Iatrogenic triggers for anorexia nervosa and bulimia nervosa: A WHO safety database disproportionality analysis.

Eating disorders, characterized by abnormal eating, weight control behaviors or both include anorexia nervosa (AN) and bulimia nervosa (BN). We investigated their potential iatrogenic triggers, using real-world data from the WHO safety database (VigiBase®). VigiBase® was queried for all AN and BN reports. The reports were classified as `pediatric' or `adult' according to age. Disproportionality analyses relied on the Information Component (IC), in which a 95% confidence interval lower-end positivity was required to suspect a signal. Our queries yielded 309 AN and 499 BN reports. Isotretinoin was disproportionately reported in pediatric AN (IC 3.6; [2.6-4.3]), adult AN (IC 3.1; [1.7-4.0]), and pediatric BN (IC 3.9; [3.0-4.7]). Lamivudine (IC 4.2; [3.2-4.9]), nevirapine (IC 3.7; [2.6-4.6]), and zidovudine (IC 3.4; [2.0-4.3]) had the highest ICs in adult AN. AN was associated with isotretinoin, anticonvulsants in minors, and antiretroviral drugs in adults. In adults, BN was related to psychotropic and hormonally active drugs. Before treatment initiation, an anamnesis should seek out mental health conditions, allowing the identification of patients at risk of developing or relapsing into AN or BN. In addition to misuse, the hypothesis of iatrogenic triggers for AN and BN should also be considered.

Childhood body mass index and the subsequent risk of anorexia nervosa and bulimia nervosa among women: A large Danish population-based study.

OBJECTIVE: Evidence linking childhood body mass index (BMI) with subsequent eating disorders is equivocal. Potential explanations include different study populations and size, and that anorexia nervosa (AN) and bulimia nervosa (BN) should be studied separately. We examined whether birthweight and childhood BMI were associated with subsequent risk of AN and BN in girls. METHOD: We included 68,793 girls from the Copenhagen School Health Records Register born between 1960 and 1996 with information on birthweight and measured weights and heights obtained from school health examinations at ages 6-15 years. Diagnoses of AN and BN were retrieved from Danish nationwide patient registers. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 355 cases of AN (median age: 19.0) and 273 cases of BN (median age: 21.8). Higher childhood BMI was linearly associated with decreasing risk of AN and increasing risk of BN at all childhood ages. At age 6, the HR for AN was 0.85 (95% CI: 0.74-0.97) per BMI z-score and the HR for BN was 1.78 (95% CI: 1.50-2.11) per BMI z-score. Birthweight >3.75 kg was associated with increased risk of BN compared to a birthweight of 3.26-3.75 kg. CONCLUSION: Higher BMI in girls at ages 6-15 years was associated with decreasing risk of AN and increasing risk of BN. Premorbid BMI could be relevant for the etiology of AN and BN, and in identifying high risk individuals. PUBLIC SIGNIFICANCE: Eating disorders are associated with elevated mortality, especially AN. Using a cohort of Copenhagen school children, we linked information on BMI at ages 6-15 years for 68,793 girls with nationwide patient registers. Low childhood BMI was associated with increased risk of AN, whereas high childhood BMI was associated with increased risk of BN. These findings may assist clinicians in identifying individuals at high-risk of these diseases.

Young women who develop anorexia nervosa exhibit a persistently low premorbid body weight on average: A longitudinal investigation of an important etiologic clue.

OBJECTIVE: test whether (1) young women who subsequently show onset of anorexia nervosa (AN) exhibit persistently lower average premorbid BMI than those who subsequently show onset of bulimia nervosa (BN), binge eating disorder (BED), purging disorder (PD), or no eating disorder; (2) a proximal spike in other risk factors occurs immediately before AN emergence; and (3) psychological and behavioral factors differentiate youth who show persistently low BMI from those who do not. METHOD: Data from a sample (N = 1952) of young women at high-risk for eating disorders followed for 3 years and a socioethno-racially representative sample (N = 496) of adolescent girls followed for 8 years were used to address these aims. RESULTS: Participants who developed AN exhibited significantly lower average measured premorbid BMI over repeated assessments than those who showed onset of other or no eating disorders. Dietary restraint, negative affect, and eating affect regulation expectancies significantly increased immediately before AN onset. Youth who showed persistently low BMI reported lower pressure for thinness, body dissatisfaction, and dieting at baseline, implying that elevations in these factors did not drive the low BMI. CONCLUSIONS: The evidence that young women who subsequently show AN onset exhibit a low premorbid BMI on average is novel and suggests that etiologic models should incorporate this finding and selective prevention programs should target low-BMI adolescent girls. The finding that dieting, negative affect, affect-regulation eating expectances spiked immediately before emergence of AN is also novel and suggests that it might be useful for selective prevention programs to target these factors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Increased risk of somatic diseases following anorexia nervosa in a controlled nationwide cohort study.

OBJECTIVE: To assess the risk of somatic diseases in connection with anorexia nervosa (AN). METHOD: This matched cohort study was based on Danish registries of all patients born 1961-2008 with a first-time diagnosis of AN in 1994-2018 at age 8-32 and matched controls without an eating disorder. For 13 somatic disease categories, time from inclusion date to time of first somatic diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. RESULTS: A total of 9985 AN patients born 1961-2008 and 49,351 controls were followed for a median (interquartile range) of 9.0 (4.4-15.7) years. During the first 2 years after entry there was a 60% higher hazard for any somatic disease among patients with AN than among controls, while the ratio from three to 11 years was reduced to 1.18. Regardless of age at diagnosis, the hazard among patients and controls were no different at approximately a decade after diagnosis of AN and the cumulative risk for patients for 12 of 13 disease categories was always higher or no less that for controls. For all disease categories, the hazard ratio (HR) was higher when close to entry. For most disease categories, age at diagnosis of AN did not modify the effect. DISCUSSION: While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls. Large HRs were seen in the early years after diagnosis during which patients require extensive medical interventions. PUBLIC SIGNIFICANCE: Based on Danish registries, a large sample of almost 10,000 patients with AN born 1961-2008 and almost 50,000 matched controls were followed for a median of 9 years. While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls.

Risk Factors for Eating Disorders and Perception of Body in Young Adults Associated with Sex.

(1) Background: The integrated approach to the prevention and treatment of eating disorders (EDs) requires knowledge and can be used only when specific risk factors are known. The aim of this study was to examine the differences in food choices and eating behavior between males and females; (2) Methods: This study comprised 148 females and 27 males aged from 18 to 26-years-old (MEAN ± SD = 21.4 ± 1.86 years old). Information about EDs was obtained from four different measures: the body mass index (BMI), the eating disorder screen for primary care (ESP), a standardized and validated questionnaire called "My Eating Habits" and the food frequency questionnaire with 10 answers (FFQ-10); (3) Results: The risk for developing eating disorders was detected in nearly 67% of respondents. It was also shown that EDs were more common in females and how body weight affected the way individuals feel about themselves. Females showed more unhealthy eating habits, which contributed to dietary restrictions and emotional overeating, as they were also afraid of gaining weight. The frequency of eating meat and drinking alcohol was higher in males, whereas eating legume seeds was less frequent in females. (4) Conclusions: This study opens a new field, which will help health care professionals recognize the problems with eating disorders and treat them based on different sex characteristics.

Is the Activity-Based Anorexia Model a Reliable Method of Presenting Peripheral Clinical Features of Anorexia Nervosa?

Anorexia nervosa (AN) causes the highest number of deaths among all psychiatric disorders. Reduction in food intake and hyperactivity/increased anxiety observed in AN are also the core features of the activity-based anorexia animal model (ABA). Our aim was to assess how the acute ABA protocol mimics common AN complications, including gonadal and cardiovascular dysfunctions, depending on gender, age, and initial body weight, to form a comprehensive description of ABA as a reliable research tool. Wheel running, body weight, and food intake of adolescent female and male rats were monitored. Electrocardiography, heart rate variability, systolic blood pressure, and magnetic resonance imaging (MRI) measurements were performed. Immediately after euthanasia, tissue fragments and blood were collected for further analysis. Uterine weight was 2 times lower in ABA female rats, and ovarian tissue exhibited a reduced number of antral follicles and decreased expression of estrogen and progesterone receptors. Cardiovascular measurements revealed autonomic decompensation with prolongation of QRS complex and QT interval. The ABA model is a reliable research tool for presenting the breakdown of adaptation mechanisms observed in severe AN. Cardiac and hormonal features of ABA with underlying altered neuroendocrine pathways create a valid phenotype of a human disease.

The Role of the Gut Microbiome, Immunity, and Neuroinflammation in the Pathophysiology of Eating Disorders.

There is a growing recognition that both the gut microbiome and the immune system are involved in a number of psychiatric illnesses, including eating disorders. This should come as no surprise, given the important roles of diet composition, eating patterns, and daily caloric intake in modulating both biological systems. Here, we review the evidence that alterations in the gut microbiome and immune system may serve not only to maintain and exacerbate dysregulated eating behavior, characterized by caloric restriction in anorexia nervosa and binge eating in bulimia nervosa and binge eating disorder, but may also serve as biomarkers of increased risk for developing an eating disorder. We focus on studies examining gut dysbiosis, peripheral inflammation, and neuroinflammation in each of these eating disorders, and explore the available data from preclinical rodent models of anorexia and binge-like eating that may be useful in providing a better understanding of the biological mechanisms underlying eating disorders. Such knowledge is critical to developing novel, highly effective treatments for these often intractable and unremitting eating disorders.

Antimicrobial peptides in patients with anorexia nervosa: comparison with healthy controls and the impact of weight gain.

Clinical observations show that patients with anorexia nervosa (AN) are surprisingly free from infectious diseases. There is evidence from studies in Drosophila melanogaster that starvation leads to an increased expression of antimicrobial peptides (AMPs). AMPs are part of the innate immune system and protect human surfaces from colonization with pathogenic bacteria, viruses and fungi. We compared the expression of AMPs between patients with AN and healthy controls (HC) and investigated the influence of weight gain. Using a standardized skin rinsing method, quantitative determination of the AMPs psoriasin and RNase 7 was carried out by ELISA. Even though non-significant, effect sizes revealed slightly higher AMP concentrations in HC. After a mean weight gain of 2.0 body mass index points, the concentration of psoriasin on the forehead of patients with AN increased significantly. We could not confirm our hypotheses of higher AMP concentrations in patients with AN that decrease after weight gain. On the contrary, weight gain seems to be associated with increasing AMP concentrations.

Parental feeding practices and the relationship with parents in female adolescents and young adults with eating disorders: A case control study.

OBJECTIVE: Perceived parental influence on diet in early adolescence in the context of the parental relationship had previously not been studied in a clinical sample. The aim of this study was to investigate a possible association between eating disorders and characteristics of the relationship with parents and the parental feeding practices in early adolescence. METHODS: 21 female adolescents and young adults with an eating disorder (ED)-bulimia nervosa or anorexia nervosa-and 22 females without eating disorder (healthy control; HC), aged between 16 and 26, were assessed via self-report questionnaires for problematic eating behaviour, relationship with parents, perceptions of parent's feeding practices at the age of 10-13 years and personality. Statistical evaluation was performed by means of group comparisons, effect sizes, regression analyses and mediator analyses. RESULTS: Adolescent and young adult females with ED reported more fears/overprotection and rejection/neglect by their mothers and less self-responsibility in terms of eating behaviour during adolescence than did the HC. The relationship with the fathers did not differ significantly. Females who perceived more cohesion, rejection/neglect and fears/overprotection by the mother were more likely to suffer from an ED. Rejection/neglect by both parents were associated with less self-acceptance of the young females with even stronger effect sizes for the fathers than the mothers. Harm prevention in the young females was a partial mediator between fears/overprotection and the drive for thinness. CONCLUSIONS: The parental relationship is partly reflected in the self-acceptance and self-responsibility in eating of the adolescent and young females, both of them are particularly affected in EDs. Stressors in the parent-child relationship should be targeted in treatment of eating disorders. Nutritional counselling for parents might be useful in early adolescence.

Weight suppression increases odds for future onset of anorexia nervosa, bulimia nervosa, and purging disorder, but not binge eating disorder.

BACKGROUND: Eating disorders affect 13% of females and contribute to functional impairment and mortality, but few studies have identified risk factors that prospectively correlate with future onset of anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD). Identifying risk factors specific to each eating disorder is critical for advancing etiologic knowledge and designing effective prevention programs. OBJECTIVES: This study examined whether weight suppression (the difference between a person's highest past weight at their adult height and their current weight) correlates with future onset of AN, BN, BED, and PD. METHODS: Data from 1165 young women with body image concerns (mean ± SD age: 21.9 ± 6.4 y) who completed annual diagnostic interviews over a 3-y follow-up period were examined. Logistic regression models evaluated the relation of baseline weight suppression to onset risk of each eating disorder controlling for age, dietary restraint, and intervention condition. RESULTS: Elevated weight suppression predicted future onset of AN (OR: 1.36; 95% CI: 1.03, 1.80), BN (OR: 1.34; 95% CI: 1.11, 1.62), PD (OR: 1.46; 95% CI: 1.23, 1.74), and any eating disorder (OR: 1.32; 95% CI: 1.12, 1.56), but not BED (OR: 1.10; 95% CI: 0.89, 1.37). Highest past weight correlated with future onset of BN and PD but not onset of AN, BED, or any eating disorder, and baseline current weight was inversely related to future AN onset only, implying that women with the largest difference between their highest past weight and current weight are at greatest risk of eating disorders. CONCLUSIONS: The results provide novel evidence that weight suppression correlates with future onset of eating disorders characterized by dietary restriction or compensatory weight control behaviors and suggest weight-suppressed women constitute an important risk group to target with selective prevention programs.These trials were registered at clinicaltrials.gov as NCT01126918 and NCT01949649.

Diagnostic and treatment challenges of eating disorders after adolescent bariatric surgery: A case report.

It is increasingly evident that bariatric surgery is an effective treatment option to manage severe obesity and its comorbidities in adolescent patients. This case report follows an adolescent who developed a restrictive eating disorder within months after bariatric surgery. Identifying and treating eating disorders after bariatric surgery can be difficult due to the conflicting goals of weight loss after surgery and weight gain in treatment of a restrictive eating disorder. Moreover, treating older adolescents can be challenging when they refuse treatment or go against medical advice. As more adolescents choose bariatric surgery, it is imperative that clinicians remain sensitive to weight-related outcomes, possible eating disorders and adolescent autonomy. Early collaboration between weight management and eating disorder programs is essential.

Characterizing the metabolic perturbations induced by activity-based anorexia in the C57Bl/6 mouse using 1H NMR spectroscopy.

BACKGROUND & AIMS: Anorexia nervosa (AN) is a severe psychological and potentially life-threatening eating disorder. The activity-based anorexia (ABA) mouse model is commonly used to investigate physiological abnormalities associated with this disorder. Characterizing the holistic biochemical alterations induced by anorexia is essential to understanding AN pathophysiology as well as to define biomarkers for prognosis. METHODS: To unravel the adaptive biochemical mechanisms occurring in this model in response to self-starvation, the urinary, plasma and fecal metabolic phenotypes of mice under different experimental conditions were compared. This included control mice with and without physical activity (CT and CTPA mice), a group with limited food access (LFA), and a group with both limited food access and physical activity (ABA). Using 1H nuclear magnetic resonance (NMR) spectroscopy, several biochemical perturbations were observed. RESULTS: Physical activity altered the abundance of 14 fecal metabolites, including those involved in gut microbial metabolism and proteolysis. Food restriction disrupted a wide range of metabolic pathways including gut microbial metabolism, proteolysis and fatty acid breakdown (24 urinary and 6 plasma metabolites). The combined impact of food restriction and physical activity resulted in the same pattern of metabolic disruption (24 urine, 6 plasma). CONCLUSIONS: This work defined the metabolic signatures of ABA mice and provides novel insights into biological adaptations of mice in response to both food restriction and physical activity. These results should be further confirmed in AN patients.

The role of body image disturbance in the onset, maintenance, and relapse of anorexia nervosa: A systematic review.

Body image disturbance is an important feature of Anorexia Nervosa (AN). Some researchers have argued that body image disturbance is not just a symptom of AN, but plays a causal role in the development, persistence, and relapse of AN. Our aim was to systematically review the existing empirical evidence concerning the role of the cognitive-affective, perceptual, and behavioral components of body image disturbance in AN. 46 studies fulfilled eligibility criteria reporting about 4928 participants with AN. There is some evidence suggesting that body image disturbance is related to the course of AN. However, experimental studies were missing and operationalizations of body image constructs and AN outcome measures varied greatly across studies. Therefore, on the basis of the available empirical data, it remained unclear whether body image disturbance is indeed a causal risk factor for AN. For future studies, it is crucial to use more consistent terminology and more specific and precise definitions of body image constructs as well as experimental designs, adequately powered samples, and well-validated measures. Altogether, this would set the stage to generate the high-quality data that are necessary to clarify the role of body image disturbance in the onset, maintenance and relapse of AN.

Gut-Brain Interactions: Implications for a Role of the Gut Microbiota in the Treatment and Prognosis of Anorexia Nervosa and Comparison to Type I Diabetes.

Anorexia nervosa has poor prognosis and treatment outcomes and is influenced by genetic, metabolic, and psychological factors. Gut microbes interact with gut physiology to influence metabolism and neurobiology, although potential therapeutic benefits remain unknown. Type 1 diabetes is linked to anorexia nervosa through energy dysregulation, which in both disease states is related to the gut microbiota, disordered eating, and genetics.

Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

The reduction of astrocytes and brain volume loss in anorexia nervosa-the impact of starvation and refeeding in a rodent model.

Anorexia nervosa (AN) is an often chronic, difficult to treat illness that leads to brain volume reductions in gray and white matter. The underlying pathophysiology is poorly understood, despite its potential importance in explaining the neuropsychological deficits and clinical symptoms associated with the illness. We used the activity-based anorexia model (ABA), which includes food reduction and running wheel access in female rats to study brain changes after starvation and refeeding. Longitudinal animal MRI and post-mortem brain sections confirmed a reduction in the mean brain volumes of ABA animals compared to controls. In addition, the mean number of astrocytes was reduced by over 50% in the cerebral cortex and corpus callosum, while the mean number of neurons was unchanged. Furthermore, mean astrocytic GFAP mRNA expression was similarly reduced in the ABA animals, as was the mean cell proliferation rate, whereas the mean apoptosis rate did not increase. After refeeding, the starvation-induced effects were almost completely reversed. The observation of the astrocyte reduction in our AN animal model is an important new finding that could help explain starvation-induced neuropsychological changes in patients with AN. Astrocyte-targeted research and interventions could become a new focus for both AN research and therapy.

Differentiating weight-restored anorexia nervosa and body dysmorphic disorder using neuroimaging and psychometric markers.

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are potentially life-threatening conditions whose partially overlapping phenomenology-distorted perception of appearance, obsessions/compulsions, and limited insight-can make diagnostic distinction difficult in some cases. Accurate diagnosis is crucial, as the effective treatments for AN and BDD differ. To improve diagnostic accuracy and clarify the contributions of each of the multiple underlying factors, we developed a two-stage machine learning model that uses multimodal, neurobiology-based, and symptom-based quantitative data as features: task-based functional magnetic resonance imaging data using body visual stimuli, graph theory metrics of white matter connectivity from diffusor tensor imaging, and anxiety, depression, and insight psychometric scores. In a sample of unmedicated adults with BDD (n = 29), unmedicated adults with weight-restored AN (n = 24), and healthy controls (n = 31), the resulting model labeled individuals with an accuracy of 76%, significantly better than the chance accuracy of 35% ([Formula: see text]). In the multivariate model, reduced white matter global efficiency and better insight were associated more with AN than with BDD. These results improve our understanding of the relative contributions of the neurobiological characteristics and symptoms of these disorders. Moreover, this approach has the potential to aid clinicians in diagnosis, thereby leading to more tailored therapy.