| 21. |
- Joas, Erik, 1983, et al.
(författare)
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Pharmacological treatment and risk of psychiatric hospital admission in bipolar disorder
- 2017
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 210:3, s. 197-202
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Tidskriftsartikel (refereegranskat)abstract
- Background Clinical trials have examined the efficacy of drugs to prevent relapse in patients with bipolar disorder, however, their design often limits generalisation to routine clinical practice. To estimate the effectiveness of drugs used for maintenance treatment in bipolar disorder. We used national registers to identify 35 022 individuals diagnosed with bipolar disorder and information on lithium, valproate, carbamazepine, lamotrigine, quetiapine and olanzapine treatment from 2006 to 2009. The main outcome was psychiatric hospital admissions. We used stratified cox regression to compare periods on and off medication within the same individual. Medication with lithium, valproate, lamotrigine, olanzapine and quetiapine was associated with reduced rates of admission to hospital. Lithium was more effective than quetiapine and olanzapine. The effects of specific drugs depended on the polarity of the mood episode. Our findings complement results from randomised controlled trails, but suggest that lithium is more effective than both quetiapine and olanzapine in routine clinical practice.
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| 22. |
- Johansson, Viktoria, et al.
(författare)
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Cerebrospinal fluid microglia and neurodegenerative markers in twins concordant and discordant for psychotic disorders.
- 2017
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Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - : Springer. - 0940-1334 .- 1433-8491. ; 267:5, s. 391-402
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia and bipolar disorder are debilitating psychiatric disorders with partially shared symptomatology including psychotic symptoms and cognitive impairment. Aberrant levels of microglia and neurodegenerative cerebrospinal fluid (CSF) markers have previously been found in schizophrenia and bipolar disorder. We aimed to analyze familial and environmental influences on these CSF markers and their relation to psychiatric symptoms and cognitive ability. CSF was collected from 17 complete twin pairs, nine monozygotic and eight dizygotic, and from one twin sibling. Two pairs were concordant for schizophrenia, and 11 pairs discordant for schizophrenia, schizoaffective disorder or bipolar disorder, and four pairs were not affected by psychotic disorders. Markers of microglia activation [monocyte chemoattractant protein-1 (MCP-1), chitinase 3-like protein 1 (YKL-40), and soluble cluster of differentiation 14 (sCD14)], markers of β-amyloid metabolism (AβX-38, AβX-40, AβX-42 and Aβ1-42), soluble amyloid precursor proteins (sAPP-α and sAPP-β), total tau (T-tau), phosphorylated tau (P-tau), and CSF/serum albumin ratio were measured in CSF using immunoassays. Heritability of the CSF markers was estimated, and associations to psychiatric and cognitive measurements were analyzed. Heritability estimates of the microglia markers were moderate, whereas several neurodegenerative markers showed high heritability. In contrast, AβX-42, Aβ1-42, P-tau and CSF/serum albumin ratio were influenced by dominant genetic variation. Higher sCD14 levels were found in twins with schizophrenia or bipolar disorder compared to their not affected co-twins, and higher sCD14-levels were associated with psychotic symptoms. The study provides support for a significant role of sCD14 in psychotic disorders and a possible role of microglia activation in psychosis.
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| 23. |
- Kegel, Magdalena E., et al.
(författare)
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Kynurenic acid and psychotic symptoms and personality traits in twins with psychiatric morbidity
- 2017
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Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 247, s. 105-112
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Tidskriftsartikel (refereegranskat)abstract
- Increased cytokines and kynurenic acid (KYNA) levels in cerebrospinal fluid (CSF) have been reported in patients with schizophrenia and bipolar disorder. The aim of the present study was to investigate cytokines and kynurenines in the CSF of twin pairs discordant for schizophrenia or bipolar disorder and to study these CSF markers in relation to psychotic symptoms and personality traits. CSF levels of tryptophan (TRP), KYNA, quinolinic acid (QUIN), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-α) were analyzed in 23 twins with schizophrenia or bipolar disorder, and in their not affected co-twins. Ratings of psychotic symptoms and personality traits were made using the Scales for Assessment of Negative and Positive symptoms, the Structured Clinical Interview for DSM-IV - Axis II Disorders, and the Schizotypal Personality Questionnaire - Brief. A total score for psychotic symptoms and personality traits was constructed for analysis. CSF KYNA was associated with the score for psychotic symptom and personality traits. TNF-α and IL-8 were associated, and the intra-pair differences scores of TNF-α and IL-8 were highly correlated. Intraclass correlations indicated genetic influences on CSF KYNA, TRP, IL-8 and TNF-α. The association between KYNA and psychotic symptoms further supports a role of KYNA in psychotic disorders.
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| 24. |
- Landen, Jaren W., et al.
(författare)
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Ponezumab in mild-to-moderate Alzheimer's disease : Randomized phase II PET-PIB study
- 2017
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Ingår i: Alzheimer's and Dementia: Translational Research and Clinical Interventions. - : Wiley. - 2352-8737. ; 3:3, s. 393-401
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The safety, pharmacokinetics, and effect on peripheral and central amyloid β (Aβ) of multiple doses of ponezumab, an anti-Aβ monoclonal antibody, were characterized in subjects with mild-to-moderate Alzheimer's disease treated for 1 year. Methods Subjects were aged ≥50 years with Mini–Mental State Examination scores 16 to 26. Cohort Q was randomized to ponezumab 10 mg/kg (n = 12) or placebo (n = 6) quarterly. Cohort M was randomized to a loading dose of ponezumab 10 mg/kg or placebo, followed by monthly ponezumab 7.5 mg/kg (n = 12) or placebo (n = 6), respectively. Results Ponezumab was generally well tolerated. Plasma concentrations increased dose dependently, but cerebrospinal fluid (CSF) penetration was low. Plasma Aβ increased dose dependently with ponezumab, but CSF biomarkers, brain amyloid burden, cognition, and function were not affected. Conclusions Both ponezumab dosing schedules were generally safe and well tolerated but did not alter CSF biomarkers, brain amyloid burden, or clinical outcomes.
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| 28. |
- Li, X, et al.
(författare)
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MicroRNA-132 promotes fibroblast migration via regulating RAS p21 protein activator 1 in skin wound healing
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 7797-
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNA (miR)-132 has been identified as a top up-regulated miRNA during skin wound healing and its inhibition impairs wound repair. In a human in vivo surgical wound model, we showed that miR-132 was induced in epidermal as well as in dermal wound–edge compartments during healing. Moreover, in a panel of cells isolated from human skin wounds, miR-132 was found highly expressed in human dermal fibroblasts (HDFs). In HDFs, miR-132 expression was upregulated by TGF-β1. By overexpression or inhibition of miR-132, we showed that miR-132 promoted HDF migration. Mechanistically, global transcriptome analysis revealed that RAS signaling pathway was regulated by miR-132 in HDFs. We found that RAS p21 protein activator 1 (RASA1), a known target of miR-132, was downregulated in HDFs upon miR-132 overexpression. Silencing of RASA1 phenocopied the pro-migratory effect of miR-132. Collectively, our study reveals an important role for miR-132 in HDFs during wound healing and indicates a therapeutic potential of miR-132 in hard-to-heal skin wounds.
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