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  • de Jong, Simone, et al. (författare)
  • Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
  • 2018
  • Ingår i: Communications Biology. - Nature Publishing Group. - 2399-3642. ; 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
  • Erlangsen, Annette, et al. (författare)
  • Key considerations for preventing suicide in older adults: consensus opinions of an expert panel.
  • 2011
  • Ingår i: Crisis. - 0227-5910. ; 32:2, s. 106-9
  • Tidskriftsartikel (refereegranskat)abstract
    • The number of older adults is growing rapidly. This fact, combined with the high rates of suicide in later life, indicates that many more older adults will die by their own hands before rigorous trials can be conducted to fully understand the best approaches to prevent late life suicide.
  • Erlangsen, Annette, et al. (författare)
  • Suicide among persons who entered same-sex and opposite-sex marriage in Denmark and Sweden, 1989-2016 : a binational, register-based cohort study
  • 2020
  • Ingår i: Journal of Epidemiology and Community Health. - 0143-005X .- 1470-2738. ; 74:1, s. 78-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Background People belonging to sexual minority groups have higher levels of suicidality than heterosexuals. However, findings regarding suicide death are sparse. Using unique national data from two countries, we investigated whether individuals entering a same-sex marriage (SSM), a proxy group of sexual minority individuals, had higher suicide rates than those entering opposite-sex marriage (OSM).Methods A cohort study of all males and females who entered an SSM (n=28649) or OSM (n=3 918 617) in Denmark and Sweden during 1989-2016 was conducted. Incidence rate ratios (IRRs) for suicide were calculated using adjusted Poisson regression models.Results In total, 97 suicides occurred among individuals who had entered an SSM compared with 6074 among those who entered an OSM, corresponding to an adjusted IRR of 2.3 (95% CI 1.9 to 2.8). For people who entered SSM, a 46% decline was noted over time from an IRR of 2.8 (95% CI 1.9 to 4.0) during 1989-2002 to 1.5 (95% CI 1.2 to 1.9) during 2003-2016. The excess suicide mortality was present in all age groups but most pronounced among younger individuals aged 18-34 years of age (IRR 2.7, 95%CI 1.5 to 4.8) and females (IRR 2.7, 95%CI 1.8 to 3.9).Conclusion This large register-based study found higher suicide rates among individuals who entered an SSM, compared with those who entered an OSM. A lower suicide rate was noted for individuals in SSMs in recent years. More research is needed to identify the unique suicide risk and protective factors for sexual minority people.
  • Forsman, Anna K, et al. (författare)
  • Research priorities for public mental health in Europe: recommendations of the ROAMER project.
  • 2015
  • Ingår i: European Journal of Public Health. - Oxford University Press. - 1101-1262. ; 25:2, s. 249-254
  • Tidskriftsartikel (refereegranskat)abstract
    • The ROAdmap for MEntal health Research in Europe project aimed to create an integrated European roadmap for mental health research. Leading mental health research experts across Europe have formulated consensus-based recommendations for future research within the public mental health field.
  • Huckins, Laura M., et al. (författare)
  • Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
  • 2019
  • Ingår i: Nature genetics. - 1546-1718. ; 51:4, s. 659-
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.
  • Krogh, Jesper, et al. (författare)
  • Growth hormone, prolactin and cortisol response to exercise in patients with depression
  • 2010
  • Ingår i: Journal of Affective Disorders. - Elsevier. - 1573-2517. ; 125:1-3, s. 189-197
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A blunted growth hormone and prolactin response to pharmacological stress test have previously been found in depressed patients, as well as an increased cortisol response to psychosocial stress. This study investigated these hormones in response to acute exercise using an incremental bicycle test. Method: A cross-sectional comparison of cortisol, growth hormone, and prolactin in depressed (n = 137) and healthy (n = 44) subjects during rest and in response to an incremental bicycle test. Secondly, we tested the depressed patients again after a 4-month randomized naturalistic exercise intervention. Results: Resting plasma levels of growth hormone (GH), cortisol, or prolactin (PRL) did not differ between depressed and healthy subjects (all p-values > .12). In response to an incremental bicycle test the GH (p = .02) and cortisol (p = .05) response in depressed was different compared to healthy controls. The effect of acute exercise stress on PRL (p = .56) did not differ between depressed and healthy subjects. Apart from a decrease in CH response in the strength-training group (p = .03) the pragmatic exercise intervention did not affect resting hormonal levels, or the response to acute exercise. Conclusions: Patients with mild to moderate depression had a different growth hormone and cortisol response to acute exercise stress compared to healthy controls. Strength training was able to reduce the growth hormone response to acute exercise stress in this patient population. Studies with more rigorous inclusion criteria and higher exercise frequencies are needed to evaluate and confirm the possible effect of exercise in depressed subjects. (C) 2010 Elsevier B.V. All rights reserved.
  • Krogh, Jesper, et al. (författare)
  • N-terminal pro-atrial natriuretic peptide response to acute exercise in depressed patients and healthy controls
  • 2011
  • Ingår i: Psychoneuroendocrinology. - Elsevier. - 1873-3360. ; 36:5, s. 656-663
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The dysfunction of hypothalamic-pituitary-adrenal (HPA) axis in major depression includes hyperactivity and reduced feedback inhibition. Atrial natriuretic peptide (ANP) is able to reduce the HPA-axis response to stress and has an anxiolytic effect in rodents and humans. We hypothesized that patients with depression would have an attenuated N-terminal proANP (NT-proANP) response to acute exercise compared to healthy controls. Secondly, we aimed to assess the effect of antidepressants on NT-proANP response to acute exercise. Methods: We examined 132 outpatients with mild to moderate depression (ICD-10) and 44 healthy controls, group matched for age, sex, and BMI. We used an incremental bicycle ergometer test as a physical stressor. Blood samples were drawn at rest, at exhaustion, and 15, 30, and 60 min post-exercise. Results: The NT-proANP response to physical exercise differed between depressed subjects and healthy controls (group x time; F-4,F-162.9 = 10.92; p < 0.001). The increase from rest to VO2max was 0.98 (SD 0.8) and 1.96 nmol/l (SD 1.1), respectively, for depressed subjects and healthy controls (mean diff: 0.98 nmol/l; 95% CI 0.7-1.3; t = 6.63; df = 170; p < 0.001). The increase in NT-proANP from rest to peak VO2max was 1.27 (SD 1.0) and 0.84 nmol/l (SD 0.6), respectively, for unmedicated and medicated patients (mean diff: 0.42 nmol/l; 95% CI 0.1-0.8; t = 2.56; df = 128; p = 0.01). Conclusion: We observed an attenuated NT-proANP response to acute physical stress in depressed patients. Antidepressants were associated with an independent suppressive effect on the NT-proANP response. (c) 2010 Elsevier Ltd. All rights reserved.
  • Laursen, Thomas Munk, et al. (författare)
  • Life expectancy and death by diseases of the circulatory system in patients with bipolar disorder or schizophrenia in the Nordic countries
  • 2013
  • Ingår i: PloS one. - 1932-6203. ; 8:6, s. e67133
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Excess mortality from diseases and medical conditions (natural death) in persons with psychiatric disorders has been extensively reported. Even in the Nordic countries with well-developed welfare systems, register based studies find evidence of an excess mortality. In recent years, cardiac mortality and death by diseases of the circulatory system has seen a decline in all the Nordic countries, but a recent paper indicates that women and men in Denmark, Finland, and Sweden, who had been hospitalised for a psychotic disorder, had a two to three-fold increased risk of dying from a cardiovascular disease. The aim of this study was to compare the mortality by diseases of the circulatory system among patients with bipolar disorder or schizophrenia in the three Nordic countries Denmark, Sweden, and Finland. Furthermore, the aim was to examine and compare life expectancy among these patients. Cause specific Standardized Mortality Rates (SMRs) were calculated for each specific subgroup of mortality. Life expectancy was calculated using Wiesler's method.RESULTS: The SMR for bipolar disorder for diseases of the circulatory system was approximately 2 in all countries and both sexes. SMR was slightly higher for people with schizophrenia for both genders and in all countries, except for men in Denmark. Overall life expectancy was much lower among persons with bipolar disorder or schizophrenia, with life expectancy being from 11 to 20 years shorter.CONCLUSION: Our data show that persons in the Nordic countries with schizophrenia or bipolar disorder have a substantially reduced life expectancy. An evaluation of the reasons for these increased mortality rates should be prioritized when planning healthcare in the coming years.
  • Liu, Xueping, et al. (författare)
  • Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
  • 2019
  • Ingår i: Nature communications. - 2041-1723. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10−14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality. © 2019, The Author(s).
  • Martin, Joanna, et al. (författare)
  • A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder
  • 2018
  • Ingår i: Biological Psychiatry. - Elsevier. - 0006-3223. ; 83:12, s. 1044-1053
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases.METHODS: We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls).RESULTS: Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with r(g) estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11-1.18], p = 1.5E-15).CONCLUSIONS: Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence.
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