The responses of the four main substitution mechanisms of H in olivine to H2O activity at 1050 °C and 3 GPa

The water solubility in olivine (CH2O) has been investigated at 1050 °C and 3 GPa as a function of water activity (aH2O) at subsolidus conditions in the piston-cylinder apparatus, with aH2O varied using H2O–NaCl fluids. Four sets of experiments were conducted to constrain the effect of aH2O on the four main substitution mechanisms. The experiments were designed to grow olivine in situ and thus achieve global equilibrium (G-type), as opposed to hydroxylating olivine with a pre-existing point-defect structure and impurity content (M-type). Olivine grains from the experiments were analysed with polarised and unpolarised FTIR spectroscopy, and where necessary, the spectra have been deconvoluted to quantify the contribution of each substitution mechanism. Olivine buffered with magnesiowüstite produced absorbance bands at high wavenumbers ranging from 3566 to 3612 cm−1. About 50% of the total absorbance was found parallel to the a-axis, 30% parallel to the b-axis and 20% parallel to the c-axis. The total absorbance and hence water concentration in olivine follows the relationship of CH2O∝aH2O2, indicating that the investigated defect must involve four H atoms substituting for one Si atom (labelled as [Si]). Forsterite buffered with enstatite produced an absorbance band exclusively aligned parallel the c-axis at 3160 cm−1. The band position, polarisation and observed CH2O∝aH2O are consistent with two H substituting for one Mg (labelled as [Mg]). Ti-doped, enstatite-buffered olivine displays absorption bands, and polarisation typical of Ti-clinohumite point defects where two H on the Si-site are charge-balanced by one Ti on a Mg-site (labelled as [Ti]). This is further supported by CH2O∝aH2O and a 1:1 relationship of molar H2O and TiO2 in these experiments. Sc-doped, enstatite-buffered experiments display a main absorption band at 3355 cm−1 with CH2O∝aH2O0.5 and a positive correlation of Sc and H, indicating the coupled substitution of a trivalent cation plus a H for two Mg (labelled as [triv]). Our data demonstrate that extreme care has to be taken when inferences from experiments conducted at aH2O=1 are applied to the mantle, where in most cases, a low aH2O persists. In particular, the higher exponent of the [Si] substitution mechanism means that the contribution of this hydrous defect to total water content will decrease more rapidly with decreasing aH2O than the contributions of the other substitution mechanisms. The experiments confirm previous results that the [Mg] mechanism holds an almost negligible amount of water under nearly all T-P-fO2-fH2O conditions that may be anticipated in nature. However, the small amounts of H2O we find in substituting by this mechanism are similar in the experiments on forsterite doped with either Sc or Ti to those in the undoped forsterite at equivalent aH2O (all buffered by enstatite), confirming the assumption that, thermodynamically, CH2O substituting by each mechanism does not depend on the water concentration that substitutes by other mechanisms.We gratefully acknowledge the Australian Research Council (ARC) support through DP110103134 to JH and HON, and FL130100066 to HON, which partly supported PT during the final stages of this project. RS acknowledges an Australian Postgraduate Award

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants with Treatment Resistance in Schizophrenia

Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective: To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Design, Setting, and Participants: Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10501) and individuals with non-TRS (n = 20325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Main Outcomes and Measures: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. Results: The study included a total of 85490 participants (48635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P =.001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P =.04). Conclusions and Relevance: In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance

Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood

J. Lönnqvist on työryhmän Psychiat Genomics Consortium jäsen.Genetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e., linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on similar to 150,000 individuals give a higher accuracy than LDSC estimates based on similar to 400,000 individuals (from combinedmeta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-datasets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.Peer reviewe

A subsidiary fast-diffusing substitution mechanism of Al in forsterite investigated using diffusion experiments under controlled thermodynamic conditions

Diffusion of Al in synthetic forsterite was studied at atmospheric pressure from 1100 to 1500 °C in air along [100] with activities of SiO2, MgO and Al2O3 (aSiO2, aMgO and aAl2O3) buffered. At low aSiO2, the buffer was forsterite + spinel + periclase (fo + sp + per) at all temperatures, while at high aSiO2 and subsolidus conditions a variety of three-phase assemblages containing forsterite and two other phases from spinel, cordierite, protoenstatite or sapphirine were used at 1100–1350 °C. Experiments at high aSiO2 and 1400 °C used forsterite + protoenstatite + melt (fo + en + melt), and at 1500 °C, fo + melt. The resulting diffusion profiles were analysed by LA–ICP–MS in scanning mode. Diffusion profiles in the high aSiO2 experiments were generally several hundred microns in length, but diffusion at low aSiO2 was three orders of magnitude slower than in high aSiO2 experiments carried out at the same temperature, producing short profiles only a few microns in length and close to the spatial resolution of the analytical method. Interface concentrations of Al in the forsterite, obtained by extrapolating the diffusion profiles to the crystal/buffer interface, were only a fraction of those expected at equilibrium, and varied among the differing buffer assemblages according to (aAl2O3)1/2 and (aSiO2)3/4, pointing to the substitution of Al in forsterite by an octahedral-site, vacancy-coupled (OSVC) component with the stoichiometry Al4/3 3+vac2/3SiO4, whereas the main substitution expected from previous equilibrium studies would be the coupled substitution of 2 Al for Mg + Si, giving the stoichiometry MgAl2O4. It is proposed that this latter substitution is not seen on the length scales of the present experiments because it requires replacement of Si by Al on tetrahedral sites, and is accordingly rate-limited by the slow diffusivity of Si. Instead, diffusion of Al by the OSVC mechanism is relatively fast, and at high aSiO2, even faster than Fe–Mg interdiffusio

The effects of temperature and pressure on the oxidation state of chromium in silicate melts

The oxidation state of Cr, Cr /ΣCr (where ΣCr = Cr + Cr = 0.35 wt%), in Fe-free silicate glasses quenched from melts equilibrated as a function of pressure to 3.5 GPa at 1500 °C, and as a function of temperature to 1500 °C at atmospheric pressure, and at oxygen fugacities (fO , in log units relative to the quartz-fayalite-magnetite (QFM) buffer) between ∆QFM = − 1 and − 2, was determined by XANES spectroscopy. Increasing temperature stabilises Cr and increasing pressure stabilises Cr . A general expression for Cr /Cr in silicate melts was derived: log(Cr /Cr ) = 1/4(∆QFM + 8.58 − 25,050/T + 940P/T − 0.02P) + 9770/T − 7.69 + 6.22Λ + (900P − 172P )/T, where P is pressure in GPa, T is temperature in K, and Λ is the optical basicity of the composition. This equation reproduces 213 Cr /ΣCr values reported here and in the literature with an average ΔCr /ΣCr of 0.02. A MORB melt at 1400 °C and QFM is predicted to have Cr /ΣCr ~ 0.35 at the surface but Cr /ΣCr ~ 0 at a depth of ~ 60 km. Although Cr is an important oxidation state in silicate melts it is not preserved at low temperatures due to an electron exchange reaction with Fe3+.Part of this work was performed at the Australian National Beamline Facility with support from the Australian Synchrotron Research Program, which was funded by the Commonwealth of Australia under the Major National Research Facilities Progra

The role of trace elements in controlling H incorporation in San Carlos olivine

We conducted a series of hydroxylation experiments using mm-sized cuboids cut from six different crystals of San Carlos olivine with a range of trace-element concentrations. The cuboids were pre-annealed and then hydroxylated under identical conditions, ensuring that variation in the amounts of H incorporated depended only on the compositional variables. The pre-anneal was at 1400 °C, atmospheric pressure and an oxygen fugacity equivalent to Δlog FMQ + 1, with the subsequent hydroxylation at 800 °C and 1.5 GPa, for 3 days. Hydrogen was incorporated into all six crystals by the four main substitution mechanisms [Si], [Mg], [Ti] and [triv], with homogeneous H contents in the cores of the crystals, indicating H diffusion rates faster than 10− 11 m2/s. Total H as H2O in the homogeneous cores calculated by summing all the infrared absorbance bands ranges from 13 to 27 wt. ppm. The total H2O in the six pre-annealed crystals is poorly correlated with any measured compositional variable. However, when the H2O associated with individual infrared bands is compared, clear trends emerge. The intensity of absorption bands at 3572 and 3525 cm− 1 are strongly correlated with Ti concentrations, whose range in the six crystals exceeds an order of magnitude. Bands between 3400 and 3300 cm− 1, correlate negatively with Na+, but are positively correlated with the difference between molar Cr3+ and Na+. This highlights a previously unrecognised role for Na in suppressing H incorporation in natural olivines. The results confirm the important role that the trace constituents of olivine play in H incorporation. Two of these trace elements, Na and Ti, tend to be similarly enriched or depleted by partial melting or metasomatism of the mantle, but have opposite effects on H incorporation, with Ti enhancing it but Na suppressing it. Models estimating the effect of H in olivine on mantle rheology must, therefore, consider carefully the availability of these trace elements

Mn-Cr relative sensitivity Factors for Secondary Ion Mass Spectrometry analysis of Mg-Fe-Ca olivine and implications for the Mn-Cr chronology of meteorites

Secondary Ion Mass Spectrometry (SIMS) is used to date meteoritic olivine using the 53Mn-53Cr short-lived decay scheme. This involves simultaneously measuring the Cr-isotope composition and Mn/Cr ratio of a sample, but the relative sensitivity of SIMS t

Substitution and diffusion of Cr2+ and Cr3+ in synthetic forsterite and natural olivine at 1200–1500?°C and 1?bar

The diffusion and substitution mechanisms of Cr in forsterite were studied as a function of crystallographic orientation and the chemical potentials of all four components in the system MgO-SiO2-Cr-O. Oxygen fugacity ( ) was varied over 15.4 log units at 1400 °C and was fixed at the iron-wüstite equilibrium for a temperature series (1200–1500 °C). The valence state changes of Cr along some diffusion profiles was also investigated using X-ray absorption near edge structure spectroscopy. Cr diffusion was found to be anisotropic (fastest along the c axis), and considerably faster in the presence of protoenstatite (high silica activity, ) than in the presence of periclase (low ). Cr diffusion profiles were longer at lower with more extreme diffusive anisotropy at higher . Determined Cr diffusion coefficients were similar to those of Fe-Mg inter-diffusion in olivine at equivalent conditions. The diffusivity of Cr was found to be a function of its own concentration, but, as an approximation, Cr diffusion (in m2/s) along the c axis of pure forsterite, at an corresponding to iron-wüstite at 200 µg/g Cr could be described using: where R is the gas constant in kJ/Kmol and T is the temperature in Kelvin. In forsterite, the valence state ratio of chromium (Cr2+/ΣCr, where ΣCr = Cr2++Cr3+) changed systematically along diffusion profiles. The equilibrium Cr2+/ΣCr ratio imposed by the of the experiment was observed at the diffusion interface, and this changed to a constant value in the crystal interior. Cr3+ always substitutes onto an octahedral site in olivine. At high , Cr3+ uses M site vacancies ([vac]) for charge balance (i.e. ), whereas at low a new mechanism was observed with charge balance achieved by Mg2+ on the tetrahedral site producing a ‘spinel type’ substitution, . Cr2+ always substitutes directly for Mg2+, forming the substitution. Comparative experiments using San Carlos olivine showed slightly faster Cr diffusion, a lesser concentration dependence of diffusion and no Cr valence state change along diffusion profiles