Pharmakologische Charakterisierung der Wirkungen von Glukokortikoiden auf die Atmungskette und die ATP-Synthese in adrenokortikotrophen Hypophysenzellen (AtT20)

Um die Effekte des Glukokortikoids Dexamethason auf Parameter des mitochondrialen Energiestoffwechsels zu untersuchen, wurden in vitro Versuche an einer AtT20-Zelllinie durchgeführt (Hypophysenvorderlappenzellen der Maus). Die untersuchten Parameter waren die ATP-Konzentration und ein mitochondrialer Funktionstest (EZ4U). Bei Langzeitinkubation (>30 Min.) zeigten sich vorwiegend supprimierende Effekte, bei kurzer Inkubationszeit (≤30 Min.) waren die Effekte unterschiedlich und dosisabhängig. Die Kurzzeiteffekte im mitochondrialen Funktionstest konnten durch den Glukokortikoidrezeptorantagonisten RU38486 nicht aufgehoben werden. Diese wahrscheinlich nicht-genomischen Effekte könnten in Regulationsvorgänge oder Störungen der Regulation innerhalb der Hypothalamus-Hypophysen-Nebennierenrindenachse involviert sein

Telomere length is repeatable, shortens with age and reproductive success, and predicts remaining lifespan in a long-lived seabird

Telomeres are protective caps at the end of chromosomes, and their length is positively correlated with individual health and lifespan across taxa. Longitudinal studies have provided mixed results regarding the within-individual repeatability of telomere length. While some studies suggest telomere length to be highly dynamic and sensitive to resource-demanding or stressful conditions, others suggest that between-individual differences are mostly present from birth and relatively little affected by the later environment. This dichotomy could arise from differences between species, but also from methodological issues. In our study, we used the highly reliable Terminal Restriction Fragment analysis method to measure telomeres over a 10-year period in adults of a long-lived seabird, the common tern (Sterna hirundo). Telomeres shortened with age within individuals. The individual repeatability of age-dependent telomere length was high (>0.53), and independent of the measurement interval (i.e., one vs. six years). A small (R-2 = .01), but significant part of the between-individual variation in telomere length was, however, explained by the number of fledglings produced in the previous year, while reproduction in years prior to the previous year had no effect. We confirmed that age-dependent telomere length predicted an individual's remaining lifespan. Overall, our study suggests that the majority of between-individual variation in adult telomere length is consistent across adult life, and that a smaller part of the variation can be explained by dynamic factors, such as reproduction

Heidelberg coping scales for delusions: psychometric evaluation of an expert rating instrument

Background: Coping is of substantial relevance in the treatment and course of psychiatric disorders. Standardized instruments to assess coping with psychotic symptoms, particularly delusions, are rare. The aim of this study was to develop and evaluate the psychometric properties of a new instrument to assess coping strategies in the context of delusional experiences: the Heidelberg Coping Scales for Delusions (HCSD). Methods: Two hundred and twelve inpatients with schizophrenia spectrum disorders and affective disorders currently experiencing delusions were interviewed with the HCSD and other coping assessment instruments. Psychometric properties and factor structure were analyzed. Results: The HCSD showed good inter-rater reliability and convergent validity. Factor analysis yielded an interpretable structure with five factors: resource-oriented coping, medical care, distraction, cognitive coping, and depressive coping. Symptomatic behavior, due to its particular characteristics, was considered apart. Conclusion: The HCSD is a reliable and valid instrument for the assessment of coping strategies in patients with delusions. Further research is needed to evaluate coping changes over time and their influence on treatment and clinical outcomes. Copyright (C) 2012 S. Karger AG, Base

Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices)

: In the European Union (EU) the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, whereas authorizing the placing on the market of medical devices is decentralized to independent 'conformity assessment' organizations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the medical device directives, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details-which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE-MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024; here we describe how it may contribute to the development of regulatory science in Europe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

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.Peer reviewe

The genetics of the mood disorder spectrum:genome-wide association analyses of over 185,000 cases and 439,000 controls

Background Mood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders. Methods To clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424). Results Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell-types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder. Conclusions The mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum

Genetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes

Background: Alzheimer's disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits. Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer's Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR=0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR=0.022, opposite direction of effect). Conclusions: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

6. Folge: Making us Matter

Ein Leader muss sich als Teil der Gruppe sehen und der Gruppe eine Identität anbieten, mit der sich die Follower gerne identifizieren. Um als ein solcher Leader aufzutreten, ist eine passend eingesetzte Rhetorik des Leaders von zentraler Bedeutung. Darüber hinaus ist die Realisierung der aufgebauten Identität wichtig dafür, als Leader auch langfristig anerkannt zu bleiben und zu beweisen, dass man am besten als der Leader geeignet ist, der die Gruppe an ihr Ziel führt

Data from: Reduced telomere length in offspring of old fathers in a long-lived seabird

Evidence for transgenerational effects of senescence, whereby offspring from older parents have a reduced lifetime reproductive success, is increasing. Such effects could arise from compromised germline maintenance in old parents, potentially reflected in reduced telomere length in their offspring. We test the relationship between parental age and offspring early-life telomere length in a natural population of common terns and find a significant negative correlation between paternal age and offspring telomere length. Offspring telomere length is reduced by 35 base pairs for each additional year of paternal age. We find no correlation with maternal age. These results fit with the idea of compromised germline maintenance in males, whose germline stem cells require continued division