BackgroundThere is a need for improved understanding of why 20-30% of individuals with anorexia nervosa (AN) develop a severe and enduring form of illness (SE-AN). Previously, we reported differences in proactive inhibition (a pre-emptive slowing of responses) in individuals with AN compared to healthy controls (after controlling for intolerance of uncertainty). The present study is a preliminary exploration of proactive inhibition in which we compared women with SE-AN with healthy comparison (HC) women and explored its association with restrictive/avoidant eating behaviours. MethodsThirty-four women with SE-AN (defined by >3 years of illness and a previous unsuccessful course of eating disorder treatment) and 30 HCs completed (a) a cued reaction time task, to assess proactive inhibition, and (b) questionnaires assessing restrictive/avoidant eating behaviours and intolerance of uncertainty. ResultsBoth SE-AN and HC participants showed slower reaction times under conditions of uncertainty, indicating proactive inhibition in both groups. There was a main effect of group, with SE-AN participants showing significantly slower reaction times compared to HC. There was no interaction between group and condition, suggesting that individuals with SE-AN did not differ in proactive inhibition compared to HCs. However, post-hoc analysis between-group tests for each trial type revealed that group differences were only present under conditions of uncertainty. Proactive inhibition was not significantly associated with self-reported restrictive/avoidant eating behaviours, including when taking intolerance of uncertainty into consideration. ConclusionsIt is unlikely that proactive inhibition contributes to avoidant and restrictive eating behaviours seen in SE-AN. Our findings suggest that the SE-AN group are relatively more cautious when responding under conditions of uncertainty. Longitudinal studies and between-group comparisons of individuals across different stages of illness will be required to elucidate the way in which proactive inhibition is specifically implicated in SE-AN, rather than in AN more generally.

Background/Objectives: Recent research has established that metabolic factors may increase the vulnerability to develop anorexia nervosa (AN). The aim of this study was to explore the serum concentrations of leptin, insulin-like growth factor-1 (IGF-1), insulin and insulin receptor substrate (IRS-1) as possible state or trait biomarkers for AN in the acute and recovery (recAN) phases. Our secondary aim was to test associations between the tested markers and demographic and clinical characteristics. Methods: This cross-sectional study included data from 56 participants with AN, 24 recAN participants and 51 healthy controls (HCs). Enzyme-linked immunosorbent assays (ELISAs) were used to quantify serum concentrations of leptin, IGF-1, insulin and IRS-1. An analysis of covariance (ANCOVA) and linear regression models were utilised to test our results. Results: There were significant differences with a large effect size between the groups for serum leptin (p < 0.001; d = 0.80), whereby people with AN had lower leptin than those with recAN (p = 0.023; d = 0.35) and HCs (p < 0.001; d = 0.74). The between-group comparison of IGF-1 did not reach significance, although the effect size was moderate (d = 0.6) and was driven by lower levels of IGF-1 in people with acute AN compared to HCs (p = 0.036; d = 0.53). Serum insulin and IRS-1 did not differ between groups. Conclusions: Low leptin levels seen in individuals with AN may be due to starvation leading to fatty tissue depletion. Understanding the regulation of IGF-1 and insulin signalling over the course of the disorder requires further investigation.

Prior research has found altered levels of cytokines in people with eating disorders (EDs). This study is an update of a previous meta-analysis, including longitudinal analyses and machine learning heterogeneity analyses (MetaForest). This pre-registered ( https://osf.io/g6d3f ) systematic review and meta-analysis following PRISMA guidelines assessed studies from four databases (PubMed, Web of Science, MEDLINE, PsycINFO) reporting cytokine concentrations in people with EDs until 10th November 2024. Random-effects models were utilised for all meta-analyses. Twenty-four new studies are incorporated, resulting in a total of 43 studies included in meta-analyses. Interleukin (IL)−6 and IL-15 are higher, and IL-7 lower, in anorexia nervosa (AN) compared with controls. When controlling for outliers, tumour necrosis factor (TNF)-α, IL-1β, IL-4, IL-8, IL-10, interferon (IFN)-γ, monocyte chemoattractant protein (MCP) and transforming growth factor (TGF)-β are similar between AN and controls. Longitudinally, IL-6 is lower in AN at follow-up compared to baseline, although this may be an artefact of publication bias. TNF-α and IL-1β do not change longitudinally. There are largely no differences in IL-6 and TNF-α in bulimia nervosa (BN) and there are insufficient studies to perform meta-analyses for binge eating disorder or other EDs. In acute AN, concentrations of IL-6 and IL-15 are elevated and IL-7 is decreased, with preliminary but unconclusive evidence for small decreases in IL-6 over the course of weight restoration. Other cytokines considered to have broadly pro-inflammatory functions are not increased in AN. In BN, there is little evidence for increases in pro-inflammatory cytokines, but the evidence base is limited. This study looked at how certain immune system markers, called cytokines, are affected in people with eating disorders (EDs). Previous research suggested that people with EDs might have altered levels of these markers. In this study, 43 studies were analysed to compare cytokine levels in people with anorexia nervosa (AN), bulimia nervosa (BN), and other EDs. It was found that people with AN had higher levels of certain cytokines (IL-6 and IL-15) and lower levels of others (IL-7), when compared to healthy people. For bulimia nervosa, there was little evidence of altered cytokine levels. These findings are important because they may help improve understanding of the immune system’s role in EDs and suggest areas for future research. Keeler et al. report an updated meta-analysis of peripheral cytokine concentrations in individuals with eating disorders. Results reveal elevations in interleukin (IL)-6 and IL-15 and reductions in IL-7 in people with anorexia nervosa in comparison to healthy controls, and no elevations in pro-inflammatory cytokines in people with bulimia nervosa.

Background A substantial proportion of anorexia nervosa patients require intensive treatments, commonly inpatient or day-patient treatment. The relative merits of these treatments for adults with anorexia nervosa are unknown. Therefore, a trial investigating the clinical effectiveness and cost-effectiveness of inpatient treatment-as-usual versus a stepped-care day-patient approach in adults with anorexia nervosa (DAISIES) was commissioned. This trial terminated prematurely due to poor recruitment, mainly resulting from COVID-19’s impact on service provision. Objective We describe the rationale, methods and available outcomes of the DAISIES trial. Reasons behind the trial’s failure and implications for future research are investigated. Design A two-arm multicentre open-label parallel-group non-inferiority randomised controlled trial, evaluating the effectiveness, acceptability and cost-effectiveness of two intensive treatments for adults with severe anorexia nervosa. Setting Specialist eating-disorder services in the United Kingdom with inpatient and/or day-patient treatment facilities. Participants Adults (age 17 +) with severe anorexia nervosa (body mass index ≤ 16 kg/m 2 ) requiring intensive treatment and (optionally) their carers. Intended sample size: 386. Interventions Inpatient treatment-as-usual and a stepped-care day-patient treatment approach (with the option of initial inpatient treatment for medical stabilisation). Main outcome measures The primary outcome was body mass index at 12 months post randomisation. Qualitative interviews conducted during the trial included semistructured interviews to investigate patients’, families’ and clinicians’ views on treatments. Results During the 16-month recruitment period (November 2020 to March 2022), 53 patients were approached. Of these, 15 were enrolled and randomly allocated to the inpatient treatment-as-usual ( n = 7) or day-patient treatment ( n = 8) treatment arms. All participants were female with a mean (standard deviation) age of 24.8 (9.1) years and a mean (standard deviation) body mass index of 14.4 (1.6) kg/m 2 . Patients’ body mass indexes had increased similarly in both groups at 12 months. Participants perceived the stepped-care day-patient treatment approach to be more acceptable than inpatient treatment-as-usual. Qualitative interviews with patients, carers and clinicians suggested valued (e.g. multidisciplinary provision of care) and disliked (e.g. perceived over-focus on weight gain) aspects of treatment. Investigation of the reasons behind the trial’s failure revealed strong treatment preferences among patients as the most common reason for non-participation, alongside the impact of COVID-19 on service provision. Limitations The main trial questions could not be answered due to low participant numbers. Conclusions No conclusions can be drawn concerning the clinical and cost-effectiveness of inpatient treatment-as-usual or stepped-care day-patient treatment. The day-patient treatment approach was perceived more positively by patients and carers. Service-related (e.g. reduced clinician time for research), patient-related (e.g. treatment preferences) and wider systemic factors (e.g. reduced service capacity and patient throughput nationally during COVID-19) seem to have contributed to the failure of the DAISIES trial. Future work Despite the trial’s failure, the need to investigate the effectiveness and experience of intensive treatments of adult anorexia nervosa remains. Alternative trial designs incorporating patient preferences and investigating community-based intensive treatment options have potential to improve acceptability and recruitment. Funding This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number HTA 17/123/03.

Background:Timely intervention is beneficial to the effectiveness of eating disorder (ED) treatment, but limited capacity within ED services means that these disorders are often not treated with sufficient speed. This service evaluation extends previous research into guided self-help (GSH) for adults with bulimic spectrum EDs by assessing the feasibility, acceptability, and preliminary effectiveness of virtually delivered GSH using videoconferencing.Method:Patients with bulimia nervosa (BN), binge eating disorder (BED) and other specified feeding and eating disorders (OSFED) waiting for treatment in a large specialist adult ED out-patient service were offered virtually delivered GSH. The programme used an evidence-based cognitive behavioural self-help book. Individuals were supported by non-expert coaches, who delivered the eight-session programme via videoconferencing.Results:One hundred and thirty patients were allocated to a GSH coach between 1 September 2020 and 30 September 2022; 106 (82%) started treatment and 78 (60%) completed treatment. Amongst completers, there were large reductions in ED behaviours and attitudinal symptoms, measured by the ED-15. The largest effect sizes for change between pre- and post-treatment were seen for binge eating episode frequency (d = -0.89) and concerns around eating (d = -1.72). Patients from minoritised ethnic groups were over-represented in the non-completer group.Conclusions:Virtually delivered GSH is feasible, acceptable and effective in reducing ED symptoms amongst those with bulimic spectrum disorders. Implementing virtually delivered GSH reduced waiting times, offering a potential solution for long waiting times for ED treatment. Further research is needed to compare GSH to other brief therapies and investigate barriers for patients from culturally diverse groups.

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: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.

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.

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/m2 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.

It is likely that the low BDNF and IGF-1 levels found in AN are consequences of starvation, which are reversible with weight restoration. The increase in BDNF and IGF-1 during therapeutic weight restoration might improve neuroplasticity, which is the basis of learning, and thus psychotherapeutic success.

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.

Abstract 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

Background Admissions to intensive treatment (i.e., inpatient [IP] and/or day patient [DP]) for individuals with severe anorexia nervosa (AN) are common. Growing literature indicates potential risks and benefits of each intensive treatment approach; however, existing research has focused on patient and carer perspectives of these treatments. Also, there is scant empirical evidence available for guiding the parameters of intensive treatments for AN. We therefore explored clinicians’ perspectives and experience of supporting adults with severe AN in intensive settings. Methods We conducted twenty one semi-structured interviews with clinicians who deliver intensive treatments (i.e., IP and/or DP) for individuals with severe AN across four specialist Eating Disorder Services in the United Kingdom between May 2020 and June 2021. We asked clinicians about their views and experiences of supporting individuals with severe AN in intensive treatment settings and the challenges and opportunities associated with IP and DP treatment. Data were analysed using reflexive thematic analysis supported by NVivo software. Results Five broad and interrelated themes were identified: (1) Intensive Support; (2) The Severity of Patients’ Illnesses; (3) Hope and Recovery; (4) Which Treatment When; (5) Limited Resources; and (6) Carer Burden. We identified various similarities between the two intensive treatment approaches, including the value of intensive and multidisciplinary support and carer involvement, and the challenge of managing complex and unique needs in resource-limited intensive settings. We also found differences in the relationship of treatment to patients’ home environments, the necessity of patient motivation, and the management of risk. Conclusions Both intensive treatment settings are valued by clinicians; however, there are unique challenges and opportunities for supporting individuals with severe AN within each. Our findings suggest DP treatment may be used as an alternative to IP treatment for individuals with severe AN. However, clear questions remain over which intensive treatment setting is best suited to which patient when and should be the focus of future research.

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-) 1α, IL-1β, 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-) 1α, MIP-1β, 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.

Alterations in certain inflammatory markers have been found in individuals with anorexia nervosa (AN). However, their relation to clinical characteristics has not been extensively explored, nor is it clear whether they are trait or state features of the disorder. This cross-sectional study measured serum concentrations of 36 inflammatory markers in people with acute AN (n = 56), recovered AN (rec-AN; n = 24) and healthy controls (HC; n = 51). The relationship between body mass index (BMI), eating disorder psychopathology, depression symptoms and inflammatory markers was assessed. Statistical models controlled for variables known to influence cytokine concentrations (i.e., age, ethnicity, smoking status and medication usage). Overall, most inflammatory markers including pro-inflammatory cytokines were unchanged in AN and rec-AN. However, in AN and rec-AN, concentrations of macrophage inflammatory protein (MIP)-1β were lower than HCs. Interleukin (IL)-7 and IL-12/IL-23p40 were reduced in AN, and concentrations of macrophage-derived chemokine, MIP-1α and tumor necrosis factor-α were reduced in rec-AN compared to HC. In conclusion, a reduction in MIP-1β may be a trait marker of the illness, whereas reductions in IL-7 and IL-12/IL-23p40 may be state markers. The absence of increased pro-inflammatory cytokines in AN is contradictory to the wider literature, although the inclusion of covariates may explain our differing findings.

Background Development of pharmaceutical interventions for schizophrenia emphasizes clinical efficacy and subsequent effectiveness and cost-effectiveness. However, given the many side effects of antipsychotic medication, it is important to consider the importance of different side effects on the preferences that people with schizophrenia have for different drugs. This study aims to use a discrete choice experiment to elicit patient preferences for antipsychotic medication with different side effects profiles. Method Preferences for antipsychotic side effects were investigated using a discrete choice experiment conducted in south London. 297 participants with a schizophrenia diagnosis who had been in receipt of anti-psychotic medication for a minimum of one month were included. Participants were presented with a sequence of choices involving five antipsychotic side effects (attributes) each with four levels. Conditional logit models were used to determine the side effects most (and least) likely to be preferred by people prescribed antipsychotics. Subgroup analyses explored the impact of side effects by gender, ethnicity, age, and symptoms. Results As expected, participants tended to value antipsychotic medications offering the least side effects, and the model coefficients were in the expected direction. For the whole sample and subgroups, memory and fatigue were the most important side effects, whereas palpations and mobility were the least important. Conclusions Participants had a strong preference for medications with the least side effects on memory and fatigue. These findings should inform drug development by pharmaceutical companies and prescribing practice by clinicians.

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.

Background Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN), but associated neurobiological changes are poorly understood. This study investigated the effect of rTMS treatment on regional cerebral blood flow (CBF) and whether any observed changes in CBF are associated with changes in clinical outcomes in people with SE-AN. Methods As part of a randomised sham-controlled feasibility trial of 20 sessions of high-frequency rTMS to the left dorsolateral prefrontal cortex, 26 of 34 trial participants completed arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) to quantify regional and global resting state CBF before (pre-randomisation baseline) and after real or sham treatment (1-month post-randomisation). A group of healthy females ( n = 30) were recruited for baseline comparison. Clinical outcomes, including BMI, and depression and anxiety symptoms, were assessed at baseline, 1-, 4-, and 18-months post-randomisation. Results No group differences in regional CBF were identified between the SE-AN and healthy comparison participants. A significant treatment-by-time interaction in a medial temporal lobe cluster with the maximal peak in the right amygdala was identified, reflecting a greater reduction in amygdala CBF following real rTMS compared to sham. Participants with the greatest rTMS-related reduction in amygdala CBF (i.e., between baseline and 1-month post-randomisation) showed the greatest sustained weight gain at 18-months post-randomisation. Higher baseline CBF in the insula predicted greater weight gain between baseline and 1-month post-randomisation and between baseline and 4-months post-randomisation. Conclusions This exploratory pilot study identified rTMS treatment related changes in CBF in adults with SE-AN and these were associated with changes in weight. Our preliminary findings also suggest that CBF (as measured by ASL fMRI) may be a marker of rTMS treatment response in this patient group. Future rTMS studies in AN should employ longitudinal neuroimaging to further explore the neurobiological changes related to rTMS treatment. Trial registration ISRCTN14329415 , registered 23rd July 2015.

Background Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment option for people with severe, enduring anorexia nervosa (SE-AN). As depression is often comorbid with AN, antidepressant medication is commonly prescribed to this patient group. Concurrent antidepressant medications may affect the rTMS treatment response. Therefore, in a secondary analysis of data from a feasibility trial, we explored the effect of antidepressant medication on responses to rTMS in people with SE-AN. Methods Twenty-six participants with SE-AN received 20 sessions (over 4 weeks) of neuronavigated high-frequency real rTMS to the left dorsolateral prefrontal cortex. Eating disorder (ED) and general psychopathology symptoms were assessed at baseline, post-treatment and at a 4-month follow-up. Results Participants taking antidepressants ( n = 16) for the duration of the rTMS treatment had a greater reduction in ED symptoms at the 4-month follow-up, compared to those not taking antidepressants ( n = 10). Antidepressant status was not however associated with significant changes in mood outcomes. Conclusions In people with SE-AN receiving rTMS treatment, preliminary findings suggest a potential synergistic effect of antidepressant medication in reducing ED symptomatology. There was however no associated reduction in affective symptoms i.e., the effect does not seem to be related to changes in mood. The sample in this exploratory study was small and heterogenous. However, the preliminary results provide a basis for hypothesis generation for future studies.