Maximal Resistance Training in the Treatment of Anorexia Nervosa - A Case Report Series.

Objective: Anorexia Nervosa (AN) has one of the highest mortality rates of all mental health disorders, low recovery rate and is associated with widespread endocrine dysfunction. Resistance training (RT) has been consistently shown to provide beneficial effects on health outcomes that are often negatively affected by AN, however participation in exercise is controversial for individuals with AN. The objective of this study was to assess the effects of maximal RT as an add-on to standard of care in patients with AN. Methods: Originally, a controlled clinical trial was planned but due to COVID-19 pandemic, the study was prematurely ended and reported as a case series design. Three female inpatients with AN (Age 18-29 years, body mass index (BMI) 14.5-16.3 kg/m2, illness duration 1-7 years) underwent a supervised 6-week RT intervention as an add-on to standard of care. Primary outcome was muscular strength, as measured by a 1-repetition maximum. Secondary outcomes included BMI, eating disorder psychopathology and maladaptive exercise tendencies. Results: No adverse events were reported. All three participants improved lower body muscle strength, ranging from 32% to 134% in the leg press. Changes of 4% to 134% in the bench press and -3% to 38% in the pulldown were also observed. Conclusions: RT improved muscular strength in the participants. RT as part of standard of care may also provide additional benefits for individuals with AN, although further research is required to determine which subtype of patients would benefit from the addition of RT to their treatment protocol.

Elevated lipid class concentrations in females with anorexia nervosa before and after intensive weight restoration treatment-A lipidomics study.

OBJECTIVE: To study the plasma lipidome of patients with anorexia nervosa (AN) before and after weight restoration treatment and report associations with AN subtypes and oral contraceptive pill (OCP) usage. METHODS: Quantitative shotgun lipidomics analysis was used to study plasma lipids of 50 female patients with AN before and after weight restoration treatment and 50 healthy female controls (HC). The AN group was assessed with blood samples and questionnaires before and after weight restoration. RESULTS: In total we quantified 260 lipid species representing 26 lipid classes of which 13 lipid class concentrations were elevated in patients with AN at admission compared with HC. Lipid classes remained elevated after weight restoration treatment of 84 days (median; interquartile range 28), and only the concentration of the ceramide lipid class increased between pre- and post-treatment (p = .03), whereas lysophosphatidylcholine (LPC, p = .02), ether-linked Phosphatidylcholine (LPCO, p = .02), and lysophosphatidylethanolamine (LPE, p = .009) decreased. CONCLUSION: In AN, 13 out of 26 lipid class concentrations were elevated at admission and remained elevated post-treatment. Ceramides increased further between pre- and post-weight restoration treatment, which could be related to the rapid weight gain during re-nutrition. Further research is needed to elucidate the effects of weight restoration treatment on short- and long-term lipid profiles in individuals with AN. PUBLIC SIGNIFICANCE STATEMENT: Lipidomics research can increase the understanding of AN, a complex and potentially life-threatening eating disorder. By analyzing lipids, or fats, in the body, we can identify biological markers that may inform diagnosis and develop more effective treatments. This research can also shed light on the underlying mechanisms of the disorder, leading to a better understanding of the processes involved in eating behavior.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines update 2023 on the pharmacological treatment of eating disorders.

OBJECTIVES: This 2023 update of the WFSBP guidelines for the pharmacological treatment of eating disorders (EDs) reflects the latest diagnostic and psychopharmacological progress and the improved WFSBP recommendations for the assessment of the level of evidence (LoE) and the grade of recommendation (GoR). METHODS: The WFSBP Task Force EDs reviewed the relevant literature and provided a timely grading of the LoE and the GoR. RESULTS: In anorexia nervosa (AN), only a limited recommendation (LoE: A; GoR: 2) for olanzapine can be given, because the available evidence is restricted to weight gain, and its effect on psychopathology is less clear. In bulimia nervosa (BN), the current literature prompts a recommendation for fluoxetine (LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1). In binge-eating disorder (BED), lisdexamfetamine (LDX; LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1) can be recommended. There is only sparse evidence for the drug treatment of avoidant restrictive food intake disorder (ARFID), pica, and rumination disorder (RD). CONCLUSION: In BN, fluoxetine, and topiramate, and in BED, LDX and topiramate can be recommended. Despite the published evidence, olanzapine and topiramate have not received marketing authorisation for use in EDs from any medicine regulatory agency.

Cortisol, Depression, and Anxiety Levels Before and After Short-Term Intensive Nutritional Stabilization in Patients With Severe Anorexia Nervosa.

Introduction: Depression and anxiety are well-known comorbid conditions in patients with anorexia nervosa (AN). Hypercortisolemia in patients with AN may be pathogenic and contribute to depression and anxiety symptomatology. Objective: The aim of this study was to investigate short-term changes in cortisol levels and depression and anxiety symptomatology following intensive re-nutrition in patients with severe AN and hospitalized in a specialized unit. Furthermore, we investigated the potential association between cortisol levels and psychometric parameters. Methods: A total of 36 patients with AN were enrolled in the study. Nine dropped out before follow-up. Patients underwent paraclinical and psychometric examinations at admission and discharge. Measurements included plasma cortisol, cortisol binding globulin (CBG), 24-h urine cortisol, and self-report questionnaires regarding eating disorder, depression, anxiety, and stress symptoms. Patients were hospitalized in the unit for somatic stabilization and intensive re-nutrition. Mean admission length was 41 days. The study was registered at ClinicalTrials.gov (NCT02502617). Results: Cortisol levels in blood and urine did not change from admission to discharge in patients with severe AN. Symptoms of depression, anxiety, stress, and eating disorder remained elevated at discharge. There were no associations between changes in cortisol levels and changes in psychometrics. Discussion: Our results suggest that short-term intensive re-nutrition did not alter hypothalamic-pituitary-adrenal axis activity or mental health in patients with severe AN. Long-term stabilization and longer follow-up after hospital discharge may be needed to detect changes in cortisol levels and whether these changes are associated with depression and anxiety symptomatology. Greater knowledge about cortisol levels and mental health in patients with severe AN may help in the development of new treatment choices for the chronically ill patients. Future studies could investigate whether cortisol-lowering drugs have a therapeutic effect on mental health in AN.

BMI at Discharge from Treatment Predicts Relapse in Anorexia Nervosa: A Systematic Scoping Review.

BACKGROUND: Anorexia nervosa (AN) has high rates of enduring disease and mortality. Currently, there is insufficient knowledge on the predictors of relapse after weight normalization and this is why a systematic literature review was performed. METHODS: PubMed, EMBASE, PsychInfo, and Cochrane databases were searched for literature published until 13 July 2021. All study designs were eligible for inclusion if they focused on predictors of relapse after weight normalization in AN. Individual study definitions of relapse were used, and in general, this was either a drop in BMI and/or reccurrence of AN symptoms. RESULTS: The database search identified 11,507 publications, leaving 9511 publications after the removal of duplicates and after a review of abstracts and titles; 191 were selected for full-text review. Nineteen publications met the criteria and included 1398 AN patients and 39 healthy controls (HC) from adults and adolescents (ages range 11-73 years). The majority used a prospective observational study design (12 studies), a few used a retrospective observational design (6 studies), and only one was a non-randomized control trial (NRCT). Sample sizes ranged from 16 to 191 participants. BMI or measures of body fat and leptin levels at discharge were the strongest predictors of relapse with an approximate relapse rate of 50% at 12 months. Other predictors included signs of eating disorder psychopathology at discharge. CONCLUSIONS: BMI at the end of treatment is a predictor of relapse in AN, which is why treatment should target a BMI well above 20. Together with the time to relapse, these outcomes are important to include in the evaluation of current and novel treatments in AN and for benchmarking.

Validating the Danish version of the Eating Disorder Quality of Life Scale (EDQLS) in anorexia nervosa.

PURPOSE: The aim of this study was to explore the factor structure of the Danish translation of the eating disorder quality of life scale and evaluate the internal reliability and convergent validity of the scale in a Danish cohort of women with AN. METHODS: The total sample comprised 211 patients diagnosed with anorexia nervosa age 13-40 years. Patients completed questionnaires assessing eating disorder psychopathology, physical and social functioning, and well-being. RESULTS: Factor analyses were not able to support the current division of the scale into 12 factors. We found excellent internal consistency of the eating disorder quality-of-life scale total score. We found relevant associations between quality of life and pre-determined variables. CONCLUSION: This study supports the use of the total score of the eating disorder quality of life scale in assessing quality of life in patients with anorexia nervosa. However, future studies should explore the factor structure of the scale further. LEVEL OF EVIDENCE: III: Evidence obtained from cohort or case-control analytic studies.

Disturbances in the experiences of embodiment related to attachment, mentalization and self-objectification in anorexia nervosa.

BACKGROUND: Body image disturbance is central to both the understanding and treatment of anorexia nervosa (AN); however, the underlying psychological processes involved are still not well understood. One way towards a better understanding of these mechanisms may be to explore the sense of embodiment in these patients in an attempt at integrating the role of the body in our understanding of the development of self in AN. It is hypothesized that difficulties in affective experiences of embodiment is related to insecure attachment, deficits in mentalization and self-objectification. METHODS: Sixteen inpatients with AN were interviewed with the Mirror Interview (MI). In the interview, the individual is asked a set of questions related to thoughts and feelings about the body while standing in front of a full-length mirror. Furthermore, all patients were assessed with the Adult Attachment Interview, which was coded for both attachment and mentalization (operationalized by the Reflective Functioning scale; RF). Self-objectification was measured with the Objectified Body Consciousness Scale (OBCS). RESULTS: Results from a multiple regression analysis showed that Global MI scores were significantly associated with Coherence of mind as an indicator of attachment, RF and scores on the OBCS. CONCLUSIONS: The study suggests that affective experiences of embodiment in patients with AN are associated with negative attachment representations, mentalizing impairments and objectified body consciousness. Body image disturbance is a key diagnostic feature in anorexia nervosa but the underlying psychological processes are poorly understood. Recently, there has been a growing interest in how disturbances in the more psychological experience of the body (embodiment) in anorexia nervosa is related to both attachment, how individuals make sense of both themselves and others and the degree to which they tend to experience ourselves from the outside. In this pilot study, this was assessed with an innovative interview, the Mirror Interview, where the individual is asked a set of question while standing in front of a full length mirror. Results showed that difficulties in embodied experiences in patients with anorexia nervosa were related to more fundamental representations of self and self-objectification. This has potential implications for both the understanding and treatment of anorexia nervosa, as disturbances in body image may be seen as an underlying factor in the development of an eating disorder.

Dialectical Behaviour Therapy Improves Emotion Dysregulation Mainly in Binge Eating Disorder and Bulimia Nervosa: A Systematic Review and Meta-Analysis.

Emotion dysregulation is a transdiagnostic phenomenon in Eating Disorders (ED), and Dialectical Behaviour Therapy (DBT) (which was developed for reducing dysregulated emotions in personality disorders) has been employed in patients with ED. This systematic review and meta-analysis investigated whether the effect of DBT was stronger on emotion dysregulation, general psychopathology, and Body Mass Index (BMI) in participants with ED, when compared to a control group (active therapy and waitlist). Eleven studies were identified in a systematic search in accordance with PRISMA guidelines. Most studies included participants with Binge Eating Disorder (BED) (n = 8), some with Bulimia Nervosa (BN) (n = 3), and only one with Anorexia Nervosa (AN). The pooled effect of DBT indicated a greater improvement in Emotion Regulation (ER) (g = -0.69, p = 0.01), depressive symptoms (g = -0.33, p < 0.00001), ED psychopathology (MD = -0.90, p = 0.005), Objective Binge Episodes (OBE) (MD = -0.27, p = 0.003), and BMI (MD = -1.93, p = 0.01) compared to the control group. No improvement was detected in eating ER following DBT (p = 0.41). DBT demonstrated greater efficacy compared with the control group in improving emotion dysregulation, ED psychopathology, and BMI in ED. The limitations included the small number of studies and high variability.

Explanatory Factors for Disease-Specific Health-Related Quality of Life in Women with Anorexia Nervosa.

A better understanding of explanatory factors for disease-specific health-related quality of life (HRQoL) in anorexia nervosa (AN) could help direct treatment providers to aspects of the most relevance for patient wellbeing and recovery. We aimed to investigate whether factors associated with HRQoL are the same for women with AN and normal-weight controls. The participants in this study were women with AN recruited from specialized eating disorder centers in Denmark and healthy, normal-weight controls invited via online social media. Participants completed online questionnaires on medical history, disease-specific HRQoL (Eating Disorders Quality of Life Scale, EDQLS) and generic HRQoL (SF-36), eating disorder symptomatology, depression, psychological wellbeing, and work and social adjustment. Questionnaires were fully completed by 211 women with AN (median age 21.7 years) and 199 controls (median age 23.9 years). Women with AN had poorer scores on all measures, i.e., worse HRQoL, psychological health, and work/social functioning. Eating disorder symptomatology affected EDQLS score in both groups, but poorer HRQoL in women with AN was also significantly associated with worse scores on bulimia, maturity fears, depression, vitality, and with older age. The factors investigated together explained 79% of the variance in EDQLS score. Management of disordered self-assessment and thought processes may be of particular importance to women with AN. Greater emphasis on these aspects alongside weight gain could enhance patient-clinician alliance and contribute to better treatment outcomes.

A Systematic Review and Meta-Analysis Finds Increased Blood Levels of All Forms of Ghrelin in Both Restricting and Binge-Eating/Purging Subtypes of Anorexia Nervosa.

Anorexia nervosa (AN) is a severe psychiatric condition associated with high mortality and chronicity. The hunt for state, trait, subtyping, and prognostic biomarkers is ongoing and the orexigenic hormone ghrelin and its different forms, acyl ghrelin and desacyl ghrelin, have been proposed to be increased in AN, especially in the restrictive subtype. A systematic literature search was performed using established databases up to 30 November 2020. Forty-nine studies met inclusion criteria for cross-sectional and longitudinal meta-analyses on total ghrelin, acyl ghrelin, and desacyl ghrelin. All forms of ghrelin were increased in the acute stage of anorexia nervosa during fasting compared to healthy controls. Previous notions on differences in ghrelin levels between AN subtypes were not supported by current data. In addition, a significant decrease in total ghrelin was observed pre-treatment to follow-up. However, total ghrelin levels at follow-up were still marginally elevated compared to healthy controls, whereas for acyl ghrelin, no overall effect of treatment was observed. Due to heterogeneity in follow-up designs and only few data on long-term recovered patients, longitudinal results should be interpreted with caution. While the first steps towards a biomarker in acute AN have been completed, the value of ghrelin as a potential indicator of treatment success or recovery status or its use in subtype differentiation are yet to be established.

Cognitive improvement following weight gain in patients with anorexia nervosa: A systematic review.

OBJECTIVE: Anorexia nervosa (AN) has been associated with cognitive impairment. While re-nutrition is one of the main treatment targets, the effect on cognitive impairments is unclear. The aim of this review was to examine whether cognitive functions improve after weight gain in patients with AN. METHOD: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines (PROSPERO CRD42019081993). Literature searches were conducted May 20th , 2019 in PubMed, EMBASE, PsychINFO and Cochrane Library. Pairs of reviewers screened reports independently based on titles/abstracts (N = 6539) and full texts (N = 378). Furthermore, they assessed the quality of reports, including whether practice effects were accounted for. RESULTS: Twenty-four longitudinal reports were included featuring 757 patients and 419 healthy controls. Six studies examined children and adolescents. Four out of four studies found processing speed to improve above and beyond what could be assigned to practice effects and three out of four studies found that cognitive flexibility was unaffected after weight gain in children and adolescents. Results from studies of adults were inconclusive. DISCUSSION: The literature on cognitive change in patients with AN following weight gain is sparse. Preliminary conclusions can be made only for children and adolescents, where weight gain appeared to be associated with improved processing speed.

Case report: cognitive performance in an extreme case of anorexia nervosa with a body mass index of 7.7.

BACKGROUND: Studies show that adult patients with anorexia nervosa display cognitive impairments. These impairments may be caused by illness-related circumstances such as low weight. However, the question is whether there is a cognitive adaptation to enduring undernutrition in anorexia nervosa. To our knowledge, cognitive performance has not been assessed previously in a patient with anorexia nervosa with a body mass index as low as 7.7 kg/m2. CASE PRESENTATION: We present the cognitive profile of a 35-year-old woman with severe and enduring anorexia nervosa who was diagnosed at the age of 10 years. She was assessed with a broad neuropsychological test battery three times during a year. Her body mass index was 8.4, 9.3, and 7.7 kg/m2, respectively. Her general memory performance was above the normal range and she performed well on verbal and design fluency tasks. Her working memory and processing speed were within the normal range. However, her results on cognitive flexibility tasks (set-shifting) were below the normal range. CONCLUSIONS: The case study suggests that it is possible to perform normally cognitively despite extreme and chronic malnutrition though set-shifting ability may be affected. This opens for discussion whether patients with anorexia nervosa can maintain neuropsychological performance in spite of extreme underweight and starvation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02502617. Registered 20 July 2015.

Sexual function and dysfunction among women with anorexia nervosa: A systematic scoping review.

OBJECTIVE: Research suggests that a variety of biological and psychosocial factors are associated with the sexual health of women diagnosed with anorexia nervosa (AN). This systematic scoping review, conducted in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, synthesizes the current literature concerning sexual function and dysfunction in women with AN. METHOD: We searched PubMed, EMBASE, and PsychInfo for literature published until April 2020. All study designs were eligible for inclusion, providing they focused on sexual function and dysfunction in women with AN. Studies that only included outcomes related to gender identity or sexual orientation were excluded. RESULTS: N = 28 studies met criteria for inclusion in the review. All studies were conducted in Western countries and the majority employed either a cohort or cross-sectional design. Although measures of sexual function and dysfunction varied markedly across studies, most studies adopted a biopsychosocial framework. Libido may be linked to body mass index (BMI), while other aspects of sexual functioning and behavior might not be specifically associated with weight status. Limited data are available on evidence-based interventions. DISCUSSION: Sexual dysfunction in women with AN is common. Although some of the variance is explained by low BMI, associated physiological sequelae and other psychosocial factors are also involved. Sexual dysfunction is a relevant clinical problem and clinicians should sensitively incorporate questions related to sexual function into their eating disorder assessments. Future research, using more robust designs and validated outcome measures, is needed to better understand causal pathways between the biological and psychosocial correlates of AN and sexual dysfunction. Identifying predictors of sexual function and dysfunction in more diverse groups of people with AN will support the development of evidence-based therapies.

OBJETIVO: La investigación sugiere que una variedad de factores biológicos y psicosociales están asociados con la salud sexual de las mujeres diagnosticadas con anorexia nervosa (AN). Esta revisión exploratoria sistemática, realizada de acuerdo con las Directrices PRISMA, sintetiza la literatura actual sobre la función y la disfunción sexual en mujeres con AN. MÉTODOS: Se realizaron búsquedas en PubMed, EMBASE y PsychInfo para la literatura publicada hasta abril de 2020. Todos los diseños de estudio fueron elegibles para su inclusión, siempre que se centraran en la función y la disfunción sexual en mujeres con AN. Se excluyeron los estudios que solo incluyeron resultados relacionados con la identidad de género u orientación sexual. RESULTADOS: Un total de N = 28 estudios cumplieron los criterios para su inclusión en la revisión. Todos los estudios se realizaron en países occidentales y la mayoría empleó un diseño de cohorte o transversal. Aunque las medidas de la función y la disfunción sexual variaron notablemente entre los estudios, la mayoría de los estudios adoptaron un marco biopsicosocial. La líbido puede estar relacionada con el IMC, mientras que otros aspectos del funcionamiento y el comportamiento sexual pueden no estar específicamente asociados con el estado de peso corporal. Se dispone de datos limitados sobre intervenciones basadas en evidencia. DISCUSIÓN: La disfunción sexual en mujeres con AN es común y plantea un problema clínico relevante. Aunque parte de la varianza se explica por el bajo IMC y las secuelas fisiológicas asociadas, otros factores psicosociales también están involucrados. Se necesitan investigaciones futuras, que usen diseños más robustos y medidas de resultado validadas, para comprender mejor las vías causales entre los correlatos biológicos y psicosociales de la AN y la disfunción sexual. La identificación de predictores de la función y la disfunción sexual en grupos más diversos de personas con AN apoyará el desarrollo de terapias basadas en la evidencia.

[The refeeding syndrome in anorexia nervosa].

The refeeding syndrome (RFS) is a potentially fatal condition involving fluid and electrolyte imbalances after refeeding in patients with anorexia nervosa. Low-calorie diet added thiamine and minerals is the standard approach to prevent RFS. In a recent systematic review starting with a higher calorie amount than earlier has been recommended, and in another review, it is proposed that a restriction in the amount of carbohydrates may allow for a higher calorie intake early on to enable a safe and faster weight gain. There are still many unanswered questions, but these studies may point to a future change in the guidelines.

[Biomarkers for anorexia nervosa].

Biomarkers for anorexia nervosa (AN) which reflect the pathophysiology and relate to the aetiology of the disease, are warranted and could bring us one step closer to targeted treatment of AN. Some leads may be found in the biochemistry which often is found disturbed in AN, although normalization in many aspects is seen at recovery from undernutrition. Recent genome-wide association studies support that genetic factors play a role in the pathophysiology of AN, of which some are independent of BMI-related mechanisms. In this review, an update on blood-based biomarkers of AN is presented.