Search

Atomic force microscopy, AFM, is a powerful tool that can produce detailed topographical images of individual nano-structures with a high signal-to-noise ratio without the need for ensemble averaging. However, the application of AFM in structural biology has been hampered by the tip-sample convolution effect, which distorts images of nano-structures, particularly those that are of similar dimensions to the cantilever probe tips used in AFM. Here we show that the tip-sample convolution results in a feature-dependent and non-uniform distribution of image resolution on AFM topographs. We show how this effect can be utilised in structural studies of nano-sized upward convex objects such as spherical or filamentous molecular assemblies deposited on a flat surface, because it causes ‘magnification’ of such objects in AFM topographs. Subsequently, this enhancement effect is harnessed through contact-point based deconvolution of AFM topographs. Here, the application of this approach is demonstrated through the 3D reconstruction of the surface envelope of individual helical amyloid filaments without the need of cross-particle averaging using the contact-deconvoluted AFM topographs. Resolving the structural variations of individual macromolecular assemblies within inherently heterogeneous populations is paramount for mechanistic understanding of many biological phenomena such as amyloid toxicity and prion strains. The approach presented here will also facilitate the use of AFM for high-resolution structural studies and integrative structural biology analysis of single molecular assemblies.

Research into the effects of calorie restriction continues to intrigue those interested in whether it may allow humans to live longer and healthier lives. Animal studies of continuous calorie restriction (CCR) and fasting have demonstrated substantial advantages to health and longevity. However, concerns remain about the impact of restricting calorie intake on human health and cognition. Given the emerging evidence of cognitive impairments in eating disorders, studies investigating restricted calorie intake in healthy humans (in an ethical way) may also have implications for understanding restrictive eating disorders. In this review, the published literature on the impact of CCR and fasting on cognitive function in healthy human participants is synthesized. Of the 33 studies of CCR and fasting in humans identified, 23 demonstrated significant changes in cognition. Despite variation across the cognitive domains, results suggest CCR benefits inhibition, processing speed, and working memory, but may lead to impairments in cognitive flexibility. The results of fasting studies suggest fasting is associated with impairments in cognitive flexibility and psychomotor abilities. Overall, the results of these studies suggest the degree (ie, the severity) of calorie restriction is what most likely predicts cognitive improvements as opposed to impairments. For individuals engaging in sustained restriction, this may have serious, irreversible consequences. However, there are mixed findings regarding the impact of CCR and fasting on this aspect of human functioning, suggesting further research is required to understand the costs and benefits of different types of calorie restriction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Background: Many individuals perceive Anorexia Nervosa (AN) as a part of their personal identity. Externalisation of the problem is a practice that is often taken up within NICE recommended treatments for AN. Dominant understandings of externalisation are that this practice involves making the "problem" a separate entity, external to the individual. It is an attitude taken by the client and family, stimulated by the therapist to build engagement with treatment and supportive relationships around the individual. However, there is a paucity of research exploring the therapeutic effects of this approach. This research aims to address this gap by exploring the role of externalisation in treatment for AN to elicit an understanding of how this practice is experienced including how it can help and hinder recovery., Methods: Thirteen adults with a current and/or past diagnosis of AN participated in semi-structured interviews. This qualitative study used a reflexive thematic analysis., Analysis: Participants described their experience of externalisation as a journey which is depicted by four main themes. 'Separating the AN from the self' reflects the tensions inherent in learning to distinguish between one's perceived sense of "self" and "the AN". 'Making sense of the AN' describes the experience of language forms used to separate the AN from the individual's identity. 'Feeling seen, or unseen as a person beyond the AN' illustrates the helpful and harmful effects of externalising practices on relationships. 'Navigating a complex relationship with the AN' depicts the effects of one-, versus two-way externalisation on the individual's relationship to AN., Conclusions: The notion of separating one's internal dialogue from one's concept of self may initially be rejected by the individual experiencing AN. However, as the individual develops trust in the therapist and becomes socialised to common forms of externalising language, they may begin to realise two sides within them, a perceived "healthy self" and "the anorexia voice". However, social-cultural discourses around eating contribute to ambiguity during the differentiation between these two voices, thus elucidating the effects of an absence of problem deconstruction alongside externalisation within ED-focussed treatments. Externalising practices were most helpful when led by the individual using their own experience-near language and least helpful when they did not permit the individual to feel seen as a person beyond the AN. Therapists, treatment teams and family members should be cognisant of the emotional effects of language used to externalise AN. Importantly, they should ensure that externalisation is practiced within the spirit of narrative therapy from which it originates., (© 2024. The Author(s).)

Background: Autistic women are at high risk of developing restrictive eating disorders (REDs), such as anorexia nervosa., Aims: This study provides an overview of the clinical characteristics of autistic women with REDs to (i) enhance understanding of increased risk, and (ii) support the identification of autistic women in eating disorder services., Method: We compared self-reported autistic and disordered eating characteristics of: autistic participants with REDs (Autism + REDs; n = 57); autistic participants without REDs (Autism; n = 69); and women with REDs who are not autistic (REDs; n = 80). We also included a group of women with high autistic traits (HATs) and REDs, but no formal autism diagnosis (HATs + REDs; n = 38)., Results: Autism + REDs participants scored similarly to Autism participants in terms of autistic characteristics and to REDs participants in terms of experiencing traditional disordered eating symptoms. Autism + REDs participants were distinguished from both groups by having more restricted and repetitive behaviours and autism-specific eating behaviours related to sensory processing, flexibility and social differences. HATs + REDs participants showed a similar pattern of scores to Autism + REDs participants, and both also presented with high levels of co-occurring mental health difficulties, particularly social anxiety., Conclusion: The presentation of autistic women with REDs is complex, including both traditional disordered eating symptoms and autism-related needs, as well as high levels of co-occurring mental health difficulties. In eating disorder services, the REDs presentation of autistic women and those with HATs should be formulated with reference to autism-specific eating behaviours and co-occurring difficulties. Treatment adaptations should be offered to accommodate autistic characteristics and related needs.

Objective: To synthesise young person and family member perspectives on processes of change in family therapy for anorexia nervosa (AN), including systemic family therapy and manualised family-based treatments, to obtain an understanding of what helps and hinders positive change., Method: A systematic search of the literature was conducted to identify qualitative studies focussing on experiences of therapeutic change within family therapies for AN from the perspectives of young people and their families. Fifteen studies met inclusion criteria and underwent quality appraisal following which they were synthesised using a meta-synthesis approach., Results: Six overarching themes were generated: "A holistic focus on the young person's overall development"; "The therapeutic relationship as a vehicle for change"; "The therapist's confinement to a script and its impact on emotional attunement"; "A disempowering therapeutic context"; "Externalisation of the eating disorder (ED)"; and "The importance of family involvement". Positive change was helped by understanding and support given to the young person's overall development including their psychological, emotional, social and physical wellbeing, positive therapeutic relationships, relational containment within the family system and externalising conversations in which young people felt seen and heard. Positive change was hindered by inflexibility in the treatment approach, counter-effects of externalisation, negative experiences of the therapist, a narrow focus on food-intake and weight, as well as the neglect of family difficulties, emotional experiences, and psychological factors., Conclusions: Positive change regarding the young person's eating-related difficulties ensued in the context of positive relational changes between the young person, their family members, the therapist and treatment team, highlighting the significance of secure and trusting relationships. The findings of this review can be utilised by ED services to consider how they may adapt to the needs of young people and their families in order to improve treatment satisfaction, treatment outcomes, and in turn reduce risk for chronicity in AN., (© 2024. The Author(s).)

Coronavirus disease 2019 (COVID-19) was initially considered a primarily respiratory disease but is now known to affect other organs including the heart and brain. A major route by which COVID-19 impacts different organs is via the vascular system. We studied the impact of apolipoprotein E (APOE) genotype and inflammation on vascular infectivity by pseudo-typed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses in mouse and human cultured endothelial cells and pericytes. Possessing the APOE4 allele or having existing systemic inflammation is known to enhance the severity of COVID-19. Using targeted replacement human APOE3 and APOE4 mice and inflammation induced by bacterial lipopolysaccharide (LPS), we investigated infection by SARS-CoV-2. Here, we show that infectivity was higher in murine cerebrovascular pericytes compared to endothelial cells and higher in cultures expressing APOE4. Furthermore, increasing the inflammatory state of the cells by prior incubation with LPS increased infectivity into human and mouse pericytes and human endothelial cells. Our findings provide insights into the mechanisms underlying severe COVID-19 infection, highlighting how risk factors such as APOE4 genotype and prior inflammation may exacerbate disease severity by augmenting the virus's ability to infect vascular cells.

Background: Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse., Methods: STORY follows 720 young people aged 16-25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings ('Ōura ring') unobtrusively measures individuals' daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months., Discussion: By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families., (© 2024. The Author(s).)

Aims and Method: In response to recommendations for improving the quality and coordination of care delivered by eating disorder services, a whole-team training programme was commissioned by Health Education England in 2020. This paper describes the development and evaluation of the Eating Disorder Services for Adults (EDSA) whole-team training course, delivered to National Health Service adult eating disorder community teams in England. Course participants ( n = 561) in the first two EDSA training cohorts (2021 and 2022) were asked to complete questionnaires at intake and after each session, asking about their views on the training., Results: All course aspects were rated as highly enjoyable, meeting participants' training needs and fostering reflective practice. Thematic analysis identified themes relating to key innovative features of the course and suggestions for improvements., Clinical Implications: Preliminary evaluation suggests that EDSA is valued by clinicians to enhance their knowledge, skills and ability to improve eating disorder patient care.

Objective: There is a lack of reliable and valid parent-report measures assessing eating disorder (ED) pathology in children and adolescents. This study aimed to develop and provide preliminary validation of a new parent-report measure, the 12-item Eating Disorder Examination Questionnaire-Short Parent Version (EDE-QS-P)., Method: The EDE-QS-P was completed by 296 parents seeking treatment for their child at an ED clinic. Children (ages 6-18, N  = 296) completed the Eating Disorder Examination-Questionnaire (EDE-Q), the seven-item Generalized Anxiety Disorder Questionnaire (GAD-7), and the nine-item Patient Health Questionnaire (PHQ-9)., Results: After removing item 10, the 11-item version of the EDE-QS-P showed borderline adequate fit to the one factor solution and strong internal consistency (α = 0.91). This measure also demonstrated strong convergent validity with child scores on the EDE-Q ( r  = .69), and moderate convergent validity with child scores on the GAD-7 ( r  = .37) and PHQ-9 ( r  = .46). The EDE-QS-P was able to differentiate children with EDs characterized by body image disturbances (e.g. anorexia nervosa) from those with avoidant/restrictive food intake disorder, who do not experience shape or weight concerns., Discussion: The 11-item EDE-QS-P may be a promising parent-report measure of ED pathology in children and adolescents.

Anorexia nervosa-focussed family therapy (FT-AN) is the first-line treatment for adolescent anorexia nervosa (AN), but the predictors of poor treatment response are not well understood. The main aim of this study was to investigate the role of attachment and mentalization in predicting treatment outcome. The secondary aims of the study were to investigate therapeutic alliance at 1 month as a predictor of outcome, and to test the associations between alliance and baseline attachment and mentalization. 192 adolescents with AN and their parents were recruited as they began family therapy in out-patient specialist eating disorder services. Self-report measures of attachment, mentalization, and emotion regulation were completed at the start of treatment by adolescent patients and one of their parents. Self-reported alliance scores were collected at one month. Higher scores on the Certainty Scale of the Reflective Functioning Questionnaire, completed by parents, which indicate over-certainty about mental states, were the strongest predictor of poor outcome (Odds Ratio: 0.42, CI: 0.20-0.87). Similarly, for adolescents, higher Lack of Clarity scores on the Difficulties in Emotion Regulation Scale, representing being unclear about one's feelings, were predictive of positive treatment outcome (OR: 1.10, CI: 1.00-1.21). Higher alliance scores at 1 month predicted positive outcome, and were associated with attachment security and mentalization. These novel findings suggest that, particularly in parents, a tendency towards excessive certainty about mental states in others may predict poor outcome in FT-AN. Further research is warranted to replicate the finding and characterise families at risk of poor outcome., (© 2021. The Author(s).)

Objective: This paper outlines the evidence base for early intervention for eating disorders; provides a global overview of how early intervention for eating disorders is provided in different regions and settings; and proposes policy, service, clinician and research recommendations to progress early intervention for eating disorders., Method and Results: Currently, access to eating disorder treatment often takes many years or does not occur at all. This is despite neurobiological, clinical and socioeconomic evidence showing that early intervention may improve outcomes and facilitate full sustained recovery from an eating disorder. There is also considerable variation worldwide in how eating disorder care is provided, with marked inequalities in treatment provision. Despite these barriers, there are existing evidence-based approaches to early intervention for eating disorders and progress is being made in scaling these., Conclusions: We propose action steps for the field that will transform eating disorder service provision and facilitate early detection, treatment and recovery for everyone affected by eating disorders, regardless of age, socioeconomic status and personal characteristics., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Alzheimer's disease is linked to increased levels of amyloid beta (Aβ) in the brain, but the mechanisms underlying neuronal dysfunction and neurodegeneration remain enigmatic. Here, we investigate whether organizational characteristics of functional presynaptic vesicle pools, key determinants of information transmission in the central nervous system, are targets for elevated Aβ. Using an optical readout method in cultured hippocampal neurons, we show that acute Aβ42 treatment significantly enlarges the fraction of functional vesicles at individual terminals. We observe the same effect in a chronically elevated Aβ transgenic model (APPSw,Ind) using an ultrastructure-function approach that provides detailed information on nanoscale vesicle pool positioning. Strikingly, elevated Aβ is correlated with excessive accumulation of recycled vesicles near putative endocytic sites, which is consistent with deficits in vesicle retrieval pathways. Using the glutamate reporter, iGluSnFR, we show that there are parallel functional consequences, where ongoing information signaling capacity is constrained. Treatment with levetiracetam, an antiepileptic that dampens synaptic hyperactivity, partially rescues these transmission defects. Our findings implicate organizational and dynamic features of functional vesicle pools as targets in Aβ-driven synaptic impairment, suggesting that interventions to relieve the overloading of vesicle retrieval pathways might have promising therapeutic value., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Intermittent fasting (IF) has grown in popularity as a weight loss tool, where caloric intake is fully/partially restricted on a recurring basis. This study aimed to assess compliance with IF fast-day calorie restriction and whether 5-2 IF leads to reduced overall energy intake, weight loss and compensatory increased energy intake on non-fast days., Method: Participants completed diet diaries at baseline and 28 days post 5-2 IF in a repeated measures within-subjects design. 5-2 IF required restricted energy intake to 500 kcal/day (women), 650 kcal/day (men) on two 'fast' days/week whilst eating ad-libitum on other days., Results: 52 participants were included (n = 42 female; age 44 ± 11.2yrs). Median weight loss after 28 days 5-2 IF was statistically significant (1.8 [-2 - 7.3 IQR = 2.2]kg; 2.8 [-2.7-11.2 IQR = 2.5]% p < 0.001). There was a significant reduction in total energy intake during 5-2 IF compared with pre-diet (median 1288.0 [IQR 423.8]kcal and median 1751.5 [IQR 505.3]kcal respectively, p < 0.001). Carbohydrate, protein and fat consumption proportionately reduced during 5-2 IF. Participants had significantly higher energy intake (p < 0.001) on non-fast days that followed a fast day (1928.4 ± 711.9 kcal) compared to non-fast days not following a fast day (1316.2 ± 310.0 kcal). 55.8% complied with fast day calorie restrictions., Conclusion: 5-2 IF was associated with significantly reduced energy intake, and weight loss over a 28-day period. Compliance rate was lower than most previous studies. Participants had significantly higher energy intake on non-fast days following fast days suggesting fasting may lead to over-compensation. Further research should investigate strategies to improve compliance and long-term sustainability of IF diets., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The APOE gene encoding the Apolipoprotein E protein is the single most significant genetic risk factor for late-onset Alzheimer's disease. The APOE4 genotype confers a significantly increased risk relative to the other two common genotypes APOE3 and APOE2. Intriguingly, APOE4 has been associated with neuropathological and cognitive deficits in the absence of Alzheimer's disease-related amyloid or tau pathology. Here, we review the extensive literature surrounding the impact of APOE genotype on central nervous system dysfunction, focussing on preclinical model systems and comparison of APOE3 and APOE4, given the low global prevalence of APOE2. A multi-hit hypothesis is proposed to explain how APOE4 shifts cerebral physiology towards pathophysiology through interconnected hits. These hits include the following: neurodegeneration, neurovascular dysfunction, neuroinflammation, oxidative stress, endosomal trafficking impairments, lipid and cellular metabolism disruption, impaired calcium homeostasis and altered transcriptional regulation. The hits, individually and in combination, leave the APOE4 brain in a vulnerable state where further cumulative insults will exacerbate degeneration and lead to cognitive deficits in the absence of Alzheimer's disease pathology and also a state in which such pathology may more easily take hold. We conclude that current evidence supports an APOE4 multi-hit hypothesis, which contributes to an APOE4 pathophysiological state. We highlight key areas where further study is required to elucidate the complex interplay between these individual mechanisms and downstream consequences, helping to frame the current landscape of existing APOE-centric literature., (© 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objective: Qualitative studies report that autistic women have poor experiences when being treated for an eating disorder (ED) and express that ED services are not appropriately tailored to meet their needs. It is unclear whether their experience differs to other women accessing ED services. The aim of the current study was to compare autistic and non-autistic women's ED illness history and experiences in ED services., Method: An online survey about ED illness history and their experience with ED treatment was completed by 46 autistic women with a restrictive ED and 110 non-autistic women with a restrictive ED., Results: Despite some similarities, there were three key differences in the experiences reported by autistic and non-autistic women. First, autistic women reported a longer duration of ED and being diagnosed with an ED at a younger age than non-autistic women. Second, autistic women reported accessing a broader range of healthcare settings and ED treatments than non-autistic women when being treated for an ED. Finally, autistic women rated their experiences of inpatient care, dietetic input, and cognitive behavioural therapy (CBT) as significantly less beneficial than non-autistic women when being treated for an ED., Conclusion: These findings increase understanding of autistic women's ED experience and can help to shape ED services and treatments to better accommodate the needs of their autistic clients., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Objective: Up to 37% of patients with anorexia nervosa score above cut-off on autism screening measures. These individuals typically have poorer outcomes from standard eating disorder interventions and could therefore benefit from adaptations. Accurately identifying these individuals is important for improving autism referral processes and clinical pathway decisions. This study's aim was to identify subscales of questionnaires measuring constructs associated with either autism or eating disorders that, when combined with traditional autism screening measures, would improve the ability to identify women with restrictive eating disorders who might benefit from a full autism assessment., Method: One hundred and sixty women with restrictive eating disorders, with (n = 42) or without (n = 118) an autism diagnosis completed a battery of questionnaires. Using conditional stepwise binary logistic regression, we attempted to improve the autism spectrum quotient 10 item's (AQ-10) ability to discriminate between autistic and non-autistic women in a restrictive eating disorder sample., Results: In a binary logistic regression model, the AQ-10 reliably discriminated between autistic and non-autistic women with an accuracy rate of 85% but had relatively low (69%) sensitivity, reflecting a high rate of false negatives. Adding three subscales to the model (Glasgow Sensory Questionnaire Auditory, Camouflaging Autistic Traits Questionnaire Compensation and Toronto Alexithymia Scale Externally Orientated Thinking) significantly improved its differentiating ability (accuracy = 88%, sensitivity = 76%, specificity = 92%)., Conclusions: We have identified three subscales that, when used in combination with the AQ-10, may help clinicians understand the pattern of autistic traits in their patients with a restrictive eating disorder. This can inform clinical decisions about whether to refer for a full autism assessment and whether to adapt standard eating disorder treatments to accommodate autistic traits. Future studies are needed to test the model in samples where participants have undergone a full autism assessment., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Co-occurring mental health difficulties among autistic adults are common and this association has implications for mental health services. Gaining a comprehensive understanding of autistic adults' experiences of accessing and receiving mental health support is a critical step to fully inform service provision. We conducted a systematic review and meta-synthesis of qualitative studies exploring autistic adults' mental health service experiences, triangulating the perspectives of autistic adults, clinicians and parents. Electronic database searches in MEDLINE, PsycINFO and Embase were conducted up to October 2021. This identified 10,068 studies, of which 38 met study inclusion criteria. Using a thematic synthesis approach, we generated three superordinate analytical themes "Lonely, difficult service experience", "Complexity needs flexibility" and "Collaboration and empowerment", each with several subthemes. Our findings show that currently, mental health services do not adequately support autistic adults, and can even cause additional harm. There is a need for a more flexible, comprehensive and holistic approach, considering how being autistic affects the individual's mental health presentation and tailoring support to their needs. Building trusting relationships, listening to autistic adults, and empowering them to take agency, appear to be fundamental steps towards more successful mental health care provision., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: First Episode Rapid Early Intervention for Eating Disorders (FREED) is a service model and care pathway for emerging adults aged 16 to 25-years with a recent onset eating disorder (ED) of <3 years. A previous single-site study suggests that FREED significantly improves clinical outcomes compared to treatment-as-usual (TAU). The present study (FREED-Up) assessed the scalability of FREED. A multi-centre quasi-experimental pre-post design was used, comparing patient outcomes before and after implementation of FREED in participating services., Methods: FREED patients (n = 278) were consecutive, prospectively ascertained referrals to four specialist ED services in England, assessed at four time points over 12 months on ED symptoms, mood, service utilization and cost. FREED patients were compared to a TAU cohort (n = 224) of similar patients, identified retrospectively from electronic patient records in participating services. All were emerging adults aged 16-25 experiencing a first episode ED of <3 years duration., Results: Overall, FREED patients made significant and rapid clinical improvements over time. 53.2% of FREED patients with anorexia nervosa reached a healthy weight at the 12-month timepoint, compared to only 17.9% of TAU patients (X 2 [1, N = 107] = 10.46, p < .001). Significantly fewer FREED patients required intensive (i.e., in-patient or day-patient) treatment (6.6%) compared to TAU patients (12.4%) across the follow-up period (X 2 [1, N = 40] = 4.36, p = .037). This contributed to a trend in cost savings in FREED compared to TAU (-£4472, p = .06, CI -£9168, £233)., Discussion: FREED is robust and scalable and is associated with substantial improvements in clinical outcomes, reduction in inpatient or day-patient admissions, and cost-savings., (© 2021 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Purpose of Review: The goal of this review was to provide an update on the literature examining how voluntary, temporary abstention from eating impacts cognitive function., Recent Findings: We evaluated peer-reviewed articles published between August 2013 and January 2021 that assessed adults, included a measure of cognitive functioning with neutral stimuli, and compared individuals in a fasted state to individuals in a fed state (either within- or between-subject designs). Nineteen articles (21 studies) met inclusion criteria. Sample sizes, fasting methods, and tasks varied across studies. Review of studies indicated that fasting was associated with deficits in cognitive functioning; few studies indicated a benefit in cognitive functioning following a single voluntary fast. The heterogeneity and rarity of available studies limits the conclusions that can be drawn. Several crucial psychosocial and sociodemographic moderators remain unexplored. Recommendations for future work are discussed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Disordered eating and eating disorders have huge impact on athletic health and performance. Understanding risk factors for disordered eating development is paramount to protecting the health and performance of these athletes. This project tested a model longitudinally to test whether body dissatisfaction (mediated by negative affect) and societal pressures (mediated by internalisation) predicted bulimic symptomatology at 1 year. The study recruited 1017 male and female athletes in a range of sports at three time points over a year. Cross-lag meditation modelling in MPLUS was utilised to test the hypothesised model. Results indicated that societal pressures mediated by general internalisation led to bulimic symptomatology and that gender and sport type do moderate the relationships. However, measurement issues indicate that scales not originally created for athletes may not reliably measure athletes' experience. This research highlights how understanding how to better assess risk factors and disordered eating related concepts in athletes is a key next step. The study is unique in its longitudinal design and in its sampling of a wide range of sports in both male and female athletes., Competing Interests: The authors have declared that no competing interests exist.

Lay Abstract: This study explores autistic women's experiences of eating disorder services. About 20%-30% of people with anorexia nervosa are also autistic, and current treatments seem not to work as well for them. We interviewed 15 autistic women with experience of anorexia nervosa, 12 parents of autistic women with anorexia nervosa, and 11 healthcare professionals working in eating disorder services. We asked autistic women and parents about their experiences of eating disorder services, and we asked healthcare professionals about their experiences treating autistic women with anorexia nervosa. Participants' views were represented by three overall themes: misunderstanding autism and autistic traits, one treatment does not fit all, and improving accessibility and engagement within services. We found that autistic women face many barriers when in treatment for anorexia nervosa, often because of a lack of autism understanding within eating disorder services. Future research should look at developing anorexia nervosa treatments that can specifically help autistic individuals.

Background: The First Episode Rapid Early Intervention for Eating Disorders (FREED) service model is associated with significant reductions in wait times and improved clinical outcomes for emerging adults with recent-onset eating disorders. An understanding of how FREED is implemented is a necessary precondition to enable an attribution of these findings to key components of the model, namely the wait-time targets and care package., Aims: This study evaluated fidelity to the FREED service model during the multicentre FREED-Up study., Method: Participants were 259 emerging adults (aged 16-25 years) with an eating disorder of <3 years duration, offered treatment through the FREED care pathway. Patient journey records documented patient care from screening to end of treatment. Adherence to wait-time targets (engagement call within 48 h, assessment within 2 weeks, treatment within 4 weeks) and care package, and differences in adherence across diagnosis and treatment group were examined., Results: There were significant increases (16-40%) in adherence to the wait-time targets following the introduction of FREED, irrespective of diagnosis. Receiving FREED under optimal conditions also increased adherence to the targets. Care package use differed by component and diagnosis. The most used care package activities were psychoeducation and dietary change. Attention to transitions was less well used., Conclusions: This study provides an indication of adherence levels to key components of the FREED model. These adherence rates can tentatively be considered as clinically meaningful thresholds. Results highlight aspects of the model and its implementation that warrant future examination.

Background: Duration of untreated eating disorder (DUED), that is, the time between illness onset and start of first evidence-based treatment, is a key outcome for early intervention. Internationally, reported DUED ranges from 2.5 to 6 years for different eating disorders (EDs). To shorten DUED, we developed FREED (First Episode Rapid Early Intervention for EDs), a service model and care pathway for emerging adults with EDs. Here, we assess the impact of FREED on DUED in a multi-centre study using a quasi-experimental design., Methods: Two hundred and seventy-eight patients aged 16-25, with first episode illness of less than 3 years duration, were recruited from specialist ED services and offered treatment via FREED. These were compared to 224 patients, of similar age and illness duration, seen previously in participating services (treatment as usual [TAU]) on DUED, waiting times and treatment uptake., Results: FREED patients had significantly shorter DUED and waiting times than TAU patients. On average, DUED was reduced by ∼4 months when systemic delays were minimal. Furthermore, 97.8% of FREED patients took up treatment, versus 75.4% of TAU., Discussion: Findings indicate that FREED significantly improves access to treatment for emerging adults with first episode ED. FREED may reduce distress, prevent deterioration and facilitate recovery., (© 2020 Eating Disorders Association and John Wiley & Sons Ltd.)

Introduction: Athletes are at increased risk of disordered eating compared to non-athletes. Inspired by previous investigation into quantitative work on an etiological model of disordered eating in athletes, the current study aimed to explore a problematic aspect of the model: athletes' lived experiences of social and sport pressures in relation to the onset of disordered eating and differing eating behaviors. Methods: Nine ( N = 9) male and female athletes representing a range of endurance sports took part in semi-structured interviews. Thematic analysis was utilized. Analysis: Analysis revealed two main themes each with two corresponding subthemes (1) Conflating physical appearance and sporting ability with the subthemes of (1a) social comparison in a sporting world and (1b) societal notions of "the athlete body" and (2) Living as an athlete with the corresponding subthemes of (2a) discipline and sacrifice and (2b) the balancing act. Discussion: It is the complex interaction between societal expectations as lived out in social messages and comparisons, and sport pressures that contributes to the development of disordered eating behaviors. These findings suggest that prevention and treatment of disordered eating in athletes can be applied from those already established in non-sporting realm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Stoyel, Delderfield, Shanmuganathan-Felton, Stoyel and Serpell.)

Rationale: Psychotherapies for eating disorders (EDs) are routinely assessed using standardised patient-reported outcome measures (PROMs). PROMs have been criticised for their lack of patient centeredness and clinical utility. The Psychological Outcome Profiles (PSYCHLOPS) is an individualised PROM that allows patients to specify their own outcomes., Aims: (1) To validate the use of the PSYCHLOPS in ED treatment, and (2) to identify patient concerns beyond those measured by common ED PROMs., Methods: Two hundred and seventy-eight emerging adult patients, presenting with a first-episode ED (aged 16-25, illness duration <3 years) completed the PSYCHLOPS and two standardised ED PROMs (the EatingDisorder Examination Questionnaire [EDE-Q] and the Clinical Impairment Assessment Questionnaire [CIA]) at four time points across 12 months. Psychometrics of the PSYCHLOPS were assessed quantitatively against the EDE-Q and CIA. Content analysis assessed unique patient concerns identified by PSYCHLOPS., Results: The PSYCHLOPS had adequate to good psychometric properties. A total of 53.3% of participants reported a concern not addressed by the EDE-Q or the CIA, the most common being depression/anxiety, academic problems, treatment concerns and disturbed sleep., Discussion: PROMs can be complemented by the PSYCHLOPS to identify problems specific to an individual's context. As ED patients are typically ambivalent about change, understanding their concerns is vital in building motivation for change., (© 2021 Eating Disorders Association and John Wiley & Sons Ltd.)

Background: Eating disorders (EDs) typically start during adolescence or emerging adulthood, periods of intense biopsychosocial development. FREED (First Episode Rapid Early Intervention for EDs) is a service model and care pathway providing rapid access to developmentally-informed care for emerging adults with EDs. FREED is associated with reduced duration of untreated eating disorder and improved clinical outcomes, but patients' experiences of treatment have yet to be assessed., Objective: This study aimed to assess emerging adults' experiences of receiving treatment through FREED., Method: This study triangulated qualitative data on participants' experiences of FREED treatment from questionnaires and semi-structured interviews. Participants were 106 emerging adults (aged 16-25; illness duration < 3 yrs) (questionnaire only = 92; interview only = 6; both = 8). Data were analysed thematically., Results: Most participants reported psychological and behavioural changes over the course of treatment (e.g. reduction in symptoms; increased acceptance and understanding of difficulties). Participants identified five beneficial characteristics of FREED treatment: i) rapid access to treatment; ii) knowledgeable and concerned clinicians; iii) focusing on life beyond the eating disorder; iv) building a support network; v) becoming your own therapist., Conclusion: This study provides further supports for the implementation of early intervention and developmentally-informed care for EDs. Future service model development should include efforts to increase early help-seeking.

Autistic women are overrepresented among people in treatment for Anorexia Nervosa (AN). The current study aimed to: (1) better understand how AN develops and persists in autistic individuals from the perspective of autistic women, parents and healthcare professionals; (2) derive a theoretical model of restrictive eating difficulties in autism. We conducted 44 semi-structured interviews and used Thematic Analysis to identify patterns of meaning across the data. Themes related to sensory sensitivities, social interaction and relationships, sense of self and identity, difficulties with emotions, thinking styles, and a need for control and predictability. We developed a model of potential autism-specific mechanisms underlying restrictive eating difficulties. This study generated novel insights, which have the potential to inform treatment adaptations following empirical testing.

This study aimed to systematically appraise cross-sectional research that compared the cognitive performance of individuals in the acute phase of BN and/or AN to HCs on measures of impulsivity and compulsivity. The results of the systematic review showed support for the trans-diagnostic approach to eating disorders. There was no strong evidence to support the characterisation of AN as high in compulsivity (and low in impulsivity), nor to support the characterisation of BN as high in impulsivity (and low in compulsivity). There appeared to be mixed findings for both impulsivity and compulsivity across AN and BN. Results were highly variable due to the heterogeneous tasks used, and lack of replication across studies. There was no consensus amongst the included studies on the most appropriate task and/or outcome measures that should be used to study the constructs of impulsivity and compulsivity., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Previous research has shown that short-term fasting in healthy individuals is associated with changes in risky decision-making. The current experiment was designed to examine the influence of short-term fasting in healthy individuals on four types of impulsivity: reflection impulsivity, risky decision-making, delay aversion, and action inhibition. Participants were tested twice, once when fasted for 20 h, and once when satiated. Participants demonstrated impaired action inhibition when fasted; committing significantly more errors of commission during a food-related Affective Shifting Task. Participants also displayed decreased reflection impulsivity when fasted, opening significantly more boxes during the Information Sampling Task (IST). There were no significant differences in performance between fasted and satiated sessions for risky decision-making or delay aversion. These findings may have implications for understanding eating disorders such as Bulimia Nervosa (BN). Although BN has been characterized as a disorder of poor impulse control, inconsistent findings when comparing individuals with BN and healthy individuals on behavioral measures of impulsivity question this characterization. Since individuals with BN undergo periods of short-term fasting, the inconsistent findings could be due to differences in the levels of satiation of participants. The current results indicate that fasting can selectively influence performance on the IST, a measure of impulsivity previously studied in BN. However, the results from the IST were contrary to the original hypothesis and should be replicated before specific conclusions can be made., (Copyright © 2020 Howard, Roiser, Gilbert, Burgess, Dayan and Serpell.)

Background: Despite their use in clinical practice, there is little evidence to support the use of therapist written goodbye letters as therapeutic tools. However, preliminary evidence suggests that goodbye letters may have benefits in the treatment of anorexia nervosa (AN)., Aims: This study aimed to examine whether therapist written goodbye letters were associated with improvements in body mass index (BMI) and eating disorder symptomology in patients with AN after treatment., Method: Participants were adults with AN (n = 41) who received The Maudsley Model of Anorexia Treatment for Adults (MANTRA) in a clinical trial evaluating two AN out-patient treatments. As part of MANTRA, therapists wrote goodbye letters to patients. A rating scheme was developed to rate letters for structure and quality. Linear regression analyses were used to examine associations between goodbye letter scores and outcomes after treatment., Results: Higher quality letters and letters that adopted a more affirming stance were associated with greater improvements in BMI at 12 months. Neither the overall quality nor the style of goodbye letters were associated with improvements in BMI at 24 months or reductions in eating disorder symptomology at either 12 or 24 months., Conclusions: The results highlight the potential importance of paying attention to the overall quality of therapist written goodbye letters in the treatment of AN, and adopting an affirming stance.

Objectives: This project examined risk factors of disordered eating in athletes by adapting and applying a theoretical model. It tested a previously proposed theoretical model and explored the utility of a newly formed model within an athletic population across gender, age, and sport type to explain disordered eating., Design: The design was cross-sectional and the first phase in a series of longitudinal studies., Methods: 1,017 athletes completed online questionnaires related to social pressures, internalisation, body dissatisfaction, negative affect, restriction, and bulimia. Structural equation modelling was employed to analyse the fit of the measurement and structural models and to do invariance testing., Results: The original theoretical model failed to achieve acceptable goodness of fit (χ2 [70, 1017] = 1043.07; p < .0001. CFI = .55; GFI = .88; NFI = .53; RMSEA = .12 [90% CI = .111-.123]). Removal of non-significant pathways and addition of social media resulted in the model achieving a parsimonious goodness of fit (χ2 [19, 1017] = 77.58; p < .0001. CFI = .96; GFI = .98; NFI = .95; RMSEA = .055 [90% CI = .043-.068]). Invariance tests revealed that the newly revised model differed across gender, age, level, competition status, and length of sport participation., Conclusion: This study showed that the formation of disordered eating symptomology might not be associated with sport pressures experienced by athletes. It revealed that disordered eating development varies across gender, competition level, sport type, and age, which must be considered to prevent and treat disordered eating in athletes., Competing Interests: The authors have declared that no competing interests exist.

Background: The Eating Disorder Examination - Questionnaire Short (EDE-QS) was developed as a 12-item version of the Eating Disorder Examination Questionnaire (EDE-Q) with a 4-point response scale that assesses eating disorder (ED) symptoms over the preceding 7 days. It has demonstrated good psychometric properties at initial testing. The purpose of this brief report is to determine a threshold score that could be used in screening for probable ED cases in community settings., Methods: Data collected from Gideon et al. (2016) were re-analyzed. In their study, 559 participants (80.86% female; 9.66% self-reported ED diagnosis) completed the EDE-Q, EDE-QS, SCOFF, and Clinical Impairment Assessment (CIA). Discriminatory power was compared between ED instruments using receiver operating characteristic (ROC) curve analyses., Results: A score of 15 emerged as the threshold that ensured the best trade-off between sensitivity (.83) and specificity (.85), and good positive predictive value (.37) for the EDE-QS, with discriminatory power comparable to other ED instruments., Conclusion: The EDE-QS appears to be an instrument with good discriminatory power that could be used for ED screening purposes.

Objective: The theoretical model by Petrie and Greenleaf (2007, 2012) is an admirable attempt to collate the causal factors of disordered eating in athletes. The aims of this systematic review are (a) to provide an overview of the findings from the relevant literature, (b) to assess whether the model is supported by the existing research, (c) to evaluate the different designs, methods, and measures used to test the mediators in the model, and (d) to highlight areas for improvements and future research., Method: A systematic review of four major online databases identified 37 relevant papers on risk factors of disordered eating in athletes, which were reviewed and critically compared with the theoretical model., Results: There is a lack of longitudinal research with the relevant mediators in athlete populations, which makes it difficult to determine whether the potential mediators described by Petrie and Greenleaf are causal risk factors rather than simply correlates of disordered eating for athletes. Findings for all the potential mediators are inconsistent, and the range of measures used makes it problematic to draw conclusions., Conclusions: Future research needs to use gold standard measures and longitudinal designs in order to fully test and possibly update the model., (© 2019 John Wiley & Sons, Ltd and Eating Disorders Association.)

Self-criticism and low self-compassion are implicated in the development and maintenance of binge eating. However, the association between these self-attitudes and binge eating symptoms remains unclear. Women with symptoms of Bulimia Nervosa (BN) or Binge Eating Disorder (BED) were randomised to either a self-compassion (n = 30) or self-critical rumination (n = 30) strategy following a negative mood induction. Responses to food cues (cue reactivity and affect) and calorie consumption in a 'taste test' were assessed. The self-compassion strategy was associated with a greater improvement in positive and negative affect following the negative mood induction. Despite the differential effects on mood, self-compassion and self-critical rumination led to similar self-reported food cravings and physiological reactivity to cues. However, participants in the self-compassion condition consumed significantly fewer calories, rated the consumed food as less pleasurable, and reported less desire to continue eating. The findings suggest that therapeutic strategies for cultivating self-compassion are associated with improved food-related self-regulation in the context of negative mood., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Apolipoprotein E4 (ApoE4) is one of three (E2, E3 and E4) human isoforms of an α-helical, 299-amino-acid protein. Homozygosity for the ε4 allele is the major genetic risk factor for developing late-onset Alzheimer's disease (AD). ApoE2, ApoE3 and ApoE4 differ at amino acid positions 112 and 158, and these sequence variations may confer conformational differences that underlie their participation in the risk of developing AD. Here, we compared the shape, oligomerization state, conformation and stability of ApoE isoforms using a range of complementary biophysical methods including small-angle x-ray scattering, analytical ultracentrifugation, circular dichroism, x-ray fiber diffraction and transmission electron microscopy We provide an in-depth and definitive study demonstrating that all three proteins are similar in stability and conformation. However, we show that ApoE4 has a propensity to polymerize to form wavy filaments, which do not share the characteristics of cross-β amyloid fibrils. Moreover, we provide evidence for the inhibition of ApoE4 fibril formation by ApoE3. This study shows that recombinant ApoE isoforms show no significant differences at the structural or conformational level. However, self-assembly of the ApoE4 isoform may play a role in pathogenesis, and these results open opportunities for uncovering new triggers for AD onset., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: Anorexia nervosa (AN) is an eating disorder characterised by restriction of energy intake, fears of gaining weight and related body image disturbances. The oxytocinergic system has been proposed as a pathophysiological candidate for AN. Oxytocin is a neuropeptide involved in bodily processes (eg, breast feeding) and in the onset of social behaviours (eg, bonding). Studies investigating the effect of intranasal oxytocin (IN-OT) in AN showed that it can improve attentional bias for high-calorie food and fat bodies stimuli, and related stress. However, less is known about the effect of IN-OT on bodily awareness and body image distortions, key features of the disorder linked to its development, prognosis and maintenance. Here, we aim to investigate the effect of IN-OT on the perception of affective, C-tactile-optimal touch, known to be impaired in AN and on multisensory integration processes underlying a body ownership illusion (ie, rubber hand illusion). For exploratory purposes, we will also investigate the effect of IN-OT on another interoceptive modality, namely cardiac awareness and its relationship with affective touch., Design, Methods and Analysis: Forty women with AN and forty matched healthy controls will be recruited and tested in two separate sessions; self-administering IN-OT (40 IU) or placebo, intranasally, in a pseudo-randomised manner. The data from this double-blind, placebo-controlled, cross-over study will be analysed using linear mixed models that allow the use of both fixed (treatment levels) and random (subjects) effects in the same analysis. To address our main hypotheses, separate analyses will be run for the affective touch task, where the primary outcome dependent variable will be the pleasantness of the touch, and for the rubber hand illusion, where we will investigate multisensory integration quantified as subjective embodiment towards the rubber hand. In the latter, we will manipulate the synchronicity of touch and the size of the hand., Ethics and Dissemination: Ethics approval has been obtained by National Research Ethics Service NRES Committee London (Queen's Square Committee, ref number 14/LO/1593). The results will be disseminated through conference presentations and publication in peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)