Umeå universitets logga

Anorexia nervosa (AN) is a complex and serious mental disorder, which may affect individuals of all ages and sex, but primarily affecting young women. The disease is characterized by a disturbed body image, restrictive eating behavior, and a lack of acknowledgment of low body weight. The underlying causes of AN remain largely unknown, and current treatment options are limited to psychotherapy and nutritional support. This paper investigates the impact of Fecal Microbiota Transplants (FMT) from patients with AN on food intake, body weight, behavior, and gut microbiota into antibiotic-treated mice. Two rounds of FMT were performed using AN and control (CO) donors. During the second round of FMT, a subset of mice received gut microbiota (GM) from a different donor type. This split-group cross-over design was chosen to demonstrate any recovery effect of FMT from a non-eating disorder state donor. The first FMT, from donors with AN, resulted in lower food intake in mice without affecting body weight. Analysis of GM showed significant differences between AN and CO mice after FMT1, before cross-over. Specific bacterial genera and families Ruminococcaceae, Lachnospiraceae, and Faecalibacterium showed different abundances in AN and CO receiving mice. Behavioral tests showed decreased locomotor activity in AN mice after FMT1. After FMT2, serum analysis revealed higher levels of appetite-influencing hormones (PYY and leptin) in mice receiving AN-GM. Overall, the results suggest that AN-GM may contribute to altered food intake and appetite regulation, which can be ameliorated with FMT from a non-eating disorder state donor potentially offering FMT as a supportive treatment for AN.

Background: Plasma lipid concentrations in patients with anorexia nervosa (AN) seem to be altered.

Methods: We conducted a naturalistic study with 75 adult female patients with AN and 26 healthy female controls (HC). We measured plasma lipid profile, sex hormones and used self-report questionnaires at admission and discharge.

Results: Total cholesterol (median (IQR): 4.9 (1.2)) and triglycerides (TG) (1.2 (0.8)) were elevated in AN at admission (BMI 15.3 (3.4)) compared with HC (4.3 (0.7), p = 0.003 and 0.9 (0.3), p = 0.006) and remained elevated at discharge (BMI 18.9 (2.9)) after weight restoration treatment. Estradiol (0.05 (0.1)) and testosterone (0.5 (0.7)) were lower in AN compared with HC (0.3 (0.3), p = < 0.001 and 0.8 (0.5), p = 0.03) and remained low at discharge. There was no change in eating disorder symptoms. Depression symptoms decreased (33 (17) to 30.5 (19), (p = 0.007)). Regression analyses showed that illness duration was a predictor of TG, age was a predictor of total cholesterol and LDL, while educational attainment predicted LDL and TG.

Conclusion: Lipid concentrations remained elevated following weight restoration treatment, suggesting an underlying, premorbid dysregulation in the lipid metabolism in AN that persists following weight restoration. Elevated lipid concentrations may be present prior to illness onset in AN.

Level of evidence: III: Evidence obtained from well-designed cohort or case–control analytic studies.

International Journal of Exercise Science 17(3): 308-326, 2024.

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.

Major depressive disorder (MDD) is highly prevalent in individuals with anorexia nervosa (AN) and is a predictor of greater clinical severity. However, there is a limited amount of evidence supporting the use of psychotropic medications for its management. A systematic scoping review was conducted to assess the current literature on brain stimulation treatments for AN with comorbid MDD, with a specific focus on MDD treatment response and weight restoration. This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the PubMed, PsycInfo, and MEDLINE databases were searched until July 2022 using specific key words related to AN and brain stimulation treatments. A total of 373 citations were identified, and 49 treatment studies that met the inclusion criteria were included in the review. The initial evidence suggests that electroconvulsive therapy, repetitive transcranial magnetic stimulation, and deep-brain stimulation may be effective in managing comorbid MDD in AN. Emerging evidence suggests that transcranial direct current stimulation may have a positive effect on body mass index in individuals with severe to extreme AN. However, there is a need for the development of better measurement techniques for assessing the severity of depression in the context of AN. Controlled trials that are adequately designed to account for these limitations are highly warranted for deep-brain stimulation, electroconvulsive therapy, and repetitive transcranial magnetic stimulation and hold promise for providing clinically meaningful results.

Objective: To investigate whether cognitive inflexibility could be identified using the Wisconsin Card Sorting Test (WCST) in patients with severe and extreme anorexia nervosa (AN) compared to healthy control participants (HCs). Method: We used the WCST to assess 34 patients with AN (mean age: 25.9 years, mean body mass index (BMI): 13.2 kg/m2) 3–7 days after admission to a specialized nutrition unit and 34 HCs. The Beck Depression Inventory II and the Eating Disorder Inventory 3 were distributed.

Results: The patients displayed more perseveration than HCs controlled for age and years of education, with moderate effect sizes (perseverative responses (%): adjusted difference = −7.74, 95% CI: −14.29–(−1.20), p-value: 0.021; perseverative errors (%): adjusted difference = −6.01, 95% CI: −11.06–(−0.96), p-value: 0.020). There were no significant relationships between perseveration and depression, eating disorder symptoms, illness duration, or BMI.

Discussion: Patients with severe and extreme AN demonstrated lower cognitive flexibility compared to HCs. Performance was not related to psychopathology or BMI. Patients with severe and extreme anorexia nervosa may not differ from less severe patients in cognitive flexibility performance. As this study exclusively focused on patients suffering from severe and extreme AN, potential correlations might be masked by a floor effect.

Purpose: Severe malnourishment may reduce cognitive performance in anorexia nervosa (AN). We studied cognitive functioning during intensive nutritional and medical stabilization in patients with severe or extreme AN and investigated associations between weight gain and cognitive improvement.

Methods: A few days after admission to a specialized hospital unit, 33 patients with severe or extreme AN, aged 16–42 years, completed assessments of memory, cognitive flexibility, processing speed, and attention. Mean hospitalization was 6 weeks. Patients completed the same assessments at discharge (n = 22) following somatic stabilization and follow-up up to 6 months after discharge (n = 18).

Results: The patients displayed normal cognitive performance at admission compared to normative data. During nutritional stabilization, body weight increased (mean: 11.3%; range 2.6–22.2%) and memory, attention, and processing speed improved (p values: ≤ 0.0002). No relationship between weight gain and cognitive improvement was observed at discharge or follow-up.

Conclusions: Cognitive performance at hospital admission was normal in patients with severe or extreme AN and improved during treatment although without association to weight gain. Based on these results, which are in line with previous studies, patients with severe or extreme AN need not be excluded from cognitively demanding tasks, possibly including psychotherapy. As patients may have other symptoms that interfere with psychotherapy, future research could investigate cognitive functioning in everyday life in patients with severe AN.

Trial registration number: The study is registered at clinicaltrials.gov (NCT02502617). Level of evidence: Level III, cohort 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.

Anorexia nervosa (AN) is a devastating psychiatric condition associated with a high mortality and chronicity and for which the etiology is unknown. Recent genomic-wide association studies suggest that AN is a psychometabolic disorder, having identified several genes that link AN to both psychiatric disorders and metabolic states. One of the metabolic factors that have since long been of interest in eating disorder pathophysiology is ghrelin, an orexigenic hormone produced by the gut. Ghrelin increases before food intake and stimulates appetite, reducing insulin, and is linked to increase in norepinephrine and growth hormone. Ghrelin exists in different forms in humans, i.e., as acyl-ghrelin, the activated form, and desacyl-ghrelin, a previously presumed inactive form, that may counteract the effects of acyl-ghrelin. Both have consistently been found to be increased in AN both in the acute stage and after weight restoration therapy, in spite of a lack of increase in appetite. Some findings indicate that individuals with long-standing AN develop resistance to the increased ghrelin levels, a process where exercise may be involved. This review present some of the most recent findings in the field of ghrelin research, as relevant for the understanding of the pathophysiology of AN.

Background: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD). Objective: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity. Methods: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo-controlled, double-blind, 6-month main study followed by an active-treatment 6-month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18F]FE-PE2I. Results: Drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies. Conclusions: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objectives: Updated international guideline recommendations for AN inpatient care rely on expert opinions/observational evidence and promote extended inpatient stays, warranting investigation using higher-level ecological evidence.

Methods: The study was conducted according to Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Data encompassing 13,885 ED inpatients (5336 adolescents and 8549 adults) was retrieved from Swedish public health registries. Variables analyzed included (1) ED inpatient care opportunities, (2) unique number of ED inpatients and (3) mean length of ED-related inpatient stays in age groups 15–19 and 20–88+, across 1998–2020.

Results: Mean length of inpatient stays was inversely correlated to relapse to ED-related inpatient care within the same year (p < 0.001, R-squaredadj = 0.5216 and p < 0.00001, R-squaredadj = 0.5090, in the 15–19 and 20–88+ age groups, respectively), independent of number of ED inpatients treated within a year in both age groups. Extending mean adolescent inpatient duration from 35 to 45 days was associated with a ∼30% reduction in the year-wise relapse rate.

Conclusions: Mean length of ED-related inpatient treatment stays was associated with reduced relapses to inpatient care within the same year, which could be interpreted as support for recommendations to include a stabilization phase in inpatient ED treatment.