Mouse psychosocial stress reduces motivation and cognitive function in operant reward tests:A model for reward pathology with effects of agomelatine

A major domain of depression is decreased motivation for reward. Translational automated tests can be applied in humans and animals to study operant reward behaviour, aetio-pathophysiology underlying deficits therein, and effects of antidepressant treatment. Three inter-related experiments were conducted to investigate depression-relevant effects of chronic psychosocial stress on operant behaviour in mice. (A) Non-manipulated mice were trained on a complex reversal learning (CRL) test with sucrose reinforcement; relative to vehicle (VEH), acute antidepressant agomelatine (AGO, 25mg/kg p.o.) increased reversals. (B) Mice underwent chronic social defeat (CSD) or control handling (CON) on days 1-15, and were administered AGO or VEH on days 10-22. In a progressive ratio schedule motivation test for sucrose on day 15, CSD mice made fewer responses; AGO tended to reverse this effect. In a CRL test on day 22, CSD mice completed fewer reversals; AGO tended to increase reversals in CSD mice associated with an adaptive increase in perseveration. (C) Mice with continuous operant access to water and saccharin solution in the home cage were exposed to CSD or CON; CSD mice made fewer responses for saccharin and water and drank less saccharin in the active period, and drank more water in the inactive period. In a separate CSD cohort, repeated AGO was without effect on these home cage operant and consummatory changes. Overall, this study demonstrates that psychosocial stress in mice leads to depression-relevant decreases in motivation and cognition in operant reward tests; partial reversal of these deficits by AGO provides evidence for predictive validity

Predictors of remission from PTSD symptoms after sexual and non-sexual trauma in the community: A mediated survival-analytic approach.

Epidemiological data on the chronicity of posttraumatic stress disorder (PTSD) symptoms in relation to trauma type and underlying pathways are rare. The current study explored how PTSD symptoms change over time across different trauma types and examined mediators of their persistence. A trauma-exposed community sample, whereof approximately one quarter met diagnostic criteria for PTSD, provided retrospective data on the duration of PTSD symptoms. Those who remitted and those who had not at the time of assessment were compared regarding worst trauma, symptom severity, comorbidity, demographic and treatment-seeking variables. Time to remission was estimated using Cox proportional hazard models including candidate predictors of remission. A mediated survival analysis was used to explore indirect pathways that explain trauma-specific differences in remission times. Both the full sample and PTSD subgroup were analyzed separately. Overall, lower socio-economic status, lifetime and childhood sexual trauma, symptom severity, comorbid depression and past treatment were associated with non- and longer remissions. PTSD avoidance symptoms and comorbid depression were found to mediate longer remission times after lifetime or childhood sexual trauma. Our findings provide insight into the mechanisms and complicating factors of remission from PTSD symptoms after trauma, which might have important implications for therapeutic interventions

Late 1920s film theory and criticism as a test-case for Benjamin’s generalizations on the experiential effects of editing

This article investigates Walter Benjamin’s influential generalization that the effects of cinema are akin to the hyper-stimulating experience of modernity. More specifically, I focus on his oft-cited 1935/36 claim that all editing elicits shock-like disruption. First, I propose a more detailed articulation of the experience of modernity understood as hyper-stimulation and call for distinguishing between at least two of its subsets: the experience of speed and dynamism, on the one hand, and the experience of shock/disruption, on the other. Then I turn to classical film theory of the late 1920s to demonstrate the existence of contemporary views on editing alternative to Benjamin’s. For instance, whereas classical Soviet and Weimar theorists relate the experience of speed and dynamism to both Soviet and classical Hollywood style editing, they reserve the experience of shock/disruption for Soviet montage. In order to resolve the conceptual disagreement between these theorists, on the one hand, and Benjamin, on the other, I turn to late 1920s Weimar film criticism. I demonstrate that, contrary to Benjamin’s generalizations about the disruptive and shock-like nature of all editing, and in line with other theorists’ accounts, different editing practices were regularly distinguished by comparison to at least two distinct hyper-stimulation subsets: speed and dynamism, and shock-like disruption. In other words, contemporaries regularly distinguished between Soviet montage and classical Hollywood editing patterns on the basis of experiential effects alone. On the basis of contemporary reviews of city symphonies, I conclude with a proposal for distinguishing a third subset – confusion. This is an original manuscript / preprint of an article published by Taylor & Francis in Early Popular Visual Culture on 02 Aug 2016 available online: https://doi.org/10.1080/17460654.2016.1199322

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution

Levels of depression in transgender people and its predictors: results of a large matched control study with transgender people accessing clinical services

Background: Depression is a serious disorder which significantly impacts wellbeing and quality of life. Studies exploring mental wellbeing in the transgender population are mostly limited by small, non-homogenous samples and lack of matched controls. This study aimed to address these limitations and explore depression rates in a large sample of transgender people, compared with matched controls from the general population, as well as factors predicting depression in those taking cross-sex hormone treatment (CHT) compared to those not. Methods: Transgender individuals (n=913) completed a measure of depression, measures which predict psychopathology (self-esteem, victimization, social support, interpersonal problems), and information regarding CHT use. Participants were matched by age and experienced gender with adults from the general population who had completed the measure of depression. Results: Individuals were categorized as having no, possible or probable depressive disorder. Transgender individuals not on CHT had a nearly four-fold increased risk of probable depressive disorder, compared to controls. Older age, lower self-esteem, poorer interpersonal function and less social support predicted depressive disorder. Use of CHT was associated with less depression. Limitations: Participants were attending a national gender identity service and therefore represent only a sub-group of transgender people. Due to the cross-sectional design, longitudinal research is required to fully confirm the finding that CHT use reduces depression. Conclusion: This study confirms that non-treated transgender individuals have an increased risk of a depressive disorder. Interventions offered alongside gender affirming treatment to develop interpersonal skills, increase self-esteem and improve social support may reduce depression and prepare individuals for a more successful transition

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

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 DLR THETA code, the incompressible brother of TAU, an overview

The DLR_THETA-Code is a numerical incompressible Reynolds Averaged Navier-Stokes ((U)-RANS) Solver. It is optimised for low Mach number, steady and unsteady flows. It uses a 3D finite volume method on unstructured hybrid grids with a dual grid approach. It can deal with very large grids and high complex geometries. It is designed for massive parallel computations using a domain decomposition approach. This lecture gives an overview over the Code