Brain Potentials Highlight Stronger Implicit Food Memory for Taste than Health and Context Associations

Increasingly consumption of healthy foods is advised to improve population health. Reasons people give for choosing one food over another suggest that non-sensory features like health aspects are appreciated as of lower importance than taste. However, many food choices are made in the absence of the actual perception of a food's sensory properties, and therefore highly rely on previous experiences of similar consumptions stored in memory. In this study we assessed the differential strength of food associations implicitly stored in memory, using an associative priming paradigm. Participants (N = 30) were exposed to a forced-choice picture-categorization task, in which the food or non-food target images were primed with either non-sensory or sensory related words. We observed a smaller N400 amplitude at the parietal electrodes when categorizing food as compared to non-food images. While this effect was enhanced by the presentation of a food-related word prime during food trials, the primes had no effect in the non-food trials. More specifically, we found that sensory associations are stronger implicitly represented in memory as compared to non-sensory associations. Thus, this study highlights the neuronal mechanisms underlying previous observations that sensory associations are important features of food memory, and therefore a primary motive in food choice.</p

‘Multi-Epitope-Targeted’ Immune-Specific Therapy for a Multiple Sclerosis-Like Disease via Engineered Multi-Epitope Protein Is Superior to Peptides

Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS) yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and “epitope spread”, have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such “multi-epitope-targeting” approach in murine experimental autoimmune encephalomyelitis (EAE) associated with a single (“classical”) or multiple (“complex”) anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc) encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as “multi-epitope-targeting” agents. Y-MSPc was superior to peptide(s) in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells). Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of “classical” or “complex EAE” or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a “multi-epitope-targeting” strategy is required for effective immune-specific therapy of organ-specific autoimmune diseases associated with complex and dynamic pathogenic autoimmunity, such as MS; our data further demonstrate that the “multi-epitope-targeting” approach to therapy is optimized through specifically designed multi-epitope-proteins, rather than myelin peptide cocktails, as “multi-epitope-targeting” agents. Such artificial multi-epitope proteins can be tailored to other organ-specific autoimmune diseases

Making new genetic diagnoses with old data:iterative reanalysis and reporting from genome-wide data in 1,133 families with developmental disorders

Purpose Given the rapid pace of discovery in rare disease genomics, it is likely that improvements in diagnostic yield can be made by systematically reanalyzing previously generated genomic sequence data in light of new knowledge. Methods We tested this hypothesis in the United Kingdom–wide Deciphering Developmental Disorders study, where in 2014 we reported a diagnostic yield of 27% through whole-exome sequencing of 1,133 children with severe developmental disorders and their parents. We reanalyzed existing data using improved variant calling methodologies, novel variant detection algorithms, updated variant annotation, evidence-based filtering strategies, and newly discovered disease-associated genes. Results We are now able to diagnose an additional 182 individuals, taking our overall diagnostic yield to 454/1,133 (40%), and another 43 (4%) have a finding of uncertain clinical significance. The majority of these new diagnoses are due to novel developmental disorder–associated genes discovered since our original publication. Conclusion This study highlights the importance of coupling large-scale research with clinical practice, and of discussing the possibility of iterative reanalysis and recontact with patients and health professionals at an early stage. We estimate that implementing parent–offspring whole-exome sequencing as a first-line diagnostic test for developmental disorders would diagnose >50% of patients.</p

Self-authorship and creative industries workers’ career decision-making

Career decision-making is arguably at its most complex within professions where work is precarious and career calling is strong. This article reports from a study that examined the career decision-making of creative industries workers, for whom career decisions can impact psychological well-being and identity just as much as they impact individuals’ work and career. The respondents were 693 creative industries workers who used a largely open-ended survey to create in-depth reflections on formative moments and career decision-making. Analysis involved the theoretical model of self-authorship, which provides a way of understanding how people employ their sense of self to make meaning of their experiences. The self-authorship process emerged as a complex, non-linear and consistent feature of career decision-making. Theoretical contributions include a non-linear view of self-authorship that exposes the authorship of visible and covert multiple selves prompted by both proactive and reactive identity work

Identical twins carry a persistent epigenetic signature of early genome programming

The mechanisms underlying how monozygotic (or identical) twins arise are yet to be determined. Here, the authors investigate this in an epigenome-wide association study, showing that monozygotic twinning has a characteristic DNA methylation signature in adult somatic tissues.Monozygotic (MZ) twins and higher-order multiples arise when a zygote splits during pre-implantation stages of development. The mechanisms underpinning this event have remained a mystery. Because MZ twinning rarely runs in families, the leading hypothesis is that it occurs at random. Here, we show that MZ twinning is strongly associated with a stable DNA methylation signature in adult somatic tissues. This signature spans regions near telomeres and centromeres, Polycomb-repressed regions and heterochromatin, genes involved in cell-adhesion, WNT signaling, cell fate, and putative human metastable epialleles. Our study also demonstrates a never-anticipated corollary: because identical twins keep a lifelong molecular signature, we can retrospectively diagnose if a person was conceived as monozygotic twin.Molecular Epidemiolog

A DNA methylation biomarker of alcohol consumption.

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10-7. In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.Medical Research Council (Grant IDs: MC_UU_12015/1, MC_UU_12015/2), Wellcome Trust. Detailed acknowledgements are included in the Supplementary Information that accompanies the paper on the Molecular Psychiatry website

Boost Camp’, a universal school-based transdiagnostic prevention program targeting adolescent emotion regulation; evaluating the effectiveness by a clustered RCT : a protocol paper

Abstract Background The transition from childhood into adolescence can be considered as a critical developmental period. Moreover, adolescence is associated with a decreased use of adaptive emotion regulation strategies and an increased use of maladaptive emotion regulation strategies increasing the risk of emotional problems. Targeting emotion regulation is therefore seen as an innovative prevention approach. The present study aims to evaluate the effectiveness of Boost camp, an innovative school-based prevention program targeting ER, on adolescents’ emotion regulation skills and emotional wellbeing. Also secondary outcomes and possible moderators will be included. Methods The aim is to reach 300 adolescents (16 class groups, 6 schools) in their first year of high school. A clustered Randomized Controlled Trial (RCT) with two conditions, intervention (n = 150) and control (n = 150), will be set up. Adolescents in the intervention condition will receive 14 lessons over the course of 2 days, followed by Booster sessions, and will be compared with adolescents in a non-intervention control group. The outcomes will be measured by self-report questionnaires at baseline, immediately after Boost camp, and at three and 6 months follow-up. Discussion Data-collection is planned to be completed in May 2018. Data-analyses will be finished the end of 2018. The presented paper describes the Boost camp program and the clustered RCT design to evaluate its effectiveness. It is expected that Boost camp will have beneficial effects. If found effective, Boost camp will have the potential to increase adolescent’s ER and well-being, and reduce the risk to become adults in need. The trials is registered on the 13th of June 2017 in ISRCTN registry [ISRCTN68235634]

Genome-wide DNA methylation profiling in whole blood reveals epigenetic signatures associated with migraine

Abstract Background Migraine is a common heritable neurovascular disorder typically characterised by episodic attacks of severe pulsating headache and nausea, often accompanied by visual, auditory or other sensory symptoms. Although genome-wide association studies have identified over 40 single nucleotide polymorphisms associated with migraine, there remains uncertainty about the casual genes involved in disease pathogenesis and how their function is regulated. Results We performed an epigenome-wide association study, quantifying genome-wide patterns of DNA methylation in 67 migraine cases and 67 controls with a matching age and sex distribution. Association analyses between migraine and methylation probe expression, after adjustment for cell type proportions, indicated an excess of small P values, but there was no significant single-probe association after correction for multiple testing (P < 1.09 × 10− 7). However, utilising a 1 kb sliding window approach to combine adjacent migraine-methylation association P values, we identified 62 independent differentially methylated regions (DMRs) underlying migraine (false discovery rate < 0.05). Migraine association signals were subtle but consistent in effect direction across the length of each DMR. Subsequent analyses showed that the migraine-associated DMRs were enriched in regulatory elements of the genome and were in close proximity to genes involved in solute transportation and haemostasis. Conclusions This study represents the first genome-wide analysis of DNA methylation in migraine. We have identified DNA methylation in the whole blood of subjects associated with migraine, highlighting novel loci that provide insight into the biological pathways and mechanisms underlying migraine pathogenesis