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Sökning: WFRF:(Treasure J)

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  • Munn-Chernoff, M. A., et al. (författare)
  • Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
  • 2021
  • Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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  • Bryois, J., et al. (författare)
  • Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
  • 2020
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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  • Watson, H. J., et al. (författare)
  • Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
  • 2019
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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  • Mullins, Niamh, et al. (författare)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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  • Docherty, Anna R, et al. (författare)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Tidskriftsartikel (refereegranskat)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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  • Harcourt, R., et al. (författare)
  • Animal-borne telemetry: An integral component of the ocean observing toolkit
  • 2019
  • Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6:JUN
  • Tidskriftsartikel (refereegranskat)abstract
    • Animal telemetry is a powerful tool for observing marine animals and the physical environments that they inhabit, from coastal and continental shelf ecosystems to polar seas and open oceans. Satellite-linked biologgers and networks of acoustic receivers allow animals to be reliably monitored over scales of tens of meters to thousands of kilometers, giving insight into their habitat use, home range size, the phenology of migratory patterns and the biotic and abiotic factors that drive their distributions. Furthermore, physical environmental variables can be collected using animals as autonomous sampling platforms, increasing spatial and temporal coverage of global oceanographic observation systems. The use of animal telemetry, therefore, has the capacity to provide measures from a suite of essential ocean variables (EOVs) for improved monitoring of Earth's oceans. Here we outline the design features of animal telemetry systems, describe current applications and their benefits and challenges, and discuss future directions. We describe new analytical techniques that improve our ability to not only quantify animal movements but to also provide a powerful framework for comparative studies across taxa. We discuss the application of animal telemetry and its capacity to collect biotic and abiotic data, how the data collected can be incorporated into ocean observing systems, and the role these data can play in improved ocean management. © 2019 Harcourt, Sequeira, Zhang, Roquet, Komatsu, Heupel, McMahon, Whoriskey, Meekan, Carroll, Brodie, Simpfendorfer, Hindell, Jonsen, Costa, Block, Muelbert, Woodward, Weise, Aarestrup, Biuw, Boehme, Bograd, Cazau, Charrassin, Cooke, Cowley, de Bruyn, Jeanniard du Dot, Duarte, Eguíluz, Ferreira, Fernández-Gracia, Goetz, Goto, Guinet, Hammill, Hays, Hazen, Hückstädt, Huveneers, Iverson, Jaaman, Kittiwattanawong, Kovacs, Lydersen, Moltmann, Naruoka, Phillips, Picard, Queiroz, Reverdin, Sato, Sims, Thorstad, Thums, Treasure, Trites, Williams, Yonehara and Fedak.
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  • Watson, Hunna J., et al. (författare)
  • Common Genetic Variation and Age of Onset of Anorexia Nervosa
  • 2022
  • Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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  • Potapov, Anton M., et al. (författare)
  • Global fine-resolution data on springtail abundance and community structure
  • 2024
  • Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.
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  • Brooks, Samantha J, et al. (författare)
  • Restraint of appetite and reduced regional brain volumes in anorexia nervosa : a voxel-based morphometric study
  • 2011
  • Ingår i: BMC Psychiatry. - 1471-244X. ; 11, s. 179-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Previous Magnetic Resonance Imaging (MRI) studies of people with anorexia nervosa (AN) have shown differences in brain structure. This study aimed to provide preliminary extensions of this data by examining how different levels of appetitive restraint impact on brain volume.METHODS:Voxel based morphometry (VBM), corrected for total intracranial volume, age, BMI, years of education in 14 women with AN (8 RAN and 6 BPAN) and 21 women (HC) was performed. Correlations between brain volume and dietary restraint were done using Statistical Package for the Social Sciences (SPSS).RESULTS:Increased right dorsolateral prefrontal cortex (DLPFC) and reduced right anterior insular cortex, bilateral parahippocampal gyrus, left fusiform gyrus, left cerebellum and right posterior cingulate volumes in AN compared to HC. RAN compared to BPAN had reduced left orbitofrontal cortex, right anterior insular cortex, bilateral parahippocampal gyrus and left cerebellum. Age negatively correlated with right DLPFC volume in HC but not in AN; dietary restraint and BMI predicted 57% of variance in right DLPFC volume in AN.CONCLUSIONS:In AN, brain volume differences were found in appetitive, somatosensory and top-down control brain regions. Differences in regional GMV may be linked to levels of appetitive restraint, but whether they are state or trait is unclear. Nevertheless, these discrete brain volume differences provide candidate brain regions for further structural and functional study in people with eating disorders.
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  • Suda, Masashi, et al. (författare)
  • Functional Neuroanatomy of Body Checking in People with Anorexia Nervosa
  • 2013
  • Ingår i: International Journal of Eating Disorders. - : Wiley. - 0276-3478 .- 1098-108X. ; 46:7, s. 653-662
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveThe neural correlates of body checking perceptions in eating disorders have not yet been identified. This functional Magnetic Resonance Imaging study examined the neuroanatomy involved in altered perception and identification with body checking in female with anorexia nervosa (AN). MethodBrain activation while viewing images depicting normal weight individuals involved in either body checking behavior or a neutral (noneating disorder) body action, was compared between 20 females with AN and 15 matched healthy controls (HC). ResultsFemales with AN reported higher anxiety compared to HC during the body checking task. The level of anxiety positively correlated with body shape concern scores. People with AN had less activation in the medial prefrontal cortex (PFC) and right fusiform gyrus compared to HC in response to body checking compared to neutral action images. Body shape concern scores correlated negatively with medial PFC activation in AN group. DiscussionThis preliminary study with modest power suggests that AN patients have reduced activation in cortical areas associated with self-reference, body action perception, and social cognition in females with AN.
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  • Treasure, Anne M., et al. (författare)
  • Marine Mammals Exploring the Oceans Pole to Pole A Review of the MEOP Consortium
  • 2017
  • Ingår i: Oceanography. - : The Oceanography Society. - 1042-8275. ; 30:2, s. 132-138
  • Tidskriftsartikel (refereegranskat)abstract
    • Polar oceans are poorly monitored despite the important role they play in regulating Earth's climate system. Marine mammals equipped with biologging devices are now being used to fill the data gaps in these logistically difficult to sample regions. Since 2002, instrumented animals have been generating exceptionally large data sets of oceanographic CTD casts (>500,000 profiles), which are now freely available to the scientific community through the MEOP data portal (http://meop.net). MEOP (Marine Mammals Exploring the Oceans Pole to Pole) is a consortium of international researchers dedicated to sharing animal-derived data and knowledge about the polar oceans. Collectively, MEOP demonstrates the power and cost-effectiveness of using marine mammals as data-collection platforms that can dramatically improve the ocean observing system for biological and physical oceanographers. Here, we review the MEOP program and database to bring it to the attention of the international community.
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  • Baenas, Isabel, et al. (författare)
  • Impact of COVID-19 Lockdown in Eating Disorders : A Multicentre Collaborative International Study
  • 2022
  • Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. Aims. (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. Methods. The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). Results. Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. Conclusions. The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients.
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  • Bergen, AW, et al. (författare)
  • Association of multiple DRD2 polymorphisms with anorexia nervosa
  • 2005
  • Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X. ; 30:9, s. 1703-1710
  • Tidskriftsartikel (refereegranskat)
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  • Brooks, Samantha J., et al. (författare)
  • Differential Neural Responses to Food Images in Women with Bulimia versus Anorexia Nervosa
  • 2011
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7, s. e22259-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. Methods: We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). Results: In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Conclusions: Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.
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  • Brooks, Samantha J., et al. (författare)
  • Subliminal food images compromise superior working memory performance in women with restricting anorexia nervosa
  • 2012
  • Ingår i: Consciousness and Cognition. - : Elsevier BV. - 1053-8100 .- 1090-2376. ; 21:2, s. 751-763
  • Tidskriftsartikel (refereegranskat)abstract
    • Prefrontal cortex (PFC) is dysregulated in women with restricting anorexia nervosa (RAN). It is not known whether appetitive non-conscious stimuli bias cognitive responses in those with RAN. Thirteen women with RAN and 20 healthy controls (HC) completed a dorsolateral PFC (DLPFC) working memory task and an anterior cingulate cortex (ACC) conflict task, while masked subliminal food, aversive and neutral images were presented. During the DLPFC task, accuracy was higher in the RAN compared to the HC group, but superior performance was compromised when subliminal food stimuli were presented: errors positively correlated with self-reported trait anxiety in the RAN group. These effects were not observed in the ACC task. Appetitive activation is intact and anxiogenic in women with RAN, and non-consciously interacts with working memory processes associated with the DLPFC. This interaction mechanism may underlie cognitive inhibition of appetitive processes that are anxiety inducing, in people with AN.
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  • Brooks, Samantha J., et al. (författare)
  • Thinking about Eating Food Activates Visual Cortex with Reduced Bilateral Cerebellar Activation in Females with Anorexia Nervosa : An fMRI Study
  • 2012
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3, s. e34000-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Women with anorexia nervosa (AN) have aberrant cognitions about food and altered activity in prefrontal cortical and somatosensory regions to food images. However, differential effects on the brain when thinking about eating food between healthy women and those with AN is unknown. Methods: Functional magnetic resonance imaging (fMRI) examined neural activation when 42 women thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24 age-matched controls (HC). Results: Group contrasts between HC and AN revealed reduced activation in AN in the bilateral cerebellar vermis, and increased activation in the right visual cortex. Preliminary comparisons between AN subtypes and healthy controls suggest differences in cortical and limbic regions. Conclusions: These preliminary data suggest that thinking about eating food shown in images increases visual and prefrontal cortical neural responses in females with AN, which may underlie cognitive biases towards food stimuli and ruminations about controlling food intake. Future studies are needed to explicitly test how thinking about eating activates restraint cognitions, specifically in those with restricting vs. binge-purging AN subtypes.
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  • Bulik, CM, et al. (författare)
  • Selection of eating-disorder phenotypes for linkage analysis
  • 2005
  • Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. - : Wiley. - 1552-4841. ; 139B:1, s. 81-87
  • Tidskriftsartikel (refereegranskat)
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  • Depelsenaire, Alexandra C. I., et al. (författare)
  • Cellular responses at the application site of a high-density microarray patch delivering an influenza vaccine in a randomized, controlled phase I clinical trial
  • 2021
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 16:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier to use and more cost-effective method for administration of vaccines when compared to the needle and syringe. Since MAPs deliver vaccine to the dermis and epidermis, a degree of local immune response at the site of application is expected. In a phase 1 clinical trial (ACTRN 12618000112268), the Vaxxas high-density MAP (HD-MAP) was used to deliver a monovalent, split inactivated influenza virus vaccine into the skin. HD-MAP immunisation led to significantly enhanced humoral responses on day 8, 22 and 61 compared with IM injection of a quadrivalent commercial seasonal influenza vaccine (Afluria Quadrivalent (R)). Here, the aim was to analyse cellular responses to HD-MAPs in the skin of trial subjects, using flow cytometry and immunohistochemistry. HD-MAPs were coated with a split inactivated influenza virus vaccine (A/Singapore/GP1908/2015 [H1N1]), to deliver 5 mu g haemagglutinin (HA) per HD-MAP. Three HD-MAPs were applied to the volar forearm (FA) of five healthy volunteers (to achieve the required 15 mu g HA dose), whilst five control subjects received three uncoated HD-MAPs (placebo). Local skin response was recorded for over 61 days and haemagglutination inhibition antibody titres (HAI) were assessed on days 1, 4, 8, 22, and 61. Skin biopsies were taken before (day 1), and three days after HD-MAP application (day 4) and analysed by flow-cytometry and immunohistochemistry to compare local immune subset infiltration. HD-MAP vaccination with 15 mu g HA resulted in significant HAI antibody titres compared to the placebo group. Application of uncoated placebo HD-MAPs resulted in mild erythema and oedema in most subjects, that resolved by day 4 in 80% of subjects. Active, HA-coated HD-MAP application resulted in stronger erythema responses on day 4, which resolved between days 22-61. Overall, these erythema responses were accompanied by an influx of immune cells in all subjects. Increased cell infiltration of CD3(+), CD4(+), CD8(+) T cells as well as myeloid CD11b(+) CD11c(+) and non-myeloid CD11b(-) dendritic cells were observed in all subjects, but more pronounced in active HD-MAP groups. In contrast, CD19(+)/CD20(+) B cell counts remained unchanged. Key limitations include the use of an influenza vaccine, to which the subjects may have had previous exposure. Different results might have been obtained with HD-MAPs inducing a primary immune response. In conclusion, influenza vaccine administered to the forearm (FA) using the HD-MAP was well-tolerated and induced a mild to moderate skin response with lymphocytic infiltrate at the site of application.
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  • Fernández-Aranda, Fernando, et al. (författare)
  • COVID Isolation Eating Scale (CIES) : Analysis of the impact of confinement in eating disorders and obesity—A collaborative international study
  • 2020
  • Ingår i: European Eating Disorders Review. - : Wiley. - 1072-4133 .- 1099-0968. ; 28:6, s. 871-883
  • Tidskriftsartikel (refereegranskat)abstract
    • Confinement during the COVID-19 pandemic is expected to have a serious and complex impact on the mental health of patients with an eating disorder (ED) and of patients with obesity. The present manuscript has the following aims: (1) to analyse the psychometric properties of the COVID Isolation Eating Scale (CIES), (2) to explore changes that occurred due to confinement in eating symptomatology; and (3) to explore the general acceptation of the use of telemedicine during confinement. The sample comprised 121 participants (87 ED patients and 34 patients with obesity) recruited from six different centres. Confirmatory Factor Analyses (CFA) tested the rational-theoretical structure of the CIES. Adequate goodness-of-fit was obtained for the confirmatory factor analysis, and Cronbach alpha values ranged from good to excellent. Regarding the effects of confinement, positive and negative impacts of the confinement depends of the eating disorder subtype. Patients with anorexia nervosa (AN) and with obesity endorsed a positive response to treatment during confinement, no significant changes were found in bulimia nervosa (BN) patients, whereas Other Specified Feeding or Eating Disorder (OSFED) patients endorsed an increase in eating symptomatology and in psychopathology. Furthermore, AN patients expressed the greatest dissatisfaction and accommodation difficulty with remote therapy when compared with the previously provided face-to-face therapy. The present study provides empirical evidence on the psychometric robustness of the CIES tool and shows that a negative confinement impact was associated with ED subtype, whereas OSFED patients showed the highest impairment in eating symptomatology and in psychopathology.
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