Plasma proteome profiling reveals metabolic and immunologic differences between Anorexia Nervosa subtypes.

AIMS/HYPOTHESIS: Anorexia Nervosa (AN) is a severe psychiatric disorder of an unknown etiology with a crude mortality rate of about 5 % per decade, making it one of the deadliest of all psychiatric illnesses. AN is broadly classified into two main subtypes, restricting and binge/purging disorder. Despite extensive research efforts during several decades, the underlying pathophysiology of AN remains poorly understood. In this study, we aimed to identify novel protein biomarkers for AN by performing a proteomics analysis of fasting plasma samples from 78 females with AN (57 restrictive and 21 binge/purge type) and 70 healthy controls. METHODS: Using state-of-the-art mass spectrometry-based proteomics technology in conjunction with an advanced bioinformatics pipeline, we quantify >500 plasma proteins. RESULTS: Differential expression analysis and correlation of proteomics data with clinical variables led to identification of a panel of novel protein biomarkers with potential pathophysiological significance for AN. Our findings demonstrate evidence of a humoral immune system response, altered lipid metabolism and potential alteration of plasma cells in AN patients. Additionally, we stratified AN patients based on the quantified proteins and suggest a potential autoimmune nature in the restrictive subtype of AN. CONCLUSIONS/INTERPRETATION: In summary, on top of biomarkers of AN subtypes, this study provides a comprehensive map of plasma proteins that constitute a resource for further studies of the pathophysiology of AN.

Cognitive performance in hospitalized patients with severe or extreme anorexia nervosa.

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.

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.

Cognitive Flexibility in Hospitalized Patients with Severe or Extreme Anorexia Nervosa: A Case-Control Study.

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.

Trauma Experiences Are Common in Anorexia Nervosa and Related to Eating Disorder Pathology but Do Not Influence Weight-Gain during the Start of Treatment.

OBJECTIVE: The main characteristics of Anorexia Nervosa (AN) in adults are restriction of energy intake relative to requirements leading to significant weight loss, disturbed body image, and intense fear of becoming fat. Traumatic experiences (TE) have been reported as common, although less is known about the relationship with other symptoms in severe AN. We investigated the presence of TE, PTSD, and the relation between TE, eating disorder (ED) symptoms, and other symptoms in moderate to severe AN (n = 97) at admission to inpatient weight-restoration treatment. All patients were enrolled in the Prospective Longitudinal all-comer inclusion study on Eating Disorders (PROLED). METHODS: TE were assessed using the Post-traumatic stress disorder checklist, Civilian version (PCL-C), and ED symptoms using the Eating Disorder Examination Questionnaire (EDE-Q); depressive symptoms were assessed using the Major Depression Inventory (MDI), and the presence of Post-traumatic Stress Disorder (PTSD) was diagnosed according to ICD-10 criteria. RESULTS: The mean score on PCL-C was high (mean 44.6 SD 14.7), with 51% having a PCL-C score at or above 44 (n = 49, suggested cut-off for PTSD), although only one individual was clinically diagnosed with PTSD. There was a positive correlation between baseline scores of PCL-C and EDE-Q-global score (r = 0.43; p < 0.01) as well as of PCL-C and all EDE-Q subscores. None of the included patients were admitted for treatment of TE/PTSD during the first 8 weeks of treatment. CONCLUSIONS: In a group of patients with moderate to severe AN, TE were common, and scores were high, although only one had a diagnosis of PTSD. TE were related to ED symptoms at baseline, but this association diminished during the weight restoration treatment.

The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice.

Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis.

Patients' perspectives on screening for disordered eating among adolescents with type 1 diabetes.

PURPOSE: People with type 1 diabetes have an increased risk of disordered eating (DE) and eating disorders (ED). Screening is recommended however little is known about patients' perspectives on screening questionnaires. This paper reports qualitative analyses of patients' perspectives on the questionnaire Diabetes Eating Problem Survey Revised (DEPS-R), including acceptability, attitudes, and cognitive understanding. RESEARCH DESIGN AND METHODS: 15 adolescents with type 1 diabetes between 11 and 18 years, were interviewed. A semi-structured format and a qualitative Interpretive Descriptive (ID) methodology was chosen. RESULTS: The analyses identified four themes: (1) The Questionnaire, (2) Reframing Diabetes Visits, (3) This is (not) for me, and (4) Out in the Open. The DEPS-R was completed with-in 5-10 min. with no technical difficulties. The questionnaire altered the diabetes visit for some, creating a new dialog, and time for self-reflection. Adolescents appreciated the direct approach in the questionnaire, and showed willingness to complete the questionnaire, when presented to them by a health care professional (HCP). One item in the DEPS-R proved difficult to understand for some participants. CONCLUSION: The study highlights DEPS-R as a clinically relevant screening questionnaire. Completing DEPS-R prior to a consultation opens the door to a consultation that invites the adolescent to address matters of eating behavior. Our findings suggest that systematic screening of DE/ED using the DEPS-R is both accepted and welcomed by adolescents with type 1 diabetes. Future research should focus on a potential update of selected items in DEPS-R. LEVEL OF EVIDENCE: V - qualitative study.

Body Contouring Surgery Improves Long-Term Satisfaction with Appearance and Health-Related Quality of Life after Bariatric Surgery.

BACKGROUND: Patient-reported outcomes are crucial in bariatric surgery (BaS) and body contouring surgery (BC) because patients' goals include improvement in appearance and health-related quality of life (HR-QOL). The BODY-Q is a patient-reported outcome measure developed to measure change in satisfaction with appearance and HR-QOL in BaS and BC patients. The aim of this study was to examine BODY-Q scores over the entire weight loss journey, and to investigate the impact of BC after BaS. METHODS: Patients completed the BODY-Q before and after BaS and BC at four hospital departments in Denmark between 2015 and 2019. Cross-sectional scores were analyzed by phase of weight loss journey using one-way analysis of variance. Scores for patients who provided longitudinal assessments were analyzed using repeated measures analysis of variance and paired t test. The impact of BC was examined over time after BaS, using an independent t test from before BaS through more than 7 years after BaS. RESULTS: The study included 1527 patients who provided 2285 BODY-Q assessments. The cross-sectional analysis by phase of weight loss journey showed higher scores after BaS, lower scores before BC, and highest-level scores after BC. The longitudinal analysis showed higher postoperative mean scores compared with preoperative scores for both BaS and BC. The analysis over time after BaS revealed lower mean scores in patients who did not receive BC. CONCLUSION: The authors' results provide evidence of the positive impact of BaS and BC on patients' lives and emphasize the importance of considering BC to finalize the weight loss journey, as it helps to maintain improvements in appearance and HR-QOL. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Normal bone mineral density and bone microarchitecture in adult males with high and low risk of exercise addiction.

Exercise addiction describes a pattern of excessive and obsessive exercise and is associated with hypoleptinemia and low testosterone that may have adverse skeletal effects. We used a validated questionnaire to identify males with high and low risk of exercise addiction. In a cross-sectional design, males (aged 21-49 years) with high (n = 20, exercise addictive) and low risk (n = 20, exercise controls) of exercise addiction had examinations of bone mass, bone microarchitecture, and estimated bone strength performed using dual-energy x-ray absorptiometry of the hip and spine and high-resolution peripheral quantitative computed tomography of the distal radius and tibia. Findings were compared between the groups and to a population-based sample of healthy men aged 20-80 years (n = 236). We found similar hip and spine bone mineral density in exercise addictive and controls. Cortical and trabecular bone microarchitecture and estimated bone strength in radius and tibia did not differ significantly between the groups. Multiple regression analyses adjusting for age, body weight, free testosterone, and hours of weekly training did not alter findings. Also, bone indices from both groups were within 95% prediction bands derived from the population-based sample for the vast majority of indices. Neither group had no associations between circulating leptin or free testosterone and bone outcomes. In conclusion, in a study on younger males, we found no associations between high risk of exercise addiction and various indices of bone mass and bone quality indicative of altered skeletal health.

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.

Anorexia Nervosa: Reduction in Depression during Inpatient Treatment Is Closely Related to Reduction in Eating Disorder Psychopathology.

Objective: Anorexia nervosa (AN) is a severe mental disorder frequently associated with high scores of depressiveness. We examined the short-term effects of inpatient treatment on depressiveness and eating disorder (ED) psychopathology using the self-rating Major Depression Inventory (MDI) and Eating Disorder Examination questionnaire (EDEq) for patients with AN. Material: Forty-nine patients with AN, all part of the PROspective Longitudinal all-comer inclusion study on EDs (PROLED), were observed over eight weeks with baseline psychometric measures, EDE-q at baseline and endpoint, and weekly MDI self-scoring. Methods: Apart from the weekly Body Mass Index (BMI) measurements, patients were assessed at baseline using the Eating Disorder Inventory (EDI) and the Symptom Check List 92 (SCL-92). Results: Inpatient treatment reduced MDI consistently over 8 weeks (Wilks Lambda = 0.59, F = 4.1, p < 0.01) and this reduction in MDI was positively correlated with a reduction in EDEq (r = 0.44; p < 0.01) during inpatient treatment. Baseline medication did not predict changes in MDI during the inpatient treatment. BMI increased from 14.9 (week 1) to 17.2 (week 8). Conclusions: Inpatient treatment of AN is associated with a reduction in depressiveness. This improvement in depressiveness scores correlates with an improvement in ED psychopathology but not with weight gain.

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.

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.

Eating disorders and subsequent risk of substance use disorders involving illicit drugs: a Danish nationwide register-based cohort study.

PURPOSE: No study has investigated the ongoing risk of substance use disorders involving illicit drugs (ISUD) after first eating disorder (ED) and whether the pattern of risk differs according to types of ED and ISUD. Therefore, we aimed to longitudinally assess the risk of a subsequent diagnosis of any ISUD (pooled category) and specific ISUD after a first-time diagnosis of anorexia nervosa (AN), bulimia nervosa (BN), or unspecified ED (USED). METHODS: A retrospective cohort study using data from Danish nationwide registers identified 20,759 ED patients and 83,038 matched controls (1:4 ratio). Risk of any ISUD diagnosis after first ED diagnosis was estimated by generating hazard ratios (HR). Logistic regression was applied to assess associations between each ED and specific ISUD. RESULTS: Patients with AN, BN, and USED (without a prior ISUD diagnosis) exhibited an increased relative risk of a subsequent diagnosis of any ISUD compared with respective controls, and the elevated risk persisted over 10 years (AN, adjusted HRs ranging from 1.60 [99% CI 1.15-2.24] to 5.16 [3.14-8.47]; BN, 2.35 [1.46-3.79] to 14.24 [6.88-29.47]; USED, 2.86 [1.35-3.79] to 8.56 [3.31-29.47]). The highest estimates were observed during the first year of follow-up. Each ED type was associated with an increased likelihood of all types of ISUD. AN and USED were most strongly associated with sedatives/hypnotics, BN with other illegal substances (e.g., ecstasy and hallucinogens). CONCLUSIONS: ED patients have a considerable risk for subsequent ISUD. Prevention efforts and treatment targeting ISUD are likely required to improve ED treatment prognosis.

The Impact of Alcohol and Other Substance Use Disorders on Mortality in Patients With Eating Disorders: A Nationwide Register-Based Retrospective Cohort Study.

OBJECTIVE: Research is lacking on the contribution of different types of substance use disorders (SUDs) to excess mortality across the full spectrum of eating disorders. The authors assessed the association of alcohol use disorders and other SUDs with mortality in anorexia nervosa, bulimia nervosa, and unspecified eating disorder compared with matched control subjects. METHODS: A retrospective cohort study was conducted using Danish nationwide registers. The study included 20,759 patients with eating disorders and 83,036 matched control subjects. Hazard ratios were calculated to compare all-cause mortality risk between eating disorder patients and control subjects both with and without a lifetime SUD diagnosis (abuse or dependence of alcohol, cannabis, or hard drugs). RESULTS: For patients with each type of eating disorder, a higher risk of all-cause mortality was observed relative to control subjects without SUDs among those who abused alcohol and/or cannabis (adjusted hazard ratios for the anorexia nervosa, bulimia nervosa, and unspecified eating disorder patients, respectively, were 11.28 [95% CI=7.01, 18.16], 5.86 [95% CI=3.37, 10.1], and 10.86 [95% CI=6.74, 17.50]), or hard drugs alone or in combination with alcohol and/or cannabis (adjusted hazard ratios, respectively, were 22.34 [95% CI=15.13, 33.00], 11.43 [95% CI=7.14, 18.28], and 15.53 [95% CI=10.15, 23.78]), than in those without SUDs (adjusted hazard ratios, respectively, were 3.21 [95% CI=2.43, 4.23], 1.24 [95% CI=0.88, 1.77], and 4.75 [95% CI=3.57, 6.31]). Control subjects with SUDs also exhibited an elevated risk of all-cause mortality relative to control subjects without SUDs, although to a much lesser extent than eating disorder patients with SUDs. CONCLUSIONS: SUDs have an additive effect on excess mortality in patients with eating disorders. The prevention and treatment of SUDs in this patient group is thus imperative to reduce mortality.

Does receiving an eating disorder diagnosis increase the risk of a subsequent alcohol use disorder? A Danish nationwide register-based cohort study.

BACKGROUND AND AIM: No large-scale, longitudinal clinical study has examined whether patients with different types of eating disorders (ED) have an increased risk of a subsequent alcohol use disorder (AUD). This study aimed to assess the ongoing risk of receiving a diagnosis of AUD following a first-time diagnosis of anorexia nervosa (AN), bulimia nervosa (BN), or unspecified ED (USED). DESIGN: Retrospective cohort study. SETTING: Danish nationwide registries, January 1994 to December 2018. PARTICIPANTS: A total of 20 759 ED patients and 83 036 controls were followed from the date of first ED diagnosis (index date) until the date of first AUD diagnosis, death, emigration, or the end of the study. Controls were selected in a 1:4 ratio and matched on month and year of birth, gender and ethnicity. MEASUREMENTS: We obtained data on ED (AN, BN, USED; exposure) and AUD (abuse/dependence; outcome) diagnoses as well as sociodemographics and other psychiatric diagnoses. Time to AUD was generated from the index date. Risk of AUD after the index date was assessed among those without a prior AUD diagnosis while adjusting for sociodemographics and prior psychiatric diagnoses. FINDINGS: Compared with controls, an increased relative risk of AUD after the index date was observed in AN patients throughout the study lasting 15 + years (adjusted hazard ratios [HRs] ranging from 2.49 [99% CI = 1.46, 4.25] to 6.83 [2.84, 16.41]), in BN patients during the first year of follow-up and from 2 years onward (2.72 [1.66, 4.44] to 17.44 [6.01, 50.63]), and in USED patients during the first year and 2-15 years of follow-up (2.52 [1.54, 4.14] to 14.17 [5.86, 34.27]). In all three groups, estimates were highest during the first year, particularly among BN patients. CONCLUSIONS: Patients with anorexia nervosa, bulimia nervosa, or unspecified eating disorders appear to have an increased ongoing risk of receiving a diagnosis of alcohol use disorder following their first eating disorder diagnosis compared with controls.

Inpatient Weight Restoration Treatment Is Associated with Decrease in Post-Meal Anxiety.

OBJECTIVE: Anorexia nervosa (AN) is characterized by weight loss, distorted body image with fear of becoming fat and associated with anxiety, especially in relation to food intake. Anxiety in relation to meals and weight restoration remains a major challenge in the treatment of AN. We examined the effects of inpatient weight restoration treatment on levels of post-meal anxiety using visual analogue scale (VAS) ratings in patients with AN. MATERIALS: Thirty-two patients with AN, all part of the PROspective Longitudinal all-comer inclusion study on Eating Disorders (PROLED) were followed over eight weeks with baseline psychometric measures and weekly VAS anxiety self-scoring. METHODS: Apart from the weekly body mass index (BMI) and VAS, patients were characterized at baseline using the Eating Disorder Examination Questionnaire (EDE-Q), Eating Disorder Inventory (EDI), Symptom Check List 92 (SCL-92), Major Depression Inventory (MDI), and Autism Quotient (AQ). RESULTS: The results showed a significant time effect, Wilks Lambda = 0.523, F = 3.12, p < 0.05 (power of 0.862), indicating a reduction in VAS scores of anxiety from baseline to week 8. There was no effect of baseline medication or scores of MDI on the results. BMI increased from a mean of 15.16 (week 1) to 17.35 (week 8). In comparison, patients dropping out after only three weeks (n = 31) also had a trend toward a reduction in VAS anxiety (ns). CONCLUSIONS: Inpatient weight restoration treatment is associated with a decrease in post-meal anxiety in AN, an effect that occurs early and becomes clinically significant in patients who stay in treatment.

The Impact of Alcohol and Other Substance Use Disorders on Mortality in Patients With Eating Disorders: A Nationwide Register-Based Retrospective Cohort Study.

OBJECTIVE: Research is lacking on the contribution of different types of substance use disorders (SUDs) to excess mortality across the full spectrum of eating disorders. The authors assessed the association of alcohol use disorders and other SUDs with mortality in anorexia nervosa, bulimia nervosa, and unspecified eating disorder compared with matched control subjects. METHODS: A retrospective cohort study was conducted using Danish nationwide registers. The study included 20,759 patients with eating disorders and 83,036 matched control subjects. Hazard ratios were calculated to compare all-cause mortality risk between eating disorder patients and control subjects both with and without a lifetime SUD diagnosis (abuse or dependence of alcohol, cannabis, or hard drugs). RESULTS: For patients with each type of eating disorder, a higher risk of all-cause mortality was observed relative to control subjects without SUDs among those who abused alcohol and/or cannabis (adjusted hazard ratios for the anorexia nervosa, bulimia nervosa, and unspecified eating disorder patients, respectively, were 11.28 [95% CI=7.01, 18.16], 5.86 [95% CI=3.37, 10.1], and 10.86 [95% CI=6.74, 17.50]), or hard drugs alone or in combination with alcohol and/or cannabis (adjusted hazard ratios, respectively, were 22.34 [95% CI=15.13, 33.00], 11.43 [95% CI=7.14, 18.28], and 15.53 [95% CI=10.15, 23.78]), than in those without SUDs (adjusted hazard ratios, respectively, were 3.21 [95% CI=2.43, 4.23], 1.24 [95% CI=0.88, 1.77], and 4.75 [95% CI=3.57, 6.31]). Control subjects with SUDs also exhibited an elevated risk of all-cause mortality relative to control subjects without SUDs, although to a much lesser extent than eating disorder patients with SUDs. CONCLUSIONS: SUDs have an additive effect on excess mortality in patients with eating disorders. The prevention and treatment of SUDs in this patient group is thus imperative to reduce mortality.

Validation of the Eating Disorder Examination Questionnaire in Danish Eating Disorder Patients and Athletes.

The Eating Disorder Examination Questionnaire (EDE-Q) is a gold standard questionnaire to identify eating disorder symptoms but has not yet been validated in Danish. The scale consists of four theoretical constructs of disordered eating: Restraint eating, Eating concerns, Shape concerns and Weight concerns. However, the four-factor structure has been difficult to replicate across cultures. This study aimed to examine the factor structure and psychometric properties of the EDE-Q in Danish. The study consisted of four samples (aged 15-70): Patients with anorexia, bulimia and unspecified eating disorders (n = 101), patients with symptoms of binge-eating disorder (n = 300), recreational athletes (n = 404), and elite athletes (n = 526). Depending on the analysis performed, participants had to complete the EDE-Q, the SCOFF questionnaire for eating disorders or the Binge Eating Disorders Questionnaire. In accordance with international research, we found no evidence for a four-factor structure in the EDE-Q among patients or among athletes. But our results showed significant, positive associations between EDE-Q and SCOFF, BED-Q and MDI in all samples. We conclude that the internal structure of EDE-Q is low, while construct validity is high, making EDE-Q useful as an instrument to identify individuals with eating disorder symptoms, including recreational, and elite athletes.

Comorbid mental disorders during long-term course in a nationwide cohort of patients with anorexia nervosa.

OBJECTIVE: Comorbid mental disorders in anorexia nervosa during long-term course require detailed studies. METHOD: This matched cohort study was based on nationwide Danish register data of all patients born 1961-2008 with a first-time ICD-10 diagnosis of anorexia nervosa (AN) between 1994 and 2018 at age 8-32 and matched controls taken from all individuals without an eating disorder (ED). For nine categories of non-eating mental disorders, time from date of first AN-diagnosis (inclusion date) to time of first diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. RESULTS: A total of 9,985 patients with AN (93.5% females) and 49,351 matched controls were followed for a median (IQR) of 9.0 (4.4-15.7) years. For patients, there was about 25% and 55% risk of receiving any non-ED disorder during the first 2 years and two decades after inclusion, respectively. A hazard ratio (HR) of seven for any non-ED was found for the first 12 months after inclusion, a ratio that reduced to two at five or more years after inclusion. During the first years, large HRs ranging in 6-9 were found for affective, autism spectrum, personality, and obsessive-compulsive disorders with the latter displaying the highest continuous increased risk. The HR at 12 months after inclusion was highest for any non-ED disorder and affective disorders in patients aged 8-13 at diagnosis. DISCUSSION: Comorbid mental disorders in AN are most frequently diagnosed in the first years after diagnosis of AN and on longer terms imply a double immediate risk.