The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity

The oxytocin receptor gene (OXTR) is of interest when investigating the effects of early adversity on DNA methylation. However, there is heterogeneity regarding the selection of the most promising CpG sites to target for analyses. The goal of this study was to determine functionally relevant clusters of CpG sites within the OXTR CpG island in 113 mother-infant dyads, with 58 of the mothers reporting childhood maltreatment (CM). OXTR DNA methylation was analyzed in peripheral/umbilical blood mononuclear cells. Different complexity reduction approaches were used to reduce the 188 CpG sites into clusters of co-methylated sites. Furthermore, associations between OXTR DNA methylation (cluster- and site-specific level) and OXTR gene expression and CM were investigated in mothers. Results showed that, first, CpG sections differed strongly regarding their statistical utility for research of individual differences in DNA methylation. Second, cluster analyses and Partial Least Squares (PLS) suggested two clusters consisting of intron1/exon2 and the protein-coding region of exon3, respectively, as most strongly associated with outcome measures. Third, cross-validated PLS regression explained 7% of variance in CM, with low cross-validated variance explained for the prediction of gene expression. Fourth, substantial mother-child correspondence was observed in correlation patterns within the identified clusters, but only modest correspondence outside these clusters. This study makes an important contribution to the mapping of the DNA methylation landscape of the OXTR CpG island by highlighting clusters of CpG sites that show desirable statistical properties and predictive value. We provide a Companion Web Application to facilitate the choice of CpG sites

A three-country comparison of psychotropic medication prevalence in youth

<p>Abstract</p> <p>Background</p> <p>The study aims to compare cross-national prevalence of psychotropic medication use in youth.</p> <p>Methods</p> <p>A population-based analysis of psychotropic medication use based on administrative claims data for the year 2000 was undertaken for insured enrollees from 3 countries in relation to age group (0–4, 5–9, 10–14, and 15–19), gender, drug subclass pattern and concomitant use. The data include insured youth aged 0–19 in the year 2000 from the Netherlands (n = 110,944), Germany (n = 356,520) and the United States (n = 127,157).</p> <p>Results</p> <p>The annual prevalence of any psychotropic medication in youth was significantly greater in the US (6.7%) than in the Netherlands (2.9%) and in Germany (2.0%). Antidepressant and stimulant prevalence were 3 or more times greater in the US than in the Netherlands and Germany, while antipsychotic prevalence was 1.5–2.2 times greater. The atypical antipsychotic subclass represented only 5% of antipsychotic use in Germany, but 48% in the Netherlands and 66% in the US. The less commonly used drugs e.g. alpha agonists, lithium and antiparkinsonian agents generally followed the ranking of US>Dutch>German youth with very rare (less than 0.05%) use in Dutch and German youth. Though rarely used, anxiolytics were twice as common in Dutch as in US and German youth. Prescription hypnotics were half as common as anxiolytics in Dutch and US youth and were very uncommon in German youth. Concomitant drug use applied to 19.2% of US youth which was more than double the Dutch use and three times that of German youth.</p> <p>Conclusion</p> <p>Prominent differences in psychotropic medication treatment patterns exist between youth in the US and Western Europe and within Western Europe. Differences in policies regarding direct to consumer drug advertising, government regulatory restrictions, reimbursement policies, diagnostic classification systems, and cultural beliefs regarding the role of medication for emotional and behavioral treatment are likely to account for these differences.</p

Training approaches for the dissemination of clinical guidelines for NSSI: a quasi-experimental trial.

BACKGROUND Non-suicidal self-injury (NSSI) is of high clinical relevance due to its high prevalence and negative long-term implications. In 2016, the German consensus-based clinical guidelines for diagnostic, assessment and treatment of NSSI in childhood and adolescence were published. However, research indicates that clinical guidelines are often poorly implemented in clinical practice. One crucial part of this process is the training of healthcare professionals to transfer knowledge and capacities to bring guideline recommendations into clinical practice. METHODS The effect of three different dissemination strategies (printed educational material, e-learning, and blended-learning) on the NSSI guidelines´ recommendations was examined among 671 physicians and psychotherapists via an online-survey. The quasi-experimental study included three measurement points (before the training, after the training, 3-month follow-up) and mixed effects models were used to test for changes in knowledge, competences and attitudes toward NSSI and treatment. Moreover, the transfer of gained competences to practical work and user satisfaction were reviewed. RESULTS With all three training formats, the intended changes of the outcome variables could be observed. Hereby, the printed educational material condition showed the lowest improvement in the scores for the 'negative attitudes toward NSSI and those who self-injure'. The training effect remained stable throughout the follow-up measurement. The highest application rate of acquired intervention techniques in clinical practice was reported for the blended-learning condition. For all three training strategies, user satisfaction was high and evaluation of training quality was positive, with printed educational material receiving the lowest and blended-learning the highest evaluations. CONCLUSIONS In summary, all three training formats were perceived to be of high quality and seem to be suited to cover the needs of a heterogeneous group of physicians and psychotherapists. The choice of training method could be driven by considering which training goals are desired to be achieved and by the benefit-cost ratio allowing for tailored training approaches

Pharmaceutical research in paediatric populations and the new EU Paediatric Legislation: an industry perspective

A large proportion of medicines used in children are prescribed off-label, and children have often been denied access to new or innovative medications. Because such situation is unethical, the need to obtain paediatric information for medicines used in children seems nowadays a matter of consensus on a global basis. Based on this, it was clear in EU, like what has happened in the US, that there was a need for a legal obligation for Pharmaceutical Companies to perform studies. This new European Paediatric Regulation that entered into force in 2007 opens a new era of European drug regulatory history and will offer a major opportunity to improve children's health through advancements in research by providing a new framework for evaluating the efficacy and safety of medicines for children. But, paediatric development remains challenging and the hurdles of conducting research in paediatric population are numerous. The article presents the new European Paediatric Regulation, illustrates its rationale through paediatric psychopharmacology, and discusses some of its consequences on paediatric research from an industry perspective. Recommendations for further international collaboration are also suggested to make global paediatric development plans

Running in the FAMILY: understanding and predicting the intergenerational transmission of mental illness

Over 50% of children with a parent with severe mental illness will develop mental illness by early adulthood. However, intergenerational transmission of risk for mental illness in one’s children is insufficiently considered in clinical practice, nor is it sufficiently utilised into diagnostics and care for children of ill parents. This leads to delays in diagnosing young offspring and missed opportunities for protective actions and resilience strengthening. Prior twin, family, and adoption studies suggest that the aetiology of mental illness is governed by a complex interplay of genetic and environmental factors, potentially mediated by changes in epigenetic programming and brain development. However, how these factors ultimately materialise into mental disorders remains unclear. Here, we present the FAMILY consortium, an interdisciplinary, multimodal (e.g., (epi)genetics, neuroimaging, environment, behaviour), multilevel (e.g., individual-level, family-level), and multisite study funded by a European Union Horizon-Staying-Healthy-2021 grant. FAMILY focuses on understanding and prediction of intergenerational transmission of mental illness, using genetically informed causal inference, multimodal normative prediction, and animal modelling. Moreover, FAMILY applies methods from social sciences to map social and ethical consequences of risk prediction to prepare clinical practice for future implementation. FAMILY aims to deliver: (i) new discoveries clarifying the aetiology of mental illness and the process of resilience, thereby providing new targets for prevention and intervention studies; (ii) a risk prediction model within a normative modelling framework to predict who is at risk for developing mental illness; and (iii) insight into social and ethical issues related to risk prediction to inform clinical guidelines

Mental Health and Wellbeing Implications of the COVID-19 Quarantine for Disabled and Disadvantaged Children and Young People: Evidence from a Cross-cultural Study in Zambia and Sierra Leone

Background The mental health impact of the COVID-19 pandemic and quarantining on children and young people (CYP) living in low- and middle-income countries (LMICs) has yet to be fully comprehended. CYP in LMICs are at utmost risk, given the COVID-19-related restrictions and social distancing measures, resulting in reduced access to school-based services for nutritional and mental health needs. This study examined mental health of CYP during the first COVID-19 lockdown in Zambia and Sierra Leone. Method A total of 468 disabled and disadvantaged CYP aged 12 to 25 completed a planning tool that comprised the short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), as well as open-ended questions covering social connectedness, physical distancing and educational challenges during the lockdown. The community coaches screened individuals and families who could be eligible to receive emergency aid, and based on a convenience sample following distribution of aid, recipients were invited to complete the online planning tool. Results The data showed that participants in the global south have increasing anxieties and fears centred on accessing offline educational resources and income loss in the family effecting food security and their ability to return to education. Mean (SD) SWEMWBS scores for all participants in Zambia and Sierra Leone, were 19.61 (3.45) and 21.65 (2.84), respectively. Mental well-being scores were lower in females, children aged 12-14 and participants with two or more disabilities. Factors significantly associated with poor mental wellbeing in the sample were: type of disability, nationality, peer relationships, connection to others during the pandemic, knowledge about COVID-19, worry about the long-term impact of COVID-19, and the types of self-isolating. Conclusion The study shows that participants who self-reported low levels of COVID-19 health literacy also scored low on the mental wellbeing self-assessment. Yet, despite undoubted limited resources, these CYP are doing well in identifying their needs and maintaining hope in the face of the problems associated with COVID-19 in countries where stigma persists around mental ill-health

The ethics of psychopharmacological research in legal minors

Research in psychopharmacology for children and adolescents is fraught with ethical problems and tensions. This has practical consequences as it leads to a paucity of the research that is essential to support the treatment of this vulnerable group. In this article, we will discuss some of the ethical issues which are relevant to such research, and explore their implications for both research and standard care. We suggest that finding a way forward requires a willingness to acknowledge and discuss the inherent conflicts between the ethical principles involved. Furthermore, in order to facilitate more, ethically sound psychopharmacology research in children and adolescents, we suggest more ethical analysis, empirical ethics research and ethics input built into psychopharmacological research design

Managing the link and strengthening transition from child to adult mental health Care in Europe (MILESTONE): Background, rationale and methodology

Background: Transition from distinct Child and Adolescent Mental Health (CAMHS) to Adult Mental Health Services (AMHS) is beset with multitude of problems affecting continuity of care for young people with mental health needs. Transition-related discontinuity of care is a major health, socioeconomic and societal challenge globally. The overall aim of the Managing the Link and Strengthening Transition from Child to Adult Mental Health Care in Europe (MILESTONE) project (2014-19) is to improve transition from CAMHS to AMHS in diverse healthcare settings across Europe. MILESTONE focuses on current service provision in Europe, new transition-related measures, long term outcomes of young people leaving CAMHS, improving transitional care through 'managed transition', ethics of transitioning and the training of health care professionals. Methods: Data will be collected via systematic literature reviews, pan-European surveys, and focus groups with service providers, users and carers, and members of youth advocacy and mental health advocacy groups. A prospective cohort study will be conducted with a nested cluster randomised controlled trial in eight European Union (EU) countries (Belgium, Croatia, France, Germany, Ireland, Italy, Netherlands, UK) involving over 1000 CAMHS users, their carers, and clinicians. Discussion: Improving transitional care can facilitate not only recovery but also mental health promotion and mental illness prevention for young people. MILESTONE will provide evidence of the organisational structures and processes influencing transition at the service interface across differing healthcare models in Europe and longitudinal outcomes for young people leaving CAMHS, solutions for improving transitional care in a cost-effective manner, training modules for clinicians, and commissioning and policy guidelines for service providers and policy makers

Die Vereinbarkeitsfrage für Männer: Welche Auswirkungen haben Elternzeiten und Teilzeitarbeit auf die Stundenlöhne von Vätern?

Studien zeigen, dass sich viele Väter in Deutschland wünschen, mehr Zeit mit ihren Kindern zu verbringen, dies aufgrund von langen Arbeitszeiten jedoch oft nicht umsetzen können. Elternzeit und Teilzeitarbeit könnten Optionen sein, die Vätern eine bessere Vereinbarkeit von Familie und Beruf ermöglichen. Arbeitsmarkttheorien legen jedoch nahe, dass die Inanspruchnahme solcher Maßnahmen mit Lohneinbußen verbunden ist. Dementsprechend entscheiden sich derzeit viele Väter gegen diese Möglichkeiten zur Vereinbarkeit von Familie und Beruf, da sie finanzielle Einbußen und Karrierenachteile befürchten. Um zu überprüfen, inwieweit diese Erwartungen empirisch fundiert sind, untersucht diese Arbeit daher den Einfluss von Elternzeit und Teilzeitarbeit auf die Stundenlöhne von Vätern. Fixed Effects-Analysen auf Basis des Sozio-oekonomischen Panels (SOEP) 1991-2013 und Familien in Deutschland (FiD) 2010-2013 zeigen, dass Teilzeitarbeit mit Lohneinbußen verbunden ist. Eine Elternzeit wirkt sich hingegen nicht auf die Löhne von Vätern aus - unabhängig davon, ob Väter nur die beiden für sie reservierten Partnermonate oder eine längere Elternzeit in Anspruch nehmen. Die Ergebnisse deuten somit darauf hin, dass die gesetzliche Elternzeit Vätern einen Rahmen bietet, in dem sie sich stärker in ihren Familien engagieren können, ohne berufliche Nachteile zu erfahren.As previous research shows, many German fathers would like to spend more time with their children, but long working hours often restrict their opportunities to do so. Parental leave and part-time work could help fathers to reconcile work and family. Yet, labor market theories predict that using such family-friendly policies may lead to wage penalties. Hence, many fathers decide against using such policies because they fear that parental leave or part-time work will lead to financial penalties and career disadvantages. This article evaluates this concern by empirically examining the effect of parental leave and part-time work on fathers’ hourly wages. Using data from the German Socio-Economic Panel (SOEP) 1991-2013 and Families in Germany (FiD) 2010-2013, results from fixed-effects regression analyses show that part-time work is associated with wage penalties, but parental leave is not - irrespective of whether fathers only took the two months fathers’ quota or longer parental leaves. The results hence indicate that the German parental leave legislation enables fathers to spend more time with their children while protecting them from wage penalties at work