited and in contrast many larger studies examining this compound in blood from psychotic patients commonly report a decrease. A major question is to what extent peripheral KYNA levels reflect brain KYNA levels under physiological as well as pathophysiological conditions. Here we measured KYNA in plasma from a total of 277 subjects with detailed phenotypic data, including 163 BD subjects and 114 matched healthy controls (HCs), using an HPLC system. Among them, 94 BD subjects and 113 HCs also had CSF KYNA concentrations analyzed. We observe a selective increase of CSF KYNA in BD subjects with previous psychotic episodes although this group did not display altered plasma KYNA levels. In contrast, BD subjects with ongoing depressive symptoms displayed a tendency to decreased plasma KYNA concentrations but unchanged CSF KYNA levels. Sex and age displayed specific effects on KYNA concentrations depending on if measured centrally or in the periphery. These findings implicate brain-specific regulation of KYNA under physiological as well as under pathophysiological conditions and strengthen our previous observation of CSF KYNA as a biomarker in BD. In summary, biomarker and drug discovery studies should include central KYNA measurements for a more reliable estimation of brain KYNA levels.
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22.
  • Smedler, Erik, et al. (författare)
  • CACNA1C polymorphism and brain cortical structure in bipolar disorder
  • 2019
  • Ingår i: Journal of psychiatry & neuroscience : JPN. - 1488-2434. ; 45:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The CACNA1C gene encodes the 1C subunit of L-type voltage-gated calcium channels and has been associated with several psychiatric syndromes — including bipolar disorder — in several genome-wide association studies. Experimental and clinical studies have reported changes with respect to behaviour and biomarkers in risk allele carriers, corroborating the essential role of the CACNA1C gene in neurons, during development and in the mature brain. However, the association of this gene with regional cortical thickness has not been evaluated in patients with bipolar disorder.Using magnetic resonance imaging, we measured the average cortical thickness of 68 brain regions in 87 patients genotyped for the single-nucleotide polymorphism rs1006737 in CACNA1C.We found associations with the mean thickness of several cortical areas: the left lateral orbitofrontal and rostral anterior cingulate cortices, as well as other parts of the frontal and parietal cortices.This cross-sectional cohort study could not fully differentiate correlation from causation.The CACNA1C polymorphism rs1006737 is associated with the mean thickness of cortical brain areas that have been shown to be altered in bipolar disorder.
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23.
  • Emmings, Edith, et al. (författare)
  • Targeting Mitochondria for Treatment of Chemoresistant Ovarian Cancer
  • 2019
  • Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1422-0067 .- 1422-0067. ; 20:1
  • Forskningsöversikt (refereegranskat)abstract
    • Ovarian cancer is the leading cause of death from gynecologic malignancy in the Western world. This is due, in part, to the fact that despite standard treatment of surgery and platinum/paclitaxel most patients recur with ultimately chemoresistant disease. Ovarian cancer is a unique form of solid tumor that develops, metastasizes and recurs in the same space, the abdominal cavity, which becomes a unique microenvironment characterized by ascites, hypoxia and low glucose levels. It is under these conditions that cancer cells adapt and switch to mitochondrial respiration, which becomes crucial to their survival, and therefore an ideal metabolic target for chemoresistant ovarian cancer. Importantly, independent of microenvironmental factors, mitochondria spatial redistribution has been associated to both tumor metastasis and chemoresistance in ovarian cancer while specific sets of genetic mutations have been shown to cause aberrant dependence on mitochondrial pathways in the most aggressive ovarian cancer subtypes. In this review we summarize on targeting mitochondria for treatment of chemoresistant ovarian cancer and current state of understanding of the role of mitochondria respiration in ovarian cancer. We feel this is an important and timely topic given that ovarian cancer remains the deadliest of the gynecological diseases, and that the mitochondrial pathway has recently emerged as critical in sustaining solid tumor progression.
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24.
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25.
  • Popiolek, K., et al. (författare)
  • Electroconvulsive therapy in bipolar depression - effectiveness and prognostic factors
  • 2019
  • Ingår i: Acta Psychiatrica Scandinavica. - : WILEY. - 0001-690X .- 1600-0447. ; 140:3, s. 196-204
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Electroconvulsive therapy (ECT) is used in patients with severe forms of bipolar depression. ECT is effective but not all patients respond. The aim of this study was to determine prognostic factors for response to ECT in patients hospitalized for bipolar depression. Methods Data were obtained from several national Swedish registers. All patients with bipolar depression treated with ECT in any hospital in Sweden between 2011 and 2016 for whom information about ECT response was available were included (n = 1251). Response was defined as a score on the Clinical Global Impression - Improvement scale of one or two. Univariate and multivariate logistic regression were conducted to investigate associations between socio-demographic and clinical factors and response. Results Response was achieved in 80.2% patients. Older age was associated with higher response rate to ECT. Patients with comorbid obsessive-compulsive disorder or personality disorder, and patients previously treated with lamotrigine had lower response rate. Conclusion Electroconvulsive therapy for bipolar depression was associated with very high response rates. The strongest prognostic factors were higher age, absence of comorbid obsessive-compulsive disorder or personality disorder, and less prior pharmacologic treatment.
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26.
  • Salarvan, Sara, et al. (författare)
  • Neuropsychological profiles of adult bipolar disorder patients with and without comorbid attention-deficit hyperactivity disorder.
  • 2019
  • Ingår i: International journal of bipolar disorders. - 2194-7511. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Comorbid attention-deficit/hyperactivity disorder (ADHD) is common in bipolar disorder and associated with worse outcomes. Cognitive testing might be a tool to identify this group. Here we compare the neuropsychological profiles of bipolar disorder patients with (BD + cADHD) and without (BD - cADHD) childhood attention-deficit hyperactivity disorder.Adult patients with BD  -  cADHD (n = 66), BD + cADHD (n = 32), and healthy controls (n = 112) were tested using a comprehensive battery of neuropsychological tests. Patients underwent rigorous diagnostic assessments for bipolar disorder and ADHD, as well as a parental interview to establish childhood ADHD.The neuropsychological profiles of the groups were similar, except that the BD + cADHD group performed significantly worse on working memory. Working memory did not differ between those in the BD + cADHD group who only had a history of childhood ADHD and those that still met criteria for ADHD in adulthood.Cognitive testing had limited power to differentiate between bipolar disorder adults with and without childhood ADHD. The BD + cADHD subgroup cannot explain the significant cognitive heterogeneity seen in bipolar disorder patients.
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27.
  • Smedler, Erik, et al. (författare)
  • Association of CACNA1C polymorphisms with serum BDNF levels in bipolar disorder.
  • 2019
  • Ingår i: The British journal of psychiatry : the journal of mental science. - 1472-1465. ; , s. 1-3
  • Tidskriftsartikel (refereegranskat)abstract
    • Variation in the CACNA1C gene has been associated with bipolar disorder in several genome-wide association studies. This gene encodes the alpha 1C subunit of L-type voltage-gated calcium channels, which play an essential role in neurons. We analysed 39 biomarkers in either cerebrospinal fluid or serum in relation to six different CACNA1C variants in 282 patients with bipolar disorder and 90 controls. We report associations of CACNA1C risk alleles with serum levels of BDNF as well as tissue plasminogen activator, which converts pro-BDNF to mature BDNF. This sheds light on links between CACNA1C genetic variants and pathophysiological mechanisms in bipolar disorder.Declaration of interestNone.
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28.
  • Smedler, Erik, et al. (författare)
  • Genes, biomarkers, and clinical features associated with the course of bipolar disorder.
  • 2019
  • Ingår i: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. - 1873-7862. ; 29:10, s. 1152-1160
  • Tidskriftsartikel (refereegranskat)abstract
    • There is considerable variability in the severity of bipolar disorder, e.g., in terms of the frequency of inpatient episodes. The long-term progression also differs, where some patients are sensitised with progressively shorter healthy intervals. Little is known about the proportion of patients being sensitised, their clinical characteristics, and biological underpinnings. We analysed long-term progression of bipolar disorder in relation to clinical characteristics (N = 3074), serum biomarkers (N = 745), and genetic variants (N = 1401) in a cohort of Swedish bipolar disorder patients. We took advantage of the National Patient Register, providing reliable data on 35,973 psychiatric inpatient care episodes in Sweden since 1973. First, one third of the cohort cluster together with a maximum of one inpatient episode per year, while the remaining two thirds had >1 episode per year. These groups did not differ with respect to clinical features or biomarkers. Second, among patients with at least five inpatient episodes (defined as severely ill), we find one group with progressively shorter cycle-lengths (one fifth of the total cohort, N = 550). Compared with those with a stable or recuperant trajectory, these patients featured lower functioning, more antidepressant treatment, as well as reduced levels of inflammatory markers in serum. Third, sensitisation was associated with a common genetic variant near the calcium channel gene CACNA2D3 at genome-wide significance. These results suggest the potential for translational research aimed at preventive actions.
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29.
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