'My dad was like "it's your brain, what are you doing?"': Participant experiences of repetitive transcranial magnetic stimulation treatment in severe enduring anorexia nervosa.

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.

The effect of repetitive transcranial magnetic stimulation on food choice-related self-control in patients with severe, enduring anorexia nervosa.

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.

Repetitive transcranial magnetic stimulation treatment in severe, enduring anorexia nervosa: An open longer-term follow-up.

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/m2 ), 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.

Therapist written goodbye letters: evidence for therapeutic benefits in the treatment of anorexia nervosa.

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.

Identifying disordered eating behaviours in adolescents: how do parent and adolescent reports differ by sex and age?

This study investigated the prevalence of disordered eating cognitions and behaviours across mid-adolescence in a large European sample, and explored the extent to which prevalence ratings were affected by informant (parent/adolescent), or the sex or age of the adolescent. The Development and Well-Being Assessment was completed by parent-adolescent dyads at age 14 (n = 2225) and again at age 16 (n = 1607) to explore the prevalence of 7 eating disorder symptoms (binge eating, purging, fear of weight gain, distress over shape/weight, avoidance of fattening foods, food restriction, and exercise for weight loss). Informant agreement was assessed using kappa coefficients. Generalised estimating equations were performed to explore the impact of age, sex and informant on symptom prevalence. Slight to fair agreement was observed between parent and adolescent reports (kappa estimates between 0.045 and 0.318); however, this was largely driven by agreement on the absence of behaviours. Disordered eating behaviours were more consistently endorsed amongst girls compared to boys (odds ratios: 2.96-5.90) and by adolescents compared to their parents (odds ratios: 2.71-9.05). Our data are consistent with previous findings in epidemiological studies. The findings suggest that sex-related differences in the prevalence of disordered eating behaviour are established by mid-adolescence. The greater prevalence rates obtained from adolescent compared to parent reports may be due to the secretive nature of the behaviours and/or lack of awareness by parents. If adolescent reports are overlooked, the disordered behaviour may have a greater opportunity to become more entrenched.

Temporal Discounting and the Tendency to Delay Gratification across the Eating Disorder Spectrum.

Bulimia nervosa (BN) and binge eating disorder (BED) have been associated with poorer reward-related inhibitory control, reflected by a reduced tendency to delay gratification. The opposite has been reported in anorexia nervosa (AN), but differences have not been directly compared across eating disorders (EDs). This study investigated self-reported (Delaying Gratification Inventory) and task-based (temporal discounting) inhibitory control in 66 women with an ED and 28 healthy controls (HCs). Poorer task-based inhibitory control was observed in the BN compared with the AN group and poorer self-reported inhibitory control in the BN and in the BED groups compared with the AN and the HC groups, suggesting that reward-related inhibitory control varies across EDs. Symptom severity correlated with poorer self-reported (but not task-based) inhibitory control across the EDs. These data provide some support for transdiagnostic mechanisms and highlight the importance of addressing perceived loss of control in the treatment of EDs. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Increased temporal discounting in bulimia nervosa.

OBJECTIVE: There is evidence that people with eating disorders display altered intertemporal choice behavior (the degree of preference for immediate rewards over delayed rewards). Compared to healthy controls (HC), individuals with anorexia nervosa and binge-eating disorder show decreased and increased rates of temporal discounting (TD; the devaluation of delayed rewards), respectively. This is the first study to investigate TD in people with bulimia nervosa (BN). METHOD: Thirty-nine individuals with BN (2 men) and 53 HC (9 men) completed a hypothetical monetary TD task. Over 80 binary choices, participants chose whether they would prefer to receive a smaller amount of money available immediately or a larger amount available in 3 months. Self-reported ability to delay gratification (the behavioral opposite of TD) was also measured. RESULTS: Individuals with BN showed greater TD (i.e., a preference for smaller-sooner rewards) and a decreased self-reported capacity to delay gratification relative to HC. Experimental groups did not differ in age, gender ratio, or BMI. DISCUSSION: Increased rates of TD may contribute to some of the core symptoms of BN that appear to involve making choices between immediate and delayed rewards (i.e., binge-eating and compensatory behaviors). Altered intertemporal choice behavior could therefore be a relevant target for intervention in this patient group. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1077-1081).

Written case formulations in the treatment of anorexia nervosa: Evidence for therapeutic benefits.

OBJECTIVE: Case formulation is a core component of many psychotherapies and formulation letters may provide an opportunity to enhance the therapeutic alliance and improve treatment outcomes. This study aimed to determine if formulation letters predict treatment satisfaction, session attendance, and symptom reductions in anorexia nervosa (AN). It was hypothesized that higher quality formulation letters would predict greater treatment satisfaction, a greater number of attended sessions, and greater improvement in eating disorder symptoms. METHOD: Patients were adult outpatients with AN (n = 46) who received Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) in the context of a clinical trial. A Case Formulation Rating Scheme was used to rate letters for adherence to the MANTRA model and use of a collaborative, reflective, affirming stance. Analyses included linear regression and mixed models. RESULTS: Formulation letters that paid attention to the development of the AN predicted greater treatment acceptability ratings (p = 0.002). More reflective and respectful letters predicted greater reductions in Eating Disorder Examination scores (p = 0.003). DISCUSSION: Results highlight the potential significance of a particular style of written formulation as part of treatment for AN. Future research should examine applicability to other psychiatric disorders. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:874-882).

Two-year follow-up of the MOSAIC trial: A multicenter randomized controlled trial comparing two psychological treatments in adult outpatients with broadly defined anorexia nervosa.

OBJECTIVE: This study reports follow-up data from a multicenter randomized controlled trial (n = 142) comparing the Maudsley Model of Anorexia Nervosa Treatment for Adults (MANTRA) with Specialist Supportive Clinical Management (SSCM) in outpatients with broadly defined anorexia nervosa (AN). At 12 months postrandomization, all patients had statistically significant improvements in body mass index (BMI), eating disorder (ED) symptomatology and other outcomes with no differences between groups. MANTRA was more acceptable to patients. The present study assessed whether gains were maintained at 24 months postrandomization. METHODS: Follow-up data at 24 months were obtained from 73.2% of participants. Outcome measures included BMI, ED symptomatology, distress, impairment, and additional service utilization during the study period. Outcomes were analyzed using linear mixed models. RESULTS: There were few differences between groups. In both treatment groups, improvements in BMI, ED symptomatology, distress levels, and clinical impairment were maintained or increased further. Estimated mean BMI change from baseline to 24 months was 2.16 kg/m(2) for SSCM and 2.25 kg/m(2) for MANTRA (effect sizes of 1.75 and 1.83, respectively). Most participants (83%) did not require any additional intensive treatments (e.g., hospitalization). Two SSCM patients became overweight through binge-eating. DISCUSSION: Both treatments have value as outpatient interventions for patients with AN. © 2016 Crown copyright. International Journal of Eating Disorders. (Int J Eat Disord 2016; 49:793-800).

Physical activity and the drive to exercise in anorexia nervosa.

OBJECTIVES: To investigate physical activity (PA) and drive for exercise in anorexia nervosa (AN) in relation to eating disorder (ED) pathology and anxiety. METHOD: Female participants were recruited into four groups: AN outpatients (n = 37), AN inpatients (n = 18), an anxiety group (n = 34), and healthy controls (HCs; n = 30). PA was measured by actigraphy and self-report together with drive/reasons for exercise, ED pathology, anxiety, depression, stress, BMI, and body composition. RESULTS: ED psychopathology, general psychopathology, and physiological measures were consistent with diagnosis. All groups showed a wide range in activity, especially on self-report. No significant group differences were observed in objective PA levels, yet AN groups reported 57-92% higher total activity than HCs. Outpatients reported more walking and moderate exercise than HCs, and inpatients reported more walking but less moderate and vigorous activity than all other groups. AN groups had significantly higher drive to exercise and valued "improving tone" as important and health and enjoyment as less important reasons to exercise. DISCUSSION: Self-perceived activity rather than objective data may partly explain the increased activity reported in AN. Drive to exercise in AN appears to be more related to ED pathology than to anxiety.

The potential of neurofeedback in the treatment of eating disorders: a review of the literature.

Neurofeedback is defined as the training of voluntary regulation of localised neural activity using real-time feedback through a brain-computer interface. It has shown initial success as a potential clinical treatment tool in proof of concept studies, but has yet to be evaluated with respect to eating disorders. This paper (i) provides a brief overview of the current status of eating disorder treatments; (ii) describes the studies to date that use neurofeedback involving electroencephalography, real-time functional magnetic resonance imaging or near-infrared spectroscopy; and (iii) considers the potential of these technologies as treatments for eating disorders.

A preliminary exploration of the effect of concurrent antidepressant medication on responses to high-frequency repetitive transcranial magnetic stimulation (rTMS) in severe, enduring anorexia nervosa.

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.

Clinicians' views on neuromodulation as a treatment for eating disorders: A qualitative study.

BACKGROUND: Neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS), are emerging as promising treatment options in eating disorders (EDs). To date, the views of ED clinicians regarding these interventions have not been explored. METHODS: Eighteen clinicians were recruited from a specialist ED Service in London, UK. Following a short educational presentation on rTMS, tDCS and DBS, they completed a semi-structured interview to explore their views on the use of these treatment options in EDs. RESULTS: Clinician knowledge of neuromodulation techniques was low. They raised safety and ethical (particularly capacity to consent) concerns mainly with regard to DBS. Neuromodulation treatments were considered most appropriate as an adjunct to psychotherapy and for patients with severe, enduring illness (who had completed previous psychological treatments). CONCLUSIONS: Improving clinicians' knowledge and understanding of neuromodulation is fundamental for bridging the gap between research and clinical work. This is especially so given the predominance of psychological theory and practice in the treatment of EDs.

A pilot study exploring the effect of repetitive transcranial magnetic stimulation (rTMS) treatment on cerebral blood flow and its relation to clinical outcomes in severe enduring anorexia nervosa.

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.

Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN). However, little is known about the neurobiological effects of this treatment. This study explored 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. Participants completed arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) before and after receiving 20 sessions (over 4 weeks) of real or sham rTMS. We found a greater reduction in amygdala CBF following real rTMS compared to sham rTMS. Participants with the greatest rTMS-related reduction in amygdala CBF showed the greatest sustained weight gain at an 18-month follow-up. Higher baseline CBF in the insula predicted greater weight gain during treatment and at a 4-month follow-up. This suggests 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 use longitudinal neuroimaging to further explore the neurobiological changes related to rTMS treatment.

Bad Things Come to Those Who Do Not Wait: Temporal Discounting Is Associated With Compulsive Overeating, Eating Disorder Psychopathology and Food Addiction.

The tendency to act on immediate pleasure-driven desires, due to the devaluation of future rewards [a process known as temporal discounting (TD)], has been associated with substance use disorders (SUD) and with conditions characterised by compulsive overeating. The study involved a large inclusive participant sample (i.e., no diagnostic or exclusion criteria were applied). They were recruited/assessed online and we investigated whether TD was related to compulsive overeating and associated problems. Participants [N = 432, (48 males)] completed an online survey, which included a hypothetical monetary TD task, the Eating Disorder Examination-Questionnaire (EDE-Q), the Yale Food Addiction Scale (YFAS) and the Depression Anxiety and Stress Scales (DASS). TD correlated with frequency of compulsive overeating and compensatory behaviours, with eating disorder psychopathology, with scores on the YFAS, and with body mass index (BMI). As our study shows that elevated rates of TD are associated with a range of behaviours/measures, we propose that it is more likely that elevated TD rates are a predisposing factor rather than a consequence of the behaviour, i.e., elevated rates of TD contribute to pathological eating-related behaviours; however, a bi-directional explanation is also possible. Future research should investigate whether interventions aimed at reducing TD have clinical potential for treating problematic eating behaviours.

Neural Correlates of Failed Inhibitory Control as an Early Marker of Disordered Eating in Adolescents.

BACKGROUND: Binge eating and other forms of disordered eating behavior (DEB) are associated with failed inhibitory control. This study investigated the neural correlates of failed inhibitory control as a potential biomarker for DEB. METHODS: The study used prospective longitudinal data from the European IMAGEN study adolescent cohort. Participants completed baseline assessments (questionnaires and a brain scan [functional magnetic resonance imaging]) at 14 years of age and a follow-up assessment (questionnaires) at 16 years of age. Self-reported binge eating and/or purging were used to indicate presence of DEB. Neural correlates of failed inhibition were assessed using the stop signal task. Participants were categorized as healthy control subjects (reported no DEB at both time points), maintainers (reported DEB at both time points), recoverers (reported DEB at baseline only), and developers (reported DEB at follow-up only). Forty-three individuals per group with complete scanning data were matched on gender, age, puberty, and intelligence (N = 172). RESULTS: At baseline, despite similar task performance, incorrectly responding to stop signals (failed inhibitory control) was associated with greater recruitment of the medial prefrontal cortex and anterior cingulate cortex in the developers compared with healthy control subjects and recoverers. CONCLUSIONS: Greater recruitment of the medial prefrontal and anterior cingulate regions during failed inhibition accords with abnormal evaluation of errors contributing to DEB development. As this precedes symptom onset and is evident despite normal task performance, neural responses during failed inhibition may be a useful biomarker of vulnerability for DEB. This study highlights the potential value of prospective neuroimaging studies for identifying markers of illness before the emergence of behavior changes.

Neurostimulation in Clinical and Sub-clinical Eating Disorders: A Systematic Update of the Literature.

INTRODUCTION: Whilst psychological therapies are the main approach to treatment of eating disorders (EDs), advances in aetiological research suggest the need for the development of more targeted, brain-focused treatments. A range of neurostimulation approaches, most prominently repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS), are rapidly emerging as potential novel interventions. We have previously reviewed these techniques as potential treatments of EDs. AIM: To provide an update of the literature examining the effects of DBS, rTMS and tDCS on eating behaviours, body weight and associated symptoms in people with EDs and relevant analogue populations. METHODS: Using PRISMA guidelines, we reviewed articles in PubMed, Web of Science, and PsycINFO from 1st January 2013 until 14th August 2017, to update our earlier search. Studies assessing the effects of neurostimulation techniques on eating and weight-related outcomes in people with EDs and relevant analogue populations were included. Data from both searches were combined. RESULTS: We included a total of 32 studies (526 participants); of these, 18 were newly identified by our update search. Whilst findings are somewhat mixed for bulimia nervosa, neurostimulation techniques have shown potential in the treatment of other EDs, in terms of reduction of ED and associated symptoms. Studies exploring cognitive, neural, and hormonal correlates of these techniques are also beginning to appear. CONCLUSIONS: Neurostimulation approaches show promise as treatments for EDs. As yet, large wellconducted randomised controlled trials are lacking. More information is needed about treatment targets, stimulation parameters and mechanisms of action.

A meta-analysis of cytokine concentrations in eating disorders.

Cytokines are signalling molecules, which play an important role in both immune system function and brain development and function, and subsequently mental states and behaviour. Cytokines have been implicated in eating disorders (EDs) due to their role in psychological health, body weight and appetite regulation. This meta-analysis examined cross-sectional and longitudinal studies measuring concentrations of cytokines in individuals with EDs. Using PRISMA guidelines, we systematically reviewed relevant articles in PubMed, Web of Science, and MEDLINE. Random-effects meta-analyses were conducted for interleukin (IL)-1ß, IL-6, transforming growth factor (TGF)-ß, and tumor necrosis factor (TNF)-α, independently, firstly with all EDs combined and then stratified by ED diagnosis. Twenty-five studies were included: serum/plasma cytokine concentrations were measured in people with anorexia nervosa (AN) in 23 studies and bulimia nervosa (BN) in 4 studies. TNF-α and IL-6 were elevated in ED participants compared to healthy controls (HCs). Specifically, this pattern was seen only when comparing AN participants to HCs. Concentrations of these cytokines did not differ between people with BN and HCs. IL-1ß and TGF-ß did not differ between HCs and any ED group. Therefore, AN seems to be associated with elevated concentrations of TNF-α and IL-6. Considering the role of cytokines in appetite, mood regulation, and anxiety, these pro-inflammatory cytokines could be a potential future drug target to help people with AN, not only with weight gain, but also with various coexisting psychological problems. Future studies should consider confounding factors that affect cytokine concentrations and report ED-relevant clinical characteristics.

Randomised controlled feasibility trial of real versus sham repetitive transcranial magnetic stimulation treatment in adults with severe and enduring anorexia nervosa: the TIARA study.

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.

Proactive and reactive inhibitory control in eating disorders.

Altered inhibitory control has been implicated in the development and maintenance of eating disorders (ED), however it is unclear how different types of inhibitory control are affected across the EDs. We explored whether individuals with bulimia nervosa (BN), binge eating disorder (BED) and anorexia nervosa (AN) differed from healthy individuals (HC) on two types of motor inhibitory control: proactive inhibition (related to the preparation/initiation of a response) and reactive inhibition (withholding a response in reaction to a signal). Ninety-four women (28 AN, 27 BN, 11 BED, 28 HC) completed two neuropsychological tasks (a cued reaction time task and a stop signal task), and questionnaires assessing clinical variables, mood, anxiety, and inhibitory control. Self-reported inhibitory control was poorer in women with BN compared to the HC and AN groups, but greater in women with AN compared to all other groups. However, no group differences in reactive inhibition were observed. Proactive inhibition was augmented in women with AN compared to HC, and this was related to self-reported intolerance of uncertainty. The findings suggest that proactive inhibition may be a relevant target for behavioural interventions for AN, and call for further research into the relationship between intolerance of uncertainty and proactive inhibition.