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Background: A large increase in the rate of hospitalizations for adolescents and children with anorexia nervosa (AN) was observed during the coronavirus disease (COVID-19) pandemic. It is still not clear whether this was a temporary effect or whether the increased admission rates persist., Methods: Data were retrieved from the largest health insurance in Germany comprising 2.5 million children between 9 and 19 y. All patients of this age group with a discharge diagnosis of typical (AN) and atypical AN (AAN) according to the International Classification of Diseases, Tenth Revision (ICD-10), were included. Admission rates per 10,000 person-years were computed separately by sex, age and type of AN for entire years from 2019 to 2022 and the first half of 2023 in relation to the entire number of insured persons of the same sex and age per year., Results: Two years after the final lockdown admission rates were still significantly higher in adolescent and childhood AN than in the pre-COVID-19 time. While admission rates declined for adolescents in 2023, those for children remained high, with an increase for girls of more than 40% compared with the rate before the pandemic (1.42 (CI 1.26, 1.60); p  < 0.0001). The highest admission risk for AAN relative to the pre-COVID-19 period was observed in adolescents in the first half of 2023 (1.6; CI 1.34; 1.90; p  < 0.0001)., Conclusions: Children appear to be especially vulnerable to the pandemic-associated disruptions. Clinicians should try to determine the ongoing effects of the pandemic and support early detection and treatment of AN to prevent its often lifelong consequences.

Background: New treatment approaches are urgently needed to improve the prognosis of children and adolescents with anorexia nervosa (AN). Recently, the feasibility of multidisciplinary home treatment that strongly involves the patients' parents/caregivers has been investigated. However, no RCT has yet been performed to test the efficacy and safety of this approach compared to standard treatment approaches, such as inpatient treatment., Methods: In this multicenter randomized-controlled trial, home treatment for children and adolescents with AN aged 12 to 18 years is established at 5 major treatment centers for AN in Germany. Approximately 240 patients who are admitted to the hospital for AN will be included in the trial. After a short inpatient somatic stabilization phase (5-8 weeks), patients are randomized to receive either treatment as usual (TAU), in the form of continued inpatient or day patient treatment, or the newly developed home treatment (HoT) (n = 82/arm, n = 164 in total). There are three assessments throughout treatment (admission, randomization, and discharge), as well as follow-up assessments at 9 and 12 months after admission. The BMI at 12 months after admission (primary outcome) is compared between groups (adjusted for premorbid BMI and admission BMI); secondary outcomes include eating disorder and general psychopathology, the number and duration of psychiatric rehospitalizations, quality of life, motivation for treatment and treatment satisfaction. Other secondary outcomes include the primary caregivers' burden and skills in handling the child's illness and direct treatment costs. Statistical analysis will be based on intention-to-treat principles, using mixed models for repeated measures. (Serious) adverse events are assessed throughout treatment. In addition, the feasibility and implementation of HoT as well as the satisfaction and workload of the members of the multidisciplinary treatment teams in both arms will be assessed., Discussion: In the case of a positive evaluation, HoT can be considered an effective treatment method to replace or complete established treatment methods, such as IP, for treating AN in children and adolescents. The home treatment setting might shorten inpatient stays in this patient group, increase treatment satisfaction, and help to reduce the risk of rehospitalization, which is associated with a better outcome in this vulnerable patient group., Trial Registration: The trial was registered with the German Clinical Trial Register (DRKS) under the ID DRKS00025925 on November 26, 2021 (prospectively registered): https://drks.de/search/de/trial/DRKS00025925 ., Competing Interests: Declarations Ethics approval and consent to participate Ethics approval was granted via a coordinated procedure lead by the Ethic board of the University Hospital RWTH Aachen (reference number for all centers: EK 323/21) for all ethics committees of the involved clinical centers: the Ethic boards of the University Hospital RWTH Aachen (reference: 323/21), the University Hospital Muenster (local registration number: 2021–572-b-S), the University Hospital Ruhr-University Bochum (local registration number: 21–7367-BR), and of the North Rhine State Chamber of Physicians (ÄkNo) (for LVR Hospital Viersen and LVR Hospital Bonn, local reference number: 2021346). Written informed consent is obtained from all young patients and their parents/legal guardians. The study is undertaken in accordance with the Declaration of Helsinki, the ICH E6 Guidelines for Good Clinical Practice (GCP), local rules, regulations, and applicable requirements with independent data management. Consent for publication Not applicable—no identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results. The participant information materials and informed consent form are available from the corresponding author on request. Competing interests Tanja Legenbauer: Royalties by various publishers such as Hogrefe, Springer, and Kohlhammer for treatment manuals on eating disorders and body image disorder, research grants from the German Ministry for Research and Education.Beate Herpertz-Dahlmann: Research grants from the German Research Society, the German Ministry for Research and Education, EU/ERA NET and the Gemeinsamer Bundesausschuss (federal joint committee), author’s honorary from Kohlhammer publisher, speaker’s honorary from Infectopharm and Editor-in-Chief honorary from Wiley.The other authors declare that they have no competing interests., (© 2024. The Author(s).)

Objective: Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression., Methods: In a preclinical study, we explored whether AN-derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase-cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety-like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests., Results: Neither antibiotic-induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose-stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients., Discussion: No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic-induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies., Public Significance: While our study did not reveal direct impacts of AN-associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic-induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa., (© 2024 The Author(s). International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Anorexia nervosa (AN) is a severe eating disorder that predominantly affects females and typically manifests during adolescence. There is increasing evidence that serum cytokine levels are altered in individuals with AN. Previous research has largely focused on adult patients, assuming a low-grade pro-inflammatory state. The serum levels of the cytokine tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6 and IL-15, which are pro-inflammatory, were examined in 63 female adolescents with AN and 41 age-matched healthy controls (HC). We included three time points (admission, discharge, and 1-year follow-up) and investigated the clinical data to assess whether the gut microbiota was associated with cytokine alterations. Relative to the HC group, serum levels of IL-1β and IL-6 were significantly lower during the acute phase (admission) of AN. IL-1β expression was normalised to control levels after weight recovery. TNF-α levels were not significantly different between the AN and HC groups. IL-15 levels were significantly elevated in patients with AN at all time points. We found associations between cytokines and bodyweight, illness duration, depressive symptoms, and the microbiome. In contrast to most findings for adults, we observed lower levels of the pro-inflammatory cytokines IL-1β and IL-6 in adolescent patients, whereas the level of IL-15 was consistently increased. Thus, the presence of inflammatory dysregulation suggests a varied rather than uniform pro-inflammatory state.

There is mounting evidence regarding the role of gut microbiota in anorexia nervosa (AN). Previous studies have reported that patients with AN show dysbiosis compared to healthy controls (HCs); however, the underlying mechanisms are unclear, and data on influencing factors and longitudinal course of microbiome changes are scarce. Here, we present longitudinal data of 57 adolescent inpatients diagnosed with AN at up to nine time points (including a 1-year follow-up examination) and compare these to up to six time points in 34 HCs. 16S rRNA gene sequencing was used to investigate the microbiome composition of fecal samples, and data on food intake, weight change, hormonal recovery (leptin levels), and clinical outcomes were recorded. Differences in microbiome composition compared to HCs were greatest during acute starvation and in the low-weight group, while diminishing with weight gain and especially weight recovery at the 1-year follow-up. Illness duration and prior weight loss were strongly associated with microbiome composition at hospital admission, whereas microbial changes during treatment were associated with kilocalories consumed, weight gain, and hormonal recovery. The microbiome at admission was prognostic for hospital readmission, and a higher abundance of Sutterella was associated with a higher body weight at the 1-year follow-up. Identifying these clinically important factors further underlines the potential relevance of gut microbial changes and may help elucidate the underlying pathophysiology of gut-brain interactions in AN. The characterization of prognostically relevant taxa could be useful to stratify patients at admission and to potentially identify candidate taxa for future supplementation studies aimed at improving AN treatment.

Background: The COVID-19 pandemic has severely impacted the mental health of children and adolescents. Young people at risk for anorexia nervosa (AN) have been especially shown to be affected. There are no studies that have investigated the respective proportions of hospitalized children, adolescents, and young adults separately as well as of both sexes during the COVID-19 crisis., Methods: This study is based on the administrative data of the largest German statutory health insurance. All children (0-14 years) and adolescents (15-19 years) with a discharge diagnosis of typical and atypical AN according to the International Classification of Diseases (ICD)-10 were included. Admission rates per 10,000 person-years were calculated separately by sex and age group, based on admission numbers from the 9-month interval from January to September of 2019, 2020, and 2021 and the number of insured persons per sex and age group of each year., Results: The entire sample comprised approximately 4.7 million children and adolescents. There was a highly significant increase of 40% (relative risk (RR): 1.4; [1.27, 1.55]; p < 0.0001) in admission rates in the female children's and the adolescents' group (RR:1.32; [1.24, 1.41]; p< 0.0001) between the pre-COVID-19 and peri-COVID-19 periods in 2019 and 2021, respectively. Among males, hospitalization rates significantly increased in the children (RR: 1.69; [1.09, 2.62]; p < 0.02)., Conclusions: Young people appear to be especially prone to develop AN during a crisis, such as with social isolation and school closures. Home-based or mobile pediatric services should be established to prevent this often chronic and disabling disorder in young patients.

Background: Anorexia nervosa (AN) is a severe psychiatric disease that often takes a chronic course due to insufficient treatment options. Emerging evidence on the gut-brain axis offers the opportunity to find innovative treatments for patients with psychiatric disorders. The gut microbiome of patients with AN shows profound alterations that do not completely disappear after weight rehabilitation. In previous studies, the administration of polyunsaturated fatty acids (PUFA) resulted in effects that might be beneficial in the treatment of AN, affecting the microbiome, body weight and executive functions. Therefore, the MiGBAN study aims to examine the effects of a nutritional supplementation with PUFA on the gut microbiome and body mass index (BMI) in patients with AN., Methods: This is a longitudinal, double-blind, randomized, placebo-controlled trial. Within 2 years, 60 adolescent patients aged 12 to 19 years with AN will receive either PUFA or placebo for 6 months additional to treatment as usual. After 1 year, the long-term effect of PUFA on the gut microbiome and consecutively on BMI will be determined. Secondary outcomes include improvement of gastrointestinal symptoms, eating disorder psychopathology, and comorbidities. Additionally, the interaction of the gut microbiome with the brain (microbiome-gut-brain axis) will be studied by conducting MRI measurements to assess functional and morphological changes and neuropsychological assessments to describe cognitive functioning. Anti-inflammatory effects of PUFA in AN will be examined via serum inflammation and gut permeability markers. Our hypothesis is that PUFA administration will have positive effects on the gut microbiota and thus the treatment of AN by leading to a faster weight gain and a reduction of gastrointestinal problems and eating disorder psychopathology., Discussion: Due to previously heterogeneous results, a systematic and longitudinal investigation of the microbiome-gut-brain axis in AN is essential. The current trial aims to further analyse this promising research field to identify new, effective therapeutic tools that could help improve the treatment and quality of life of patients. If this trial is successful and PUFA supplementation contributes to beneficial microbiome changes and a better treatment outcome, their administration would be a readily applicable additional component of multimodal AN treatment., Trial Registration: German Clinical Trials Register DRKS00017130 . Registered on 12 November 2019., (© 2022. The Author(s).)

Caring for a child with anorexia nervosa (AN) puts a strain on many parents. At the same time, actively involving the parents in treatment to increase their skills tomanage the disorder is important, as it seems to improve the child's prognosis. Home treatment requires the parents to be particularly involved. The aim of this study was to assess parental burden and caregiving skills and the association of these factors with the child's AN pathology in the course of a multidisciplinary home treatment (HoT). After 4 to 8 weeks of inpatient treatment, 22 adolescent patients with AN received home treatment with intensive involvement of their parents as co-therapists. Caregiving burden and caregiving behavior and the symptom severity of the child's AN were assessed using standardized questionnaires on admission to the hospital, at discharge from the HoT, and 1 year after admission (Eating Disorder Inventory-2 (EDI-II), Beck Depression Inventory-2 (BDI-II), Accommodation and Enabling Scale for Eating Disorders (AESED), Eating Disorders Symptom Impact Scale (EDSIS)). Parental burden was reduced and the parents' ability to manage their child's AN improved after the step-down treatment frominpatient treatment to home treatment and was also associated with lower eating disorder-specific psychopathology of the patients. HoT as a treatment setting does not seem to burden the parents as co-therapists and is associated with an improvement in skills in dealing with the child's AN.

Objective: Knowledge on gut-brain interaction might help to develop new therapies for patients with anorexia nervosa (AN), as severe starvation-induced changes of the microbiome (MI) do not normalise with weight gain. We examine the effects of probiotics supplementation on the gut MI in patients with AN., Method: This is a study protocol for a two-centre double-blind randomized-controlled trial comparing the clinical efficacy of multistrain probiotic administration in addition to treatment-as-usual compared to placebo in 60 patients with AN (13-19 years). Moreover, 60 sex- and age-matched healthy controls are included in order to record development-related changes. Assessments are conducted at baseline, discharge, 6 and 12 months after baseline. Assessments include measures of body mass index, psychopathology (including eating-disorder-related psychopathology, depression and anxiety), neuropsychological measures, serum and stool analyses. We hypothesise that probiotic administration will have positive effects on the gut microbiota and the treatment of AN by improvement of weight gain, gastrointestinal complaints and psychopathology, and reduction of inflammatory processes compared to placebo., Conclusions: If probiotics could help to normalise the MI composition, reduce inflammation and gastrointestinal discomfort and increase body weight, its administration would be a readily applicable additional component of multi-modal AN treatment., (© 2021 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Background: Brain-derived neurotrophic factor (BDNF) influences brain plasticity and feeding behaviour, and it has been linked to anorexia nervosa in numerous studies. Findings in mostly adult patients point to reduced serum BDNF levels in the acute stage of anorexia nervosa and rising levels with weight recovery. However, it is unclear whether this increase leads to normalization or supranormal levels, a difference that is potentially important for the etiology of anorexia nervosa and relapse., Methods: We measured serum BDNF at admission ( n = 149), discharge ( n = 130), 1-year follow-up ( n = 116) and 2.5-year follow-up ( n = 76) in adolescent female patients with anorexia nervosa hospitalized for the first time, and in healthy controls ( n = 79). We analyzed associations with body mass index, eating disorder psychopathology and comorbidities., Results: Serum BDNF was only nominally lower at admission in patients with anorexia nervosa compared to healthy controls, but it increased continuously and reached supranormal levels at 2.5-year follow-up. BDNF was inversely associated with eating disorder psychopathology at discharge and positively associated with previous weight gain at 1-year follow-up., Limitations: We compensated for attrition and batch effects using statistical measures., Conclusion: In this largest longitudinal study to date, we found only nonsignificant reductions in BDNF in the acute stage of anorexia nervosa, possibly because of a shorter illness duration in adolescent patients. Supranormal levels of BDNF at 2.5-year follow-up could represent a pre-existing trait or a consequence of the illness. Because of the anorexigenic effect of BDNF, it might play an important predisposing role for relapse and should be explored further in studies that test causality., Competing Interests: Competing interests: K. Egberts reports membership in the ANDI-Konsortium. N. Timmesfeld reports grants from Bundes-ministerium für Bildung und Forschung during the conduct of the study. No other competing interests declared., (© 2021 CMA Joule Inc. or its licensors.)

Objective: Gut microbiota are linked to metabolic function, body weight regulation, and brain and behavioral changes. Alteration of gut microbiota is repeatedly demonstrated in adults with anorexia nervosa (AN) and transplantation of stool from adult patients with AN reduces weight gain, food consumption and food efficiency in germ-free mice. No similar data are available for adolescents, who might differ from adults due to their shorter duration of illness., Method: Nineteen female adolescent patients with AN at admission and after short-term weight recovery were included in a longitudinal study and compared to 20 healthy controls (HC). DNA was extracted from stool samples and subjected to 16S rRNA gene sequencing and analysis. Group comparisons, indicator genera and simper analysis were applied. Taxon abundances at admission was used to predict inpatient treatment duration., Results: Alpha diversity is increased in patients with AN after short-term weight recovery, while beta diversity shows clear group differences with HC before and after weight gain. A reduction in Romboutsia and taxa belonging to Enterobacteriaceae at both timepoints and an increase in taxa belonging to Lachnospiraceae at discharge are most indicative of patients. Lachnospiraceae abundance at admission helped to predict shorter inpatient treatment duration., Discussion: This pilot study provides first evidence of gut microbiota alterations in adolescent patients with AN that do not normalize with weight gain. If verified in larger studies, the predictive power of taxa belonging to Lachnospiraceae for clinical outcome could complement known predictors at admission, inform clinicians and serve as a target for nutritional interventions., (© 2020 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Objective: It was the aim of this pilot study to apply a novel eating disorder (ED)-specific home treatment (HoT) to adolescents with anorexia nervosa (AN) and to investigate its feasibility, effects and safety., Method: Twenty-two patients consecutively admitted to the hospital and fulfilling DSM-5 criteria for typical or atypical AN received HoT after 4-8 weeks of inpatient treatment. During the first two months of HoT, the patient and her family were visited on average three to four times per week, during the third and fourth months of HoT once or twice a week by a multi-professional team. Body mass index, ED and general psychopathology, quality of life and treatment satisfaction were assessed in the patients at admission, start and end of HoT and the 1-year follow-up as well as carers' skills and burden., Results: The majority of patients successfully achieved target weight within HoT and maintained it successfully at the 1-year follow-up. ED and general psychopathology in the patients and carers' skills improved significantly associated with a high treatment satisfaction., Conclusions: HoT seems to be a promising new tool to improve outcome in adolescent AN and to reduce time of hospitalisation. Larger randomised controlled trials are needed to generalise these results., (© 2020 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

We aimed to compare the clinical data at first presentation to inpatient treatment of children (<14 years) vs. adolescents (≥14 years) with anorexia nervosa (AN), focusing on duration of illness before hospital admission and body mass index (BMI) at admission and discharge, proven predictors of the outcomes of adolescent AN. Clinical data at first admission and at discharge in 289 inpatients with AN (children: n = 72; adolescents: n = 217) from a German multicenter, web-based registry for consecutively enrolled patients with childhood and adolescent AN were analyzed. Inclusion criteria were a maximum age of 18 years, first inpatient treatment due to AN, and a BMI <10th BMI percentile at admission. Compared to adolescents, children with AN had a shorter duration of illness before admission (median: 6.0 months vs. 8.0 months, p = 0.004) and higher BMI percentiles at admission (median: 0.7 vs. 0.2, p = 0.004) as well as at discharge (median: 19.3 vs. 15.1, p = 0.011). Thus, in our study, children with AN exhibited clinical characteristics that have been associated with better outcomes, including higher admission and discharge BMI percentile. Future studies should examine whether these factors are actually associated with positive long-term outcomes in children.

Objective: Although admissions of children with anorexia nervosa (AN) are increasing, there remains a dearth of up-to-date knowledge of the course and outcome of early-onset AN. The aim of the present study was to investigate the outcomes of patients with AN onset before the age of 14., Method: Sixty-eight consecutive former patients who met the DSM-IV criteria for AN and who had been treated at one of three German university hospitals were asked to participate in a follow-up study. Body mass index, body height, outcome of the eating disorder (ED), psychiatric morbidity, and health related quality of life (HRQoL) were assessed through a personal examination after an average time span of 7.5 years (range: 4.5-11.5 years) after admission., Results: One patient had died. Fifty-two subjects with a mean age of 12.5 (SD 1.0) years at admission and of 20.2 (SD 2.0) years at follow-up agreed to participate in the follow-up assessment, aggregating to 77.9% of the original sample. Approximately 41% of the participants had a good outcome, while 35% and 24% had intermediate and poor outcomes, respectively. Twenty-eight percent of the sample met the DSM-IV criteria for a current non-ED psychiatric disorder, and 64% met the criteria for a past non-ED psychiatric disorder. Mental HRQoL and ED-specific psychopathology was strongly associated with the outcome of AN. Average body height was below the normal range. A higher weight at admission was the only significant positive indicator of outcome., Discussion: Childhood AN is a serious disorder with an unfavorable course in many patients and high rates of chronicity and psychiatric comorbidity in young adulthood. Early detection and intervention are urgently needed., (© 2018 Wiley Periodicals, Inc.)

Objective: The first web-based registry for childhood and adolescent anorexia nervosa (AN) in Germany was established to systematically collect demographic and clinical data. These data as well as information on how young individuals with AN can find access to healthcare services are presented., Method: Patients´ data from child and adolescent psychiatry departments of 12 university hospitals and two major nonuniversity hospitals in Germany were collected between January 2015 and December 2016. All patients met the ICD-10 diagnostic criteria for (atypical) AN. Sociodemographic data, type and amount of healthcare utilization before admission, and clinical data at admission and discharge were compiled., Results: 258 patients with a mean age of 14.7 years and a mean BMI at admission of 15.3 kg/m 2 were included. The parents and patients had a higher educational level than the general German population. More than 80 % of the patients reported having utilized healthcare before hospitalization. The mean duration of outpatient treatment before hospitalization was 7 months., Conclusions: There seem to be major barriers to specialist treatment for young patients with AN in Germany, which should be analyzed in future studies.

Objective: High levels of expressed emotions (EE) and depressive symptoms (DS) are often found in caregivers of patients with anorexia nervosa (AN). Both parameters are considered to influence AN symptoms of the patient., Methods: One hundred seventy adolescent women with AN and their caregivers were assessed at admission, discharge, at 1-year and 2.5-year follow up to evaluate AN symptoms of the patient and EE and DS of caregivers., Results: The EE and DS were elevated at admission and decreased during treatment, criticism (as part of EE) exhibited again at the 2.5-year follow up. Caregivers of more severely ill patients reported significantly greater levels of EE and DS. Mothers were more affected than fathers. EE and DS were interrelated., Conclusion: Caregivers of adolescent AN patients suffer from elevated levels of EE and DS. Further studies are needed to examine whether therapeutic interventions to reduce caregivers' EE and DS might have a positive influence on treatment outcome. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association., (© 2016 John Wiley & Sons, Ltd and Eating Disorders Association.)

Elevated serum leptin levels following rapid therapeutically induced weight gain in anorexia nervosa (AN) patients are discussed as a potential biomarker for renewed weight loss as a result of leptin-related suppression of appetite and increased energy expenditure. This study aims to analyze the predictive value of leptin levels at discharge as well as the average rate of weight gain during inpatient or day patient treatment for body weight at 1-year follow-up. 121 patients were recruited from the longitudinal Anorexia Nervosa Day patient versus Inpatient (ANDI) trial. Serum leptin levels were analyzed at referral and discharge. A multiple linear regression analysis to predict age-adjusted body mass index (BMI-SDS) at 1-year follow-up was performed. Leptin levels, the average rate of weight gain, premorbid BMI-SDS, BMI-SDS at referral, age and illness duration were included as independent variables. Neither leptin levels at discharge nor rate of weight gain significantly predicted BMI-SDS at 1-year follow-up explaining only 1.8 and 0.4 % of the variance, respectively. According to our results, leptin levels at discharge and average rate of weight gain did not exhibit any value in predicting weight at 1-year follow-up in our longitudinal observation study of adolescent patients with AN. Thus, research should focus on other potential factors to predict weight at follow-up. As elevated leptin levels and average rate of weight gain did not pose a risk for reduced weight, we found no evidence for the beneficial effect of slow refeeding in patients with acute AN.

Background: In patients with anorexia nervosa (AN), there is evidence that readiness to change is an important predictor of outcome with respect to weight gain and improvement in eating disorder psychopathology. In particular, young patients are characterized by a low level of motivation for recovery and perceive more coercion at hospitalization. Thus, a better understanding of the variables that influence readiness to change and perception of the admission process in adolescent AN may help to support patients in initiating change and staying motivated for treatment., Methods: In 40 adolescent patients diagnosed with AN according to DSM-IV criteria, we assessed in a prospective clinical cohort study the motivation to change using the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ) at admission to inpatient treatment, in week 9 after admission and at discharge. Additional variables were assessed, including depressive symptoms (Beck Depression Inventory, BDI), eating disorder-specific psychopathology (Eating Disorder Inventory, EDI-2), body mass index (BMI) and the percentage of expected body weight (%EBW). The patients' perceptions of the admission process and their perceived need for hospitalization were assessed using a self-report scale developed by Guarda et al. (2007)., Results: Younger patients perceived more coercion than older patients did. Low %EBW and more severe eating disorder-specific psychopathology were associated with a greater perceived need for hospitalization. Moreover, low %EBW at admission and a longer duration of illness were accompanied by a greater motivation to change at admission, whereas more severe eating disorder psychopathology was associated with a low motivation to change. The motivation to change increased significantly between admission and discharge. Patients with a greater motivation to change at admission exhibited a higher weekly weight gain during treatment but did not show better outcome in eating disorder-specific psychopathology and depression., Conclusions: Motivation to change is an important predictor of short-term outcome with respect to weight gain trajectory during treatment of adolescent AN. As patients with a higher BMI at admission and those with more severe eating disorder-specific symptoms seem to be less motivated to change, the crucial issue of motivation to change should be addressed with these patients during the therapeutic process.

Body mass index (BMI) is one of the most important outcome predictors in patients with anorexia nervosa (AN). A low premorbid BMI percentile calculated by the patients recalled premorbid weight and the height at first admission has been found to predict the BMI at first inpatient admission. In this study, we sought to confirm this relationship. We additionally analyze the relationship between premorbid BMI percentile and BMI percentile at discharge from the first inpatient treatment and at 1-year follow-up or alternatively if applicable upon readmission within this time period. We included 161 female patients aged 11-18 years of the multisite ANDI-trial with a DSM-IV diagnosis of AN. We used a multivariate statistical model including the independent variables age, duration of illness, duration of treatment, BMI at admission and BMI percentile at discharge. The relationship between premorbid BMI percentile and BMI at admission was solidly confirmed. In addition to premorbid BMI percentile, BMI at admission and age were significant predictors of BMI percentile at discharge. BMI percentile at discharge significantly predicted BMI percentile at 1-year follow-up. An additional analysis that merely included variables available upon referral revealed that premorbid BMI percentile predicts the 1-year follow-up BMI percentile. Further studies are required to identify the underlying biological mechanisms and to address the respective treatment strategies for AN patients with a low or high premorbid BMI percentile.

Background: In-patient treatment (IP) is the treatment setting of choice for moderately-to-severely ill adolescents with anorexia nervosa, but it is costly, and the risks of relapse and readmissions are high. Day patient treatment (DP) is less expensive and might avoid problems of relapse and readmission by easing the transition from hospital to home. We investigated the safety and efficacy of DP after short inpatient care compared with continued IP., Methods: For this multicentre, randomised, open-label, non-inferiority trial, we enrolled female patients (aged 11-18 years) with anorexia nervosa from six centres in Germany. Patients were eligible if they had a body-mass index (BMI) below the tenth percentile and it was their first admission to hospital for anorexia nervosa. We used a computer-generated randomisation sequence to randomly assign patients to continued IP or DP after 3 weeks of inpatient care (1:1; stratified for age and BMI at admission). The treatment programme and treatment intensity in both study groups were identical. The primary outcome was the increase in BMI between the time of admission and a 12-month follow-up adjusted for age and duration of illness (non-inferiority margin of 0·75 kg/m(2)). Analysis was done by modified intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number Register, number ISRCTN67783402, and the Deutsches Register Klinischer Studien, number DRKS00000101., Findings: Between Feb 2, 2007, to April 27, 2010, we screened 660 patients for eligibility, 172 of whom we randomly allocated to treatment: 85 to IP and 87 to DP. DP was non-inferior to IP with respect to the primary outcome, BMI at the 12-month follow-up (mean difference 0·46 kg/m(2) in favour of DP (95% CI, -0·11 to 1·02; pnon-inferiority<0·0001). The number of treatment-related serious adverse events was similar in both study groups (eight in the IP group, seven in the DP group). Three serious adverse events in the IP group and two in the DP group were related to suicidal ideation; one patient in the DP attempted suicide 3 months after she was discharged., Interpretation: DP after short inpatient care in adolescent patients with non-chronic anorexia nervosa seems no less effective than IP for weight restoration and maintenance during the first year after admission. Thus, DP might be a safe and less costly alternative to IP. Our results justify the broad implementation of this approach., Funding: German Ministry for Education and Research., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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 15th and 20th 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.

Body mass index (BMI) at admission is an important predictor of outcome in adolescent eating disorders. However, few studies have investigated BMI at admission, its changes in recent years, or modifying factors, such as duration of illness and age at onset in different geographical regions. Thus, this study aimed to investigate changes in BMI at admission over the past decade in one clinic, the differences in BMI between various treatment sites and the influence of duration of illness before admission and age at admission. Our sample consisted of 158 adolescent female patients with anorexia nervosa (AN) admitted between 2001 and 2009 to a major university hospital and 169 adolescent female patients recruited in a multicenter study between 2007 and 2010. We assessed the differences between departments in different regions of Germany in the multi-site sample. Changes over time in age-adjusted BMI and age at admission as well as modifying factors for age-adjusted BMI at admission, such as age at admission and duration of illness, were assessed in a representative local sample. There were no significant differences between departments in different regions of Germany. Over the course of the local study, there was a small but significant increase in the age-adjusted BMI score and absolute BMI at admission. In addition, there was a positive association between year of admission and age at admission. Older adolescents with AN had a lower age-adjusted BMI score and a longer duration of illness at the time of admission. The BMI at admission, which is one of the most important predictors of outcome in AN, has increased slightly during the past 10 years. Education strategies for parents and professionals should continue to be improved to further shorten the duration of illness before admission, especially for older adolescents.

Introduction: Anorexia nervosa (AN) is an often chronic and debilitating psychiatric disease whose etiology is not completely understood. Recently, a potential role of inflammation has emerged in other psychiatric diseases, such as depression, PTSD and schizophrenia. The first results in adults with AN seemed to confirm a low-grade proinflammatory state until recent studies presented more differential findings. Studying adolescents with a shorter illness duration and fewer confounding factors might help elucidate the role of inflammation in the underlying pathophysiology of AN; however, the few available studies in adolescents remain ambiguous, and no longitudinal data are available in this age range. Methods: We examined the proinflammatory cytokines Tumor Necrosis Factor-alpha (TNF-a), Interleukin (IL)-1b, IL-6, IL-15, and the cytokine-receptor IL-6 Receptor alpha (IL-6 Ra) in the serum of twenty-two hospitalized female adolescent patients with AN longitudinally at admission and discharge and compared their results to nineteen healthy controls (HC). We also collected clinical data and stool samples that were analyzed with 16S rRNA amplicon sequencing to explore potential influencing factors of cytokine changes. Results: TNF-a serum levels were significantly elevated in patients with AN at admission, while IL-1b and IL-6 levels were lower at admission and discharge than in HC. After treatment, we also found significantly elevated levels of IL-6 Ra compared to HC, while IL-15 did not show significant changes. Exploratory analyses revealed positive associations of cytokine and genuslevel changes between admission and discharge for IL-1b (Bacteroides) and IL-15 (Romboutsia), and negative associations for IL-15 (Anaerostipes) and TNF-a (uncultured Lachnospiraceae). Conclusion: We confirmed a previous finding of elevated levels of TNF-a also in adolescents with AN; however, the reduced IL-1b and IL-6 levels differed from the mostly increased levels found in adults. A mixed pro- and antiinflammatory state appears to be present in adolescents, potentially due to their shorter illness duration. The gut microbiota, with its regulatory function on cytokine production, might play a role in mediating these inflammatory processes in AN and could offer targets for new therapeutic approaches. [ABSTRACT FROM AUTHOR]

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Introduction: Anorexia nervosa (AN) is a serious mental disorder that typically manifests in adolescence. Motivation to change is an important predictor for treatment outcome in adolescent AN, even though its development over the often long therapeutic process, with transitions between treatment settings, has not yet been studied. In this pilot study, the course of motivation to change and its effect on treatment outcome were investigated over the course of a step-down treatment approach during a 12-month observation period. Methods: Twenty-one adolescents admitted to inpatient treatment because of AN received multidisciplinary home treatment (HoT) with several weekly visits after short inpatient stabilization. Eating disorder (ED-)specific cognitive [Eating Disorder Inventory 2 (EDI-2) subscales] and physical [% expected body weight (%EBW)] illness severity and motivation to change [Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ)] were assessed at the time of admission, discharge from hospital, at the end of HoT, and at a 12-month follow-up. Changes in motivation over time and its relationship with treatment outcome were investigated. Results: Mean motivation to change improved significantly over the course of treatment from the contemplation stage [2nd stage, mean ANSOCQ sum score 47.26 (SD 17.60)] at admission to the action stage [4th stage, mean ANSOCQ sum score 77.64 (SD 18.97)] at the end of HoT (p < 0.001) and remained stable during the follow-up period. At each assessment, higher motivation to change was significantly correlated with lower ED-specific cognitive illness severity (Spearman ρs: −0.53 to −0.77, all p < 0.05). Only pretreatment motivation to change significantly predicted ED-specific cognitive illness severity after the first inpatient treatment phase when taking prior illness severity into account. Conclusions: Motivation to change is an important aspect of treatment success in adolescent AN, especially in the early phase of treatment. In addition, home treatment contributed significantly to a higher motivation. Further longitudinal research into how motivation to change in adolescent patients with AN is related to outcome in this often severe and enduring disease and into targeted therapeutic strategies and interventions that reliably enhance the motivation to change in adolescent patients with AN seems promising. [ABSTRACT FROM AUTHOR]

Interactions between the gut microbiome and the brain are of increasing interest to both researchers and clinicians. Evidence is mounting on the causal role of an altered gut microbiome in inflammatory diseases such as arthritis, inflammatory bowel disease, obesity and diabetes, and psychiatric diseases like anxiety and depression. Mechanisms include altered energy harvest from food, hormonal changes, increased gut permeability, inflammation, immune response, and a direct influence on the brain and behavior. Anorexia nervosa (AN) is the third most common disease in adolescence and exacts a high burden on patients and caregivers. It often becomes chronic and has the highest mortality of all psychiatric diseases. As AN is characterized by nutritional restrictions, weight loss, and severe behavioral symptoms including weight phobia, comorbid anxiety and depression, accompanied by endocrine alterations, increased inflammation, and immune response, exploring the role of the gut microbiome is crucial. Here, we present an overview of the potential mechanisms of interaction between the gut microbiome, the host and particularly the brain in AN and summarize the initial findings of microbiome research on AN. We conclude by identifying future research directions and potential therapeutic approaches, including nutritional interventions, probiotics, prebiotics and food supplements, that could become important additions to current AN therapy. [ABSTRACT FROM AUTHOR]