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Background: Personality traits have been associated with eating disorders (EDs) and comorbidities. However, it is unclear which personality profiles are premorbid risk rather than diagnostic markers., Methods: We explored associations between personality and ED-related mental health symptoms using canonical correlation analyses. We investigated personality risk profiles in a longitudinal sample, associating personality at age 14 with onset of mental health symptoms at ages 16 or 19. Diagnostic markers were identified in a sample of young adults with anorexia nervosa (AN, n = 58) or bulimia nervosa (BN, n = 63) and healthy controls (n = 47)., Results: Two significant premorbid risk profiles were identified, successively explaining 7.93 % and 5.60 % of shared variance (R c 2 ). The first combined neuroticism (canonical loading, r s  = 0.68), openness (r s  = 0.32), impulsivity (r s  = 0.29), and conscientiousness (r s  = 0.27), with future onset of anxiety symptoms (r s  = 0.87) and dieting (r s  = 0.58). The other, combined lower agreeableness (r s  = -0.60) and lower anxiety sensitivity (r s  = -0.47), with future deliberate self-harm (r s  = 0.76) and purging (r s  = 0.55). Personality profiles associated with "core psychopathology" in both AN (R c 2  = 80.56 %) and BN diagnoses (R c 2  = 64.38 %) comprised hopelessness (r s  = 0.95, 0.87) and neuroticism (r s  = 0.93, 0.94). For BN, this profile also included impulsivity (r s  = 0.60). Additionally, extraversion (r s  = 0.41) was associated with lower depressive risk in BN., Limitations: The samples were not ethnically diverse. The clinical cohort included only females. There was non-random attrition in the longitudinal sample., Conclusions: The results suggest neuroticism and impulsivity as risk and diagnostic markers for EDs, with neuroticism and hopelessness as shared diagnostic markers. They may inform the design of more personalised prevention and intervention strategies., Competing Interests: Declaration of competing interest Dr. Banaschewski served in an advisory or consultancy role for ADHS digital, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda. He received conference support or speaker's fee by Medice and Takeda. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. Dr. Poustka served in an advisory or consultancy role for Roche and Viforpharm and received speaker's fee by Shire. She received royalties from Hogrefe, Kohlhammer and Schattauer. The present work is unrelated to these relationships. The other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Antipsychotics are routinely prescribed off-label for anorexia nervosa (AN) despite limited evidence. This article presents a protocol of a study aiming to assess the feasibility of a future definitive trial on olanzapine in young people with AN., Methods and Analysis: In an open-label, one-armed feasibility study, 55 patients with AN or atypical AN, aged 12-24, receiving outpatient, inpatient or day-care treatment who are considered for olanzapine treatment will be recruited from NHS sites based in England. Assessments will be conducted at screening, baseline and at 8-, 16 weeks, 6- and 12 months. Primary feasibility parameters will be proportions of patients who agree to take olanzapine and who adhere to treatment and complete study assessments. Qualitative methods will be used to explore acceptability of the intervention and study design. Secondary feasibility parameters will be changes in body mass index, psychopathology, side effects, health-related quality of life, carer burden and proportion of participants who would enrol in a future randomised controlled trial. The study is funded by the National Institute for Health Research via Health Technology Assessment programme., Discussion: Olanzapine for young PEople with aNorexia nervosa will inform a future randomised controlled trial on the efficacy and safety of prescribing olanzapine in young people with AN., (© 2024 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Objective: We present the protocol of a feasibility randomised controlled trial (RCT) of intermittent theta burst stimulation (iTBS) for young people with anorexia nervosa (AN). Effective first-line psychological therapies exist for young people with AN, but little is known about how to treat those who do not respond. Non-invasive neuromodulation, such as iTBS, could address unmet treatment needs by targeting neurocircuitry associated with the development and/or maintenance of AN., Design: Sixty-six young people (aged 13-30 years) with persistent AN will be randomly allocated to receive 20 sessions of real or sham iTBS over the left dorsolateral prefrontal cortex in addition to their usual treatment. Outcomes will be measured at baseline, post-treatment (1-month post-randomisation) and 4-months post-randomisation (when unblinding will occur). Additional open follow-ups will be conducted at 12- and 24-months post-randomisation. The primary feasibility outcome is the proportion of participants retained in the study at 4-months. Secondary outcomes include AN symptomatology, other psychopathology, quality of life, service utilisation, neurocognitive processes, and neuroimaging measures., Discussion: Findings will inform the development of a future large-scale RCT. They will also provide exploratory data on treatment efficacy, and neural and neurocognitive predictors and correlates of treatment response to iTBS in AN., (© 2024 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Objective: The relative merits of inpatient or day-treatment for adults with anorexia nervosa (AN) are unknown. The DAISIES trial aimed to establish the non-inferiority of a stepped-care day patient treatment (DPT) approach versus inpatient treatment as usual (IP-TAU) for improving body mass index (BMI) at 12 months in adults with AN. The trial was terminated due to poor recruitment. This paper presents outcomes and investigates the reasons behind the trial's failure., Method: Fifteen patients with AN (of 53 approached) participated and were followed-up to 6 or 12 months. Summary statistics were calculated due to low sample size, and qualitative data concerning treatment experiences were analysed using thematic analysis., Results: At baseline, participants in both trial arms rated stepped-care DPT as more acceptable. At 12 months, participants' BMIs had increased in both trial arms. Qualitative analysis highlighted valued and challenging aspects of care across settings. Only 6/12 sites opened for recruitment. Among patients approached, the most common reason for declining participation was their treatment preference (n = 12/38)., Conclusions: No conclusions can be drawn concerning the effectiveness of IP-TAU and stepped-care DPT, but the latter was perceived more positively. Patient-related, service-related and systemic factors (COVID-19) contributed to the trial's failure. Lessons learnt can inform future studies., (© 2023 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

While individuals with Bulimia Nervosa (BN) and Binge Eating Disorder (BED) often present with a higher rate of Alcohol Use Disorder (AUD) than the general population, it is unclear whether this extends to AN. This cross-sectional study examined differences in alcohol-related behaviours, measured using the Alcohol Use Identification Test (AUDIT), between AN participants ( n = 58), recovered AN (rec-AN) participants ( n = 25), and healthy controls ( n = 57). Statistical models controlled for age and ethnicity. The relationship between alcohol-related behaviours with ED psychopathology and with depression was also assessed. The findings indicated that acute AN participants were not at greater risk of AUD than healthy controls. However, rec-AN participants displayed greater total audit scores than those with acute AN, and more alcohol-related behaviours than healthy controls. Acute AN participants consumed significantly less alcohol than both the healthy control group and rec-AN group. No associations were found between ED psychopathology and alcohol-related behaviours in the AN group or rec-AN. This highlights alcohol as a potential coping mechanism following AN recovery. Clinicians should consider assessments for AUD and targeted interventions aimed at encouraging healthy coping mechanisms in this group. Future studies should look at alcohol use as a moderating factor for AN recovery.

Objective: An extensive number of predictors has been examined across the literature to improve knowledge of relapse in anorexia nervosa (AN). These studies provide various recovery and relapse definitions, follow-up durations and relapse rates. The current study summarizes these values and predictors of relapse in AN in a review and meta-analysis., Method: The study was executed according to PRISMA guidelines. Different databases were searched and studies in which participants did not receive an official clinical diagnosis were excluded. A quality analysis was performed using the National Institute of Health's Study Quality Assessment Tool. Random-effects meta-analyses were conducted to summarize data., Results: Definitions of relapse and recovery were diverse. During an average follow-up period of 31 months an average relapse rate of 37% was found. Predictive variables from 28 studies were grouped in six categories: age and sex, symptoms and behaviors, AN subtype and duration, weight or weight change, comorbidity, and personality. The studies were characterized by non-significant and contradictory results. Meta-analyses were performed for the predictors age, AN duration, pre-treatment BMI, post-treatment BMI and depression. These yielded significant effects for post-treatment BMI and depression: higher pre-treatment depression (SMD = .40 CI [.21-.59] and lower post-treatment BMI (SMD = -.35 CI [-.63 to -.07]) increased relapse chances in AN., Discussion: Our results emphasized a lack of sufficiently powered studies, consistent results, and robust findings. Solely post-treatment BMI and pre-treatment depression predicted relapse. Future research should use uniform definitions, larger samples and better designs, to improve our understanding of relapse in AN., Public Significance: Knowledge about predictors is important to understand high relapse rates. Our study performed a review and meta-analysis of relapse predictors in AN. Related to the heterogeneity in studies examining predictors, an overview of relapse and recovery definitions, follow-up durations and relapse rates for AN was provided. Significant effects were found for post-treatment BMI and pre-treatment depression. More studies with uniform definitions are needed to improve clinical implications., (© 2023 Wiley Periodicals LLC.)

Introduction: Clinical staging models in psychiatry assert that there are earlier, less severe or more malleable forms of illness that are distinguishable from later, more chronic forms of illness, and that these stages may have different prognostic and treatment implications. Previous reviews on clinical staging in eating disorders (EDs) suggest a staging heuristic could be useful for anorexia nervosa, but less research is available on how this applies to other EDs. An up-to-date review is required to synthesise new and heterogenous avenues of research. This scoping review aims to explore the extent and types of evidence in relation to illness staging for EDs and how these concepts are associated with treatment response and outcomes., Methods and Analysis: This protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol extension for Scoping Reviews checklist and the Joanna Briggs Institute Reviewer's Manual. We will consider any documents providing evidence for clinical staging such as those which describe full or partial staging models, for all EDs, across various domains of assessment and functioning. Participants will include clinical or non-clinical population samples with full-syndrome EDs or disordered eating behaviour. PubMed, PsycINFO, MEDLINE and Web of Science databases will be systematically searched for relevant literature. Two authors will export documents and screen titles, abstracts and full texts. Data will be extracted into a charting form drafted by the authors. A narrative summary of the documents will be conducted in line with the study aims. Finally, clinical and research recommendations will be outlined., Ethics and Dissemination: Ethical approval will not be required to synthesise published and unpublished literature. The study will be published in a peer-reviewed journal and shared at conferences, via social media, and in other communications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Multi-family therapy (MFT-AN) is a promising group-based treatment for adolescent anorexia nervosa. This study aimed to explore how young people and parents perceived change to occur during MFT treatment., Methods: Young people (10-18 years) diagnosed with anorexia nervosa or atypical anorexia nervosa and their parents who completed MFT-AN alongside family therapy for anorexia nervosa within the preceding 2 years were eligible for this study. Semi-structured qualitative interviews were conducted. Recordings were transcribed verbatim and analysed using reflexive thematic analysis., Results: Twenty-three participants (8 young people, 10 mothers and 5 fathers) completed interviews. Five main themes were identified; (1) Powerful connection, (2) Intensity, (3) New learning and perspective shifts, (4) Comparisons, and (5) Discharge is not recovery. There was a strong sense that being with others in a similar position in an intense environment were key factors in promoting change. Comparisons were inevitable and could promote insight and foster motivation, but could also be unhelpful at times. Participants spoke about how recovery continues beyond service use and requires ongoing attention and support., Conclusions: Through the mechanisms of connection, intensity, new learning and comparisons change is perceived to occur in MFT-AN. Some of these are considered unique to this treatment format., (© 2023 Eating Disorders Association and John Wiley & Sons Ltd.)

Objective: The DAISIES trial, comparing inpatient and stepped-care day patient treatment for adults with severe anorexia nervosa was prematurely terminated in March 2022 due to poor recruitment. This qualitative study seeks to understand the difficulties faced during the trial by investigating stakeholders' views on and experiences of its implementation., Method: Semi-structured interview and focus group transcripts, and trial management and oversight group meeting minutes from May 2020-June 2022 were analysed using thematic analysis. Participants were 47 clinicians and co-investigators involved with the DAISIES trial. The Non-Adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework was applied to the interpretive themes to classify barriers and facilitators to implementation., Results: Five themes were identified: incompatible participation interests; changing standard practice; concerns around clinical management; systemic capacity and capability issues; and Covid-19 disrupting implementation. Applying the NASSS framework indicated the greatest implementation challenges to arise with the adopters (e.g. patients, clinicians), the organisational systems (e.g. service capacity), and the wider socio-political context (e.g. Covid-19 closing services)., Conclusions: Our findings emphasise the top-down impact of systemic-level research implementation challenges. The impact of the Covid-19 pandemic accentuated pre-existing organisational barriers to trial implementation within intensive eating disorder services, further limiting the capacity for research., (© 2023 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

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.)

Background: Anorexia nervosa (AN) is a serious and disabling mental disorder with a high disease burden. In a proportion of cases, intensive hospital-based treatments, i.e. inpatient or day patient treatment, are required, with day patient treatment often being used as a 'step-down' treatment after a period of inpatient treatment. Demand for such treatment approaches has seen a sharp rise. Despite this, the relative merits of these approaches for patients, their families, and the NHS and wider society are relatively unknown. This paper describes the rationale for, and protocol of, a two-arm multi-centre open-label parallel group non-inferiority randomised controlled trial, evaluating the effectiveness and cost-effectiveness of these two intensive treatments for adults with severe AN: inpatient treatment as usual and a stepped care day patient approach (the combination of day patient treatment with the option of initial inpatient treatment for medical stabilisation). The main aim of this trial is to establish whether, in adults with severe AN, a stepped care day patient approach is non-inferior to inpatient treatment as usual in relation to improving body mass index (BMI) at 12 months post-randomisation., Methods: 386 patients with a Diagnostic and Statistical Manual 5th edition diagnosis of severe AN or related disorder, with a BMI of ≤16 kg/m 2 and in need of intensive treatment will be randomly allocated to either inpatient treatment as usual or a stepped care day patient approach. Patients in both groups will receive treatment until they reach a healthy weight or get as close to this point as possible. Assessments will be conducted at baseline (prior to randomisation), and at 6 and 12 months post-randomisation, with additional monthly symptom monitoring. The primary outcome will be BMI at the 12-month post-randomisation assessment. Other outcomes will include psychosocial adjustment; treatment motivation, expectations and experiences; cost-effectiveness; and carer burden., Discussion: The results of this study will provide a rigorous evaluation of two intensive treatment approaches which will inform future national and international treatment guidelines and service provision., Trial Registration: ISRCTN ISRCTN10166784 . Registered 28 February 2020. ISRCTN is a primary registry of the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) network and includes all items from the WHO Trial Registration Data Set., (© 2022. The Author(s).)

Brain-derived neurotrophic factor (BDNF) is a neuroprotective molecule known to be involved in neuroplasticity, learning and memory. Additionally, it may mitigate the effects of inflammation on the brain. There is inconclusive evidence as to whether reductions in BDNF found in AN are related to features associated with the illness such as changes in inflammatory markers and comorbidities, and whether they persist after recovery. This cross-sectional study measured BDNF and 36 inflammatory markers in the serum of individuals recovered from AN (rec-AN; n = 24), with acute AN (n = 56), and healthy controls (n = 51). We (a) compared BDNF concentrations between AN, rec-AN and controls including four pre-determined covariates; (b) assessed the relationship between BDNF and body mass index, eating disorder (ED) psychopathology and depression; and (c) correlated BDNF with inflammatory markers, stratified by group. The AN group showed reductions in BDNF compared to controls and rec-AN. BDNF was negatively associated with depression and ED psychopathology in the whole sample, but not the AN sample. BDNF was positively correlated with three inflammatory markers in the control group (interleukin (IL)-8, Eotaxin-3, tumor necrosis factor (TNF)-α) and negatively correlated with one (IL-16). The only pro-inflammatory marker associated with BDNF in the AN group was TNF-α, and no pro-inflammatory markers were associated with BDNF in the rec-AN group. These results indicate that BDNF serum concentrations may be a state marker of AN. In people with acute AN, BDNF levels seem to be linked to TNF-α signalling. However, BDNF concentrations do not appear to reflect AN symptom severity., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Repetitive transcranial magnetic stimulation (rTMS) is a promising emerging treatment for anorexia nervosa (AN). However, to date, patients' views and experiences of this treatment have not been fully explored. To assess these, we integrated a qualitative study into a feasibility randomised controlled trial of rTMS in individuals with severe enduring AN., Method: Twenty-nine (of 34) trial participants contributed to this study. Semi-structured interviews were conducted 3-months following the completion of rTMS treatment (4-months post-randomisation), prior to unblinding. Transcripts were analysed using content analysis., Results: rTMS was deemed an acceptable but time-consuming treatment. Many emphasised how their lives had changed to some extent during, but mainly after treatment by making them more positive, open-minded, flexible and willing to try new things in relation to their AN and other aspects of their lives., Conclusions: These qualitative data will be valuable in shaping participant information, recruitment and planning of future large-scale trials of rTMS in AN., Trial Registration: ISRCTN14329415, registered 23rd July 2015, https://www.isrctn.com/ISRCTN14329415., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Background: Anorexia nervosa is a serious illness leading to substantial morbidity and mortality. The Anorexia Nervosa Treatment of Outpatients (ANTOP) study is the largest randomised controlled trial (RCT) globally that uses psychotherapy in outpatients with anorexia nervosa. In this Article, we report the results of the 5-year follow-up., Methods: The ANTOP study is an open-label, multicentre RCT involving 242 adult female outpatients with anorexia nervosa. Participants were recruited from ten university hospitals in Germany, had to be aged at least 18 years and female, and have a diagnosis of anorexia nervosa with a body-mass index (BMI) of 15·0-18·5 kg/m 2 . Participants were randomly allocated (1:1:1) to 10 months of treatment with focal psychodynamic therapy, enhanced cognitive behaviour therapy, or optimised treatment as usual; complete masking of the participants was not possible. The mean duration of the follow-up was 5·96 years (SD 0·2) after randomisation. The primary outcome was change in BMI from baseline at the end of treatment; here, we present the change in BMI from baseline to the 5-year follow-up, using an intention-to-treat approach with a mixed model for repeated measurements. Groups were also compared according to global outcome (based on the combination of BMI and measures of anorexia severity), eating pathology (based on the Eating Disorder Inventory 2), and other secondary mental health outcomes. We did a linear regression analysis to identify the predictors of BMI at follow-up., Findings: Between May, 2007, and June, 2009, we screened 727 patients for eligibility; at baseline, 242 patients with a mean BMI of 16·7 kg/m 2 (SD 1·0) were included and randomly allocated to 10 months of treatment with focal psychodynamic therapy, enhanced cognitive behaviour therapy, or optimised treatment as usual. 154 (64%) of 242 patients completed the 5-year follow-up assessment (53 [66%] of 80 in the focal psychodynamic therapy group, 55 [69%] of 80 in the enhanced cognitive behaviour therapy group, and 46 [56%] of 82 in the optimised treatment-as-usual group), with a mean age of 32·4 years; all reported their ethnicity as White. At the 5-year follow-up, there was an improvement in mean BMI, eating pathology, and global outcome in all treatment groups with no significant differences between treatment groups. Estimated mean BMI was: 18·64 kg/m 2 (95% CI 18·07-19·21) in the focal psychodynamic therapy group (with an estimated mean BMI gain from baseline to 5-year follow-up of 1·91 kg/m 2 [1·34-2·48]); 18·70 kg/m 2 (18·15-19·25) in the enhanced cognitive behaviour therapy group (with an estimated mean BMI gain of 1·98 kg/m 2 [1·43-2·53]); and 18·99 kg/m 2 (18·39-19·59) in the optimised treatment-as-usual group (with an estimated mean BMI gain of 2·26 kg/m 2 [1·67-2·86]). There were no significant differences between treatment groups regarding BMI at the 5-year follow-up; the estimated difference was -0·06 (-0·85 to 0·73) between the focal psychodynamic therapy and enhanced cognitive behaviour therapy groups; -0·35 (-1·18 to 0·47) between the focal psychodynamic therapy and optimised treatment-as-usual groups; and -0·29 (-1·10 to 0·52) between the enhanced cognitive behaviour therapy and optimised treatment-as-usual groups. On the basis of observed data, global outcome at the 5-year follow-up showed 41% (33-49) full recoveries, 41% (33-49) partial recoveries, and 18% (12-24) with full-syndrome anorexia nervosa. One patient initially treated in the enhanced cognitive behaviour therapy group died by suicide between the 1-year and 5-year follow-up. BMI at the 5-year follow-up was predicted by BMI at baseline (p=0·0021), illness duration (p=0·0004), and depression at baseline (p=0·012)., Interpretation: The long-term results of the ANTOP trial confirm the improvement in BMI of patients with anorexia nervosa in all groups; however, a substantial proportion of patients had a poor global outcome. The predictors for the long-term course of anorexia nervosa in our ANTOP study show that we need to treat patients with anorexia nervosa at an earlier stage of the disease, with a clear focus on weight gain and considering other comorbidities (especially depression)., Funding: German Federal Ministry of Education and Research., Competing Interests: Declaration of interests We declare no competing interests., (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: We review recent evidence on the use of neuromodulation for treating eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge eating disorder. We evaluate studies on (a) modern non-invasive methods of brain stimulation, such as transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), (b) electroconvulsive therapy (ECT) and (c) more invasive techniques, including deep brain stimulation (DBS)., Recent Findings: Most reports on the clinical applications of neuromodulation in EDs are limited to case studies, case series and small clinical trials. The majority have focused on severe, enduring and hard-to-treat cases of AN. In this population, data suggest that both rTMS and DBS have therapeutic potential and are safe and acceptable. High-quality clinical trials in different ED populations are needed which investigate different stimulation methods, sites and parameters, the use of neuromodulation as stand-alone and/or adjunctive treatment, as well as the mechanisms of action., (© 2022. The Author(s).)

Anorexia nervosa (AN) is characterised by disrupted and restrictive eating patterns. Recent investigations and meta-analyses have found altered concentrations of inflammatory markers in people with current AN. We aimed to assess nutrient intake in participants with current or recovered AN, as compared to healthy individuals, and explore group differences in dietary inflammatory potential as a possible explanation for the observed alterations in inflammatory markers. We recruited participants with current AN ( n = 51), those recovered from AN ( n = 23), and healthy controls ( n = 49). We used the Food Frequency Questionnaire (FFQ), to calculate a Dietary Inflammatory Index (DII ® ) score and collected blood samples to measure serum concentrations of inflammatory markers. In current AN participants, we found lower intake of cholesterol, compared to HCs, and lower consumption of zinc and protein, compared to HC and recovered AN participants. A one-way ANOVA revealed no significant group differences in DII score. Multivariable regression analyses showed that DII scores were significantly associated with tumour necrosis factor (TNF)-α concentrations in our current AN sample. Our findings on nutrient intake are partially consistent with previous research. The lack of group differences in DII score, perhaps suggests that diet is not a key contributor to altered inflammatory marker concentrations in current and recovered AN. Future research would benefit from including larger samples and using multiple 24-h dietary recalls to assess dietary intake.

Objective: This study reviewed the quantitative and qualitative evidence-base for multi-family therapy (MFT) for eating disorders regarding change in physical and psychological symptoms, broader individual and family factors, and the experience of treatment., Method: A systematic scoping review was conducted. Four databases (PsycInfo, Medline, Embase, CENTRAL) and five grey literature databases were searched on 24th June 2021 for relevant peer-reviewed journal articles, book chapters, and dissertations. No beginning time-point was specified. Only papers that presented quantitative or qualitative data were included. No restrictions on age or diagnosis were imposed. Studies were first mapped by study design, participant age, and treatment setting, then narratively synthesized., Results: Outcomes for 714 people who received MFT across 27 studies (one mixed-method, 17 quantitative and nine qualitative) were synthesized. MFT is associated with improvements in eating disorder symptomatology and weight gain for those who are underweight. It is also associated with improvements in other individual and family factors including comorbidities, self-esteem, quality of life, and some aspects of the experience of caregiving, although these findings are more mixed. MFT is generally experienced as both helpful and challenging due to the content addressed and intensive group process., Discussion: MFT is associated with significant improvements in eating disorder symptoms across the lifespan and improvement in broader individual and family factors. The evidence base is small and studies are generally underpowered. Larger, higher-quality studies are needed, as is research investigating the unique contribution of MFT on outcomes, given it is typically an adjunctive treatment., (© 2021 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Objective: This study aimed to evaluate the effectiveness of evidenced-based psychological treatments (specifically, Cognitive-Behaviour Therapy for Eating Disorders [CBT-ED] and Maudsley Anorexia Nervosa Treatment for Adults [MANTRA]) for a transdiagnostic eating disorder population in a routine clinical setting. In particular, it aimed to determine the extent to which treatment was provided in line with current clinical guidelines (NICE, 2017) and how effective treatment was in improving eating disorder and general psychopathology., Method: Three hundred and seventy-nine participants meeting criteria for DSM-5 anorexia nervosa, bulimia nervosa, binge-eating disorder or other specified feeding or eating disorder completed pre- and posttreatment measures of eating disorder pathology and general distress. Clinicians recorded weight and episodes of bingeing and purging., Results: Ninety seven percent of participants received treatment in line with evidence-based psychotherapies. Treatment was completed by 59.9% of the whole sample. Using stringent criteria and ITT analysis 21.4% met criteria for remission at end of treatment. In the underweight sample, there was a significant increase in BMI, averaging 1.38 kg/m 2 over treatment, with similar outcomes for MANTRA and CBT-ED., Discussion: These findings, in a large transdiagnostic population, add to emerging literature on the translation of evidence-based psychotherapies to real-world clinical settings. Our results converge well with prior similar studies. Findings highlight the need for routine data collection in services and for the ongoing improvement of treatments for the eating disorders., (© 2021 Wiley Periodicals LLC.)

A growing body of evidence suggests that a high level of self-control may, despite its positive effects, influence cognitive processing in an unfavorable manner. However, the affective costs of self-control have only rarely been investigated. Anorexia nervosa (AN) is an eating disorder that is often characterized by excessive self-control. Here, we used fMRI to explore whether over-control in AN may have negative affective consequences. 36 predominantly adolescent female AN patients and 36 age-matched healthy controls (HC) viewed negative and neutral pictures during two separate fMRI sessions before and after 10 min of rest. We tested whether abnormally elevated neural activity during the initial presentation in a brain region broadly implicated in top-down control, the dorsolateral prefrontal cortex (dlPFC), could predict subsequent activation in limbic areas relevant to bottom-up affective processing. Using ecological momentary assessment (EMA), we also tested for associations between the aforementioned neuroimaging markers and negative affective states in the two weeks following the experiment. fMRI data revealed that higher initial activation of the dlPFC in AN predicted increased amygdala reactivity during the second fMRI session, which in turn was related to increased self-reported tension during two weeks following the scan. These data suggest that over-control in AN patients may come at a cost including negative affective states on a short (minutes) as well as a longer time scale (days). This mechanism may significantly contribute to the persistence of AN.

Objective: The purpose of the study was to identify latent classes of trajectory of change in body mass index (BMI) between the initial and thirteenth session of outpatient treatment for adult anorexia nervosa and identify the association with outcome., Method: Participants (n = 120) were randomised to one of three outpatient therapies., Results: Four latent classes were identified; two classes (higher, rapid and higher, moderate) had BMI > 17 kg/m 2 at initial assessment, and both gained significantly more weight over the 13 sessions compared to the other two classes. The third and fourth classes (middle, stable and low, stable) had an initial BMI of 16.44 and 15.31, respectively, and neither gained weight over the first 13 sessions. Compared to the other three classes, the higher, rapid class (N = 19, 16%) showed a significantly greater BMI increase over the first 13 sessions of therapy and a significantly higher rate of remission at end of treatment and 12-month follow-up (18-22 months post-randomisation)., Conclusions: The group with the greatest early weight gain had significantly higher levels of remission. Higher BMI at baseline without substantial early weight gain was insufficient to produce higher levels of remission than those with lower weight at baseline., (© 2020 Eating Disorders Association and John Wiley & Sons Ltd.)

Objective: This systematic review assesses the average duration of untreated eating disorder (DUED) in help-seeking populations at the time of first eating disorder (ED) treatment and investigates the relationship between DUED and symptom severity/clinical outcomes., Method: PRISMA guidelines were followed throughout. Selected studies provided information on either: (i) length of DUED, (ii) components of DUED, (iii) cross-sectional associations between DUED and symptom severity, (iv) associations between DUED and clinical outcomes, or (v) experimental manipulation of DUED. Study quality was assessed., Results: Fourteen studies from seven countries were included. Across studies, average DUED weighted by sample size was 29.9 months for anorexia nervosa, 53.0 months for bulimia nervosa and 67.4 months for binge eating disorder. A younger age at time of first treatment was indicative of shorter DUED. Retrospective studies suggest that a shorter DUED may be related to a greater likelihood of remission. Manipulation of DUED by shortening service-related delays may improve clinical outcomes., Conclusions: Data on length of DUED provide a benchmark for early intervention in EDs. Preliminary evidence suggests DUED may be a modifiable factor influencing outcomes in EDs. To accurately determine the role of DUED, definition and measurement must be uniformly operationalised. Highlights This systematic review is the first to examine duration of untreated eating disorder (DUED) across different eating disorders. Definitions and measurement of DUED and its components vary considerably between studies. Across different eating disorders average DUED weighted by sample size ranges from approximately two and a half years (for anorexia nervosa) to nearly 6 years (for binge eating disorder). DUED appears to be related to age such that younger patients have shorter DUED., (© 2020 John Wiley & Sons, Ltd and Eating Disorders Association.)

In patients with anorexia nervosa (AN), decreased intracellular (ICW), extracellular (ECW), and total body water (TBW) as well as changes in serum cytokine concentrations have been reported. In this exploratory study, we measured body composition and serum cytokine levels in patients with AN ( n = 27) and healthy controls (HCs; n = 13). Eating disorder symptom severity was assessed using the Eating Disorder Examination-Questionnaire (EDE-Q). Body composition was determined by bioimpedance analysis (BIA) which provided information on ICW, ECW, and TBW. Following blood collection, 27 cytokines and chemokines were quantified using multiplex ELISA-based technology: Eotaxin, Eotaxin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon- (IFN-) γ , interleukin- (IL-) 1 α , IL-1 β , IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, interferon γ -induced protein- (IP-) 10, macrophage inflammatory protein- (MIP-) 1 α , MIP-1 β , monocyte chemoattractant protein- (MCP-) 1, MCP-4, thymus and activation-regulated chemokine (TARC), TNF- α , and TNF- β . ICW, ECW, and TBW volumes were significantly lower in patients with AN than in HCs. In the whole sample, GM-CSF, MCP-4, and IL-4 were positively, whereas IFN- γ , IL-6, and IL-10 were negatively associated with all three parameters of body water. In AN participants, we found a statistically significant negative correlation of IL-10 with ICW, ECW, and TBW. Our results suggest an interaction between body water and the cytokine system. Underlying mechanisms are unclear but may involve a loss of water from the gut, kidneys, or skin due to AN-associated inflammatory processes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Hubertus Himmerich et al.)

Background: No consistent first-option psychological interventions for adult outpatients with anorexia nervosa emerges from guidelines. We aimed to compare stand-alone psychological interventions for adult outpatients with anorexia nervosa with a specific focus on body-mass index, eating disorder symptoms, and all-cause dropout rate., Methods: In this systematic review and network meta-analysis, we assessed randomised controlled trials about stand-alone pharmacological or non-pharmacological treatments of adult outpatients with anorexia nervosa, defined according to standardised criteria, with data for at least two timepoints relating to either body-mass index or global eating disorder psychopathology. We searched Cochrane CENTRAL, CINAHL, MEDLINE, and PsychINFO for published and unpublished literature from inception until March 20, 2020. The primary outcomes were the change in body mass index and clinical symptoms, and the secondary outcome was all-cause dropout rate, which were all assessed for treatment as usual, cognitive behavioural therapy (CBT), Maudsley anorexia treatment for adults, family-based treatment, psychodynamic-oriented psychotherapies, a form of CBT targeting compulsive exercise, and cognitive remediation therapy followed by CBT. Global and local inconsistencies for the network meta-analysis were measured, and CINeMA was used to assess the confidence in evidence for primary outcomes. The protocol is registered in PROSPERO (CRD42017064429)., Findings: Of 14 003 studies assessed for their title and abstract, 16 (0·1%) randomised controlled trials for psychological treatments were included in the systematic review, of which 13 (0·1%) contributed to the network meta-analysis, with 1047 patients in total (of whom 1020 [97·4%] were female). None of the interventions outperformed treatment as usual in our primary outcomes, but the all-cause dropout rate was lower for CBT than for psychodynamic-oriented psychotherapies (OR 0·54, 95% CI 0·31-0·93). Heterogeneity or inconsistency emerged only for a few comparisons. Confidence in the evidence was low to very low., Interpretation: Compared with treatment as usual, specific psychological treatments for adult outpatients with anorexia nervosa can be associated with modest improvements in terms of clinical course and quality of life, but no reliable evidence supports clear superiority or inferiority of the specific treatments that are recommended by clinical guidelines internationally. Our analysis is based on the best data from existing clinical studies, but these findings should not be seen as definitive or universally applicable. There is an urgent need to fund new research to develop and improve therapies for adults with anorexia nervosa. Meanwhile, to better understand the effects of available treatments, participant-level data should be made freely accessible to researchers to eventually identify whether specific subgroups of patients are more likely to respond to specific treatments., Funding: Flinders University, National Institute for Health Research Oxford Health Biomedical Research Centre., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: This study assessed longer-term outcomes from a randomised controlled feasibility trial of 20 sessions of real versus sham high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex in adults with severe, enduring anorexia nervosa (SE-AN)., Methods: Thirty participants who completed the original study protocol were invited to take part in an open follow-up (18-months post-randomisation), assessing body mass index (BMI), eating disorder (ED) symptoms and other psychopathology., Results: Twenty-four participants (12 each originally allocated to real/sham) completed the 18-month follow-up. Ten of 12 participants who originally received sham treatment had real rTMS at some stage during the follow-up. A medium between-group effect size was seen for BMI change from baseline to 18-months, favouring those originally allocated to real rTMS. In this group at 18-months, five participants were weight recovered (BMI ≥18.5 kg/m 2 ), compared with one participant in the original sham group. Both groups showed further improvement in ED symptoms during the follow-up. Effects on mood were largely maintained at follow-up, with catch-up effects in the original sham group., Conclusions: Findings suggest that rTMS treatment effects on mood are durable and that BMI and ED symptom improvements need time to emerge. Large-scale trials are needed., (© 2020 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Background: Outpatient interventions for adult anorexia nervosa typically have a modest impact on weight and eating disorder symptomatology. This study examined whether adding a brief online intervention focused on enhancing motivation to change and the development of a recovery identity (RecoveryMANTRA) would improve outcomes in adults with anorexia nervosa., Methods: Participants with anorexia nervosa (n = 187) were recruited from 22 eating disorder outpatient services throughout the UK. They were randomised to receiving RecoveryMANTRA in addition to treatment as usual (TAU) (n = 99; experimental group) or TAU only (n = 88; control group). Outcomes were measured at end-of-intervention (6 weeks), 6 and 12 months., Results: Adherence rates to RecoveryMANTRA were 83% for the online guidance sessions and 77% for the use of self-help materials (workbook and/or short video clips). Group differences in body mass index at 6 weeks (primary outcome) were not significant. Group differences in eating disorder symptoms, psychological wellbeing and work and social adjustment (at 6 weeks and at follow-up) were not significant, except for a trend-level greater reduction in anxiety at 6 weeks in the RecoveryMANTRA group (p = 0.06). However, the RecoveryMANTRA group had significantly higher levels of confidence in own ability to change (p = 0.02) and alliance with the therapist at the outpatient service (p = 0.005) compared to the control group at 6 weeks., Conclusions: Augmenting outpatient treatment for adult anorexia nervosa with a focus on recovery and motivation produced short-term reductions in anxiety and increased confidence to change and therapeutic alliance.

Several objectives underlie the current article. First, to review historical diagnostic issues and clinical strategies for treating SE-AN. Second, to provide an overview of recent evidence informed strategies and clinical innovations for the treatment of SE-AN. Third, based on the authors' collective clinical and research experience, we offer eight observations that we believe capture the current clinical experience of patients with SE-AN. Some of these observations represent empirically testable hypotheses, but all are designed to generate a meaningful discussion about the treatment of this group of individuals with eating disorders. Finally, we hope to call clinicians, scientists, professional organizations, advocates, and policy makers to action to attend to critical issues related to the care of individuals with SE-AN. We believe that an international discussion could clarify areas of need for these patients and identify opportunities for clinical innovation that would enhance the lives of individuals with SE-AN and their families., (© 2020 Wiley Periodicals, Inc.)

Objective: Individuals with anorexia nervosa (AN) pursue low-fat, low-calorie diets even when in a state of emaciation. These maladaptive food choices may involve fronto-limbic circuitry associated with cognitive control, habit, and reward. We assessed whether high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC) influenced food-related choice behavior in patients with severe, enduring (SE)-AN., Method: Thirty-four females with SE-AN completed a Food Choice Task before and after 20 sessions of real or sham rTMS treatment and at a 4-month follow-up. During the task, participants rated high- and low-fat food items for healthiness and tastiness and then made a series of choices between a neutral-rated food and high- and low-fat foods. Outcomes included the proportion of high-fat and self-controlled choices made. A comparison group of 30 healthy women completed the task at baseline only., Results: Baseline data were consistent with previous findings: relative to healthy controls, SE-AN participants showed a preference for low-fat foods and exercised self-control on a greater proportion of trials. There was no significant effect of rTMS treatment nor time on food choices related to fat content. However, among SE-AN participants who received real rTMS, there was a decrease in self-controlled food choices at post-treatment, relative to baseline. Specifically, there was an increase in the selection of tasty-unhealthy foods., Discussion: In SE-AN, rTMS may promote more flexibility in relation to food choice. This may result from neuroplastic changes in the DLPFC and/or in associated brain areas., (© 2020 The Authors. International Journal of Eating Disorders published by Wiley Periodicals, Inc.)

Background: We explored the utility of "staging" anorexia nervosa (AN) by duration of illness and psychological wellbeing. We also investigated 12-month symptom trajectories and service usage in a large cohort of patients with AN assessed for outpatient treatment., Method: We conducted secondary analyses on data from a multisite clinical trial of adults with AN (n = 187) recruited from 22 NHS England specialist eating disorder (ED) services into a digital treatment augmentation study. Clinical outcomes and service use were measured at postintervention (six weeks), 6 and 12 months. We grouped patients into two categories: "early stage" (illness duration <3 years; n = 60) and "severe and enduring" stage (SE-AN; n = 41) indicated by distress (Depression Anxiety and Stress Scales, DASS ≥60) and illness duration (≥7 years)., Results: At 12 months, patients reported large improvements in body mass index, small to moderate improvements in ED symptoms, mood, and work/social adjustment, and 23.6% met criteria for recovery. However, patients classified as SE-AN reported higher rates of accessing intensive services, higher ED symptomatology, and poorer work/social adjustment at baseline, and lower rates of improvement in work/social adjustment at 12 months compared to "early stage" respondents., Discussion: Although present findings suggest overall symptomatic improvements, exploratory results highlight marked differences in course and service use between people at different stages of AN, suggesting a need to consider staging for clinical decision-making. Further research differentiating between clinical subtypes of AN and adoption of a more personalized approach may ensure that services and care pathways better fit patient needs., (© 2020 Wiley Periodicals, Inc.)

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.

Objective: Inflammation has been proposed to have a pathophysiological role in anorexia nervosa (AN) and to contribute to the maintenance of the disorder. Longitudinal cytokine research in AN has focused on only a few pro-inflammatory cytokines. We assessed a broad range of cytokines over time in people undergoing specialised treatment for AN., Method: We measured serum concentrations of 27 cytokines in people with AN (n = 23). Body mass index (BMI), eating disorder (ED) symptoms and general psychopathology were assessed and blood samples were collected within four weeks of the commencement of specialised ED treatment (baseline) and at 12- and 24-week follow-ups., Results: Both BMI and ED symptoms improved over the assessment period. Linear mixed models showed that log IL-6 decreased between baseline and week 12 assessments. By week 12, log IL-6 values were comparable to levels in healthy individuals. Log IL-7 increased from week 12 to week 24., Discussion: Initially elevated IL-6 serum concentrations appear to 'normalize' during the first 3-months of specialised treatment for AN and this co-occurs with improvements in ED symptoms. Therefore, IL-6 has the potential to be a state biomarker for AN., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: We describe 2-year outcomes of a novel first episode early intervention service for young adults with a recent onset eating disorder (FREED). Outcomes in FREED patients with anorexia nervosa (AN) were compared with those from patients previously seen in our service [treatment as usual (TAU) cohort], matched for age, illness duration and diagnosis., Methods: Electronic case records of FREED-AN (n = 22) and TAU-AN patients (n = 35) were examined to identify service utilisation and clinical outcomes over 24 months., Results: Outpatient service utilisation was similar in both groups, but FREED-AN patients needed intensive (in- or day-patient) treatment less frequently than TAU-AN (23% vs 32%). FREED-AN patients had a higher estimated mean body mass index [19.2 kg/m 2 ; 95% CI (18.21, 20.16)] than TAU patients [18.0 kg/m 2 ; 95% CI (16.90, 19.15)] at last contact., Conclusion: Introduction of FREED led to a more complete recovery in patients with AN at 24 months., (© 2019 John Wiley & Sons Australia, Ltd.)

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness 1 , affecting 0.9-4% of women and 0.3% of men 2-4 , with twin-based heritability estimates of 50-60% 5 . Mortality rates are higher than those in other psychiatric disorders 6 , and outcomes are unacceptably poor 7 . Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI) 8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

The aim of this case study is to illustrate the importance of collaborative care as part of Maudsley Anorexia Nervosa Treatment for Adults (MANTRA). Mothers are often at the foreground of providing support within the family. However, fathers have the potential to play a profound role. In this paper, we describe a patient with anorexia nervosa treated with the MANTRA. The formulation of this case included autistic spectrum traits in both the father and daughter leading to social isolation. We describe how the family members were engaged into treatment and how paternal support was used to promote social connection and an improved quality of life in the daughter. Some details of the case have been altered to maintain confidentiality., (© 2019 Wiley Periodicals, Inc.)

Objective: Attention processing for food may be biased in people with Anorexia Nervosa (AN). However, previous studies have had inconsistent results. This is likely to be due to indirect assessment of attention, which does not inform on the underlying attention processes, and/or the heterogeneity of participants across studies, testing either adults or adolescents with AN, that is, people at very different developmental and illness stages., Method: Eye-tracking was employed as a direct assessment of attention during a visual probe task with food versus non-food pictures. Attention bias for food was measured in 39 adults and 34 adolescents with AN and in 53 adults and 31 adolescents without AN., Results: All participants had a direction bias for food, specifically for high-calorie food. However, adults with AN subsequently avoided maintaining attention on food versus non-food cues, compared to adults without AN. Adolescents with or without AN demonstrated increased attention maintenance on food versus non-food cues, and, contrary to our hypothesis, did not differ in their attention bias for food cues. Accordingly, adults with AN differed significantly from adolescents with AN in attention maintenance for food cues: while adolescents with AN showed significantly increased attention maintenance on food stimuli, adults avoided maintaining attention on food cues., Discussion: Adults with AN may apply attention strategies to facilitate restrictive eating. This strategy is absent in adolescents with AN. This difference in food-related attention bias between adolescents and adults with AN suggests that attention biases develop over time as the illness progresses., (© 2019 Wiley Periodicals, Inc.)

The authors provide an overview of the current state of research on self-help interventions for eating disorders. The efficacy of different forms of self-help interventions for bulimia nervosa, binge eating disorder, and other eating disorders at various stages of the care pathway (from prevention to relapse prevention) is described. Cost-effectiveness studies are also presented. Moderators of outcome, such as guidance and adherence, are discussed. Overall, the findings are promising and support the use of self-help interventions in the treatment of bulimic disorders, across the stages of the care pathway. Less is known about the use of self-help in anorexia nervosa., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Anorexia nervosa (AN) is found associated with increased mortality. Frequent comorbidities of AN include substance use disorders (SUD), affective disorders (AD) and personality disorders (PD). We investigated the influence of these psychiatric comorbidities on all-cause mortality with demographic and socioeconomic factors considered as confounders in the observation window between January 2007 and March 2016 for 1970 people with AN, using data from the case register of the South London and Maudsley (SLaM) NHS Foundation Trust, an almost monopoly-secondary mental healthcare service provider in southeast London. We retrieved data from its Clinical Records Interactive Search (CRIS) system as data source. Mortality was ascertained through nationwide tracing by the UK Office for National Statistics (ONS) linked to CRIS database on a monthly basis. A total of 43 people with AN died during the observation period. Standardized Mortality Ratio (SMR) with England and Wales population in 2012 as standard population for our study cohort was 5.21 (95% CI 3.77, 7.02). In univariate analyses, the comorbidity of SUD or PD was found to significantly increase the relative risks of mortality (HRs = 3.10, 95% CI 1.21, 7.92; and 2.58, 95% CI 1.23, 5.40, respectively). After adjustment for demographic and socioeconomic covariates as confounders, moderately but not significantly elevated risks were identified for SUD (adjusted HR = 1.39, 95% CI 0.53, 3.65) and PD (adjusted HR = 1.58, 95% CI 0.70, 3.56). These results suggest an elevated mortality in people with AN, which might be, at least partially, explained by the existence of the comorbidities SUD or PD.

Inflammation has been suggested to play a pathophysiological role in anorexia nervosa (AN). In this exploratory cross-sectional study, we measured serum concentrations of 40 inflammatory markers (including cytokines, chemokines, and adhesion molecules) and brain-derived neurotrophic factor (BDNF) in people with AN ( n = 27) and healthy controls (HCs) ( n = 13). Many of these inflammatory markers had not been previously quantified in people with AN. Eating disorder (ED) and general psychopathology symptoms were assessed. Body mass index (BMI) and body composition data were obtained. Interleukin (IL)-6, IL-15, and vascular cell adhesion molecule (VCAM)-1 concentrations were significantly elevated and concentrations of BDNF, tumor necrosis factor (TNF)-β, and vascular endothelial growth factor (VEGF)-A were significantly lower in AN participants compared to HCs. Age, BMI, and percentage body fat mass were identified as potential confounding variables for several of these inflammatory markers. Of particular interest is that most of the quantified markers were unchanged in people with AN, despite them being severely underweight with evident body fat loss, and having clinically significant ED symptoms and severe depression and anxiety symptoms. Future research should examine the replicability of our findings and consider the effect of additional potential confounding variables, such as smoking and physical activity, on the relationship between AN and inflammation.

Objective: Treatment options for severe, enduring anorexia nervosa (SE-AN) are limited. Non-invasive neuromodulation is a promising emerging intervention. Our study is a feasibility randomised controlled trial of repetitive transcranial magnetic stimulation (rTMS) in individuals with SE-AN, which aims to inform the design of a future large-scale trial., Design: Double-blind, parallel group, two-arm, sham-controlled trial., Setting: Specialist eating disorders centre., Participants: Community-dwelling people with anorexia nervosa, an illness duration of ≥3 years and at least one previous completed treatment., Interventions: Participants received 20 sessions (administered over 4 weeks) of MRI-guided real or sham high-frequency rTMS to the left dorsolateral prefrontal cortex in addition to treatment-as-usual., Outcomes: Primary outcomes were recruitment, attendance and retention rates. Secondary outcomes included body mass index (BMI), eating disorder symptoms, mood, quality of life and rTMS safety and tolerability. Assessments were conducted at baseline, post-treatment and follow-up (ie, at 0 month, 1 month and 4 months post-randomisation)., Results: Thirty-four participants (17 per group) were randomly allocated to real or sham rTMS. One participant per group was withdrawn prior to the intervention due to safety concerns. Two participants (both receiving sham) did not complete the treatment. rTMS was safe and well tolerated. Between-group effect sizes of change scores (baseline to follow-up) were small for BMI ( d= 0.2, 95% CI -0.49 to 0.90) and eating disorder symptoms ( d =0.1, 95% CI -0.60 to 0.79), medium for quality of life and moderate to large ( d =0.61 to 1.0) for mood outcomes, all favouring rTMS over sham., Conclusions: The treatment protocol is feasible and acceptable to participants. Outcomes provide preliminary evidence for the therapeutic potential of rTMS in SE-AN. Largest effects were observed on variables assessing mood. This study supports the need for a larger confirmatory trial to evaluate the effectiveness of multi-session rTMS in SE-AN. Future studies should include a longer follow-up period and an assessment of cost-effectiveness., Trial Registration Number: ISRCTN14329415; Pre-results., Competing Interests: Competing interests: OGO receives salary support from an NIHR Infrastructure grant for the Wellcome Trust/KCL Clinical Research Facility. Ulrike Schmidt is supported by an NIHR Senior Investigator Award. US, ASD and ICC receive salary support from the NIHR Mental Health BRC at SLaM NHS Foundation Trust and KCL., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Emotional, social, and neurocognitive factors are theorised to maintain anorexia nervosa (AN). Yet whether they predict outcomes or relate to clinical change remains unclear., Methods: Seventy-one consecutive adult outpatient eating disorder service referrals presenting with AN, who participated in a randomised controlled trial comparing 2 psychotherapies, were assessed for emotional processing, social cognition, and neurocognition pretherapy and posttherapy. Intention-to-treat analysis employed maximum-likelihood methods to model missing data. Baseline self-reported emotional processing, social cognitive, or neurocognitive task performance was entered into forward stepwise regression models with posttreatment clinical outcomes (weight, eating disorder psychopathology, psychosocial functioning) as dependent variables. Correlation analyses examined relationships between clinical and self-report/task score change., Results: Self-reported emotional avoidance (behavioural/cognitive avoidance, low acceptance) and submissive behaviour predicted clinical outcomes. Social cognitive (emotion recognition, emotional theory of mind) and neurocognitive performance (set-shifting, detail focus) had limited predictive ability., Conclusions: Emotional avoidance and submissiveness may represent maintenance factors for AN., (Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.)

Background: Anorexia nervosa (AN) is a disabling, deadly and costly mental disorder. Until recently, treatment recommendations were based on expert opinion and limited evidence. The aim of this systematic review is to synthesise recent evidence on established and emerging AN treatments and to forecast trends for future developments., Methods: We systematically review trials of established treatments and associated process outcome studies from the last 5 years, published since a previous review in this journal. 'Established' treatments were those that are widely used in AN, recommended by guidelines and/or have been tested in at least one large randomised controlled trial. Secondly, we summarise emerging treatments for AN, i.e. those that have only been (or are currently being) tested in proof-of concept, feasibility or pilot trials., Results: We identified 19 published trials of established treatments (15 of high or moderate quality), mostly assessing psychological therapies (n = 17). We also found 11 published trials of emerging treatments, and a total of 34 registered, as yet unpublished trials. Promising emerging treatments include cognitive remediation therapy, exposure therapy and non-invasive neuromodulation., Conclusions: Evidence generation on the treatment of AN has dramatically accelerated, with our understanding of the role of family-based approaches for adolescents more nuanced and a range of psychological approaches available for the treatment of adults. Evidence on emerging treatments and from forthcoming trials suggests that there is a shift towards more targeted brain-based interventions. Future studies need to focus on elucidating mechanisms of action of treatments and what works best for whom.

People with anorexia nervosa (AN) report socioemotional difficulties; however, measurement has been criticised for lacking ecological validity and the state or trait nature of difficulties remains unclear. Participants (n = 122) were recruited across 3 groups: people who are currently ill with AN (n = 40); people who recovered (RecAN, n = 18); healthy-control participants (n = 64). Participants completed clinical questionnaires and the Social Attribution Task. The Social Attribution Task involves describing an animation of moving shapes, scored for number of propositions offered, accuracy, and social relevance. Groups were compared cross-sectionally. Those with current AN were assessed prepsychological and postpsychological treatments. People with AN provided fewer propositions than other groups and fewer salient social attributions than healthy-control participants. Those who recovered scored intermediately and not significantly different from either group. Following treatment, people with AN demonstrated (nonsignificant) improvements, and no significance between group differences were observed. Findings suggest difficulties for people with AN in providing spontaneous social narrative and in identifying social salience., (Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.)

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10 -6 ), and rs7700147, an intergenic variant (P=2.93 × 10 -5 ). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

This pilot study assesses the impact of FREED (First Episode Rapid Early Intervention for Eating Disorders [ED]), a novel transdiagnostic service for emerging adults with recent ED onset, on clinical outcomes. Data were collected from 56 patients and 19 carers for 12 months following enrolment. FREED patients showed significant improvements in ED and other symptoms across time. Carers also showed psychological improvements. For FREED anorexia nervosa (AN) patients, body mass index (BMI) at initial clinical assessment was similar to that of comparable patients (audit cohort) seen in our service before (16.4 vs 16.1 kg/m 2 ). By start of treatment, because of their shorter wait, FREED-AN had gained weight whereas audit patients had lost (16.7 vs 15.8 kg/m 2 ). This difference continued throughout treatment, and at 12 months, nearly 60% FREED-AN patients returned to a BMI of 18.5 or greater. FREED shows promise as a service model for emerging adults with EDs., (Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.)

Objectives: To compare the clinical outcomes of adolescents and young adults with anorexia nervosa (AN) comorbid with broad autism spectrum disorder (ASD) or ASD traits., Method: The developmental and well-being assessment and social aptitude scale were used to categorize adolescents and young adults with AN (N = 149) into those with ASD traits (N = 23), and those who also fulfilled diagnostic criteria for a possible/probable ASD (N = 6). We compared both eating disorders specific measures and broader outcome measures at intake and 12 months follow-up., Results: Those with ASD traits had significantly more inpatient/day-patient service use (p = .015), as well as medication use (p < .001) at baseline. Both groups had high social difficulties and poorer global functioning (strengths and difficulties questionnaire) at baseline, which improved over time but remained higher at 12 months in the ASD traits group (p = .002). However, the improvement in eating disorder symptoms at 12 months was similar between groups with or without ASD traits. Treatment completion rates between AN only and ASD traits were similar (80.1 vs. 86.5%)., Discussion: Adolescents with AN and ASD traits show similar reductions in their eating disorder symptoms. Nevertheless, their social difficulties remain high suggesting that these are life-long difficulties rather than starvation effects., (© 2018 Wiley Periodicals, Inc.)

Background: There is a lack of evidence pointing to the efficacy of any specific psychotherapy for adults with anorexia nervosa (AN). The aim of this study was to compare three psychological treatments for AN: Specialist Supportive Clinical Management, Maudsley Model Anorexia Nervosa Treatment for Adults and Enhanced Cognitive Behavioural Therapy., Method: A multi-centre randomised controlled trial was conducted with outcomes assessed at pre-, mid- and post-treatment, and 6- and 12-month follow-up by researchers blind to treatment allocation. All analyses were intention-to-treat. One hundred and twenty individuals meeting diagnostic criteria for AN were recruited from outpatient treatment settings in three Australian cities and offered 25-40 sessions over a 10-month period. Primary outcomes were body mass index (BMI) and eating disorder psychopathology. Secondary outcomes included depression, anxiety, stress and psychosocial impairment., Results: Treatment was completed by 60% of participants and 52.5% of the total sample completed 12-month follow-up. Completion rates did not differ between treatments. There were no significant differences between treatments on continuous outcomes; all resulted in clinically significant improvements in BMI, eating disorder psychopathology, general psychopathology and psychosocial impairment that were maintained over follow-up. There were no significant differences between treatments with regard to the achievement of a healthy weight (mean = 50%) or remission (mean = 28.3%) at 12-month follow-up., Conclusion: The findings add to the evidence base for these three psychological treatments for adults with AN, but the results underscore the need for continued efforts to improve outpatient treatments for this disorder. Trial Registration Australian New Zealand Clinical Trials Registry (ACTRN 12611000725965) http://www.anzctr.org.au/.

Aim: The aim of the study is to establish the acceptability, feasibility and approximate size of the effect of adding a carer intervention [Experienced Caregivers Helping Others (ECHO)] to treatment as usual (TAU) for adolescents with anorexia nervosa., Methods: The study is a pilot randomised trial comparing TAU (n = 50) alone or TAU plus ECHO with (n = 50) or without (n = 49) telephone guidance. Effect sizes (ESs) were regression coefficients standardised by baseline standard deviations of measure., Results: Although engagement with ECHO was poor (only 36% of carers in the ECHO group read over 50% of the book), there were markers of intervention fidelity, in that caregivers in the ECHO group showed a moderate increase in carer skills (ES = 0.4) at 12 months and a reduction in accommodating and enabling behaviour at 6 months (ES = 0.17). In terms of efficacy, in the ECHO group, carers spent less time care giving (ES = 0.40, p = 0.04) at 1 year, and patients had a minor advantage in body mass index (ES = 0.17), fewer admissions, decreased peer problems (ES = -0.36) and more pro-social behaviours (ES = 0.53). The addition of telephone guidance to ECHO produced little additional benefit., Conclusions: The provision of self-management materials for carers to standard treatment for adolescent anorexia nervosa shows benefits for both carers and patients. This could be integrated as a form of early intervention in primary care. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association., (Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.)