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Pharmacological efforts to treat anorexia nervosa (AN) have predominantly repurposed medications that treat conditions with overlapping symptoms and yielded generally disappointing results. Despite limited empirical support, SSRIs are often prescribed to patients with AN. Whether SSRIs are effective in a subgroup of individuals with AN, such as those with depression, is not known. A secondary analysis of a randomized trial of fluoxetine versus placebo for relapse prevention in AN was conducted. Participants (  = 92) were weight-restored women with AN who completed the Beck Depression Inventory (BDI) at the time of randomization. BDI scores were dichotomized to reflect moderate/severe depression (BDI > 20,  = 26). A Cox Proportional Hazards model estimated the association of the level of depression, medication, and their interaction with time to relapse. Mixed effects models examined the effects of medication on symptom trajectories in high versus low depression groups and whether depression severity modified the effect of the drug on symptom trajectory. There was a significant interaction between medication and depression severity in time to relapse (hazard ratio = 0.46, 95% CI: [0.25, 0.85],  = .01). Depression severity modified the effect of fluoxetine on the time course of symptoms of depression (  = -0.27, 95% CI: [-0.42,-0.12],  = 0.001) and bulimia (  = -0.15, 95% CI: [-0.25,-0.05],  = 0.004) in the twelve month follow-up period. Fluoxetine was more effective than placebo in reducing relapse among more depressed, weight-restored individuals with AN. These results require replication but provide support for the use of antidepressant medication for patients with AN who remain depressed following weight restoration.

IntroductionAnorexia nervosa (AN) is a severe mental health condition associated with high mortality rates and significantly impaired quality of life. National guidelines outline psychotherapeutic interventions as treatments of choice for adults with AN, but outcomes are limited and therapy drop-out high, resulting in calls for new innovative treatments. The Specialist Psychotherapy with Emotion for Anorexia in Kent and Sussex (SPEAKS) research programme sought to develop the SPEAKS intervention avoiding some difficulties inherent in development of earlier interventions, such unclear hypotheses about change processes. SPEAKS focuses on a core hypothesised maintaining factor (emotional experience) with clear proposed model of change. The current feasibility trial aims to provide an initial test of SPEAKS and inform design of a full randomised controlled trial protocol.Methods and analysisThis study employs a multisite, single-arm, within-group, mixed-methods design. Up to 60 participants (36 therapy completers) meeting inclusion criteria will be offered the SPEAKS intervention instead of treatment-as-usual (TAU). SPEAKS is a weekly psychotherapy lasting nine to 12 months, provided by trained and experienced eating disorders therapists. All other clinical input remains inline with TAU. Acceptability will be assessed using VAS scales and end of therapy interview. Reach and recruitment, such as recruitment yield, will be monitored. To support sample size estimation and economic estimation, data pertaining to eating disorder-related symptoms will be recorded every 3 months, alongside service usage and intervention-specific measures. Videoed therapy sessions will inform model adherence. Additional analyses coding videoed therapy will test SPEAKS change process hypotheses.Ethics and disseminationEthical approval has been granted by London–Bromley Research Ethics Committee (NHS Rec Reference: 19/LO/1530). Data will be disseminated via high-impact, peer-reviewed journals (Open Access preferred), conferences, service user and charity networks (eg, UK charity BEAT) and through a free open conference hosted by National Health Service Trusts and Higher Education Institutions.Trial registration numberISRCTN11778891.Trial statusRecruitment began on 12 December 2019 and ends on 28 February 2021. All data will be collected and the trial ended by 28 February 2022.Protocol versionSPEAKS protocol V.3.0 (30 August 2020). Changes were made to the original protocol due to the COVID-19 pandemic. A further set of changes were made to incorporate the measures of change processes, resulting in this being the third version of the protocol.

Purpose Insomnia and anorexia nervosa (AN) are frequently comorbid, negatively affecting the evolution and the prognosis of AN. Within this framework, the management of sleep disorders appears as critical. The aim of this retrospective study is to assess, for the first time, the efficacy of cognitive and behavioural therapy for insomnia (CBT-I) on sleep disturbances in adolescents with AN. To do so, we investigated the impact of CBT-I on sleep disturbances and sleep-related outcomes, in BMI, AN symptoms, anxiety and depressive symptoms, emotionality and quality of life. These features were compared between two groups of patients with AN, one following CBT-I, and the other receiving the regular treatment at the psychiatric unit. Methods Data collection occurred between January and May 2022. The study included 42 adolescents in-treatment at the Eating Disorders care specialised unit at Salvator Hospital in Marseille. They were randomly assigned to the CBT-I group ( N  = 31) or the control group ( N  = 11). Several clinical elements were assessed using sleep diaries and self-report questionnaires. Results Participants undergoing CBT-I showed a significant improvement in sleep latency, total wake time and sleep efficacy, as well as in physical well-being. No significant effects were found regarding AN symptoms. Conclusion These preliminary findings provide support for CBT-I effectiveness in adolescents with AN, as shown by significant improvements in several sleep parameters, as well as in physical well-being. These promising results, underline the relevance of this topic and its potential benefits for a more appropriate treatment for adolescents with AN. Level of evidence: Level V, retrospective study.

Background Evidence from observational studies suggests an association between anxiety disorders and anorexia nervosa (AN), but causal inference is complicated by the potential for confounding in these studies. We triangulate evidence across a longitudinal study and a Mendelian randomization (MR) study, to evaluate whether there is support for anxiety disorder phenotypes exerting a causal effect on AN risk. Methods Study One assessed longitudinal associations of childhood worry and anxiety disorders with lifetime AN in the Avon Longitudinal Study of Parents and Children cohort. Study Two used two-sample MR to evaluate: causal effects of worry, and genetic liability to anxiety disorders, on AN risk; causal effects of genetic liability to AN on anxiety outcomes; and the causal influence of worry on anxiety disorder development. The independence of effects of worry, relative to depressed affect, on AN and anxiety disorder outcomes, was explored using multivariable MR. Analyses were completed using summary statistics from recent genome-wide association studies. Results Study One did not support an association between worry and subsequent AN, but there was strong evidence for anxiety disorders predicting increased risk of AN. Study Two outcomes supported worry causally increasing AN risk, but did not support a causal effect of anxiety disorders on AN development, or of AN on anxiety disorders/worry. Findings also indicated that worry causally influences anxiety disorder development. Multivariable analysis estimates suggested the influence of worry on both AN and anxiety disorders was independent of depressed affect. Conclusions Overall our results provide mixed evidence regarding the causal role of anxiety exposures in AN aetiology. The inconsistency between outcomes of Studies One and Two may be explained by limitations surrounding worry assessment in Study One, confounding of the anxiety disorder and AN association in observational research, and low power in MR analyses probing causal effects of genetic liability to anxiety disorders. The evidence for worry acting as a causal risk factor for anxiety disorders and AN supports targeting worry for prevention of both outcomes. Further research should clarify how a tendency to worry translates into AN risk, and whether anxiety disorder pathology exerts any causal effect on AN.

Background The resumption of menses is an important indicator of recovery in anorexia nervosa (AN). Patients with early-onset AN are at particularly great risk of suffering from the long-term physical and psychological consequences of persistent gonadal dysfunction. However, the clinical variables that predict the recovery of menstrual function during weight gain in AN remain poorly understood. The aim of this study was to investigate the impact of several clinical parameters on the resumption of menses in first-onset adolescent AN in a large, well-characterized, homogenous sample that was followed-up for 12 months. Methods A total of 172 female adolescent patients with first-onset AN according to DSM-IV criteria were recruited for inclusion in a randomized, multi-center, German clinical trial. Menstrual status and clinical variables (i.e., premorbid body mass index (BMI), age at onset, duration of illness, duration of hospital treatment, achievement of target weight at discharge, and BMI) were assessed at the time of admission to or discharge from hospital treatment and at a 12-month follow-up. Based on German reference data, we calculated the percentage of expected body weight (%EBW), BMI percentile, and BMI standard deviation score (BMI-SDS) for all time points to investigate the relationship between different weight measurements and resumption of menses. Results Forty-seven percent of the patients spontaneously began menstruating during the follow-up period. %EBW at the 12-month follow-up was strongly correlated with the resumption of menses. The absence of menarche before admission, a higher premorbid BMI, discharge below target weight, and a longer duration of hospital treatment were the most relevant prognostic factors for continued amenorrhea. Conclusions The recovery of menstrual function in adolescent patients with AN should be a major treatment goal to prevent severe long-term physical and psychological sequelae. Patients with premenarchal onset of AN are at particular risk for protracted amenorrhea despite weight rehabilitation. Reaching and maintaining a target weight between the 15 th and 20 th BMI percentile is favorable for the resumption of menses within 12 months. Whether patients with a higher premorbid BMI may benefit from a higher target weight needs to be investigated in further studies.

SummaryWe sought to determine whether low-magnitude mechanical stimulation (LMMS) normalizes bone turnover among adolescents hospitalized for anorexia nervosa (AN). Brief, daily LMMS prevents the decline in bone turnover typically seen during bed rest in AN. LMMS may have application for patients with AN in the inpatient setting to protect bone health.IntroductionMalnourished adolescents with AN requiring medical hospitalization are at high risk for rapid reduction in skeletal quality. Even short-term bed rest can suppress normal patterns of bone turnover. We sought to determine whether LMMS normalizes bone turnover among adolescents hospitalized for complications of AN.MethodsIn this randomized, double-blind trial, we prospectively enrolled adolescent females (n = 41) with AN, age 16.3 ± 1.9 years (mean ± SD) and BMI 15.6 ± 1.7 kg/m2. Participants were randomized to stand on a platform delivering LMMS (0.3 g at 32-37 Hz) or placebo platform for 10 min/day for 5 days. Serum markers of bone formation [bone-specific alkaline phosphatase (BSAP)], turnover [osteocalcin (OC)], and bone resorption [serum C-telopeptides (CTx)] were measured. From a random coefficients model, we constructed estimates and confidence intervals for all outcomes.ResultsBSAP decreased by 2.8% per day in the placebo arm (p = 0.03) but remained stable in the LMMS group (p = 0.51, pdiff = 0.04). CTx did not change with placebo (p = 0.56) but increased in the LMMS arm (+6.2% per day, p = 0.04; pdiff = 0.01). Serum OC did not change in either group (p > 0.70).ConclusionsBed rest during hospitalization for patients with AN is associated with a suppression of bone turnover, which may contribute to diminished bone quality. Brief, daily LMMS prevents a decline in bone turnover during bed rest in AN. Protocols prescribing strict bed rest may not be appropriate for protecting bone health for these patients. LMMS may have application for these patients in the inpatient setting.

Anorexia nervosa (AN) is a severe mental illness characterized in part by rigid thinking and ritualized behaviors involving eating and weight. Cognitive rigidity may play a role in the perpetuation of symptoms, and may provide information as to important brain-based abnormalities. Neuropsychological studies of patients with AN have shown cognitive dysfunction, but few have focused on cognitive flexibility. This study assessed set shifting in patients with AN, as a measure of cognitive flexibility. In this study, 15 patients with AN were compared with 11 healthy controls using a neuropsychological battery including the Wisconsin Card Sort Test (WCST). While patients with AN did not differ from controls on 5 measures of neuropsychological function, they made significantly more perseverative errors on the WCST, indicating a problem in set shifting. This finding suggests that patients with AN have a specific neurocognitive abnormality that may play a role in the development and persistence of this disorder. (JINS, 2006, 12, 431–435.)

Anorexia nervosa is associated with a high incidence of coexisting psychiatric conditions, marked treatment resistance, frequent medical complications, and a substantial risk of death. Several psychotherapeutic approaches are used; family therapy is commonly used in adolescents.

Purpose Autonomic dysfunction of the cardiovascular system in anorexia nervosa (AN) was reported not only in the rest position, but also in the standing position in some previous studies, which might contribute to cardiac complications such as lethal arrhythmia. However, there has not been sufficient literature in this issue. Therefore, we performed a head-up tilt test, and compared the changes after tilting in indices of autonomic function between AN patients and healthy subjects by heart rate variability (HRV) and blood pressure variability (BPV). Methods The subjects were 21 females with AN and 30 age-matched healthy women. A head-up tilt test was performed following the protocol recommended by the American Heart Association. Blood pressure and heart rate data were collected for 10 min before and after tilting. In the frequency analysis, the powers of low-frequency (LF) and high-frequency (HF) components were calculated by a fast Fourier transformation. Results Regarding interactions between groups and head-up tilting, the head-up tilting-induced reduction of the HF component of HRV was significantly greater in the AN group. In addition, increases in the LF/HF of HRV and the LF component of BPV after head-up tilting were significantly smaller in the AN group. Conclusions Regardless of the posture, changes in HF and LF/HF of HRV and LF of BPV in AN patients suggested the presence of autonomic insufficiency.

The gut microbiota not only influences host metabolism but can also affect brain function and behaviour through the microbiota-gut-brain axis. To explore the potential role of the intestinal microbiota in anorexia nervosa (AN), we comprehensively investigated the faecal microbiota and short-chain fatty acids in these patients before (n = 55) and after weight gain (n = 44) in comparison to normal-weight participants (NW, n = 55) along with dietary intake and gastrointestinal complaints. We show profound microbial perturbations in AN patients as compared to NW participants, with higher levels of mucin-degraders and members of Clostridium clusters I, XI and XVIII and reduced levels of the butyrate-producing Roseburia spp. Branched-chain fatty acid concentrations, being markers for protein fermentation, were elevated. Distinct perturbations in microbial community compositions were observed for individual restrictive and binge/purging AN-subtypes. Upon weight gain, microbial richness increased, however perturbations in intestinal microbiota and short chain fatty acid profiles in addition to several gastrointestinal symptoms did not recover. These insights provide new leads to modulate the intestinal microbiota in order to improve the outcomes of the standard therapy.