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- de Zwarte, Sonja M. C., et al.
(författare)
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The association between familial risk and brain abnormalities is disease specific : an ENIGMA-relatives study of schizophrenia and bipolar disorder
- 2019
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:7, s. 545-556
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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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- Gurholt, Tiril P., et al.
(författare)
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Intracranial and subcortical volumes in adolescents with early‐onset psychosis : A multisite mega‐analysis from the ENIGMA consortium
- 2020
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Ingår i: Human Brain Mapping. - Stockholm : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 373-384
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Tidskriftsartikel (refereegranskat)abstract
- Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = −0.39) and hippocampal (d = −0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = −0.34) and affective psychosis (d = −0.42), and early-onset schizophrenia showed lower hippocampal (d = −0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = −0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.
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- Krabbendam, M., et al.
(författare)
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Glaciotectonic disintegration of roches moutonnées during glacial ripping in east Sweden
- 2022
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Ingår i: Geografiska Annaler. Series A, Physical Geography. - : Informa UK Limited. - 0435-3676 .- 1468-0459. ; 104:1, s. 35-56
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Tidskriftsartikel (refereegranskat)abstract
- Roches moutonnées are typical landforms of glacial erosion developed in hard rocks, with an asymmetric profile caused by abrasion and lee-side plucking. In eastern Sweden, some roches moutonnées show extensive damage, including open fractures, disintegration into blocks, fracture caves and short boulder trains. Disintegration increases along ice-flow directions during deglaciation of the last Weichselian Fennoscandian Ice Sheet, indicating a subglacial origin: limited edge rounding can be explained by a combination of hard rock, slow abrasion rates and disintegration just prior to deglaciation. The roches moutonnées initially developed in kernels of gneissic rocks with a wide fracture spacing (large block size) and interlocking fracture pattern, and hence high overall rock mass strength. Dilated fractures and ‘fracture caves’ occur up to 15 m below the ice-bed interface. It is proposed that hydraulic jacking by overpressured water opened up the rock mass along pre-existing fractures. Jacking reduced rock mass strength, allowing glaciotectonic deformation of the roches moutonnées. Uneven hydraulic jacking led to uplift of individual fracture-bound blocks above the pre-existing smooth, abraded surface of the roches moutonnées, creating blunt, step-like edges. These edges allowed high ice pushing forces to act on large blocks: where blocks extend into the deeper rock mass, they further aided the disintegration of the rock mass. The disintegrated roches moutonnées can be regarded as transient features between intact bedrock and complete disintegration into boulders. The jacking-disintegration-transport sequence is characteristic of glacial ripping and very different from classic lee-side plucking.
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- Hall, Adrian M., et al.
(författare)
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Glacial ripping: geomorphological evidence from Sweden for a new process of glacial erosion
- 2020
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Ingår i: Geografiska Annaler Series a-Physical Geography. - : Informa UK Limited. - 0435-3676 .- 1468-0459. ; 2:4, s. 333-53
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Tidskriftsartikel (refereegranskat)abstract
- In low relief Precambrian gneiss terrain in eastern Sweden, abraded bedrock surfaces were ripped apart by the Fennoscandian Ice Sheet. The resultantboulder spreadsare covers of large, angular boulders, many with glacial transport distances of 1-100 m. Boulder spreads occur alongside partly disintegrated roches moutonnees and associated fracture caves, and are associated withdisrupted bedrock, which shows extensive fracture dilation in the near surface. These features are distributed in ice-flow parallel belts up to 10 km wide and extend over distances of >500 km. Our hypothesis is that the assemblage results from (1) hydraulic jacking and bedrock disruption, (2) subglacial ripping and (3) displacement, transport and final deposition of boulders. Soft sediment fills indicate jacking and dilation of pre-existing bedrock fractures by groundwater overpressure below the ice sheet. Overpressure reduces frictional resistance along fractures. Where ice traction overcomes this resistance, the rock mass strength is exceeded, resulting in disintegration of rock surfaces and ripping apart into separate blocks. Further movement and deposition create boulder spreads and moraines. Short boulder transport distances and high angularity indicate that glacial ripping operated late in the last deglaciation. The depths of rock mobilized in boulder spreads are estimated as 1-4 m. This compares with 0.6-1.6 m depths of erosion during the last glaciation derived from cosmogenic nuclide inventories of samples from bedrock surfaces without evidence of disruption. Glacially disrupted and ripped bedrock is also made ready for removal by future ice sheets. Henceglacial rippingis a highly effective process of glacial erosion.
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- Carlstrom, KE, et al.
(författare)
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Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas-Casp8-Bid-axis
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4071-
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Tidskriftsartikel (refereegranskat)abstract
- Arrest of oligodendrocyte (OL) differentiation and remyelination following myelin damage in multiple sclerosis (MS) is associated with neurodegeneration and clinical worsening. We show that Glutathione S-transferase 4α (Gsta4) is highly expressed during adult OL differentiation and that Gsta4 loss impairs differentiation into myelinating OLs in vitro. In addition, we identify Gsta4 as a target of both dimethyl fumarate, an existing MS therapy, and clemastine fumarate, a candidate remyelinating agent in MS. Overexpression of Gsta4 reduces expression of Fas and activity of the mitochondria-associated Casp8-Bid-axis in adult oligodendrocyte precursor cells, leading to improved OL survival during differentiation. The Gsta4 effect on apoptosis during adult OL differentiation was corroborated in vivo in both lysolecithin-induced demyelination and experimental autoimmune encephalomyelitis models, where Casp8 activity was reduced in Gsta4-overexpressing OLs. Our results identify Gsta4 as an intrinsic regulator of OL differentiation, survival and remyelination, as well as a potential target for future reparative MS therapies.
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| 10. |
- Hall, Adrian M., et al.
(författare)
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Glacial Ripping in Sedimentary Rocks : Loch Eriboll, NW Scotland
- 2021
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Ingår i: Geosciences. - : MDPI AG. - 2076-3263. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Glacial ripping is a newly recognized process sequence in which subglacial erosion is triggered by groundwater overpressure. Investigations in gneiss terrain in lowland Sweden indicate that ripping involves three stages of (i) hydraulic jacking, (ii) rock disruption under subglacial traction, and (iii) glacial transport of rock blocks. Evidence for each stage includes, respectively, dilated fractures with sediment fills, disintegrated roches moutonnees, and boulder spreads. Here, we ask: can glacial ripping also occur in sedimentary rocks, and, if so, what are its effects? The case study area is in hard, thinly bedded, gently dipping Cambrian quartz-arenites at Loch Eriboll, NW Scotland. Field surveys reveal dilated, sediment filled, bedding-parallel fractures, open joints, and brecciated zones, interpreted as markers for pervasive, shallow penetration of the quartz-arenite by water at overpressure. Other features, including disintegrated rock surfaces, boulder spreads, and monomict rubble tills, indicate glacial disruption and short distance subglacial transport. The field results together with cosmogenic isotope ages indicate that glacial ripping operated with high impact close to the former ice margin at Loch Eriboll at 17.6-16.5 ka. Glacial ripping thus can operate effectively in bedded, hard sedimentary rocks, and the accompanying brecciation is significant-if not dominant-in till formation. Candidate markers for glacial ripping are identified in other sedimentary terrains in former glaciated areas of the Northern Hemisphere.
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