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Sökning: WFRF:(Jönsson Erik G.)

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1.
  • Satizabal, Claudia L., et al. (författare)
  • Genetic architecture of subcortical brain structures in 38,851 individuals
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
  • Tidskriftsartikel (refereegranskat)abstract
    • Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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2.
  • Dima, Danai, et al. (författare)
  • Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
  • 2022
  • Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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3.
  • Schijven, Dick, et al. (författare)
  • Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
  • 2023
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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4.
  • Abolfathi, Bela, et al. (författare)
  • The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
  • 2018
  • Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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5.
  • Blanton, Michael R., et al. (författare)
  • Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
  • 2017
  • Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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6.
  • Sønderby, Ida E., et al. (författare)
  • 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
  • 2021
  • Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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7.
  • de Zwarte, Sonja M. C., et al. (författare)
  • Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder
  • 2022
  • Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 414-430
  • Tidskriftsartikel (refereegranskat)abstract
    • First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.
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8.
  • de Zwarte, Sonja M. C., et al. (författare)
  • The association between familial risk and brain abnormalities is disease specific : an ENIGMA-relatives study of schizophrenia and bipolar disorder
  • 2019
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:7, s. 545-556
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects.CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
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9.
  • Tønnesen, Siren, et al. (författare)
  • Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder : A Multisample Diffusion Tensor Imaging Study
  • 2020
  • Ingår i: Biological Psychiatry. - : Elsevier BV. - 2451-9022 .- 2451-9030. ; 5:12, s. 1095-1103
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (DTI) indices of white matter structure and organization to estimate and compare brain age between patients with SZ, patients with BD, and healthy control (HC) subjects across 10 cohorts.METHODS: We trained 6 cross-validated models using different combinations of DTI data from 927 HC subjects (18-94 years of age) and applied the models to the test sets including 648 patients with SZ (18-66 years of age), 185 patients with BD (18-64 years of age), and 990 HC subjects (17-68 years of age), estimating the brain age for each participant. Group differences were assessed using linear models, accounting for age, sex, and scanner. A meta-analytic framework was applied to assess the heterogeneity and generalizability of the results.RESULTS: Tenfold cross-validation revealed high accuracy for all models. Compared with HC subjects, the model including all feature sets significantly overestimated the age of patients with SZ (Cohen's d = -0.29) and patients with BD (Cohen's d = 0.18), with similar effects for the other models. The meta-analysis converged on the same findings. Fractional anisotropy-based models showed larger group differences than the models based on other DTI-derived metrics.CONCLUSIONS: Brain age prediction based on DTI provides informative and robust proxies for brain white matter integrity. Our results further suggest that white matter aberrations in SZ and BD primarily consist of anatomically distributed deviations from expected lifespan trajectories that generalize across cohorts and scanners.
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10.
  • van der Meer, Dennis, et al. (författare)
  • Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
  • 2020
  • Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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11.
  • Aguado, D. S., et al. (författare)
  • The Fifteenth Data Release of the Sloan Digital Sky Surveys : First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library
  • 2019
  • Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 240:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July-2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA-we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.
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12.
  • Andreou, Dimitrios, et al. (författare)
  • Polymorphisms in genes implicated in dopamine, serotonin and noradrenalin metabolism suggest association with cerebrospinal fluid monoamine metabolite concentrations in psychosis
  • 2014
  • Ingår i: Behavioral and Brain Functions. - : Springer Science and Business Media LLC. - 1744-9081. ; 10, s. 26-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major monoamine metabolites in the central nervous system (CNS). Their cerebrospinal fluid (CSF) concentrations, reflecting the monoamine turnover rates in CNS, are partially under genetic influence and have been associated with schizophrenia. We have hypothesized that CSF monoamine metabolite concentrations represent intermediate steps between single nucleotide polymorphisms (SNPs) in genes implicated in monoaminergic pathways and psychosis.METHODS: We have searched for association between 119 SNPs in genes implicated in monoaminergic pathways [tryptophan hydroxylase 1 (TPH1), TPH2, tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT), monoamine oxidase A (MAOA) and MAOB] and monoamine metabolite concentrations in CSF in 74 patients with psychotic disorder.RESULTS: There were 42 nominally significant associations between SNPs and CSF monoamine metabolite concentrations, which exceeded the expected number (20) of nominal associations given the total number of tests performed. The strongest association (p = 0.0004) was found between MAOB rs5905512, a SNP previously reported to be associated with schizophrenia in men, and MHPG concentrations in men with psychotic disorder. Further analyses in 111 healthy individuals revealed that 41 of the 42 nominal associations were restricted to patients with psychosis and were absent in healthy controls.CONCLUSIONS: The present study suggests that altered monoamine turnover rates in CNS reflect intermediate steps in the associations between SNPs and psychosis.
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13.
  • Barth, Claudia, et al. (författare)
  • In vivo white matter microstructure in adolescents with early-onset psychosis : a multi-site mega-analysis
  • 2023
  • Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28, s. 1159-1169
  • Tidskriftsartikel (refereegranskat)abstract
    • Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age=16.6 years, interquartile range (IQR)=2.14, 46.4% females) and 265 adolescent healthy controls (median age=16.2 years, IQR=2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d=0.37), posterior corona radiata (d=0.32), and superior fronto-occipital fasciculus (d=0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.
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14.
  • Comasco, Erika, 1982-, et al. (författare)
  • Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia
  • 2017
  • Ingår i: Neuropsychobiology. - Basel : S. Karger. - 0302-282X .- 1423-0224. ; 74:2, s. 96-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.
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15.
  • Jönsson, Erik G., et al. (författare)
  • Two methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, schizophrenia and bipolar disorder : An association study
  • 2008
  • Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics. - : Wiley. - 1552-4841. ; 147B:6, s. 976-982
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent meta-analyses of the methylenetetrahydrofolate reductase gene (MTHFR) have suggested association between two of its functional single gene polymorphisms (SNPs, C677T and A1298C) and schizophrenia. Studies have also suggested association between MTHFR C677T and A1298C variation and bipolar disorder. In a replication attempt the MTHFR C677T and A1298C SNPs were analyzed in three Scandinavian schizophrenia case-control samples. In addition, Norwegian patients with bipolar disorder were investigated. There were no statistically significant allele or genotype case-control differences. The present Scandinavian results do not verify previous associations between the putative functional MTHFR gene polymorphisms and schizophrenia or bipolar disorder. However, when combined with previous studies in meta-analyses there is still evidence for association between the MTHFR C677T polymorphism. and schizophrenia. Additional studies are warranted to shed further light on these relationships. (c) 2007 Wiley-Liss, Inc.
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16.
  • Smith, Henrik G., et al. (författare)
  • Slututvärdering av det svenska landsbygdsprogrammet 2007–2013 : Delrapport II: Utvärdering av åtgärder för bättre miljö
  • 2016
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • SammanfattningRapporten är en del av slututvärderingen av Landsbygdsprogram för Sverige 2007-2013 och har tagits fram på uppdrag av Jordbruksverket. Den redovisar resultat och effekter som uppnåddes genom miljö- och klimatåtgärderna inom landsbygdsprogrammet, vilket omfattar samtliga insatser och ersättningar i axel 2, samt miljö- och klimatrelaterade utvärderingsfrågor för en del åtgärder i axel 1 och 3.Med hjälp av vetenskapliga analyser, kunskapsbaserade resonemang och de för varje insats i landsbygdsprogrammet specificerade indikatorerna har bland annat följande EU-gemensamma (QEC) och programspecifika (PSEQ) utvärderingsfrågor besvarats:• QEC 16: I vilken utsträckning har åtgärden bidragit till att förbättra miljösituationen?• CEQ 20: Vilka andra effekter, bl.a. de som rör andra mål/axlar, är kopplade tillgenomförandet av denna åtgärd?• PSEQ 16A: Hur ändamålsenlig och effektiv har den geografiska styrningen avmiljöåtgärden i programmet varit?• PSEQ 20A: I vilken utsträckning har kompetensutvecklingsåtgärderna bidragittill programmets miljömål?• PSEQ 20B: Vad kan man lära sig av hur klimatåtgärderna fungerat när det gällerutformningen och utvärderingen av klimatåtgärder i framtida program?• PSEQ 20C: Vilka sysselsättningseffekter ger miljöåtgärderna?Utredarnas generella slutsats är att landsbygdsprogrammet spelat en stor och i många fall avgörande roll för miljön, t.ex. genom att förhindra nedläggning av jordbruk i områden med svåra förutsättningar för jordbruk, bevara betes- och slåttermarker av värde för biologisk mångfald och skapa och restaurera våtmarker för biologisk mångfald och näringsretention. Detta bidrar till uppfyllelsen av de svenska miljömålen och internationella åtaganden. Även de klimatrelaterade åtgärderna bidrar i viss mån till att uppfylla miljömålen, men en låg anslutning till vissa åtgärder och programmets ensidiga fokus på produktion av förnybar energi (som bortser från ur klimatsynvinkel mycket större biogena utsläppskällor) gör att effekten på miljömålen bedöms som relativt små. Bedömningen av kompetensutvecklingens effekter på miljömålen har försvårats av brist på tillämpningsbart underlag, men utvärderingen av rådgivningsprogrammet Greppa näringen visar att det bidragit till att reducerakvävetillförseln till Östersjön. För en del andra åtgärder är det empiriska underlaget för vilken effekt de har mycket svagt. Detta behöver i sig inte innebära att dessa åtgärder saknar effekt, men gör det svårt att bedöma deras bidrag till uppfyllelsen av miljömålen och begränsar kunskapen om huruvida alternativa utformningar av insatserna skulle ge större effekt.Den explicita geografiska styrningen som förekommer i programmet bedöms generellt som relevant, men dess effekt varierar stort mellan olika åtgärder/insatser och är i vissa fall svårt att utreda. Det finns dock en del åtgärder/insatser som idag saknar explicit geografisk styrning, men där vi bedömer att kostnadseffektiviteten skulle kunna öka markant om man införde en sådan (t.ex. Certifierad ekologisk produktion).Miljöåtgärdernas sysselsättningseffekter har endast kunnat bedömas för ett fåtalåtgärder/insatser (kompensationsbidraget samt ersättningarna för Extensiv vallodling och Skötsel av betesmarker och slåtterängar) och anses generellt vara marginellt positiv. Detta bör dock tolkas med stor försiktighet eftersom bedömningen gjordes enbart via dessa åtgärders effekt på markanvändningen.Miljö- och klimatåtgärders effekterUnder programperioden 2007-2013 innehöll landsbygdsprogrammet en mängd olika åtgärder med syfte att gynna miljö och klimat. Utvärderingen visar att det finns en stor variation i såväl upptaget av de olika åtgärderna som deras effekt. Miljöåtgärdernas syften fokuserar huvudsakligen på att gynna bevarandet av biologisk mångfald, minskat växtnäringsläckage och giftfri miljö. De flesta miljöåtgärder bidrar generellt till att uppnå sitt syfte, men om de gör det på ett kostnadseffektivt sätt har ofta varit svårt och ibland omöjligt att utvärdera. För syftet giftfri miljö har det inte funnits resurser till en djupare utvärdering.Ersättningarna för Skötsel av betesmarker och slåtterängar samt för Certifieradekologisk och kretsloppsinriktad produktion är exempel på insatser med konstaterad positiv effekt på biologisk mångfald. Andra ersättningar, såsom ersättningen för Värdefulla natur- och kulturmiljöer, adresserar visserligen för biologisk mångfald viktiga livsmiljöer, men deras utformning och skötselvillkor har visat sig inte vara anpassade till detta syfte med insatsen. För en del ersättningar saknas tillräckligt kunskap eller dataunderlag för att kunna göra tillfredställande utvärderingar av effekterna på biologisk mångfald. Bland dessa finns exempelvis ersättningarna för Extensiv vallodling och Skötsel av våtmarker.Minskat näringsämnesläckage och miljömålet Ingen övergödning fanns som syfte för flera insatser inom åtgärden Miljövänligt jordbruk och den generella bedömningen är att insatserna bidrar till att uppfylla detta syfte. Det finns dock stor skillnad i hur effektiva insatserna är. Minskat kväveläckage anses ha en god kostnadseffektivitet, särskilt efter att ersättningsnivåerna anpassades under senare delen av programperioden. Även reduceringen av fosfor genom skyddszoner bedöms ha en högre kostnadseffektivitet jämfört med förra programperioden på grund av regionala skillnader i anslutning. När det gäller Extensiv vallodling visar utvärderingen stora regionala skillnader, och för andra insatser, såsom Restaurering och anläggning av våtmarker och Certifierad ekologisk odling, har det varit svårt att bedöma om de på ett kostnadseffektivt sätt bidragit till att uppfylla miljömålen.Miljöåtgärdernas effekter på miljömålet Giftfri miljö har inom ramen för dennautvärdering inte kunnat analyseras specifikt på grund av bristande underlag ochbegränsade resurser. Eftersom det generellt är svårt att utvärdera det specifika bidraget av de berörda ersättningarna till en giftfri miljö, kan utvärderingen därför inte på ett tillfredställande sätt svara på hur stor deras bidrag till detta miljökvalitetsmål har varit.När det gäller klimatåtgärder har programmet ett tydligt fokus på produktion ochanvändning av energi och relaterade emissioner av växthusgaser. Samtidigt konstateras det att emissionerna av växthusgaser från jordbrukssektorn primärt härrör från biogena processer i form av metan från idisslarnas matsmältning och lustgas från det kväve som tillförs åkermarken. För en fortsatt reduktion av jordbrukssektorns emissioner av växthusgaser bör satsningarna på en minskad användning av fossila bränslen fortsätta, men det är samtidigt nödvändigt att lägga ett större fokus på de biogena emissionerna. För att tydliggöra vikten av klimatåtgärder och satsningar på förnybar energi bör dessa insatser också lyftas fram som egna åtgärder istället för att finnas insprängda bland åtgärder som har annat huvudfokus.För ett fåtal åtgärder och ersättningar har det gått att härleda möjliga sysselsättningseffekter via de markanvändningseffekter som estimerats med modeller. Även om dessa resultat bör tolkas med stor försiktighet, bedöms sysselsättningseffekten av miljöåtgärderna generellt vara marginellt positiv. Ersättningen Skötsel av betesmarker och slåtterängar har i beräkningar som bygger på kontrafaktiska markanvändningsscenarier lett till en märkbar förändring av markanvändningen (ökad areal betesmarker med stöd) vilket, eftersom animalieproduktion generellt anses vara mer tidskrävande än spannmålsproduktion, bedöms leda till högre sysselsättning. Extensiv vallodling och kompensationsbidrag har däremot en mycket begränsad påverkanpå markanvändningen, varför sysselsättningseffekten bedöms som marginell.Generella förbättringsförslag inför utformningen av kommande programÄven om utvärderarnas samlade bedömning är att landsbygdsprogrammets upplägg, d.v.s. dess syften och motiv, ingående medel och val av åtgärder, är relevant och generellt bidrar till att förbättra situationen för miljö och klimat, så finns det en hel del som kan och bör förbättras för att möjliggöra kostnadseffektiva program i framtiden. De enstaka insatsernas syften och mål bör preciseras och kopplas till tydliga indikatorer som på ett relevant sätt kan mäta måluppfyllandet. Detta är avgörande för att man ska kunna utforma ett kostnadseffektivt landsbygdsprogram och utvärdera det på ett adekvat sätt. Dessutom behöver beskrivningarna för syften och motiv för många av ersättningarna ses över och anpassas till det aktuella kunskapsläget. Exempelvis skulle syftet ”bevara biologisk mångfald” leda till helt olika åtgärder beroende på om man vill bevara sällsynta arter eller ekosystemtjänstgynnare.Det empiriska underlaget för utvärdering behöver stärkas inför utvärderingen avframtida landsbygdsprogram. Detta kan exempelvis göras genom systematiskaöversikter och empirisk primärforskning som undersöker konsekvenser av olikaåtgärder. För att optimera detta bör utvärderingen byggas in som en organisk del av landsbygdsprogrammet. Utredarna föreslår att en procent av programmets budget används till att utforma och implementera relevanta metoder för kontinuerlig insamling av lämplig data under hela programperioden.För att i högre grad kunna utvärdera landsbygdsprogrammets kostnadseffektivitetkrävs en fortsatt utveckling av metoder för att studera konsekvenserna för målet av att åtgärden/insatsen/delinsatsen finns eller inte finns (eller var annorlunda utformad) (kontrafaktiska scenarier) och modeller som föruts
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17.
  • The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
  • 2022
  • Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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18.
  • Andreou, Dimitrios, et al. (författare)
  • Dystrobrevin-binding protein 1 gene (DTNBP1) variants associated with cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid concentrations in healthy volunteers
  • 2011
  • Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 21:9, s. 700-704
  • Tidskriftsartikel (refereegranskat)abstract
    • The dystrobrevin binding protein-1 (DTNBP1) gene encodes dysbindin-1, a protein involved in neurodevelopmental and neurochemical processes related mainly to the monoamine dopamine. We investigated possible associations between eleven DTNBP1 polymorphisms and cerebrospinal fluid (CSF) concentrations of the major dopamine metabolite homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and the major noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy human subjects (n=132). Two polymorphisms, rs2619538 and rs760666, were nominally associated with CSF HVA and 5-HIAA concentrations, whereas a third polymorphism, rs909706, showed association only with HVA. After correction for multiple testing only the associations between rs2619538 and HVA and 5-HIAA concentrations remained significant. No significant association was found between any of the investigated DTNBP1 polymorphisms and CSF MHPG concentrations. The results suggest that genetic variation in DTNBP1 gene affects the regulation of dopamine and serotonin turnover in the central nervous system of healthy volunteers.
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19.
  • Andreou, Dimitrios, et al. (författare)
  • Tryptophan hydroxylase gene 1 (TPH1) variants associated with cerebrospinal fluid 5-hydroxyindole acetic acid and homovanillic acid concentrations in healthy volunteers
  • 2010
  • Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 180:2-3, s. 63-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. We investigated possible relationships between five TPH1 gene polymorphisms and cerebrospinal fluid (CSF) concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the major dopamine metabolite homovanillic acid (HVA), and the major norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 132). The G-allele of the TPH1 rs4537731 (A-6526G) polymorphism was associated with 5-HIM and HVA, but not MHPG concentrations. None of the other four TPH1 polymorphisms (rs211105, rs1800532, rs1799913 and rs7933505) were significantly associated with any of the monoamine metabolite concentrations. Two (rs4537731G/rs211105T/rs1800532C/rs1799913C/rs7933505G and rs4537731A/rs211105T/rs1800532C/rs1799913C/rs7933505G) of five common TPH1 five-allele haplotypes were associated with 5-HIAA and HVA concentrations in opposite directions. None of the common haplotypes was associated with MHPG concentrations in the CSF. The results suggest that TPH1 gene variation participates in the regulation of serotonin and dopamine turnover rates in the central nervous system of healthy human subjects.
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20.
  • Blomqvist, S, et al. (författare)
  • Early post-traumatic changes in hemodynamics and pulmonary ventilation in alcohol-pretreated pigs
  • 1987
  • Ingår i: Journal of Trauma. - 0022-5282. ; 27:1, s. 40-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Time relations among trauma, pulmonary and systemic circulation, and lung function were studied in pigs. Eleven animals (b.w. 25-30 kg) were investigated under balanced anesthesia. Ventilation was mechanically controlled. Hemodynamics, pulmonary ventilation, and gas exchange were serially recorded. Seven animals were pretreated with 40% ethanol in saline and four with saline only. Ninety minutes after the ingestion of alcohol or saline, the animals were subjected to a standardized soft-tissue trauma. Cardiac output decreased significantly 2 minutes after trauma and remained low in both groups throughout the observation period of 30 minutes. Pulmonary vascular resistance was significantly increased in the alcohol-pretreated group but was virtually unchanged in the control animals. Systemic vascular resistance was similarly reduced in the two groups. Total compliance was somewhat lower in alcohol-pretreated animals and 10 minutes after the trauma arterial oxygen tension was significantly lower in the alcohol group than in control animals. Carbon dioxide elimination was reduced after trauma in both groups. It is concluded that pulmonary vascular response increased and that total pulmonary compliance is somewhat decreased shortly after trauma in the alcohol group while gas exchange is almost unchanged. The results indicate a negative interaction between alcohol and trauma
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21.
  • Boen, Rune, et al. (författare)
  • Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
  • 2024
  • Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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22.
  • Carlborg, Andreas, et al. (författare)
  • Attempted suicide predicts suicide risk in schizophrenia spectrum psychosis
  • 2010
  • Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 64:1, s. 68-72
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: People with schizophrenia have an increased risk of suicide and attempted suicide is suggested to be an important risk factor.AIM: Our objective was to assess the cumulative survival, predictive values and odds ratios of attempted suicide for suicide in a long-term cohort of patients with schizophrenia spectrum psychosis with and without previous attempted suicide.METHOD: Inpatients (n=224) hospitalized with schizophrenia spectrum psychosis were followed for a mean of 25 years. All patients were followed up for causes of death. Information on suicide attempt before the end of the observation period was retrieved from medical records.RESULTS: Eight percent died by suicide during the follow-up. Eighteen percent of suicide attempters died by suicide. Two percent of non-attempters died by suicide. There was a strong association between previous suicide attempt and suicide in men and women. Odds ratio for attempters vs. non-attempters was 10. Suicide risk was almost three times higher in male than female suicide attempters.CONCLUSION: Previous attempted suicide is an important risk factor for suicide in both men and women with schizophrenia spectrum psychosis, particularly in male suicide attempters. The suicide risk remains high over a long period. Continuous assessment of risk factors and appropriate treatment are crucial for this patient group to prevent suicide.
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23.
  • Carlborg, Andreas, et al. (författare)
  • CSF kynurenic acid and suicide risk in schizophrenia spectrum psychosis
  • 2013
  • Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 205:1-2, s. 165-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Relationships between concentrations of cerebrospinal fluid (CSF) kynurenic acid (KYNA) and suicidal behavior were evaluated in 59 patients with psychosis after 22 years of follow-up. Three patients died from suicide and nine patients had a history of attempted suicide. Patients with attempted suicide had significantly lower concentrations of CSF KYNA.
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24.
  • Carlborg, Andreas, et al. (författare)
  • Early death and CSF monoamine metabolites in schizophrenia spectrum psychosis
  • 2011
  • Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 65:2, s. 101-5
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Patients with schizophrenia have higher rates of mortality than the general population. Lower concentrations of the cerebrospinal fluid (CSF) monoamine metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) have been associated with suicidal, aggressive and impulsive behavior. Mortality has been suggested as a measure of impulsivity and a relationship between early death and lower concentrations of CSF monoamine metabolites has been reported but the studies are few with short periods of follow-up and small numbers.AIM: The objective of this study was to investigate a relationship between early death and concentrations of CSF 5-HIAA and HVA.METHODS: Three hundred and eighty-five inpatients with schizophrenia spectrum psychosis were lumbar punctured in a standardized manner and followed for a median of 26 years. Patients were searched to identify those who had died. Causes of death were obtained from the Causes of Death Register.RESULTS: During the time of follow-up, 97 patients died. Schizophrenia spectrum psychosis patients died at an earlier age from both natural and unnatural causes of death. No significant associations were found between CSF 5-HIAA and HVA concentrations and non-suicidal death. Attempted suicide was not a risk factor for non-suicidal death at younger age.CONCLUSION: Patients with schizophrenia spectrum psychosis die at an earlier age from both natural and unnatural causes of death. Attempted suicide is not a risk factor for non-suicidal death at younger age. Low concentrations of CSF HVA and 5-HIAA were not a risk factor for non-suicidal death at younger age in schizophrenia spectrum psychosis.
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25.
  • Carlborg, Andreas, et al. (författare)
  • Suicide in schizophrenia
  • 2010
  • Ingår i: Expert Review of Neurotherapeutics. - : Informa UK Limited. - 1473-7175 .- 1744-8360. ; 10:7, s. 1153-64
  • Forskningsöversikt (refereegranskat)abstract
    • Schizophrenia is a disorder with an estimated suicide risk of 4-5%. Many factors are involved in the suicidal process, some of which are different from those in the general population. Clinical risk factors include attempted suicide, depression, male gender, substance abuse and hopelessness. Biosocial factors, such as a high intelligence quotient and high level of premorbid function, have also been associated with an increased risk of suicide in patients with schizophrenia. Suicide risk is especially high during the first year after diagnosis. Many of the suicides occur during hospital admission or soon after discharge. Management of suicide risk includes both medical treatment and psychosocial interventions. Still, risk factors are crude; efforts to predict individual suicides have not proved useful and more research is needed.
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26.
  • Córdova-Palomera, Aldo, et al. (författare)
  • Genetic control of variability in subcortical and intracranial volumes
  • 2021
  • Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 26:8, s. 3876-3883
  • Tidskriftsartikel (refereegranskat)abstract
    • Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.
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27.
  • Ekholm, Birgit, et al. (författare)
  • Evaluation of diagnostic procedures in Swedish patients with schizophrenia and related psychoses
  • 2005
  • Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 59:6, s. 457-464
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to estimate the value of structured interviews, medical records and Swedish register diagnoses for assessing lifetime diagnosis of patients with schizophrenia. Psychiatric records and diagnostic interviews of 143 Swedish patients diagnosed by their treating physician with schizophrenia and related disorders were scrutinized. Based on record analysis only, or a combined record and interview analysis, DSM-IV diagnoses were obtained by the OPCRIT algorithm. Independent of the OPCRIT algorithm, a standard research DSM-IV diagnosis, based on both record and interview analysis, was given by the research psychiatrist. Concordance rates for the different psychosis diagnoses were calculated. DSM-IV diagnoses based on records only, showed a good to excellent agreement with diagnoses based on records and interviews. Swedish register diagnoses displayed generally poor agreement with the research diagnoses. Nevertheless, 94% of subjects sometimes registered with a diagnosis of schizophrenic psychoses (i.e. schizophrenia, schizoaffective psychosis or schizophreniform disorder) displayed a standard research DSM-IV diagnosis of these disorders. For patients in long-term treatment for schizophrenia in Sweden, psychiatric record reviews should be optimal, cost effective and sufficient for assessment of lifetime research diagnoses of schizophrenia. For these patients a research interview adds little new information. The results further indicate that a Swedish register diagnosis of schizophrenic psychoses has a high positive predictive power to a standard research DSM-IV diagnosis of the disorders. It is concluded that for future Swedish large-scale genetic studies focusing on a broad definition of schizophrenia, it would be sufficient to rely on the Swedish register diagnoses of schizophrenic psychosis.
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28.
  • Grip, Carl-Erik, et al. (författare)
  • Prediction of emptying flows in ladles and verification with data from trace element plant trials
  • 1997
  • Ingår i: ISIJ International. - : Iron and Steel Institute of Japan. - 0915-1559 .- 1347-5460. ; 37:11, s. 1081-1090
  • Tidskriftsartikel (refereegranskat)abstract
    • A three-dimensional mathematical model of a casting ladle based on fundamental transport equations has been developed. The model may be used for predictions of both a standing ladle and a ladle from which steel is teemed into a tundish. An additional feature of the model is that it can predict concentration profiles of tracer elements which are added to the steel. The predicted concentration profiles during teeming are compared to experimental data from plant trials performed at SSAB and the agreement is found to be good. The model is used as a tool in the development of process control models.
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29.
  • Harring, Niklas, 1979, et al. (författare)
  • Cross-national analysis of attitudes towards fossil fuel subsidy removal
  • 2023
  • Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 13, s. 244-249
  • Tidskriftsartikel (refereegranskat)abstract
    • Removing fossil fuel subsidy could reduce the CO2 emissions and improve the use of government budget, while the feasibility is in doubt. This research demonstrates the public attitudes in developing countries are not worse than that for carbon tax, and better use of the public fund is preferred. In 2021, governments of 51 countries spent US$697 billion on subsidizing fossil fuels. Removing fossil fuel subsidies is crucial not only for reducing CO2 emissions and making carbon pricing more effective, but also for making more valuable use of government funds. Currently, however, scientific evidence on the scale and scope of public attitudes towards fossil fuel subsidy-removal policies is lacking, yet it is instrumental for gauging political feasibility. Furthermore, previous studies tend to focus on carbon pricing in the developed world only. Here we present a comparative analysis of attitudes towards both carbon taxation and fossil fuel subsidy removal, focusing on five developing countries across four continents. It is found that (1) removing fossil fuel subsidies is not more undesirable than introducing carbon taxation and (2) the public has more-positive attitudes towards subsidy removal if optimal use of the saved fiscal revenues is specified.
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30.
  • Jönsson, Erik G, et al. (författare)
  • Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers.
  • 2004
  • Ingår i: BMC psychiatry. - 1471-244X. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences. METHODS: We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C), the serotonin 3A receptor (HTR3A), the dopamine D4 receptor (DRD4), and the dopamine beta-hydroxylase (DBH) genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 90). RESULTS: The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02). The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005) and HVA (p = 0.009) concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites. CONCLUSIONS: The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system.
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31.
  • Jönsson, Marie E, et al. (författare)
  • Activation of endogenous retroviruses during brain development causes an inflammatory response
  • 2021
  • Ingår i: EMBO Journal. - : EMBO Press. - 0261-4189 .- 1460-2075. ; 40:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for an inflammatory response, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERVs in excitatory neurons in the adult brain. Neuronal ERV expression was linked to activated microglia and the presence of ERV-derived proteins in aggregate-like structures. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in an inflammatory response.
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32.
  • Jönsson, Peter, et al. (författare)
  • Chest wall sarcoma: outcome in 22 patients after resection requiring thoracic cage reconstruction.
  • 1998
  • Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 2:3-4, s. 143-147
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose. To evaluate the outcome after resection of malignant chest wall sarcoma, requiring reconstruction of the chest wall.Subjects. Twenty-two patients, 15 with primary tumours, were operated on in our institution between 1983 and 1996. Four patients underwent surgery after a previous intralesional or marginal excision and three patients because of a local recurrence.Methods. The tumour was resected 'en bloc', including skin, muscle and thoracic skeleton. When necessary, adjacent organs invaded by the tumour, such as lung, pericardium and diaphragm, were also removed to obtain a wide margin. Reconstruction of the chest wall was performed with Marlex mesh (n=9), methylmethacrylate cement (n=2) or a Marlex methylmethacrylate 'sandwich' (n=11).Results. The median tumour size was 9.5 (2-20) cm. The most common type of tumour was chondrosarcoma (12 cases). No patient died in hospital. Five patients required reoperation because of complications, two patients because of loosening of the acrylate prosthesis, two because of necrosis of soft tissue coverage and one was reoperated because of bleeding. Four patients died of generalized tumour disease between 5 and 77 months after surgery and one patient died of a local recurrence 32 months after the primary operation. Seventeen patients are alive, with a median follow-up of 36 (4-162) months. Microscopic radicality (negative margin) was achieved in 17 patients but 5 of these had local recurrences. Two of five patients with positive margins had a local recurrence of the tumour. Of the seven patients with local recurrences, two also developed metastases.Discussion. Large chest wall sarcomas can be successfully resected and the chest wall reconstructed with low morbidity and mortality.
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33.
  • Malmström, Per, et al. (författare)
  • Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening.
  • 2003
  • Ingår i: European journal of cancer (Oxford, England : 1990). - 0959-8049. ; 39, s. 1690-
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy. Median age was 60 years, and median size of the detected tumours was 12 mm. Of the women 65% had their tumours detected by mammographical screening. The relative risk (RR) of ipsilateral breast recurrence was significantly higher in the non-irradiated patients compared with the irradiated patients, RR=3.33 (95% Confidence Interval (CI) 2.13-5.19, P<0.001). The corresponding cumulative incidence at 5 years was 14% versus 4%, respectively. Overall survival (OS) was similar, RR=1.16 (95% CI 0.81-1.65, P=0.41), with 5 year probabilities of 93 and 94%, respectively. Recurrence-free survival (RFS) at 5 years was significantly lower in the non-irradiated women, 77% versus 88% (P<0.001). Although women above 49 years of age, whose tumours were detected with mammographical screening, had the lowest rate of ipsilateral breast recurrence in this study, the cumulative incidence of such event amounted to 10% at 5 years if radiotherapy was not given. Such a recurrence rate has been considered as unacceptably high, but is, however, in the same range as that reported after lumpectomy and postoperative radiotherapy in published series.
  •  
34.
  • Moberg, Tomas, et al. (författare)
  • Psychiatric and neurological disorders in late adolescence and risk of convictions for violent crime in men
  • 2015
  • Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The relationship between mental illness and violent crime is complex because of the involvement of many other confounding risk factors. In the present study, we analysed psychiatric and neurological disorders in relation to the risk of convictions for violent crime, taking into account early behavioural and socio-economic risk factors. Methods: The study population consisted of 49,398 Swedish men, who were thoroughly assessed at conscription for compulsory military service during the years 1969-1970 and followed in national crime registers up to 2006. Five diagnostic groups were analysed: anxiety-depression/neuroses, personality disorders, substance-related disorders, mental retardation and neurological conditions. In addition, eight confounders measured at conscription and based on the literature on violence risk assessment, were added to the analyses. The relative risks of convictions for violent crime during 35 years after conscription were examined in relation to psychiatric diagnoses and other risk factors at conscription, as measured by odds ratios (ORs) and confidence intervals (CIs) from bivariate and multivariate logistic regression analyses. Results: In the bivariate analyses there was a significant association between receiving a psychiatric diagnosis at conscription and a future conviction for violent crime (OR = 3.83, 95 % CI = 3.47-4.22), whereas no significant association between neurological conditions and future violent crime (OR = 1.03, 95 % CI = 0.48-2.21) was found. In the fully adjusted multivariate logistic regression model, mental retardation had the strongest association with future violent crime (OR = 3.60, 95 % CI = 2.73-4.75), followed by substance-related disorders (OR = 2.81, 95 % CI = 2.18-3.62), personality disorders (OR = 2.66, 95 % CI = 2.21-3.19) and anxiety-depression (OR = 1.29, 95 % CI = 1.07-1.55). Among the other risk factors, early behavioural problem had the strongest association with convictions for violent crime. Conclusions: Mental retardation, substance-related disorders, personality disorders and early behavioural problems are important predictors of convictions for violent crime in men.
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35.
  • Moberg, Tomas, et al. (författare)
  • Risk factors for adult interpersonal violence in suicide attempters
  • 2014
  • Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 14, s. 195-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicidal and violent behaviours are interlinked and share common biological underpinnings. In the present study we analysed the association between violent behaviour as a child, childhood trauma, adult psychiatric illness, and substance abuse in relation to interpersonal violence as an adult in suicide attempters with mood disorders.METHODS: A total of 161 suicide attempters were diagnosed with Structured Clinical Interviews and assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behaviour in childhood (between 6-14 years of age) and during adult life (15 years or older). Ninety five healthy volunteers were used as a comparison group. A logistic regression analysis was conducted with the two KIVS subscales, expressed violent behaviour as a child and exposure to violence in childhood together with substance abuse, personality disorder diagnoses and age as possible predictors of adult interpersonal violence in suicide attempters.RESULTS: Violent behaviour as a child, age and substance abuse were significant predictors of adult interpersonal violence. ROC analysis for the prediction model for adult violence with the KIVS subscale expressed violence as a child gave an AUC of 0.79. Using two predictors: violent behaviour as a child and substance abuse diagnosis gave an AUC of 0.84. The optimal cut-off for the KIVS subscale expressed violence as a child was higher for male suicide attempters.CONCLUSIONS: Violent behaviour in childhood and substance abuse are important risk factors for adult interpersonal violent behaviour in suicide attempters.
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36.
  • Nilsson, Linda K, et al. (författare)
  • Cerebrospinal fluid kynurenic acid in male and female controls - Correlation with monoamine metabolites and influences of confounding factors
  • 2007
  • Ingår i: Journal of Psychiatric Research. - : Elsevier BV. - 0022-3956 .- 1879-1379. ; 41:1-2, s. 144-151
  • Tidskriftsartikel (refereegranskat)abstract
    • The concentrations of the tryptophan metabolite kynurenic acid (KYNA) and the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were determined in the cerebrospinal fluid (CSF) from 43 healthy volunteers (30 males and 13 females). Healthy female controls displayed higher CSF concentration of KYNA (1.91 nM ± 0.20) compared to healthy male controls (1.06 nM ± 0.07) and lower CSF levels of HMPG (39.2 nM ± 2.0 and 43.4 ± 1.2, respectively). CSF levels of HVA and 5-HIAA did not differ between females (181.3 nM ± 21.9 and 93.7 nM ± 11.4, respectively) and males (138.9 nM ± 12.6 and 74.8 nM ± 5.9, respectively). Positive intercorrelations were found between CSF KYNA, HVA and 5-HIAA while CSF content of HMPG did not correlate with KYNA or the other monoamine metabolites in CSF. A negative correlation was found between back length and CSF concentrations of KYNA, HVA and 5-HIAA and also between CSF KYNA levels and body height. The results of the present study suggest that concentrations of KYNA and the monoamine metabolites in CSF from healthy controls are dependent on gender and back length, which must be taken in consideration when analysing mixed groups of men and women. The higher KYNA concentration found in female controls compared to male might be attributed to a shorter back in women compared to men. Furthermore, these findings suggest that increased KYNA formation is associated with an increased dopamine and serotonin turnover. © 2005 Elsevier Ltd. All rights reserved.
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37.
  • Nilsson-Todd, Linda K, et al. (författare)
  • Cerebrospinal fluid kynurenic acid in male patients with schizophrenia - Correlation with monoamine metabolites
  • 2007
  • Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 19:1, s. 45-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The tryptophan metabolite kynurenic acid (KYNA) is an endogenous glutamate/nicotinic receptor antagonist. Previous studies have shown that the concentration of the compound is increased in cerebrospinal fluid (CSF) of patients with schizophrenia. Furthermore, it has been found that the CSF concentration of KYNA is positively correlated to CSF concentrations of the monoamine metabolites homovanillic acid (HVA) and 5-hydroxy indoleacetic acid (5-HIAA) in healthy control subjects. Objectives: To study the correlations between KYNA and the monoamine metabolites HVA, 5-HIAA and 4-hydroxy-3- methoxyphenylglycol (HMPG) in CSF of male patients (n = 53, ranging from 20 to 48 years of age) with verified schizophrenia. Methods: CSF was obtained by lumbar puncture, and KYNA analysis was performed with an isocratic reversed-phase high-performance liquid chromatography system connected to a fluorescence detector. HVA, 5-HIAA and HMPG concentrations were measured by mass fragmentography with deuterium-labelled internal standards. Results: Positive intercorrelations were found between CSF KYNA, HVA and 5-HIAA, while CSF content of HMPG did not correlate to KYNA or any of the monoamine metabolites in CSF. Conclusion: The results of this study suggest that increased KYNA formation is associated with an increased dopamine and serotonin turnover in male patients with schizophrenia. © 2007 Blackwell Munksgaard.
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38.
  • Olsson, Sara K., et al. (författare)
  • Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder
  • 2010
  • Ingår i: Journal of Psychiatry & Neuroscience. - : CMA Joule Inc.. - 1180-4882 .- 1488-2434. ; 35:3, s. 195-199
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with schizophrenia show elevated brain levels of the neuroactive tryptophan metabolite kynurenic acid (KYNA) This astrocyte] derived mediator acts as a neuroprotectant and modulates sensory gating and cognitive functiona We measured the levels of KYNA in the cerebrospinal fluid T vSyU of patients with bipolar disorder and healthy volunteers to investigate the putative involvement of KYNA in bipolar disorder. Methods: We obtained CSF by lumbar puncture from 23 healthy men and 31 euthymic men with bipolar disorder. We analyzed the samples using high] performance liquid chromatography. Results: Patients with bipolar disorder had increased levels of KYNA in their CSF compared with healthy volunteers (1.71 nM, standard error of the mean [SEM] cad, va dad, nM, SEM cacln p = 0.002. The levels of KYNA were positively correlated with age among bipolar patients but not healthy volunteersa Limitations: The influence of ongoing drug treatment among patients cannot be ruled outa We conducted our study during the euthymic phase of the diseasea Conclusion: Brain KYNA levels are increased in euthymic men with bipolar disorder. In addition, KYNA levels increased with age in these patientsa These findings indicate shared mechanisms between bipolar disorder and schizophrenia. Elevated levels of brain KYNA may provide further insight to the pathophysiology and progression of bipolar disorder.
  •  
39.
  • Reutfors, Johan, et al. (författare)
  • Medication and suicide risk in schizophrenia : A nested case-control study
  • 2013
  • Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 150:2-3, s. 416-420
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Patients with schizophrenia are at increased risk of suicide, but data from controlled studies of pharmacotherapy in relation to suicide risk is limited.AIM: To explore suicide risk in schizophrenia in relation to medication with antipsychotics, antidepressants, and lithium.METHODS: Of all patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n=4000), patients who died by suicide within five years from diagnosis were defined as cases (n=84; 54% male). Individually matched controls were identified from the same population. Information on prescribed medication was retrieved from psychiatric records in a blinded way. Adjusted odds ratios [OR] of the association between medication and suicide were calculated by conditional logistic regression.RESULTS: Lower suicide risk was found in patients who had been prescribed a second generation antipsychotic (clozapine, olanzapine, risperidone, or ziprasidone; 12 cases and 20 controls): OR 0.29 (95% confidence interval [CI], 0.09-0.97). When the 6 cases and 8 controls who had been prescribed clozapine were excluded, the OR was 0.23 (95% CI 0.06-0.89). No significant association was observed between suicide and prescription of any antipsychotic, depot injection antipsychotics, antidepressants, SSRI, or lithium.CONCLUSIONS: Lower suicide risk for patients who had been prescribed second generation antipsychotics may be related to a pharmacological effect of these drugs, to differences in adherence, or to differences in other patient characteristics associated with lower suicide risk.
  •  
40.
  • Reutfors, Johan, et al. (författare)
  • Suicide risk and antipsychotic side effects in schizophrenia : nested case-control study.
  • 2016
  • Ingår i: Human Psychopharmacology. - : Wiley. - 0885-6222 .- 1099-1077. ; 31:4, s. 341-345
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: This study explores suicide risk in schizophrenia in relation to side effects from antipsychotic medication.METHODS: Among patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4000), those who died by suicide within 5 years from diagnosis were defined as cases (n = 84; 54% male). For each case, one individually matched control was identified from the same population. Information on antipsychotic side effects, including extrapyramidal symptoms (EPS) and akathisia, as well as prescriptions of anticholinergic medication, was retrieved from clinical records in a blinded fashion. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of the association between suicide and side effects as well as anticholinergic medication were estimated using conditional logistic regression.RESULTS: A lower suicide risk was found in patients with a history of EPS (aOR 0.33, 95% CI 0.12-0.94). There was no statistically significant association between akathisia or anticholinergic medication use and the suicide risk.CONCLUSIONS: A lower suicide risk identified among patients with EPS could potentially reflect higher antipsychotic adherence, exposure to higher dosage, or polypharmacy among these patients.
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41.
  •  
42.
  • Roos, Erik, et al. (författare)
  • An Experimental and Thermodynamic Study of Non-Metallic Inclusions in High Si Stainless Steels Regarding Clogging During Casting
  • 2014
  • Ingår i: Steel Research International. - : Wiley. - 1611-3683 .- 1869-344X. ; 85:10, s. 1410-1417
  • Tidskriftsartikel (refereegranskat)abstract
    • Clogging of high Si-containing stainless steel grades was studied by metallographic examinations of steel samples from clogged and non-clogged heats as well as by thermodynamic modeling using Thermo-Calc and FactSage. Morphology, composition, number and size of inclusions and clusters in the steel samples were determined on a polished surface of the steel samples by using a scanning electron microscope equipped with energy-dispersive X-ray spectrometer. The results showed that the content of Al in ferroalloys added during ladle treatment should be controlled to avoid a formation of spinel MgO-Al2O3 inclusions in liquid steel and a resulting clogging during casting. The thermodynamic calculations showed that the Al content in a melt during ladle treatment and casting should not be larger than 0.003% to obtain < 1% of MgO-Al2O3 inclusions in the liquid steel for a 1.9% silicon content. Moreover, calculations also showed that if the Si content increased from 1.9% (non-clogging heats) to 2.65% (clogging heats), the number of MgO-Al2O3 inclusions decreased slightly. Moreover, it was found that an increased amount of FeSi additions for correction of Si content in the melt increase the Al content. As a result, the number of spinels and clusters increases, which is the primary cause for clogging during casting of these steel grades.
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43.
  • Saetre, Peter, et al. (författare)
  • Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms and Age of Onset in Schizophrenia : A Combined Analysis of Independent Samples
  • 2011
  • Ingår i: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-4841. ; 156B156:2, s. 215-224
  • Tidskriftsartikel (refereegranskat)abstract
    • Methylenetetrahydrofolate reductase (MTHFR) is involved in the one-carbon cycle, which is of importance for nucleotide synthesis and methylation of DNA, membranes, proteins and lipids. The MTHFR gene includes two common polymorphisms (rs1801133 or C677T; rs1801131 or A1298C) which both alter enzyme activity. The T-allele of the C677T polymorphism has recently been associated with earlier age at onset of schizophrenia. In the present study we examined the association between the MTHFR C677T and A1298C polymorphisms and age at onset of schizophrenia in twelve samples consisting of 3,213 unrelated schizophrenia patients, including the original Scandinavian sample. There was no consistent relationship between MTHFR C677T, A1298C or combined 677T/1298C carriers and age of onset in schizophrenia when the results of each study were combined using meta-analysis. The present results suggest that the investigated MTHFR polymorphisms do not influence age of onset in schizophrenia.
  •  
44.
  • Saetre, Peter, et al. (författare)
  • The Tryptophan Hydroxylase 1 (TPH1) Gene, Schizophrenia Susceptibility, and Suicidal Behavior : A Multi-Centre Case-Control Study and Meta-Analysis
  • 2010
  • Ingår i: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-4841. ; 153B:2, s. 387-396
  • Tidskriftsartikel (refereegranskat)abstract
    • Serotonin (5-hydroxytryptamin; 5-HT) alternations has since long been suspected in the pathophysiology of schizophrenia. Tryptophan hydroxylase (tryptophan 5-monooxygenase; TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT, and sequence variation in intron 6 of the TPH1 gene has been associated with schizophrenia. The minor allele (A) of this polymorphism (A218C) is also more frequent in patients who have attempted suicide and individuals who died by suicide, than in healthy control individuals. In an attempt to replicate previous findings, five single nucleotide polymorphisms (SNPs) were genotyped in 837 Scandinavian schizophrenia patients and 1,473 controls. Three SNPs spanning intron 6 and 7, including the A218C and A779C polymorphisms, were associated with schizophrenia susceptibility (P = 0.019). However there were no differences in allele frequencies of these loci between affected individuals having attempted suicide at least once and patients with no history of suicide attempts (P=0.84). A systematic literature review and meta-analysis support the A218C polymorphism as a susceptibility locus for schizophrenia (odds ratio 1.17, 95% confidence interval 1.07-1.29). Association studies on suicide attempts are however conflicting (heterogeneity index I-2 = 0.54) and do not support the A218C/A779C polymorphisms being a susceptibility locus for suicidal behavior among individuals diagnosed with a psychiatric disorder (OR = 0.96 [0.80-1.16]). We conclude that the TPH1 A218/A779 locus increases the susceptibility of schizophrenia in Caucasian and Asian populations. In addition, the data at hand suggest that the locus contributes to the liability of psychiatric disorders characterized by elevated suicidal rates, rather than affecting suicidal behavior of individuals suffering from a psychiatric disorder.
  •  
45.
  • Suchankova, Petra, 1979, et al. (författare)
  • Is the Gly82Ser polymorphism in the RAGE gene relevant to schizophrenia and the personality trait psychoticism?
  • 2012
  • Ingår i: Journal of psychiatry & neuroscience : JPN. - : CMA Joule Inc.. - 1488-2434 .- 1180-4882. ; 37:2, s. 122-128
  • Tidskriftsartikel (refereegranskat)abstract
    • The receptor for advanced glycation end products (RAGE) is the main receptor for S100B, an astrogial proinflammatory mediator that has been suggested to be involved in the pathophysiology of schizophrenia. To further elucidate the possible relevance of inflammation for mental functions, we investigated a functional polymorphism in the gene coding for RAGE in relation to personality traits and susceptibility to schizophrenia.
  •  
46.
  • Vares, Maria, et al. (författare)
  • Association Between Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Age of Onset in Schizophrenia
  • 2010
  • Ingår i: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-4841. ; 153B:2, s. 610-618
  • Tidskriftsartikel (refereegranskat)abstract
    • Different lines of evidence indicate that methylenetetrahydrofolate reductase (MTHFR) functional gene polymorphisms, causative in aberrant folate-homocysteine metabolism, are associated with increased vulnerability to several heritable developmental disorders. Opposing views are expressed considering the possible association between MTHFR and susceptibility for schizophrenia. In order to evaluate if age of onset could explain some of this discrepancy we investigated the relationship between two functional MTHFR gene polymorphisms and age at onset in this disorder. Scandinavian patients (n = 820) diagnosed with schizophrenia, schizoaffective disorder, and schizophreniform disorder were investigated. Two functional MTHFR single nucleotide polymorphisms (SNPs; rs1801131 and rs1801133) were genotyped and the effect of MTHFR polymorphisms on the age of onset was examined with survival analysis. In an attempt to replicate the findings from the Scandinavian sample, the association between rs1801133 and age at onset was also analyzed in Chinese high-risk families, with two or more affected siblings (n = 243). Among the Scandinavian patients the functional MTHFR SNP rs1801133 (C677T) significantly affected age at onset of schizophrenia in a dose-dependent manner (P = 0.0015), with lower age of onset with increasing numbers of the mutant T-allele. There was no evidence of rs1801131 (A1298C) affecting age of onset in schizophrenia. Within the Chinese high-risk families carriers of the MTHFR 677T allele showed earlier age at onset than siblings being homozygous for the wild-type allele (P = 0.008). The MTHFR C677T polymorphism may play a role as a modifying factor for age of onset in schizophrenia.
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