| 11. |
- Mattheisen, Manuel, et al.
(författare)
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2.127 The Relationship of ADHD with PTSD : A Mendelian Randomization and Population-Based Sibling Comparison Study
- 2022
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier. - 0890-8567 .- 1527-5418. ; 61:10, Sup., s. S225-S225
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Observational studies have reported associations between ADHD and PTSD. But these observed associations can reflect causal relationships in either direction or be confounding. We thus aimed to estimate the potential causal effect of ADHD on the risk of subsequently developing PTSD conducting a 2-sample Mendelian randomization (MR) and a population-based sibling comparison study.Methods: This 2-sample MR and population-based sibling comparison study assessed the association between ADHD and PTSD using a genome-wide association study (GWAS) summary data of European individuals and a population-based cohort of 2,082,118 individuals. The ADHD GWAS data consisted of 20,183 cases and 35,191 controls. PTSD GWAS data sets included up to 320,369 individuals. Two-sample MR tested potential causal associations of genetic variants associated with ADHD and PTSD symptoms adjusting for potential confounders. In the population-based comparisons, Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons).Results: Based on large GWAS data sources, regression (rg) analyses revealed consistent associations (rg range, 0.43-0.52; p < .001) between ADHD and PTSD. ADHD genetic liability was causally linked with increased risk for PTSD (inverse variance weighted [IVW] OR = 1.45; 95% CI, 1.20-1.74; p = 7.68x10-5). This result was not affected by heterogeneity or horizontal pleiotropy (MR Egger intercept = 4.34x10-4; p = .961), and was consistent across PTSD data sets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Results from the sibling comparison showed an increased risk for developing PTSD in individuals diagnosed with ADHD compared to their undiagnosed full siblings (hazard ratio = 2.64 [95% CI, 1.98-3.53]) after adjustments. Adjusting for plausible mediators did not affect the MR results but attenuated the estimates in sibling comparisons.Conclusions: Our findings add impetus to the need for early and effective treatment of ADHD because the condition may put individuals at risk for PTSD later in life.
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| 12. |
- McWhinney, Sean R, et al.
(författare)
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Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:11, s. 6806-6819
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.
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| 13. |
- McWhinney, Sean R, et al.
(författare)
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Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals.
- 2022
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 24:5, s. 509-520
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Tidskriftsartikel (refereegranskat)abstract
- Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry.We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14 sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles.We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex.We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.
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| 14. |
- McWhinney, Sean R, et al.
(författare)
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Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.
- 2023
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Ingår i: Psychological medicine. - 1469-8978. ; , s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 15. |
- Meier, H. E. Markus, et al.
(författare)
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Assessment of Eutrophication Abatement Scenarios for the Baltic Sea by Multi-Model Ensemble Simulations
- 2018
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- To assess the impact of the implementation of the Baltic Sea Action Plan (BSAP) on the future environmental status of the Baltic Sea, available uncoordinated multi-model ensemble simulations for the Baltic Sea region for the twenty-first century were analyzed. The scenario simulations were driven by regionalized global general circulation model (GCM) data using several regional climate system models and forced by various future greenhouse gas emission and air- and river-borne nutrient load scenarios following either reference conditions or the BSAP. To estimate uncertainties in projections, the largest ever multi-model ensemble for the Baltic Sea comprising 58 transient simulations for the twenty-first century was assessed. Data from already existing simulations from different projects including regionalized GCM simulations of the third and fourth assessment reports of the Intergovernmental Panel on Climate Change based on the corresponding Coupled Model Intercomparison Projects, CMIP3 and CMIP5, were collected.Various strategies to weigh the ensemble members were tested and the results for ensemble mean changes between future and present climates are shown to be robust with respect to the chosen metric. Although (1) the model simulations during the historical period are of different quality and (2) the assumptions on nutrient load levels during present and future periods differ between models considerably, the ensemble mean changes in biogeochemical variables in the Baltic proper with respect to nutrient load reductions are similar between the entire ensemble and a subset consisting only of the most reliable simulations.Despite the large spread in projections, the implementation of the BSAP will lead to a significant improvement of the environmental status of the Baltic Sea according to both weighted and unweighted ensembles. The results emphasize the need for investigating ensembles with many members and rigorous assessments of models’ performance.
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| 16. |
- Meier, H. E. Markus, et al.
(författare)
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Assessment of Uncertainties in Scenario Simulations of Biogeochemical Cycles in the Baltic Sea
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Forskningsöversikt (refereegranskat)abstract
- Following earlier regional assessment studies, such as the Assessment of Climate Change for the Baltic Sea Basin and the North Sea Region Climate Change Assessment, knowledge acquired from available literature about future scenario simulations of biogeochemical cycles in the Baltic Sea and their uncertainties is assessed. The identification and reduction of uncertainties of scenario simulations are issues for marine management. For instance, it is important to know whether nutrient load abatement will meet its objectives of restored water quality status in future climate or whether additional measures are required. However, uncertainties are large and their sources need to be understood to draw conclusions about the effectiveness of measures. The assessment of sources of uncertainties in projections of biogeochemical cycles based on authors' own expert judgment suggests that the biggest uncertainties are caused by (1) unknown current and future bioavailable nutrient loads from land and atmosphere, (2) the experimental setup (including the spin up strategy), (3) differences between the projections of global and regional climate models, in particular, with respect to the global mean sea level rise and regional water cycle, (4) differing model-specific responses of the simulated biogeochemical cycles to long-term changes in external nutrient loads and climate of the Baltic Sea region, and (5) unknown future greenhouse gas emissions. Regular assessments of the models' skill (or quality compared to observations) for the Baltic Sea region and the spread in scenario simulations (differences among projected changes) as well as improvement of dynamical downscaling methods are recommended.
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| 17. |
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| 18. |
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| 19. |
- Strom, Nora I., et al.
(författare)
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Genome-Wide Association Study of Obsessive-Compulsive Symptoms including 33,943 individuals from the general population
- 2024
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578.
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Tidskriftsartikel (refereegranskat)abstract
- While 1-2% of individuals meet the criteria for a clinical diagnosis of obsessive-compulsive disorder (OCD), many more (~13-38%) experience subclinical obsessive-compulsive symptoms (OCS) during their life. To characterize the genetic underpinnings of OCS and its genetic relationship to OCD, we conducted the largest genome-wide association study (GWAS) meta-analysis of parent- or self-reported OCS to date (N = 33,943 with complete phenotypic and genome-wide data), combining the results from seven large-scale population-based cohorts from Sweden, the Netherlands, England, and Canada (including six twin cohorts and one cohort of unrelated individuals). We found no genome-wide significant associations at the single-nucleotide polymorphism (SNP) or gene-level, but a polygenic risk score (PRS) based on the OCD GWAS previously published by the Psychiatric Genetics Consortium (PGC-OCD) was significantly associated with OCS (Pfixed = 3.06 × 10-5). Also, one curated gene set (Mootha Gluconeogenesis) reached Bonferroni-corrected significance (Ngenes = 28, Beta = 0.79, SE = 0.16, Pbon = 0.008). Expression of genes in this set is high at sites of insulin mediated glucose disposal. Dysregulated insulin signaling in the etiology of OCS has been suggested by a previous study describing a genetic overlap of OCS with insulin signaling-related traits in children and adolescents. We report a SNP heritability of 4.1% (P = 0.0044) in the meta-analyzed GWAS, and heritability estimates based on the twin cohorts of 33-43%. Genetic correlation analysis showed that OCS were most strongly associated with OCD (rG = 0.72, p = 0.0007) among all tested psychiatric disorders (N = 11). Of all 97 tested phenotypes, 24 showed a significant genetic correlation with OCS, and 66 traits showed concordant directions of effect with OCS and OCD. OCS have a significant polygenic contribution and share genetic risk with diagnosed OCD, supporting the hypothesis that OCD represents the extreme end of widely distributed OCS in the population.
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| 20. |
- Strom, Nora I., et al.
(författare)
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Meta-analysis of genome-wide association studies of hoarding symptoms in 27,537 individuals
- 2022
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Hoarding Disorder (HD) is a mental disorder characterized by persistent difficulties discarding or parting with possessions, often resulting in cluttered living spaces, distress, and impairment. Its etiology is largely unknown, but twin studies suggest that it is moderately heritable. In this study, we pooled phenotypic and genomic data from seven international cohorts (N = 27,537 individuals) and conducted a genome wide association study (GWAS) meta-analysis of parent- or self-reported hoarding symptoms (HS). We followed up the results with gene-based and gene-set analyses, as well as leave-one-out HS polygenic risk score (PRS) analyses. To examine a possible genetic association between hoarding symptoms and other phenotypes we conducted cross-trait PRS analyses. Though we did not report any genome-wide significant SNPs, we report heritability estimates for the twin-cohorts between 26-48%, and a SNP-heritability of 11% for an unrelated sub-cohort. Cross-trait PRS analyses showed that the genetic risk for schizophrenia and autism spectrum disorder were significantly associated with hoarding symptoms. We also found suggestive evidence for an association with educational attainment. There were no significant associations with other phenotypes previously linked to HD, such as obsessive-compulsive disorder, depression, anxiety, or attention-deficit hyperactivity disorder. To conclude, we found that HS are heritable, confirming and extending previous twin studies but we had limited power to detect any genome-wide significant loci. Much larger samples will be needed to further extend these findings and reach a "gene discovery zone". To move the field forward, future research should not only include genetic analyses of quantitative hoarding traits in larger samples, but also in samples of individuals meeting strict diagnostic criteria for HD, and more ethnically diverse samples.
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