No abstract

Highlights d Three groups of highly genetically-related disorders among 8 psychiatric disorders d Identified 109 pleiotropic loci affecting more than one disorder d Pleiotropic genes show heightened expression beginning in 2 nd prenatal trimester d Pleiotropic genes play prominent roles in neurodevelopmental processes Authors Cross-Disorder Group of the Psychiatric Genomics Consortium

Objective To conduct a genome-wide association study (GWAS) of anorexia nervosa and to calculate genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Method Following uniform quality control and imputation using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, we performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression (LDSC) was used to calculate genome-wide common variant heritability [ hSNP2, partitioned heritability, and genetic correlations (rg)] between anorexia nervosa and other phenotypes. Results Results were obtained for 10,641,224 single nucleotide polymorphisms (SNPs) and insertion-deletion variants with minor allele frequency > 1% and imputation quality scores > 0.6. The hSNP2 of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. We identified one genome-wide significant locus on chromosome 12 (rs4622308, p=4.3×10−9) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high density lipoprotein (HDL) cholesterol, and significant negative genetic correlations between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Conclusions Anorexia nervosa is a complex heritable phenotype for which we have found the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. Our results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

Background Since the COVID-19 pandemic has affected the education of medical students, medical faculties have faced the challenge of adapting instruction to digital platforms. Although medical students are willing to support pandemic response efforts, how the crisis will affect their medical training remains uncertain. Thus, in this study, we investigated the teaching- and learning-related stressors and expectations of medical students in Germany during the COVID-19 pandemic. Methods A cross-sectional survey was distributed online to undergraduate medical students at medical faculties in Germany. Students answered questions about COVID-19 and teaching (on a 7-point Likert scale from 0 (“not at all”) to 6 (“completely”)) and completed mental well-being measurements, including the State–Trait Anxiety Inventory (STAI), the Generalised Anxiety Disorder scale (GAD-7) and the Perceived Health Questionnaire (PHQ-9). Descriptive data analysis, a t-test and Pearson correlations were performed to process the data. Results Medical students felt well-informed about COVID-19 in general (M = 5.64, SD = 1.28) and in the medical context (M = 5.14, SD = 1.34) but significantly less informed about the pandemic in the academic context, M = 2.47, SD = 1.49, t(371) = 31.98, p < .001. Their distress levels were high (STAI: M = 45.12, SD = 4.73) and significantly correlated with the academic context (rp = .164, p < .01) but not their private lives. Concerning how they were taught, they most often expected online lectures (91.7%) and live broadcasts (67.2%) and less often expected innovative digital teaching strategies, including serious games (17.3%) and virtual-reality exercises (16.7%). Discussion Medical students seem to be aware of the COVID-19 pandemic and its consequences for academic and healthcare contexts. They also seem to think that their teachers will enhance their digital competencies during the pandemic. Therefore, faculties of medicine need to rapidly and adequately digitalise their approaches to teaching.

Primer articlesNature Reviews publishes timely, authoritative articles that are of broad interest and exceptional quality. Thank you for taking the time to help us to ensure that our articles meet these high standards.Primer articles in Nature Reviews provide an overview of a disease or disorder. Primers are intended to provide an authoritative, global perspective for the benefit of biomedical scientists, putting current clinical and translational challenges into context. These overview articles are meant to be introductory and cover all aspects from epidemiology to disease mechanisms, diagnosis and treatment.Please submit your report in narrative form and provide detailed justifications for all statements. Confidential comments to the editor are welcome, but it is helpful if the main points are stated in the comments for transmission to the authors.Please note that all Primer articles follow the same set organization of the main headings. Additionally, Nature Reviews articles will be thoroughly edited before publication and all figures will be redrawn by our in-house art editors. We therefore request that you concentrate on the scientific content of the article and display items, rather than the 'order' of the content or any minor errors in language or grammar that might be present in the draft version. Please consider and comment on the following points when reviewing this manuscript:• Is the article written for a broad audience, including biomedical scientists, translational researchers, medical students and clinicians?• Is the global perspective well represented?• Does the article present the current state of the art in the disease, without much emphasis on historical aspects?• Are the open research questions outlines and comprehensive?• Does the length of the article seem appropriate?• Are the ideas logically presented and discussed?• Does the article provide a balanced overview of the literature? Please bear in mind that it may not be possible to cover all aspects of a field within such a concise article.• Is the discussion fair and accurate? Although our authors are encouraged to be opinionated, they should not ignore alternative points of view. • Do the figures, boxes and tables provide clear and accurate information? Are there any additional or alternative display items that you think that the authors should include?• Are the references appropriate and up-to-date? Do they reflect the scope of the article?• Are you aware of any undeclared conflicts of interest that might affect the balance, or perceived balance, of the article?

Uterus transplantation (UTx) can provide a route to motherhood for women with Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS), a congenital disorder characterized by uterovaginal aplasia, but with functional ovaries. Based on our four successful living-donor transplantations and two resulting births, this analysis presents parameters relevant to standardizing recipient/donor selection, UTx surgery, and postoperative treatment, and their implementation in routine settings. We descriptively analyzed prospectively collected observational data from our four uterus recipients, all with MRKHS, their living donors, and the two newborns born to two recipients, including 1-year postnatal follow-ups. Analysis included only living-donor/recipient pairs with completed donor/recipient surgery. Two recipients, both requiring ovarian restimulation under immunosuppression after missed pregnancy loss in one case and no pregnancy in the other, each delivered a healthy boy by cesarean section. We conclude that parameters crucial to successful transplantation, pregnancy, and childbirth include careful selection of donor/recipient pairs, donor organ quality, meticulous surgical technique, a multidisciplinary team approach, and comprehensive follow-up. Surgery duration and blood vessel selection await further optimization, as do the choice and duration of immunosuppression, which are crucial to timing the first embryo transfer. Data need to be collected in an international registry due to the low prevalence of MRKHS.

Objective A history of an eating disorder (ED) might constitute a risk for symptom deterioration and relapse during COVID‐19 pandemic. This longitudinal study investigates ED symptom trajectories until the first COVID‐19 lockdown in Spring 2020 in patients with a history of binge eating disorder (BED). Method Participants of the randomised‐controlled BED treatment trial IMPULS participated in a re‐assessment directly after the first COVID‐19 lockdown in Germany. We used expert‐rated clinical interviews and self‐report to investigate binge eating (BE) frequency, ED and general psychopathology, distress, emotion regulation and sense of coherence. Symptom trajectories were analysed for baseline when entering the trial, end of trial participation and the time point directly after lockdown. BE frequency was assessed on a recall basis for 4 weeks directly before lockdown and 4 weeks during lockdown. Results BE frequency, general ED pathology and depressive symptoms markedly increased after as compared to before the COVID‐19 outbreak. Individuals scoring high on reappraisal as emotion regulation strategy and sense of coherence scored lower on general ED pathology. Conclusion Individuals with a history of an ED are at risk for symptom deterioration and relapse during the pandemic. Intervention and service dissemination strategies are needed to support vulnerable groups throughout the pandemic.

This scoping review presents an overview of cognitive and social congruence in peer assisted learning (PAL), as the positive effects of PAL have been shown to rely on these critical factors. The scoping review followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Databases were systematically searched for articles that focus on PAL and cognitive and social congruence. Participants of the studies included were medical, health science, polytechnic, law and paramedic students. Studies that assessed cognitive and social congruence by questionnaires with a 5-point Likert scale were regarded for meta-analytic pooling. Sixteen of 786 identified articles were included in the review, whereof 9 studies were considered for meta-analytic pooling. The meta-analytic pooling showed that tutees tend to see their student tutors as cognitively (Mweighted = 3.84; range of Mweighted = 2.69–4.56) and socially congruent (Mweighted = 3.95; range of Mweighted = 2.33–4.57). Further, characteristics of student tutors are summarized. This scoping review presents an overview and operationalization of cognitive and social congruence in PAL. Based on the presented meta-analytic pooling, cognitive and social congruence were found to represent relevant key factors in the PAL context. Thus, this theoretical background should be acknowledged as a core concept for tutorials within the medical curriculum.