A Dried Blood Spot protocol for high-throughput quantitative analysis of SARS-CoV-2 RBD serology based on the Roche Elecsys system.

SARS-CoV-2 spreads pandemically since 2020; in 2021, effective vaccinations became available and vaccination campaigns commenced. Still, it is hard to track the spread of the infection or to assess vaccination success in the broader population. Measuring specific anti-SARS-CoV-2 antibodies is the most effective tool to track the spread of the infection or successful vaccinations. The need for venous-blood sampling however poses a significant barrier for large studies. Dried-blood-spots on filter-cards (DBS) have been used for SARS-CoV-2 serology in our laboratory, but so far not to follow quantitative SARS-CoV-2 anti-spike reactivity in a longitudinal cohort. We developed a semi-automated protocol or quantitative SARS-CoV-2 anti-spike serology from self-sampled DBS, validating it in a cohort of matched DBS and venous-blood samples (n = 825). We investigated chromatographic effects, reproducibility, and carry-over effects and calculated a positivity threshold as well as a conversion formula to determine the quantitative binding units in the DBS with confidence intervals. Sensitivity and specificity reached 96.63% and 97.81%, respectively, compared to the same test performed in paired venous samples. Between a signal of 0.018 and 250 U/mL, we calculated a correction formula. Measuring longitudinal samples during vaccinations, we demonstrated relative changes in titers over time in several individuals and in a longitudinal cohort over four follow-ups. DBS sampling has proven itself for anti-nucleocapsid serosurveys in our laboratory. Similarly, anti-spike high-throughput DBS serology is feasible as a complementary assay. Quantitative measurements are accurate enough to follow titer dynamics in populations also after vaccination campaigns. This work was supported by the Bavarian State Ministry of Science and the Arts; LMU University Hospital, LMU Munich; Helmholtz Center Munich; University of Bonn; University of Bielefeld; German Ministry for Education and Research (proj. nr.: 01KI20271 and others) and the Medical Biodefense Research Program of the Bundeswehr Medical Service. Roche Diagnostics provided kits and machines for analyses at discounted rates. The project is funded also by the European-wide Consortium ORCHESTRA. The ORCHESTRA project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 101016167. The views expressed in this publication are the sole responsibility of the author, and the Commission is not responsible for any use that may be made of the information it contains.IMPORTANCESARS-CoV-2 has been spreading globally as a pandemic since 2020. To determine the prevalence of SARS-CoV-2 antibodies among populations, the most effective public health tool is measuring specific anti-SARS-CoV-2 antibodies induced by infection or vaccination. However, conducting large-scale studies that involve venous-blood sampling is challenging due to the associated feasibility and cost issues. A more cost-efficient and less invasive method for SARS-CoV-2 serological testing is using Dried-Blood-Spots on filter cards (DBS). In this paper, we have developed a semi-automated protocol for quantifying SARS-CoV-2 anti-spike antibodies from self-collected DBS. Our laboratory has previously successfully used DBS sampling for anti-nucleocapsid antibody surveys. Likewise, conducting high-throughput DBS serology for anti-spike antibodies is feasible as an additional test that can be performed using the same sample preparation as the anti-nucleocapsid analysis. The quantitative measurements obtained are accurate enough to track the dynamics of antibody levels in populations, even after vaccination campaigns.

Studying temporal titre evolution of commercial SARS-CoV-2 assays reveals significant shortcomings of using BAU standardization for comparison.

BACKGROUND: Measuring specific anti-SARS-CoV-2 antibodies has become one of the main epidemiological tools to survey the ongoing SARS-CoV-2 pandemic, but also vaccination response. The WHO made available a set of well-characterized samples derived from recovered individuals to allow normalization between different quantitative anti-Spike assays to defined Binding Antibody Units (BAU). METHODS: To assess sero-responses longitudinally, a cohort of ninety-nine SARS-CoV-2 RT-PCR positive subjects was followed up together with forty-five vaccinees without previous infection but with two vaccinations. Sero-responses were evaluated using a total of six different assays: four measuring anti-Spike proteins (converted to BAU), one measuring anti-Nucleocapsid proteins and one SARS-CoV-2 surrogate virus neutralization. Both cohorts were evaluated using the Euroimmun Anti-SARS-CoV-2-ELISA anti-S1 IgG and the Roche Elecsys Anti-SARS-CoV-2 anti-S1 assay. RESULTS: In SARS-CoV-2-convalesce subjects, the BAU-sero-responses of Euroimmun Anti-SARS-CoV-2-ELISA anti-S1 IgG and Roche Elecsys Anti-SARS-CoV-2 anti-S1 peaked both at 47 (43-51) days, the first assay followed by a slow decay thereafter (> 208 days), while the second assay not presenting any decay within one year. Both assay values in BAUs are only equivalent a few months after infection, elsewhere correction factors up to 10 are necessary. In contrast, in infection-naive vaccinees the assays perform similarly. CONCLUSION: The results of our study suggest that the establishment of a protective correlate or vaccination booster recommendation based on different assays, although BAU-standardised, is still challenging. At the moment the characteristics of the available assays used are not related, and the BAU-standardisation is unable to correct for that.

Temperature Stable Ion Exchange Resins as Catalysts for the Manufacturing of Vitamin Precursors by Aldol Reaction.

This study explores the potential of robust, strongly basic type I ion exchange resins-specifically, Amberlyst® A26 OH and Lewatit® K 6465-as catalysts for the aldol condensation of citral and acetone, yielding pseudoionone. Emphasis is placed on their long-term stability and commendable performance in continuous operational settings. The aldol reaction, which traditionally is carried out using aqueous sodium hydroxide as the catalyst, holds the potential for enhanced sustainability and reduced waste production through the use of basic ion exchange resins in heterogeneous catalysis. Density Functional Theory (DFT) calculations are employed to investigate catalyst deactivation mechanisms. The result of these calculations indicates that the active sites of Amberlyst® A26 OH are cleaved more easily than the active sites of Lewatit® K 6465. However, the experimental data show a gradual decline in catalytic activity for both resins. Batch experiments reveal Amberlyst® A26 OH's active sites diminishing, while Lewatit® K 6465 maintains relative consistency. This points to distinct deactivation processes for each catalyst. The constant count of basic sites in Lewatit® K 6465 during the reaction suggests additional factors due to its unique polymer structure. This intriguing observation also highlights an exceptional temperature stability for Lewatit® K 6465 compared to Amberlyst® A26 OH, effectively surmounting one of the prominent challenges associated with the utilization of ion exchange resins in catalytic applications.

The representative COVID-19 cohort Munich (KoCo19): from the beginning of the pandemic to the Delta virus variant.

BACKGROUND: Population-based serological studies allow to estimate prevalence of SARS-CoV-2 infections despite a substantial number of mild or asymptomatic disease courses. This became even more relevant for decision making after vaccination started. The KoCo19 cohort tracks the pandemic progress in the Munich general population for over two years, setting it apart in Europe. METHODS: Recruitment occurred during the initial pandemic wave, including 5313 participants above 13 years from private households in Munich. Four follow-ups were held at crucial times of the pandemic, with response rates of at least 70%. Participants filled questionnaires on socio-demographics and potential risk factors of infection. From Follow-up 2, information on SARS-CoV-2 vaccination was added. SARS-CoV-2 antibody status was measured using the Roche Elecsys® Anti-SARS-CoV-2 anti-N assay (indicating previous infection) and the Roche Elecsys® Anti-SARS-CoV-2 anti-S assay (indicating previous infection and/or vaccination). This allowed us to distinguish between sources of acquired antibodies. RESULTS: The SARS-CoV-2 estimated cumulative sero-prevalence increased from 1.6% (1.1-2.1%) in May 2020 to 14.5% (12.7-16.2%) in November 2021. Underreporting with respect to official numbers fluctuated with testing policies and capacities, becoming a factor of more than two during the second half of 2021. Simultaneously, the vaccination campaign against the SARS-CoV-2 virus increased the percentage of the Munich population having antibodies, with 86.8% (85.5-87.9%) having developed anti-S and/or anti-N in November 2021. Incidence rates for infections after (BTI) and without previous vaccination (INS) differed (ratio INS/BTI of 2.1, 0.7-3.6). However, the prevalence of infections was higher in the non-vaccinated population than in the vaccinated one. Considering the whole follow-up time, being born outside Germany, working in a high-risk job and living area per inhabitant were identified as risk factors for infection, while other socio-demographic and health-related variables were not. Although we obtained significant within-household clustering of SARS-CoV-2 cases, no further geospatial clustering was found. CONCLUSIONS: Vaccination increased the coverage of the Munich population presenting SARS-CoV-2 antibodies, but breakthrough infections contribute to community spread. As underreporting stays relevant over time, infections can go undetected, so non-pharmaceutical measures are crucial, particularly for highly contagious strains like Omicron.

The Prospective COVID-19 Post-Immunization Serological Cohort in Munich (KoCo-Impf): Risk Factors and Determinants of Immune Response in Healthcare Workers.

Antibody studies analyze immune responses to SARS-CoV-2 vaccination and infection, which is crucial for selecting vaccination strategies. In the KoCo-Impf study, conducted between 16 June and 16 December 2021, 6088 participants aged 18 and above from Munich were recruited to monitor antibodies, particularly in healthcare workers (HCWs) at higher risk of infection. Roche Elecsys® Anti-SARS-CoV-2 assays on dried blood spots were used to detect prior infections (anti-Nucleocapsid antibodies) and to indicate combinations of vaccinations/infections (anti-Spike antibodies). The anti-Spike seroprevalence was 94.7%, whereas, for anti-Nucleocapsid, it was only 6.9%. HCW status and contact with SARS-CoV-2-positive individuals were identified as infection risk factors, while vaccination and current smoking were associated with reduced risk. Older age correlated with higher anti-Nucleocapsid antibody levels, while vaccination and current smoking decreased the response. Vaccination alone or combined with infection led to higher anti-Spike antibody levels. Increasing time since the second vaccination, advancing age, and current smoking reduced the anti-Spike response. The cumulative number of cases in Munich affected the anti-Spike response over time but had no impact on anti-Nucleocapsid antibody development/seropositivity. Due to the significantly higher infection risk faced by HCWs and the limited number of significant risk factors, it is suggested that all HCWs require protection regardless of individual traits.

Nutrition in City Ecosystems (NICE): Protocol of a multi-sectoral development project to improve food and nutrition security of secondary city populations in Bangladesh, Kenya and Rwanda.

Background: Secondary cities tend to be better linked with local food systems than primate cities, acting as important platforms to trade agricultural produce with rural surrounding. COVID-19, conflicts and climate change continue to expose inefficiencies in food systems and have further exacerbated malnutrition, calling for substantial food systems transformations. However, tackling current food systems' challenges requires new approaches to ensure food and nutrition security. Nutritious and agroecologically produced food offer the potential to transform food systems by improving diets and alleviating pressure on the environment, as well as by creating jobs and reducing poverty. This paper describes the design of a project by a Swiss public-private consortium to improve food and nutrition security and to reduce poverty in city ecosystems in six secondary cities in Bangladesh, Kenya and Rwanda through governance/policy and supply and demand side interventions. Methods: The Nutrition in City Ecosystems (NICE) project promotes well-balanced nutrition for city populations through interdisciplinary agricultural, food, and health sector collaborations along city-specific value chains. Adopting a transdiciplinary systems approach, the main interventions of NICE are (i) advocacy and policy dialogue, (ii) building of decentralized institutional capacity in multi-sectoral collaborations, (iii) support of data-driven planning, coordination and resource mobilization, (iv) anchoring of innovations and new approaches in city-level partnerships, (v) capacity building in the agricultural, retail, health and education sectors, as well as (vi) evidence generation from putting policies into practice at the local level. NICE is coordinated by in-country partners and local offices of the Swiss public-private consortium partners. Discussion: The NICE project seeks to contribute to urban food system resilience and enhanced sustainable nutrition for city populations by (A) strengthening urban governance structures involving key stakeholders including women and youth, (B) generating income for producers along the supply chain, (C) triggering change in producers' and consumers' behavior such that nutritious and agroecologically produced foods are both in demand as well as available and affordable in urban markets, and (D) allowing a scale up of successful approaches to other national and international cities and city networks.

Coronary Artery Disease Detected by Low Frequency Heart Sounds.

OBJECTIVES: Previous studies have observed an increase in low frequency diastolic heart sounds in patients with coronary artery disease (CAD). The aim was to develop and validate a diagnostic, computerized acoustic CAD-score based on heart sounds for the non-invasive detection of CAD. METHODS: Prospective study enrolling 463 patients referred for elective coronary angiography. Pre-procedure non-invasive recordings of heart sounds were obtained using a novel acoustic sensor. A CAD-score was defined as the power ratio between the 10-90 Hz frequency spectrum and the 90-300 Hz frequency spectrum of the mid-diastolic heart sound. Quantitative coronary angiography analysis was performed by a blinded core laboratory and patients grouped according to the results: obstructive CAD defined by the presence of at least one ≥ 50% stenosis, non-obstructive CAD as patients with a maximal stenosis in the 25-50% interval and non-CAD as no coronary lesions exceeding 25%. We excluded patients with potential confounders or incomplete data (n = 245). To avoid over-fitting the final cohort of 218 patients was randomly divided into to a training group for development (n = 127) and a validation group (n = 91). RESULTS: In both the training and the validation group the CAD-score was significantly increased in CAD patients compared to non-CAD patients (p < 0.0001). In the validation group the area under the receiver-operating curve was 77% (95% CI 63-91%). Sensitivity was 71% (95% CI 59-82%) and specificity 64% (95% CI 45-83%). CONCLUSION: The acoustic CAD-score is a new, inexpensive, non-invasive method to detect CAD, which may supplement clinical risk stratification and reduce the need for subsequent non-invasive and invasive testing.

Nutrition as a driver and outcome of agroecology.

The principles of agroecology do not explicitly state a link with nutrition. Yet, we argue that among them, input reduction, biodiversity, economic diversification, social values and diets, fairness, connectivity and participation are directly linked to nutrition. Nutrition can serve as a critical outcome and driver of agroecological practices and can drive transformative change across the food system.

From first to second wave: follow-up of the prospective COVID-19 cohort (KoCo19) in Munich (Germany).

BACKGROUND: In the 2nd year of the COVID-19 pandemic, knowledge about the dynamics of the infection in the general population is still limited. Such information is essential for health planners, as many of those infected show no or only mild symptoms and thus, escape the surveillance system. We therefore aimed to describe the course of the pandemic in the Munich general population living in private households from April 2020 to January 2021. METHODS: The KoCo19 baseline study took place from April to June 2020 including 5313 participants (age 14 years and above). From November 2020 to January 2021, we could again measure SARS-CoV-2 antibody status in 4433 of the baseline participants (response 83%). Participants were offered a self-sampling kit to take a capillary blood sample (dry blood spot; DBS). Blood was analysed using the Elecsys® Anti-SARS-CoV-2 assay (Roche). Questionnaire information on socio-demographics and potential risk factors assessed at baseline was available for all participants. In addition, follow-up information on health-risk taking behaviour and number of personal contacts outside the household (N = 2768) as well as leisure time activities (N = 1263) were collected in summer 2020. RESULTS: Weighted and adjusted (for specificity and sensitivity) SARS-CoV-2 sero-prevalence at follow-up was 3.6% (95% CI 2.9-4.3%) as compared to 1.8% (95% CI 1.3-3.4%) at baseline. 91% of those tested positive at baseline were also antibody-positive at follow-up. While sero-prevalence increased from early November 2020 to January 2021, no indication of geospatial clustering across the city of Munich was found, although cases clustered within households. Taking baseline result and time to follow-up into account, men and participants in the age group 20-34 years were at the highest risk of sero-positivity. In the sensitivity analyses, differences in health-risk taking behaviour, number of personal contacts and leisure time activities partly explained these differences. CONCLUSION: The number of citizens in Munich with SARS-CoV-2 antibodies was still below 5% during the 2nd wave of the pandemic. Antibodies remained present in the majority of SARS-CoV-2 sero-positive baseline participants. Besides age and sex, potentially confounded by differences in behaviour, no major risk factors could be identified. Non-pharmaceutical public health measures are thus still important.

Broad T Cell Targeting of Structural Proteins After SARS-CoV-2 Infection: High Throughput Assessment of T Cell Reactivity Using an Automated Interferon Gamma Release Assay.

Background: Adaptive immune responses to structural proteins of the virion play a crucial role in protection against coronavirus disease 2019 (COVID-19). We therefore studied T cell responses against multiple SARS-CoV-2 structural proteins in a large cohort using a simple, fast, and high-throughput approach. Methods: An automated interferon gamma release assay (IGRA) for the Nucleocapsid (NC)-, Membrane (M)-, Spike-C-terminus (SCT)-, and N-terminus-protein (SNT)-specific T cell responses was performed using fresh whole blood from study subjects with convalescent, confirmed COVID-19 (n = 177, more than 200 days post infection), exposed household members (n = 145), and unexposed controls (n = 85). SARS-CoV-2-specific antibodies were assessed using Elecsys® Anti-SARS-CoV-2 (Ro-N-Ig) and Anti-SARS-CoV-2-ELISA (IgG) (EI-S1-IgG). Results: 156 of 177 (88%) previously PCR confirmed cases were still positive by Ro-N-Ig more than 200 days after infection. In T cells, most frequently the M-protein was targeted by 88% seropositive, PCR confirmed cases, followed by SCT (85%), NC (82%), and SNT (73%), whereas each of these antigens was recognized by less than 14% of non-exposed control subjects. Broad targeting of these structural virion proteins was characteristic of convalescent SARS-CoV-2 infection; 68% of all seropositive individuals targeted all four tested antigens. Indeed, anti-NC antibody titer correlated loosely, but significantly with the magnitude and breadth of the SARS-CoV-2-specific T cell response. Age, sex, and body mass index were comparable between the different groups. Conclusion: SARS-CoV-2 seropositivity correlates with broad T cell reactivity of the structural virus proteins at 200 days after infection and beyond. The SARS-CoV-2-IGRA can facilitate large scale determination of SARS-CoV-2-specific T cell responses with high accuracy against multiple targets.

Prevalence and Risk Factors of Infection in the Representative COVID-19 Cohort Munich.

Given the large number of mild or asymptomatic SARS-CoV-2 cases, only population-based studies can provide reliable estimates of the magnitude of the pandemic. We therefore aimed to assess the sero-prevalence of SARS-CoV-2 in the Munich general population after the first wave of the pandemic. For this purpose, we drew a representative sample of 2994 private households and invited household members 14 years and older to complete questionnaires and to provide blood samples. SARS-CoV-2 seropositivity was defined as Roche N pan-Ig ≥ 0.4218. We adjusted the prevalence for the sampling design, sensitivity, and specificity. We investigated risk factors for SARS-CoV-2 seropositivity and geospatial transmission patterns by generalized linear mixed models and permutation tests. Seropositivity for SARS-CoV-2-specific antibodies was 1.82% (95% confidence interval (CI) 1.28-2.37%) as compared to 0.46% PCR-positive cases officially registered in Munich. Loss of the sense of smell or taste was associated with seropositivity (odds ratio (OR) 47.4; 95% CI 7.2-307.0) and infections clustered within households. By this first population-based study on SARS-CoV-2 prevalence in a large German municipality not affected by a superspreading event, we could show that at least one in four cases in private households was reported and known to the health authorities. These results will help authorities to estimate the true burden of disease in the population and to take evidence-based decisions on public health measures.

Children's Attention to Mother and Adolescent Stress Moderate the Attachment-Depressive Symptoms Link.

The breadth of children's attentional field around their mother determines whether securely or insecurely attached children are at risk to develop depressive symptoms when confronted with distress in adolescence. To test this effect longitudinally, we measured children's (M age = 10.93; N = 109) baseline attentional breadth around their mother, attachment status (combining attachment coherence, secure base script knowledge, and self-reported trust), and self-reported depressive symptoms. One and two years later, we measured self-reported distress and depressive symptoms. We tested three-way interactions between attentional breadth × attachment × distress on changes in depressive symptoms. This three-way interaction was marginally significantly linked with changes in depressive symptoms from baseline to year 1, and significantly with changes in depressive symptoms from baseline to year 2. Results pointed to the protective role of a narrow attentional field around the mother in middle childhood for securely attached children who are confronted with distress later in life.

Combining oxytocin and cognitive bias modification training in a randomized controlled trial: Effects on trust in maternal support.

BACKGROUND AND OBJECTIVES: Research on the social effects of intranasal oxytocin in children is scarce. Oxytocin has been proposed to have clearer beneficial effects when added to social learning paradigms. The current study tested this proposition in middle childhood by assessing effects of cognitive bias modification (CBM) training and oxytocin on trust in maternal support. METHODS: Children (N = 100, 8-12 years) were randomly assigned to one of two training conditions: CBM training aimed at increasing trust or neutral placebo training. Within each training condition, half the participants received oxytocin and half a placebo. Main and interaction effects were assessed on measures of trust-related interpretation bias and trust. We explored whether child characteristics moderated intervention effects. RESULTS: Children in the CBM training were faster to interpret maternal behaviour securely versus insecurely. Effects did not generalize to interpretation bias measures or trust. There were no main or interaction effects of oxytocin. Exploratory moderation analyses indicated that combining CBM training with oxytocin had less positive effects on trust for children with more internalizing problems. LIMITATIONS: As this was the first study combining CBM and oxytocin, replication of the results is needed. CONCLUSIONS: This study combined a social learning paradigm with oxytocin in children. CBM training was effective at an automatic level of processing. Oxytocin did not enhance CBM effects or independently exert effects. Research in larger samples specifying when oxytocin might have beneficial effects is necessary before oxytocin can be used as intervention option in children.

Trust development as an expectancy-learning process: Testing contingency effects.

Trust in parental support and subsequent support seeking behavior, a hallmark of secure attachment, result from experiences with sensitive parents during distress. However, the underlying developmental mechanism remains unclear. We tested the hypothesis that trust is the result of an expectancy-learning process condtional upon contingency (the probability that caregiver support has a positive outcome). We developed a new paradigm in which a novel caregiver provides help to solve a problem. Contingency of the caregiver's support was manipulated and participants' trust in the caregiver and their help seeking behavior was measured in three independent samples. The hypothesis was supported suggesting that trust and support seeking result from an expectancy-learning process. These findings' potential contribution to attachment theory is discussed.

A Further Validation of the Cognitive Bias Modification Effect on Trust in Middle Childhood.

Recent middle childhood research suggests that children's trust in maternal support can be manipulated using Cognitive Bias Modification (CBM) aimed at changing children's interpretation of ambiguous maternal support-related behavior. The current study with 60 children (40 girls, Mage = 10.62, SDage = 1.20) aimed to replicate previous research and to test whether the CBM effect is specific to trust or generalizes to other child evaluations of maternal behavior. More specifically, CBM effects on children's evaluation of parenting behavior were tested. Trust and maternal parenting behaviors were assessed using children's self-report. Results largely replicated previous findings, including the positive effect of CBM on children's trust in maternal support. Suggesting that this effect was specific for trust, the CBM manipulation did not affect children's appraisal of maternal parenting behavior. This finding supports the validity of CBM effects.

Stability and change in secure base script knowledge during middle childhood and early adolescence: A 3-year longitudinal study.

There is limited research examining stability and change in attachment security in middle childhood. The current study addresses this gap using data from a 3-year longitudinal study. Specifically, we examined stability and change in secure base script knowledge during middle childhood using a sample of 157 children (Wave 1 mean age [Mage] = 10.91, standard deviation [SD] = 0.87) assessed at 1-year intervals across 4 waves. Secure base script knowledge was moderately stable over time, as script scores were significantly correlated between each wave. We also investigated the impact of life stress on change in secure base script knowledge within individuals across waves. The results demonstrated that daily hassles (minor and frequently occurring stressful life events) but not major (more severe and infrequent) stressful life events predicted change in script knowledge. Implications for attachment-based interventions and, more broadly, the stability of attachment security are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Peripheral resolution and contrast sensitivity: effects of monochromatic and chromatic aberrations.

Correction and manipulation of peripheral refractive errors are indispensable for people with central vision loss and in optical interventions for myopia control. This study investigates further enhancements of peripheral vision by compensating for monochromatic higher-order aberrations (with an adaptive optics system) and chromatic aberrations (with a narrowband green filter, 550 nm) in the 20° nasal visual field. Both high-contrast detection cutoff and contrast sensitivity improved with optical correction. This improvement was most evident for gratings oriented perpendicular to the meridian due to asymmetric optical errors. When the natural monochromatic higher-order aberrations are large, resolution of 10% contrast oblique gratings can also be improved with correction of these errors. Though peripheral vision is mainly limited by refractive errors and neural factors, higher-order aberration correction beyond conventional refractive errors can still improve peripheral vision under certain circumstances.

Interpretation bias in middle childhood attachment: Causal effects on attachment memories and scripts.

Attachment theory implies the causal influence of interpretation bias on the attachment-related expectations. Previous research demonstrated that training children to interpret maternal behavior as more supportive increased their trust in maternal support. The current study explored possible training effects on two attachment script-related processes: recollection of attachment-related memories and secure base script knowledge. Children (9-12 years old; N = 84) were assigned to either a secure training condition, training children to interpret mother's behavior as supportive, or a neutral placebo condition, where interpretations about maternal behavior were unrelated to support. Findings replicated the training effect on interpretation bias and trust. Furthermore, children's recollection of attachment-related memories became more positive. No training effect was found for secure base script knowledge.

The effects of Cognitive Bias Modification training and oxytocin administration on trust in maternal support: study protocol for a randomized controlled trial.

BACKGROUND: Lack of trust in parental support is a transdiagnostic risk factor for the development of psychological problems throughout the lifespan. Research suggests that children's cognitive attachment representations and related information processing biases could be an important target for interventions aiming to build trust in the parent-child relationship. A paradigm that can alter these biases and increase trust is that of Cognitive Bias Modification (CBM), during which a target processing bias is systematically trained. Trust-related CBM training effects could possibly be enhanced by oxytocin, a neuropeptide that has been proposed to play an important role in social information processing and social relationships. The present article describes the study protocol for a double-blind randomized controlled trial (RCT) aimed at testing the individual and combined effects of CBM training and oxytocin administration on trust in maternal support. METHODS/DESIGN: One hundred children (aged 8-12 years) are randomly assigned to one of four intervention conditions. Participants inhale a nasal spray that either contains oxytocin (OT) or a placebo. Additionally, they receive either a CBM training aimed at positively modifying trust-related information processing bias or a neutral placebo training aimed to have no trust-related effects. Main and interaction effects of the interventions are assessed on three levels of trust-related outcome measures: trust-related interpretation bias; self-reported trust; and mother-child interactional behavior. Importantly, side-effects of a single administration of OT in middle childhood are monitored closely to provide further information on the safety of OT administration in this age group. DISCUSSION: The present RCT is the first study to combine CBM training with oxytocin to test for individual and combined effects on trust in mother. If effective, CBM training and oxytocin could be easily applicable and nonintrusive additions to interventions that target trust in the context of the parent-child relationship. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02737254 . Registered on 23 March 2016.

Exploring the Causal Effect of Interpretation Bias on Attachment Expectations.

Attachment theory implies that children's inclination to interpret attachment figures behavior as supportive and available causally influences children's trust in their attachment figure's availability. An experiment was conducted to test whether training children (8-12 years old) to interpret ambiguous interactions with their mothers in a more secure way increases their trust in their mother's availability. Participants (N = 49) were randomly assigned to either a secure condition to train children to interpret their mother's behavior as supportive or a neutral placebo condition, where interpretations were unrelated to maternal support. Results supported the hypothesis: After the secure training, children interpreted maternal behavior more securely and trusted more in her availability. This suggests that attachment-related processing biases causally affect attachment expectations.