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Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
The investigators conducted a psychosocial needs assessment of mesothelioma patients through self-report measures of quality of life (QOL), coping, depression, and social support.
Patients with malignant pleural mesothelioma (MPM) (N = 67) completed a battery of assessments at a single timepoint after being approached during routine medical oncology clinic appointments or by letter.
Participants were predominately male (70.0%; n = 47) and ranged in age from 35 to 83 years old (M = 65.61, SD = 9.71). Most participants were white (88.0%; n = 59), and 10.0% (n = 7) were identified as Hispanic. The majority were married or living with a partner (93.0%; n = 62) and had some college or more education (64.0%; n = 43). Fourteen percent of participants (n = 11) endorsed significantly elevated depression symptoms. No significant demographic or clinical differences in depressed compared to nondepressed participants were observed, with a trend toward those identifying as Hispanic and those who were divorced as being more likely to be depressed. For the total sample, the most frequently endorsed coping strategies were active coping, emotional support, and acceptance.
Significance of results
The present study did not identify any clear correlates of depression or QOL among patients with MPM. This research contributes to the small literature on psychosocial functioning in patients with MPM and provides putative directions for future larger studies and the development of interventions to provide appropriate support to diverse patients with MPM.
Post-traumatic growth (PTG) is a positive psychological consequence of trauma. The aims of this study were to investigate whether combat injury was associated with deployment-related PTG in a cohort of UK military personnel who were deployed to Afghanistan, and whether post-traumatic stress disorder (PTSD), depression and pain mediate this relationship.
521 physically injured (n = 138 amputation; n = 383 non-amputation injury) and 514 frequency-matched uninjured personnel completed questionnaires including the deployment-related Post-Traumatic Growth Inventory (DPTGI). DPTGI scores were categorised into tertiles of: no/low (score 0–20), moderate (score 21–34) or a large (35–63) degree of deployment-related PTG. Analysis was completed using generalised structural equation modelling.
A large degree of PTG was reported by 28.0% (n = 140) of the uninjured group, 36.9% (n = 196) of the overall injured group, 45.4% (n = 62) of amputee and 34.1% (n = 134) of the non-amputee injured subgroups. Combat injury had a direct effect on reporting a large degree of PTG [Relative risk ratio (RRR) 1.59 (95% confidence interval (CI) 1.17–2.17)] compared to sustaining no injury. Amputation injuries also had a significant direct effect [RRR 2.18 (95% CI 1.24–3.75)], but non-amputation injuries did not [RRR 1.35 (95% CI 0.92–1.93)]. PTSD, depression and pain partially mediate this relationship, though mediation differed depending on the injury subtype. PTSD had a curvilinear relationship with PTG, whilst depression had a negative association and pain had a positive association.
Combat injury, in particular injury resulting in traumatic amputation, is associated with reporting a large degree of PTG.
The COVID-19 pandemic has affected all our lives, not only through the infection itself but also through the measures taken to control the spread of the virus (e.g. lockdown).
Here, we investigated how the COVID-19 pandemic and unprecedented lockdown affected the mental health of young adults in England and Wales.
We compared the mental health symptoms of up to 4773 twins in their mid-20s in 2018 prior to the COVID-19 pandemic (T1) and during four-wave longitudinal data collection during the pandemic in April, July and October 2020, and in March 2021 (T2–T5) using phenotypic and genetic longitudinal designs.
The average changes in mental health were small to medium and mainly occurred from T1 to T2 (average Cohen d = 0.14). Despite the expectation of catastrophic effects of the pandemic on mental health, we did not observe trends in worsening mental health during the pandemic (T3–T5). Young people with pre-existing mental health problems were disproportionately affected at the beginning of the pandemic, but their increased problems largely subsided as the pandemic persisted. Twin analyses indicated that the aetiology of individual differences in mental health symptoms did not change during the lockdown (average heritability 33%); the average genetic correlation between T1 and T2–T5 was 0.95, indicating that genetic effects before the pandemic were substantially correlated with genetic effects up to a year later.
We conclude that on average the mental health of young adults in England and Wales has been remarkably resilient to the effects of the pandemic and associated lockdown.
Since the advent of direct-acting antiviral therapy, the elimination of hepatitis c virus (HCV) as a public health concern is now possible. However, identification of those who remain undiagnosed, and re-engagement of those who are diagnosed but remain untreated, will be essential to achieve this. We examined the extent of HCV infection among individuals undergoing liver function tests (LFT) in primary care. Residual biochemistry samples for 6007 patients, who had venous blood collected in primary care for LFT between July 2016 and January 2017, were tested for HCV antibody. Through data linkage to national and sentinel HCV surveillance databases, we also examined the extent of diagnosed infection, attendance at specialist service and HCV treatment for those found to be HCV positive. Overall HCV antibody prevalence was 4.0% and highest for males (5.0%), those aged 37–50 years (6.2%), and with an ALT result of 70 or greater (7.1%). Of those testing positive, 68.9% had been diagnosed with HCV in the past, 84.9% before the study period. Most (92.5%) of those diagnosed with chronic infection had attended specialist liver services and while 67.7% had ever been treated only 38% had successfully cleared infection. More than half of HCV-positive people required assessment, and potentially treatment, for their HCV infection but were not engaged with services during the study period. LFT in primary care are a key opportunity to diagnose, re-diagnose and re-engage patients with HCV infection and highlight the importance of GPs in efforts to eliminate HCV as a public health concern.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
While previous studies have suggested that higher levels of cognitive performance may be related to greater wellbeing and resilience, little is known about the associations between neural circuits engaged by cognitive tasks and wellbeing and resilience, and whether genetics or environment contribute to these associations.
The current study consisted of 253 monozygotic and dizygotic adult twins, including a subsample of 187 early-life trauma-exposed twins, with functional Magnetic Resonance Imaging data from the TWIN-E study. Wellbeing was measured using the COMPAS-W Wellbeing Scale while resilience was defined as a higher level of positive adaptation (higher levels of wellbeing) in the presence of trauma exposure. We probed both sustained attention and working memory processes using a Continuous Performance Task in the scanner.
We found significant negative associations between resilience and activation in the bilateral anterior insula engaged during sustained attention. Multivariate twin modelling showed that the association between resilience and the left and right insula activation was mostly driven by common genetic factors, accounting for 71% and 87% of the total phenotypic correlation between these variables, respectively. There were no significant associations between wellbeing/resilience and neural activity engaged during working memory updating.
The findings suggest that greater resilience to trauma is associated with less activation of the anterior insula during a condition requiring sustained attention but not working memory updating. This possibly suggests a pattern of ‘neural efficiency’ (i.e. more efficient and/or attenuated activity) in people who may be more resilient to trauma.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Although mental wellbeing has been linked with positive health outcomes, including longevity and improved emotional and cognitive functioning, studies examining the underlying neural mechanisms of both subjective and psychological wellbeing have been sparse. We assessed whether both forms of wellbeing are associated with neural activity engaged during positive and negative emotion processing and the extent to which this association is driven by genetics or environment.
We assessed mental wellbeing in 230 healthy adult monozygotic and dizygotic twins using a previously validated questionnaire (COMPAS-W) and undertook functional magnetic resonance imaging during a facial emotion viewing task. We used linear mixed models to analyse the association between COMPAS-W scores and emotion-elicited neural activation. Univariate twin modelling was used to evaluate heritability of each brain region. Multivariate twin modelling was used to compare twin pairs to assess the contributions of genetic and environmental factors to this association.
Higher levels of wellbeing were associated with greater neural activity in the dorsolateral prefrontal cortex, localised in the right inferior frontal gyrus (IFG), in response to positive emotional expressions of happiness. Univariate twin modelling showed activity in the IFG to have 20% heritability. Multivariate twin modelling suggested that the association between wellbeing and positive emotion-elicited neural activity was driven by common variance from unique environment (r = 0.208) rather than shared genetics.
Higher mental wellbeing may have a basis in greater engagement of prefrontal neural regions in response to positive emotion, and this association may be modifiable by unique life experiences.
The integration of biostratigraphical, wireline log, geophysical and available geochronological ages has identified two principal periods of volcanism in the Faroe–Shetland and Rockall basins. The first is pre-breakup, upper Danian to lower Thanetian: in the Rockall and Faroe–Shetland basins, isolated volcanic activity from 62 Ma to 58.7 Ma is identified in areas closely linked to the SSW–NNE structural fabric of the continental margin. Volcanic activity was concentrated at basin flank fissures and localised point sources. This rift-flank volcanism led to widespread volcanic ash deposition, localised lava flow fields and the formation of igneous centres. Some of the Hebridean and onshore central complexes (e.g., Rum) were uplifted and rapidly eroded during the later pre-breakup period, while additional accommodation space was developed in the adjacent offshore basins. Onset and termination of pre-breakup volcanism is correlated to intra-plate stress regimes in Europe, following the cessation of convergence of Africa and Europe in the Danian. The second is syn-breakup, upper Thanetian to Ypresian, initiated at ca.57 Ma in the Rockall and Faroe–Shetland basins. Initial high-volume extrusive igneous successions were focussed to the W in the Faroe–Shetland Basin. In the centre and E of the Faroe–Shetland and Rockall basins, separate eruption loci developed along pre-existing lineaments either as fissure or point-sourced lava fields. Short-term cessation of eruption at ~55.8 Ma was followed by resumption of flood basalt eruptions and a shift in focus to the NW. Fluctuations in the syn-breakup eruption tempo are reflected in the formation and subsequent rejuvenation of prominent unconformities, only previously recognised as a single erosive event. The W and northward shift of eruption focus, and the eruption of mid ocean ridge basalt-type lavas in the syn-breakup period reflect the onset of lithospheric thinning in the nascent North Atlantic Rift prior to flooding of the rift and eruption of the widespread lower Ypresian Balder Formation tephras.
The advantages of X-ray absorption spectroscopy have been utilized to assess the Cu and Zn ordering in aurichalcite, (Cu5−xZnx)(OH)6(CO3)2. We have examined one hydrozincite sample and three aurichalcite samples in which the Cu:Zn ratios are in the range 1:3 to 2:3. Copper 2p XAS confirms that there is no monovalent copper in aurichalcite and that in each sample the copper might be distributed across more than one metal site. EXAFS, at the Cu and Zn K-edges, shows that the copper atoms preferentially enter the Jahn-Teller elongated, octahedral (M2) and trigonal bipyramidal (M4) sites, with the zinc atoms entering the more regular octahedral (M1) and tetrahedral (M3) site. Substantial solid solution towards the zinc rich region is facilitated by the substitution of copper by zinc on the M2 and M4 sites. This information, not easily obtained by X-ray diffraction, substantially enhances the understanding of the structure of aurichalcite.
EXAFS spectroscopy has been used to monitor changes in divalent cation site geometries across the P2/c-P1̄ phase transition in the sanmartinite (ZnWO4)-cuproscheelite (CuWO4) solid solution at ambient and liquid nitrogen temperatures. In the ZnWO4 end member, Zn occupies axially-compressed ZnO6 octahedra with two axial Zn-O bonds at approximately 1.95 Å and four square planar Zn-O bonds at approximately 2.11 Å. The substitution of Zn by Cu generates a second Zn environment with four short square planar Zn-O bonds and two longer axial Zn-O bonds. The proportion of the latter site increases progressively as the Cu content increases. Cu EXAFS reveals that the CuO6 octahedra maintain their Jahn-Teller axially-elongate geometry throughout the majority of the solid solution and only occur as axially-compressed octahedra well within the stability field of the Zn-rich phase with monoclinic long-range order.
The commissioning and operation of apparatus for neutron diffraction at simultaneous high temperatures and pressures is reported. The basic design is based on the Paris-Edinburgh cell using opposed anvils, with internal heating. Temperature is measured using neutron radiography. The apparatus has been shown in both on-line and off-line tests to operate to a pressure of 7 GPa and temperature of 1700°C. The apparatus has been used in a neutron diffraction study of the crystal structure of deuterated brucite, and results for 520°C and 5.15 GPa are presented. The diffraction data that can be obtained from the apparatus are of comparable quality to previous high-pressure studies at ambient temperatures, and are clearly good enough for Rietveld refinement analysis to give structural data of reasonable quality.
The Fe 2p X-ray absorption spectra of single crystal gillespite, BaFeSi4O10, show a strong linear dichroism, i.e. a large difference in the absorption when measured with the polarization of the X-rays either parallel or perpendicular to the plane of the FeO4 group. The isotropic spectrum, obtained from measurement at the ‘magic angle’, and the polarization dependent spectra have been compared to atomic multiplet calculations and show an excellent agreement with theory. Analysis of the branching ratio, the linear dichroism, and the detailed peak structure confirms that the 5A1 level is the ground state at room temperature and pressure. The 5B2 level is sufficiently low in energy that a distortion of the electronic charge density, induced by increased pressure, may result in a 5B2 ground state.
Synchrotron based μ-XRF, μ-XAS and μ-XRD have made a major impact in the field of environmental science in the last ten years. One of the first seven ‘day one’ beamlines on the Diamond Light Source is a microfocus spectroscopy beamline, beamline I18. Here the current status of the beamline and the opportunities it presents in the field of environmental science are described, with results from two of the first experiments also included. The first is based on the use of bonemeal to remediate soil. We used Zn K-edge and Pb L3-edge spectroscopy to characterize the speciation of these two elements on a soil after bonemeal treatment. The results are compared with bulk measurements taken on the whole soil and standard materials. The second experiment described here is a study of the speciation and association of Ni in a laterite from Moa Bay, Cuba. Here the differences in the Ni speciation associated with Mn oxides are examined and compared with Fe oxides phases.
Conventional experiments designed to investigate the mechanical properties of polycrystalline geological materials are generally restricted to measurements of whole-rock properties. However, when comparing the measurements with theoretical models, it is frequently essential to understand how the deformation is accommodated at the grain-scale. This is particularly true for polymineralic rocks because in this case most theories express the whole-rock properties as some function of the properties of their constituent minerals, and hence the contribution which each phase makes to those properties must be measured if the theories are to be fully assessed. The penetrating nature of neutrons offers a method of addressing this problem. By performing deformation experiments in the neutron beam-line and collecting neutron diffraction patterns at different applied loads, the lattice parameters of all the mineral phases present may be determined as a function of load. The elastic strain experienced by each phase is then easily determined. Moreover, the strain in different lattice directions is also obtained. From this information a wide range of problems relevant for the characterization of the elastic and plastic deformation behaviour of polymineralic geological materials can be explored. An experimental technique for carrying out such experiments is described, and its validity is demonstrated by showing that the results obtained from deforming an elastically isotropic olivine + magnesiowüstite sample agree, to within very tight bounds, with the behaviour predicted by theory for elastically isotropic composites.
The development of protocols for the identification of metal phosphates in phosphate-treated, metalcontaminated soils is a necessary yet problematical step in the validation of remediation schemes involving immobilization of metals as phosphate phases. The potential for Raman spectroscopy to be applied to the identification of these phosphates in soils has yet to be fully explored. With this in mind, a range of synthetic mixed-metal hydroxylapatites has been characterized and added to soils at known concentrations for analysis using both bulk X-ray powder diffraction (XRD) and Raman spectroscopy.
Mixed-metal hydroxylapatites in the binary series Ca –Cd, Ca –Pb, Ca –Sr and Cd –Pb synthesized in the presence of acetate and carbonate ions, were characterized using a range of analytical techniques including XRD, analytical scanning electron microscopy (SEM), infrared spectroscopy (IR), inductively coupled plasma-atomic emission spectrometry (ICP-AES) and Raman spectroscopy. Only the Ca –Cd series displays complete solid solution, although under the synthesis conditions of this study the Cd5(PO4)3OH end member could not be synthesized as a pure phase. Within the Ca –Cd series the cell parameters, IR active modes and Raman active bands vary linearly as a function of Cd content. X-ray diffraction and extended X-ray absorption fine structure spectroscopy (EXAFS) suggest that the Cd is distributed across both the Ca(1) and Ca(2) sites, even at low Cd concentrations.
In order to explore the likely detection limits for mixed-metal phosphates in soils for XRD and Raman spectroscopy, soils doped with mixed-metal hydroxylapatites at concentrations of 5, 1 and 0.5 wt.% were then studied. X-ray diffraction could not confirm unambiguously the presence or identity of mixed-metal phosphates in soils at concentrations below 5 wt.%. Raman spectroscopy proved a far more sensitive method for the identification of mixed-metal hydroxylapatites in soils, which could positively identify the presence of such phases in soils at all the dopant concentrations used in this study. Moreover, Raman spectroscopy could also provide an accurate assessment of the degree of chemical substitution in the hydroxylapatites even when present in soils at concentrations as low as 0.1%.
Background: In the past decade, a great deal of research has examined the efficacy and mechanisms of attentional bias modification (ABM), a computerized cognitive training intervention for anxiety and other disorders. However, little research has examined how anxious patients perceive ABM, and it is unclear to what extent perceptions of ABM influence outcome. Aims: To examine patient perceptions of ABM across two studies, using a mixed methods approach. Method: In the first study, participants completed a traditional ABM program and received a hand-out with minimal information about the purpose of the task. In the second study, participants completed an adaptive ABM program and were provided with more extensive rationale and instructions for changing attentional biases. Results: A number of themes emerged from qualitative data related to perceived symptom changes and mechanisms of action, acceptability, early perceptions of the program, barriers/facilitators to engagement, and responses to adaptive features. Moreover, quantitative data suggested that patients’ perceptions of the program predicted symptom reduction as well as change in attentional bias. Conclusions: Our quantitative data suggest that it may be possible to quickly and inexpensively identify some patients who may benefit from current ABM programs, although our qualitative data suggest that ABM needs major modifications before it will be an acceptable and credible treatment more broadly. Although the current study was limited by sample size and design features of the parent trials from which these data originated, our findings may be useful for guiding hypotheses in future studies examining patient perceptions towards ABM.
To assess the association of fish consumption with risk of dementia and its dose–response relationship, and investigate variations in the association among low-, middle- and high-income countries.
A new community-based cross-sectional study and a systematic literature review.
Urban and rural communities in China; population-based studies systematically searched from worldwide literature.
Chinese adults aged ≥60 years in six provinces (n 6981) took part in a household health survey of dementia prevalence and risk factors. In addition, 33 964 participants from eleven published and eligible studies were included in the systematic review and meta-analysis.
In the new study in China, 326 participants were diagnosed with dementia (4·7 %); those who consumed any amount of fish in the past two years v. those who consumed no fish had reduced risk of dementia (adjusted OR=0·73, 95 % CI 0·64, 0·99), but the dose–response relationship was not statistically significant. The meta-analysis of available data from the literature and the new study showed relative risk (RR) of dementia of 0·80 (95 % CI 0·74, 0·87) for people with fish consumption; the impact was similar among countries with different levels of income. Pooled dose–response data revealed RR (95 % CI) of 0·84 (0·72, 0·98), 0·78 (0·68, 0·90) and 0·77 (0·61, 0·98) in people with low, middle and high consumption of fish, respectively. Corresponding figures for Alzheimer’s disease were 0·88 (0·74, 1·04), 0·79 (0·65, 0·96) and 0·67 (0·58, 0·78), respectively.
Greater consumption of fish is associated with a lower risk of dementia. Increasing fish consumption may help prevent dementia worldwide regardless of income level.