Norwegische 'Wehrmachtskinder': Psychosoziale Aspekte, Identitätsentwicklung und Stigmatisierung

Am 09. April 1940 überfielen deutsche Truppen Norwegen. Neun Monate später kamen die ersten 'Wehrmachtskinder' zur Welt. Im Laufe des Krieges wurden 72 Heime des 'Lebensborn' (ein von der SS getragener Verein zur Erhöhung der Geburtenrate 'arischer' Kinder) in Norwegen gegründet, so viele wie in keinem anderen durch das NS-Regime besetzten Land; darunter befand sich das erste außerhalb des damaligen Deutschen Reiches gelegene. In den Archiven des Lebensborn wurden knapp 8000 Kinder registriert. Schätzungen gehen davon aus, dass während der deutschen Okkupationszeit in Norwegen 10000 bis 12 000 Kinder geboren wurden, deren Väter den deutschen Truppen angehörten und deren Mütter norwegische Staatsbürgerinnen waren. Die 'Wehrmachtskinder' trugen ein doppeltes Stigma: Sie waren häufig unehelich geboren und waren durch die Beziehung mit dem Feind entstanden. Aus Zeitzeugnissen geht hervor, dass ihr soziales Umfeld sie diskriminierte und ausgrenzte; sie wurden verhöhnt und zum Teil körperlich und seelisch misshandelt. Auch von staatlicher Seite widerfuhren Ihnen unterschiedliche Repressalien. Die geistes- und sozialwissenschaftlichen Fächer haben die Umstände und Bedingungen der norwegischen 'Wehrmachtskinder' bereits Ende des letzten Jahrhunderts als Forschungsgegenstand aufgegriffen. Die psychosozialen Fächer haben dieses Thema jedoch erst kürzlich begonnen zu bearbeiten. Im Rahmen des hier vorgestellten Forschungsvorhabens werden erstmalig mittels eines umfangreichen Fragebogens die psychosozialen Konsequenzen des Aufwachsens als 'Wehrmachtskind' im Nachkriegsnorwegen erfasst. Das Projekt ist in eine bereits etablierte internationale und interdisziplinäre Forschungsstruktur zu den 'Kinder[n] des Krieges' eingebunden (www.childrenbornofwar.org), wobei an den Universitäten Leipzig und Greifswald die psychosoziale Belastung von Besatzungskindern in Deutschland parallel untersucht wird. Eine Besonderheit der norwegischen Situation sind die umfangreichen Aktivitäten des 'Lebensborn', der während des Krieges für viele Wehrmachtskinder und deren Mütter eine wichtige Rolle spielte.On 9 April 1940, German troops invaded Norway. Nine months later the first 'Wehrmacht children' were born. In the course of the war, 13 'Lebensborn' homes were established in Norway, more than in any other country occupied by the Nazis and including the first ever of these homes to be set up outside the former German Reich. (The Lebensborn was an SS-initiated association dedicated to raising the number of 'Aryan' births via extramarital relations between people living up to Nazi standards of health and racial purity). In the archives of the Lebensborn almost 8,000 children were registered. It is estimated that 10,000 to 12,000 children were born during the German occupation of Norway whose fathers belonged to the German troops and whose mothers were Norwegian nationals. 'Wehrmacht children' labored under a dual stigma. They were (often) born out of wedlock and they were the fruit of relations with the enemy. Socially they were discriminated and marginalized. They were ridiculed and, in many cases, physically and mentally abused. These children also suffered a variety of reprisals from the state. Initial investigations of the biographies and careers of the 'Wehrmacht children' in Norway date back to the end of the last century, most of them undertaken by scholars working in the humanities and the social sciences. Recently, the psychosocial sciences have also taken up this issue. The research project discussed here is the first to investigate the psychosocial consequences of growing up as a 'Wehrmacht child' in post-war Norway. The project is part of an established international and interdisciplinary research network named 'Children Born of War' (www.childrenbornofwar.org). The Universities of Leipzig and Greifswald have conducted a parallel study on occupation-born German children after WWII. A special feature of the Norwegian situation is the extensive activity of the 'Lebensborn', which played an important role for many 'Wehrmacht children' and their mothers during the war

Towards Adaptive Technology in Routine Mental Healthcare

This paper summarizes the information technology-related research findings after 5 years with the INTROducing Mental health through Adaptive Technology project. The aim was to improve mental healthcare by introducing new technologies for adaptive interventions in mental healthcare through interdisciplinary research and development. We focus on the challenges related to internet-delivered psychological treatments, emphasising artificial intelligence, human-computer interaction, and software engineering. We present the main research findings, the developed artefacts, and lessons learned from the project before outlining directions for future research. The main findings from this project are encapsulated in a reference architecture that is used for establishing an infrastructure for adaptive internet-delivered psychological treatment systems in clinical contexts. The infrastructure is developed by introducing an interdisciplinary design and development process inspired by domain-driven design, user-centred design, and the person based approach for intervention design. The process aligns the software development with the intervention design and illustrates their mutual dependencies. Finally, we present software artefacts produced within the project and discuss how they are related to the proposed reference architecture. Our results indicate that the proposed development process, the reference architecture and the produced software can be practical means of designing adaptive mental health care treatments in correspondence with the patients’ needs and preferences. In summary, we have created the initial version of an information technology infrastructure to support the development and deployment of Internet-delivered mental health interventions with inherent support for data sharing, data analysis, reusability of treatment content, and adaptation of intervention based on user needs and preferences.publishedVersio

The Pharmacogenomics of Bipolar Disorder study (PGBD): Identification of genes for lithium response in a prospective sample

Background: Bipolar disorder is a serious and common psychiatric disorder characterized by manic and depressive mood switches and a relapsing and remitting course. The cornerstone of clinical management is stabilization and prophylaxis using mood-stabilizing medications to reduce both manic and depressive symptoms. Lithium remains the gold standard of treatment with the strongest data for both efficacy and suicide prevention. However, many patients do not respond to this medication, and clinically there is a great need for tools to aid the clinician in selecting the correct treatment. Large genome wide association studies (GWAS) investigating retrospectively the effect of lithium response are in the pipeline; however, few large prospective studies on genetic predictors to of lithium response have yet been conducted. The purpose of this project is to identify genes that are associated with lithium response in a large prospective cohort of bipolar patients and to better understand the mechanism of action of lithium and the variation in the genome that influences clinical response. Methods/Design: This study is an 11-site prospective non-randomized open trial of lithium designed to ascertain a cohort of 700 subjects with bipolar I disorder who experience protocol-defined relapse prevention as a result of treatment with lithium monotherapy. All patients will be diagnosed using the Diagnostic Interview for Genetic Studies (DIGS) and will then enter a 2-year follow-up period on lithium monotherapy if and when they exhibit a score of 1 (normal, not ill), 2 (minimally ill) or 3 (mildly ill) on the Clinical Global Impressions of Severity Scale for Bipolar Disorder (CGI-S-BP Overall Bipolar Illness) for 4 of the 5 preceding weeks. Lithium will be titrated as clinically appropriate, not to exceed serum levels of 1.2 mEq/L. The sample will be evaluated longitudinally using a wide range of clinical scales, cognitive assessments and laboratory tests. On relapse, patients will be discontinued or crossed-over to treatment with valproic acid (VPA) or treatment as usual (TAU). Relapse is defined as a DSM-IV manic, major depressive or mixed episode or if the treating physician decides a change in medication is clinically necessary. The sample will be genotyped for GWAS. The outcome for lithium response will be analyzed as a time to event, where the event is defined as clinical relapse, using a Cox Proportional Hazards model. Positive single nucleotide polymorphisms (SNPs) from past genetic retrospective studies of lithium response, the Consortium on Lithium Genetics (ConLiGen), will be tested in this prospective study sample; a meta-analysis of these samples will then be performed. Finally, neurons will be derived from pluripotent stem cells from lithium responders and non-responders and tested in vivo for response to lithium by gene expression studies. SNPs in genes identified in these cellular studies will also be tested for association to response. Discussion: Lithium is an extraordinarily important therapeutic drug in the clinical management of patients suffering from bipolar disorder. However, a significant proportion of patients, 30–40 %, fail to respond, and there is currently no method to identify the good lithium responders before initiation of treatment. Converging evidence suggests that genetic factors play a strong role in the variation of response to lithium, but only a few genes have been tested and the samples have largely been retrospective or quite small. The current study will collect an entirely unique sample of 700 patients with bipolar disorder to be stabilized on lithium monotherapy and followed for up to 2 years. This study will produce useful information to improve the understanding of the mechanism of action of lithium and will add to the development of a method to predict individual response to lithium, thereby accelerating recovery and reducing suffering and cost.publishedVersio

Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools

Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to date and novel statistical tools, we aimed to determine the extent to which migraine’s polygenic architecture overlaps with bipolar disorder, depression and schizophrenia beyond genetic correlation, and to identify shared genetic loci. Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine (n cases = 59 674; n controls = 316 078), bipolar disorder (n cases = 20 352; n controls = 31 358), depression (n cases = 170 756; n controls = 328 443) and schizophrenia (n cases = 40 675, n controls = 64 643). We applied the bivariate causal mixture model to estimate the number of disorder-influencing variants shared between migraine and each mental disorder, and the conditional/conjunctional false discovery rate method to identify shared loci. Loci were functionally characterized to provide biological insights. Univariate MiXeR analysis revealed that migraine was substantially less polygenic (2.8 K disorder-influencing variants) compared to mental disorders (8100–12 300 disorder-influencing variants). Bivariate analysis estimated that 800 (SD = 300), 2100 (SD = 100) and 2300 (SD = 300) variants were shared between bipolar disorder, depression and schizophrenia, respectively. There was also extensive overlap with intelligence (1800, SD = 300) and educational attainment (2100, SD = 300) but not height (1000, SD = 100). We next identified 14 loci jointly associated with migraine and depression and 36 loci jointly associated with migraine and schizophrenia, with evidence of consistent genetic effects in independent samples. No loci were associated with migraine and bipolar disorder. Functional annotation mapped 37 and 298 genes to migraine and each of depression and schizophrenia, respectively, including several novel putative migraine genes such as L3MBTL2, CACNB2 and SLC9B1. Gene-set analysis identified several putative gene sets enriched with mapped genes including transmembrane transport in migraine and schizophrenia. Most migraine-influencing variants were predicted to influence depression and schizophrenia, although a minority of mental disorder-influencing variants were shared with migraine due to the difference in polygenicity. Similar overlap with other brain-related phenotypes suggests this represents a pool of ‘pleiotropic’ variants that influence vulnerability to diverse brain-related disorders and traits. We also identified specific loci shared between migraine and each of depression and schizophrenia, implicating shared molecular mechanisms and highlighting candidate migraine genes for experimental validation

Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E–09 and 4.10E–18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.publishedVersio

Den sårbare tiden etter utskrivelse fra psykiatrisk sykehus – selvmordsrisiko og dokumentasjonspraksis

Tiden like etter utskrivelse fra psykiatrisk døgnenhet innebærerforhøyet selvmordsrisiko. Nasjonale retningslinjer for selvmordsforebyggingi psykisk helsevern anbefaler at når selvmordsrisiko harvært en problemstilling under oppholdet eller tidligere skal pasienterselvmordsrisikovurderes og det er en fordel med timeavtale hosoppfølgende instans. Hensikten med denne studien var å kartleggedokumentert etterlevelse av disse anbefalingene og identifisering avprediktorer for manglende timeavtale.En journalstudie i Divisjon psykisk helsevern, Haukeland Universitetssykehus,ble gjennomført for å vurdere i hvilken grad dokumentasjonspraksisi epikriser og overføringsnotat samsvarte medretningslinjeanbefalingene. Opplysninger om selvmordsrisikovurderingog timeavtale ble kartlagt sammen med kjønn, alder, tidligereselvmordsforsøk, andre risikofaktorer og mulige beskyttende faktorerfor selvmord, hoveddiagnoser, henvisnings- og mottaksformalitet.Analyser var deskriptiv statistikk og Generalized Estimating Equation.Selvmordsrisikovurdering var dokumentert i nesten alle epikriser/overføringsnotat. Begrunnelser for selvmordsrisikovurderingene vari liten grad dokumentert. Lavere sannsynlighet for dokumentasjon avtimeavtale var knyttet til utskrivelser med rus som hoveddiagnose,schizofrenidiagnose for kvinner, samt å bli henvist til tvangsinnleggelsemen mottatt til frivillig sykehusopphold for kvinner.Dokumentasjonspraksis vedrørende selvmordsrisikovurdering vargod, men vurderingene inneholdt i liten grad utdypende beskrivelserslik retningslinjen anbefaler. Gode beskrivelser gir oppfølgendeinstans viktig informasjon for videre pasientbehandling. Bedret dokumentasjonspraksis kan bidra til økt kontinuitet i helsetjenestetilbudetfor pasientene

Ordre du jour

Ordre du jour. In: Comptes rendus des séances de l'Académie des Inscriptions et Belles-Lettres, 126ᵉ année, N. 2, 1982. p. 383

Brain changes induced by electroconvulsive therapy are broadly distributed

Background Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response. Methods Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites. Results Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean ± SD of 1.04 ± 1.03% (Cohen’s d = 1.01, p < .001) and the subcortical gray matter volume increased by 1.47 ± 1.05% (d = 1.40, p < .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman’s rank correlation ρ = −.44, p < .001), while total white matter volume remained unchanged (d = −0.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome. Conclusions The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response