The impact of weight and negative body image on the body schema in undergraduate women.

BACKGROUND AND OBJECTIVES: Alterations of the sensory-motor body schema question the origins of such distortions. For example, in anorexia nervosa where patients think they are broader than they really are (body image) but act as if it was really the case (body schema). To date, the results of studies about what hinders the updating of the body schema so much (weight, body image) have been contradictory. METHODS: We therefore conducted two studies that aimed to assess the impact of weight and body image problems on body schema in 92 young women without anorexia nervosa. For this purpose, we used a new body schema assessment tool (SKIN) that is sensitive enough to detect fine alterations of body schema in seven different body parts. RESULTS: In Study 1, the thinness or overweight of the young women had a major impact on their tactile perception, especially because the assessed body part was a sensitive area for body dissatisfaction in young women (e.g., belly, thigh). In Study 2, the level of body dissatisfaction of the participants in its attitudinal and perceptual dimension also had a negative impact on their body schema, again in interaction with weight and body part. CONCLUSIONS: These results imply that body dissatisfaction and thinness are predictors of massive body schema distortions. An oversized body schema could maintain various weight-control behaviors, thus risking the development, maintenance, or relapse of an eating disorder.

Autobiographical memory following weight gain in adult patients with Anorexia Nervosa: A longitudinal study.

BACKGROUND: Patients with anorexia nervosa (AN) show overgeneralization of memory (OGM) when generating autobiographical episodes related to food and body shape. These memories are central for the construction of a coherent self-concept, interpersonal relationships, and problem-solving abilities. The current study aims to investigate changes in autobiographical memory following weight gain. METHODS: OGM was assessed with an adapted version of the Autobiographical Memory Test including food-, body-, depression-related, and neutral cues. N = 41 female patients with AN (28 restricting-, 13 binge-eating/purging-subtype; mean disease duration: 4.5 years; mean BMI: 14.5 kg/m2) and N = 27 healthy controls (HC) were included at baseline. After inpatient treatment (mean duration: 11 weeks), 24 patients with AN and 24 age-matched HC were reassessed. Group differences were assessed using independent samples t-tests for cross-sectional comparisons and repeated measures ANOVAs for longitudinal data. RESULTS: At baseline, patients with AN generated significantly fewer specific memories than HC, independent of word category (F(1.66) = 27.167, p < 0.001). During inpatient stay, the average weight gain of patients with AN was 3.1 body mass index points. At follow-up, patients with AN showed a significant improvement in the number of specific memories for both depression-related and neutral cues, but not for food- and body-related cues. CONCLUSIONS: Generalised OGM (i.e., independent of word category) in patients with AN before weight restoration may be a general incapacity to recall autobiographical memory. After weight gain, the previously well-studied pattern of eating disorder-related OGM emerges. The clinical relevance of the continuing disorder-related OGM in patients with AN after weight gain is discussed.

Pragmatic clinical trials to advance research in children and adolescents with eating disorders.

OBJECTIVE: To discuss the utility of pragmatic clinical trials (PCTs) to help advance research in eating disorders (EDs). METHODS: We describe challenges associated with traditional explanatory research trials and examine PCTs as an alternative, including a review of the PRECIS-2 tool. RESULTS: There are many challenges associated with the design and completion of traditional RCTs within the field of EDs. Pragmatic clinical trials are studies that closely align with conditions available in everyday practice and focus on outcomes that are relevant to patients and clinicians. Results of PCTS maximize applicability and generalizability to clinical settings. DISCUSSION: Available therapies established for the treatment of EDs provide remission rates that rarely exceed 50%, implying a need for additional research on new or adjunctive treatments. In addition to a general overview of PCTs, we draw upon published literature and our own experiences involving adjunctive olanzapine for the treatment of children and youth with anorexia nervosa to help highlight challenges associated with randomized controlled trial (RCT) design and implementation, and offer pragmatic suggestions that would allow patients greater choice in treatment trials, while at the same time capturing outcomes that are most likely to advance treatment efforts. CONCLUSIONS: Pragmatic clinical trials provide alternatives to RCT design that can help bolster research in EDs that aims to explore real-world effects of interventions. PUBLIC SIGNIFICANCE: Available therapies established for the treatment of eating disorders (EDs) in children and adolescents provide remission rates that rarely exceed 50%, implying a need for additional research on new or adjunctive treatments. In this article, we discuss the utility of pragmatic trials to help promote research that can help advance knowledge that is relevant to clinical care settings.

Investigating machine learning and natural language processing techniques applied for detecting eating disorders: a systematic literature review.

Recent developments in the fields of natural language processing (NLP) and machine learning (ML) have shown significant improvements in automatic text processing. At the same time, the expression of human language plays a central role in the detection of mental health problems. Whereas spoken language is implicitly assessed during interviews with patients, written language can also provide interesting insights to clinical professionals. Existing work in the field often investigates mental health problems such as depression or anxiety. However, there is also work investigating how the diagnostics of eating disorders can benefit from these novel technologies. In this paper, we present a systematic overview of the latest research in this field. Our investigation encompasses four key areas: (a) an analysis of the metadata from published papers, (b) an examination of the sizes and specific topics of the datasets employed, (c) a review of the application of machine learning techniques in detecting eating disorders from text, and finally (d) an evaluation of the models used, focusing on their performance, limitations, and the potential risks associated with current methodologies.

Atypical anorexia nervosa: A scoping review to determine priorities in research and clinical practice.

BACKGROUND: There is currently a limited understanding of the identification, nature, and treatment of Atypical Anorexia Nervosa (AAN). Recent systematic reviews have identified only small numbers of candidate papers, and some areas lack any meaningful review so far - particularly treatment outcomes. A key issue is the lack of clarity in the literature regarding the definition of weight loss criteria. OBJECTIVES: This scoping review aimed to determine the nature and extent of our knowledge of AAN, in order to assist in the development of future systematic reviews and meta-analyses, as well as indicating what further research is needed. METHOD: Following the identification of 6747 records, 317 records using the term AAN or a defined equivalent were identified from six databases, including the 'grey' literature. RESULTS: Of the 317 studies, 111 provided participant characteristics, and only 10 provided discrete treatment outcomes. Each of these subsets of the data are tabulated and supported with supplementary material, so that future systematic reviewers can access this resource. DISCUSSION: The pattern and content of the existing studies allows recommendations to be made regarding future reviews, research and clinical practice. There is a particular need for clear weight/weight loss criteria and adequate interventions.

Factors predicting long-term weight maintenance in anorexia nervosa: a systematic review.

PURPOSE: Eating disorder recovery is a poorly defined concept, with large variations among researchers' definitions. Weight maintenance is a key aspect of recovery that remains relatively underexplored in the literature. Understanding the role of weight maintenance may help guide the development of treatments. This paper aims to address this by (1) investigating the factors predicting long-term weight maintenance in anorexia nervosa (AN) patients; (2) exploring differences in predictive factors between adolescent and adult populations; and (3) exploring how weight maintenance is conceptualised in the literature. METHODS: We conducted a systematic review following PRISMA guidelines to address our research questions. Five databases were searched and filtered according to our exclusion criteria. RESULTS: From the search, 1059 studies were yielded, and 13 studies were included for review. A range of weight, biological and psychological factors were found to predict weight maintenance among these papers. BMI at admission and discharge from inpatient treatment was the most common predictor among the papers. Few studies investigated biological factors and mixed evidence was found for psychological factors. We found no observable differences between adult and adolescent populations. Finally, weight maintenance was defined and measured differently across studies. CONCLUSION: This review's findings can help contribute to a well-rounded understanding of weight maintenance, and ultimately, of recovery. This can help support clinicians in tailoring interventions to improve long-term outcomes in AN. Future research should aim to replicate studies to better understand the relationship between the factors identified and weight maintenance. LEVEL I: Systematic review.

Originalbeiträge (Originals). Altered microvascular density in patients with anorexia nervosa ­ an optical coherence tomography angiography (OCTA) pilot study.

OBJECTIVES: To investigate macular and peripapillary vascular density (VD) in patients with anorexia nervosa (AN) compared to healthy controls. Methods:Whole face scans of the superficial and deep macular layers and whole face and peripapillary scans of the radial peripapillary capillaries (RPC) were obtained using optical coherence tomography angiography (OCTA, AngioVueR, Optovue) in ten patients with AN and ten age-matched controls.The primary objective was to determine whether there was a difference between the vessel density (VD) in the above areas in AN and controls. P-values ≤ 0.0125 were considered statistically significant. Results: VD in the superficialmacular en-face OCTA image was significantly lower in the study group compared to the control group. Neither the deepmacula nor the radial peripapillary capillary (RPC) in the whole-face image nor the RPC-peripapillary imaging appeared to be significantly different. Conclusion: Patients with AN showed reduced VD in the superficialmacular layers compared to healthy controls, which can be discussed as a consequence of the malnutrition. OCTA could be a useful non- invasive tool to detect reduced peripheral blood supply to show vascular changes that occur before ocular symptoms.

Eating disorders: is there a correlation between severity of physical compromise and admission outcomes?

BACKGROUND: The Medical Emergencies in Eating Disorders (MEED) report was first released by the Royal College of Psychiatrists in 2022 (updated 2023) to aid clinicians in recognising medical compromise due to an eating disorder and to provide guidance for management. AIMS: This study looked at admissions over 5 years to explore whether there is a correlation between MEED medical compromise parameters and three outcomes: length of stay, detainment under the Mental Health Act 1983, and discharge destination. METHODS: A retrospective study of 26 patients admitted to a large teaching hospital for an eating disorder between 2018 and 2023. The risk assessment from the MEED report was used to create a score for physical compromise and analysed to determine whether there was a correlation between the score and discharge destination, detainment under the Mental Health Act and length of stay. FINDINGS: Demographic data were comparable with larger studies, with increasing numbers and 19.2% having autism spectrum disorder. There was no correlation between the scoring tool and detainment under the Act, discharge destination or length of stay. CONCLUSION: Increasing numbers of patients are presenting with eating disorders. Physical compromise was not a predictor for admission outcomes, but this could be further explored in larger studies.

Oral nutritional supplements in older outpatients with heart failure: rationale and design of the ALIMENT-HF trial.

AIMS: The ALIMENT-HF trial aims to determine whether high-calorie and high-protein oral nutritional supplements (ONS) are safe and beneficial for older adult outpatients with heart failure (HF). METHODS AND RESULTS: This multicentre, single-arm, interventional pilot trial is designed to evaluate the tolerance, efficacy, and safety of ONS in older adult outpatients with chronic HF, malnutrition, and anorexia. In total, 80 outpatients with HF regardless of their left ventricular ejection fraction will be treated with ONS, including high-energy (900 kcal/day) and high protein (36 g/day) supplementation, at eight sites in Japan. Inclusion criteria are as follows: age, ≥65 years; outpatients receiving maximally tolerated guideline-directed medical therapy for HF and without change in their diuretic dosage during the last 3 months; outpatients at risk of malnutrition, defined as a Malnutrition Universal Screening Tool score ≥1 point, and anorexia, defined using a Simplified Nutritional Appetite Questionnaire for the Japanese Elderly (SNAQ-JE) score of ≤14 points. Nutritional intervention will continue for up to 120 days, with an observational period lasting for a further 60 days. The primary outcome is a change in body weight between baseline and day 120. CONCLUSIONS: The ALIMENT-HF trial will evaluate the tolerance, efficacy, and safety of high-calorie and high-protein-rich ONS in older outpatients with HF co-morbid with malnutrition and anorexia and will provide insightful information for future randomized controlled trials.

Transition support for patients admitted to intensive treatment for anorexia nervosa: qualitative study of patient and carer experiences of a hybrid online guided self-help intervention (ECHOMANTRA).

BACKGROUND: Adults with anorexia nervosa experience high levels of relapse following in-patient treatment. ECHOMANTRA is a novel online aftercare intervention for patients and carers, which provides psychoeducation and support to augment usual care. AIMS: To explore patient and carer experiences of receiving the ECHOMANTRA intervention. METHOD: This is part of the process evaluation of the ECHOMANTRA intervention as delivered in the TRIANGLE trial (ISRCTN: 14644379). Semi-structured interviews were conducted with 20 participants randomised to the ECHOMANTRA (ten patients and ten carers). Thematic analysis was used to analyse the interview transcripts. RESULTS: Five major themes were identified: (1) Mixed experience of the intervention; (2) tailoring the intervention to the stage of recovery; (3) involvement of carers; (4) acceptability of remote support; and (5) impact of self-monitoring and accountability. CONCLUSIONS: Participants were mostly positive about the support offered. The challenges of using remote and group support were counterbalanced with ease of access to information when needed. Components of the ECHOMANTRA intervention have the potential to improve care for people with eating disorders.

Supplementing low protein diets with methionine or threonine during mixed Eimeria challenge.

We investigated the effects of supplementing low protein diets with methionine (Met) or threonine (Thr) during a mixed Eimeria (consisting of E. acervulina, E. maxima and E. tenella) challenge in broilers. All birds were fed the same starter diet (d1-9) and finisher diet (d28-35) which met Cobb 500 nutrient specifications. Birds were allocated to 1 of 4 dietary treatments from d9 to 28: a standard protein diet (19% CP); a low protein diet (16% CP); or the low protein diet supplemented with Met or Thr at 50% above recommendations. On d14, half of the birds were challenged, and half of the birds were unchallenged. From d14 to 28, feed intake was recorded daily and BW every 3 or 4 d. Oocyst excretion was measured daily from d18 to 27. On d21 and 28, 3 birds per pen were euthanized to assess nutrient digestibility, cytokine expression and intestinal histology. During the acute stage of the challenge, challenged birds reduced ADFI and ADG (P < 0.05). In the pre-patent and recovery stages, birds given the 16% CP diets increased ADFI (P < 0.05), meanwhile there were no differences in ADG in these stages (P > 0.05). Nutrient digestibility was reduced in challenged birds in the acute stage (P < 0.05) but tended to be greater than in unchallenged birds during the recovery stage. There was no significant effect of diet on oocyst excretion or intestinal histology (P > 0.05). Interactions were observed between diet and challenge on IL-10 and IL-21 expression in the cecal tonsils during the acute stage of the challenge (P < 0.05), due to reduced IL-10 expression in challenged Thr birds and greater IL-21 expression in challenged Met birds. Supplementation with Thr or Met had limited effects on the outcomes of a mixed Eimeria challenge but provides benefits to the host by enhancing their immune response.

A life lost to anorexia nervosa: A case report of rapid progressive disease and its psychological aspects.

The prevalence of anorexia nervosa has been on the rise. Exploring key factors in treating this condition as well as psychological factors influencing the onset and maintenance of the disorder can increase the chance of treatment success.

Neurological Resilience in Patients With Anorexia Nervosa Following Prolonged Cardiopulmonary Resuscitation.

Anorexia nervosa (AN) is a psychiatric disorder with metabolic abnormalities. Prolonged cardiopulmonary resuscitation (CPR) is predicted to result in death and poor neurological outcomes. This report describes the case of a patient with AN who had an unexpectedly favorable outcome after prolonged CPR. A 12-year-old female with AN presented to the emergency department, requiring intubation due to worsening consciousness and respiratory distress. Refractory hypotension led to cardiac arrest. After 135 minutes of CPR, venoarterial extracorporeal membrane oxygenation (EMCO) was started, and the patient was treated for post-resuscitation management, refeeding syndrome, and sepsis. The cardiac function gradually improved, the patient was weaned from EMCO eight days after admission, and the patient was extubated 30 days after admission. The patient maintained a good central nervous system function. AN patients tend to be youngsters and have a lower metabolism, which may be associated with a favorable neurological prognosis after prolonged CPR.

Haematological adverse effects associated with olanzapine in adolescents with anorexia nervosa: Three case reports.

OBJECTIVES: To describe haematological adverse effects in adolescents with anorexia nervosa who are taking olanzapine. METHODS: Case series report. CASE REPORT: The reported cases (two female patients and one male) were found to have blood test abnormalities after starting olanzapine and to rapidly recover their platelet and neutrophil values after the drug was discontinued. Low haemoglobin values persisted longer than observed in other series. These abnormalities became more noticeable when the dose of olanzapine was increased to 5 mg/day (initial dose 2.5 mg/day). It should be noted that two of the patients already had values indicative of mild neutropenia before they started the antipsychotic drug, and that these worsened as they continued taking the drug. In one of the patients there was only a decrease in neutrophil values, as well as mild anaemia. CONCLUSIONS: This first case series of haematological abnormalities in adolescents with anorexia nervosa who are taking olanzapine found values corresponding to pancytopenia in two of the three cases reported. It would be worthwhile to consider heightening haematological surveillance in this population when starting treatment with olanzapine and rethinking our knowledge regarding the frequency of these side effects.

Weight gain and eating disorder symptoms among individuals with atypical anorexia nervosa.

OBJECTIVE: The purpose of this study was to examine the association between weight gain and eating disorder (ED) symptoms among adults receiving treatment for atypical anorexia nervosa (AAN), to determine whether those who had a higher percent of expected body weight (%EBW) at discharge exhibited lower ED symptoms than those who gained less weight, and to compare this group to a matched sample of patients with anorexia nervosa (AN). METHOD: Participants were 96 adults receiving treatment at an ED treatment facility between December 2020 and May 2023. The Eating Disorder Examination-Questionnaire (EDE-Q) was completed at admission and discharge, and %EBW was obtained at admission and discharge. RESULTS: All EDE-Q subscale scores improved from admission to discharge for patients with AAN and patients with AN. Neither %EBW at discharge nor weight gain were associated with EDE-Q subscale scores for those with AAN. For patients with AN, %EBW at discharge and weight gain were associated with EDE-Q Restraint at discharge. CONCLUSIONS: Weight restoring to a higher level and gaining more weight were not associated with EDE-Q scores at discharge for AAN. Further research is needed to determine how weight restoration using intensive treatment settings affects remission and recovery in patients with AAN.

Repeated stress triggers seeking of a starvation-like state in anxiety-prone female mice.

Elevated anxiety often precedes anorexia nervosa and persists after weight restoration. Patients with anorexia nervosa often describe self-starvation as pleasant, potentially because food restriction can be anxiolytic. Here, we tested whether repeated stress can cause animals to prefer a starvation-like state. We developed a virtual reality place preference paradigm in which head-fixed mice can voluntarily seek a starvation-like state induced by optogenetic stimulation of hypothalamic agouti-related peptide (AgRP) neurons. Prior to stress exposure, males but not females showed a mild aversion to AgRP stimulation. Strikingly, following multiple days of stress, a subset of females developed a strong preference for AgRP stimulation that was predicted by high baseline anxiety. Such stress-induced changes in preference were reflected in changes in facial expressions during AgRP stimulation. Our study suggests that stress may cause females predisposed to anxiety to seek a starvation state and provides a powerful experimental framework for investigating the underlying neural mechanisms.

Weight gained during treatment predicts 6-month body mass index in a large sample of patients with anorexia nervosa using ensemble machine learning.

OBJECTIVE: This study used machine learning methods to analyze data on treatment outcomes from individuals with anorexia nervosa admitted to a specialized eating disorders treatment program. METHODS: Of 368 individuals with anorexia nervosa (209 adolescents and 159 adults), 160 individuals had data available for a 6-month follow-up analysis. Participants were treated in a 6-day-per-week partial-hospital program. Participants were assessed for eating disorder-specific and non-specific psychopathology. The analyses used established machine learning procedures combined in an ensemble model from support vector machine learning, random forest prediction, and the elastic net regularized regression with an exploration (training; 75%) and confirmation (test; 25%) split of the data. RESULTS: The models predicting body mass index (BMI) at 6-month follow-up explained a 28.6% variance in the training set (n = 120). The model had good performance in predicting 6-month BMI in the test dataset (n = 40), with predicted BMI significantly correlating with actual BMI (r = .51, p = 0.01). The change in BMI from admission to discharge was the most important predictor, strongly correlating with reported BMI at 6-month follow-up (r = .55). Behavioral variables were much less predictive of BMI outcome. Results were similar for z-transformed BMI in the adolescent-only group. Length of stay was most predictive of weight gain in treatment (r = .56) but did not predict longer-term BMI. CONCLUSIONS: This study, using an agnostic ensemble machine learning approach in the largest to-date sample of individuals with anorexia nervosa, suggests that achieving weight gain goals in treatment predicts longer-term weight-related outcomes. Other potential predictors, personality, mood, or eating disorder-specific symptoms were relatively much less predictive. PUBLIC SIGNIFICANCE: The results from this study indicate that the amount of weight gained during treatment predicts BMI 6 months after discharge from a high level of care. This suggests that patients require sufficient time in a higher level of care treatment to meet their specific weight goals and be able to maintain normal weight.

Psychotic-like anomalous self-experiences in feeding and eating disorders: Their role in eating psychopathology through the mediation of body uneasiness and embodiment and identity disorders.

BACKGROUND: Psychotic-like anomalous self-experiences (ASEs) are core and early features of schizophrenia spectrum disorders, which have been recently also postulated to underlie embodiment disturbance in feeding and eating disorders (FEDs). The present study was aimed at investigating the interplay between ASEs and specific psychopathology in FED. METHODS: Ninety persons with Anorexia Nervosa and 41 with Bulimia Nervosa were evaluated with the inventory of psychotic-like anomalous self-experiences (IPASE), identity and eating disorders (IDEA), body uneasiness test (BUT), and eating disorder examination questionnaire (EDE-Q). The same assessment was performed for 92 subjects recruited from the general population. Structural equation modelling was employed to test the role of embodiment/identity disorders in mediating the relationship between ASEs and ED psychopathology. RESULTS: Patients with FED displayed high scores on IPASE, comparable with people with schizophrenia spectrum disorders. A significant correlation was also demonstrated between IPASE, BUT and EDE-Q. All IPASE domains were strongly related to feeling extraneous from one's own body by IDEA. All IPASE domains demonstrated a high relationship with BUT Depersonalization scale. A strong correlation was also reported between total scores of IPASE and IDEA. The mediation model confirmed that ASEs impact on FED symptomatology through the mediation of both embodiment/identity disorders and body image. DISCUSSION: Anomalous interoceptive processes may represent the first step of a maladaptive process-impairing embodiment, selfhood, and identity in FED. Assessment of ASEs might be a valid tool to identify an early-shared vulnerability of severe disorders characterized by embodiment alterations.

Increased eating disorder frequency and body image disturbance among fashion models due to intense environmental pressure: a content analysis.

Introduction: Female fashion models are under intense occupational pressure. The present study focuses on assessing the lived experience of fashion models with regards to their dieting and exercising habits, body image perception, eating disorder-like symptoms, and experience of abuse via self-narrated reports. Methods: Series of open questions were distributed among international fashion models (N=84, mean age=23.2 years; mean BMI=16.9) selected by convenience and snowball sampling. Models from 17 countries participated. The questions targeted models' eating, exercising, dieting habits, body image perception, and eating disorder symptoms. The average word count of the transcripts was 2473.9 (SD = 2791.6). Thematic content analysis was performed on the transcripts. A total of 31 codes were created to address disordered eating and body image concerns. Results: Negative body-related claims appeared in 89.3%, and positive claims in 64.3% of the models' transcripts. Negative remarks about eating were made by 45.2% of the participants, and 23.8% positively. Control over their food intake was exercised by 78.6% of the participants and 40.5% used extreme calorie restriction. Models who talked more positively about their bodies expressed significantly more frequently extreme calorie restriction. Extreme sports habits occurred in 23.8% of the transcripts, obsessive sports habits were claimed by 11.9% of participants. Self-induced vomiting was prominent in 14.3% of the answers. Criticism from other industry members was experienced by 83.3% of the participants while 44.0% received body appreciation. Body image disorder-like symptoms were expressed by 63.1% of models. Such models mentioned significantly more often content about eating disorders and talked significantly more negatively about eating. Psychological problems were mentioned by 48.8%, whereas 16.7% took part in psychotherapy. Those who partake in therapy mentioned significantly more eating disorder content in their narratives. Abuse was mentioned by 25.0% of the models. Conclusion: Fashion models are experiencing increased environmental pressure to conform to the extreme slimness ideal. There is a heightened prevalence of disordered eating and other weight-controlling behaviours among fashion models to succeed in their careers. Qualitative research is crucial in understanding the more subtle dynamics in conforming to and maintaining the thin beauty ideal.

Sustained insulin treatment restoring metabolic status, body weight, and cognition in an anorexia nervosa-like animal model in mice.

INTRODUCTION: Anorexia Nervosa (AN) is a psycho-socio-biological disease characterized by severe weight loss as result of dieting and hyperactivity. Effective treatments are scarce, despite its significant prevalence and mortality. AN patients show lower basal insulin levels and increased metabolic clearance, leading to weight loss, cognitive deficits, and hormonal imbalances. Low-dose polymer insulin could potentially reverse these effects by restoring brain function, reducing fear of weight gain, encouraging food intake, and restoring fat depots. This study evaluates an insulin delivery system designed for sustained release and AN treatment. METHODS: AN-like model was established through dietary restriction (DR). On days 1-25, mice were on DR, and on days 26-31 they were on ad libitum regimen. An insulin-loaded delivery system was administered subcutaneously (1% w/w insulin). The impact of insulin treatment on gene expression in the hippocampus (cognition, regulation of stress, neurogenesis) and hypothalamus (eating behavior, mood) was assessed. Behavioral assays were conducted to evaluate motor activity and cognitive function. RESULTS: The delivery system demonstrated sustained insulin release, maintaining therapeutic plasma levels. Diet restriction mice treated with the insulin delivery system showed body weight restoration. Gene expression analysis revealed enhanced expression of CB1 and CB2 genes associated with improved eating behavior and cognition, while POMC expression was reduced. Insulin-polymer treatment restored cognitive function and decreased hyperactivity in the AN-like model. CONCLUSION: The PSA-RA-based insulin delivery system effectively restores metabolic balance, body weight, and cognitive function in the AN model. Its ability to steadily release insulin makes it a promising candidate for AN treatment."