Alin Andries

Gender differences in outcome of eating disorders: a retrospective cohort study.

Eating disorders (EDs) are uncommon in males. The majority of outcome studies on ED have not presented gender-specific results, mostly because of small study samples or exclusion of males. Furthermore, psychometric tools and outcome criteria used in ED have mainly been validated for females only. The objective of this study was to evaluate gender differences in weight restoration in different EDs. We studied the male representation and outcome in a large retrospective single centre cohort, the Funen Anorexia Nervosa Study (FANS). A total of 1015 patients were included in the study. A total of 356 (35%) patients were diagnosed with anorexia nervosa (AN), 298 (29%) with eating disorder not otherwise specified (EDNOS) and 361 (36%) with bulimia nervosa (BN). The male fractions in AN and EDNOS were similar, but significantly lower in BN. When remission was defined as body weight restoration to at least 85% of ideal body weight (IBW) and no self-reported binge or purgative behaviors in six months, the median time from onset to remission for patients with AN was significantly shorter for males: 7 years for females vs. 3 years for males. Among patients with a 5 years history of disease, remission rates in AN were 39% for females vs. 59% for males. The median time to remission for patients with EDNOS was similar to that of AN: 6 years for females vs. 3 years for males. In patients with EDNOS, 45% of the females remitted within 5 years vs. 77% of the males. With regard to body weight restoration and remission of purging behavior, this study suggests a better outcome for males than for females.

Dronabinol in severe, enduring anorexia nervosa: A randomized controlled trial

OBJECTIVE The evidence for pharmacological treatment of severe, longstanding anorexia nervosa (AN) is sparse and the few controlled pharmacologic studies have focused on a narrow range of drugs. The aim of the present study was to investigate the effects of treatment with a synthetic cannabinoid agonist on body weight and eating disorder-related psychopathological personality traits in women with severe, enduring AN. METHOD This add-on, prospective, randomized, double blind, controlled crossover study was conducted between 2008 and 2011 at a specialized care center for eating disorders. Twenty-five women over 18 years with AN of at least 5 years duration were randomized to treatment with either dronabinol-placebo or placebo-dronabinol. In addition to the standardized baseline therapeutic regime, the participants received dronabinol, 2.5 mg twice daily for 4 weeks and matching placebo for 4 weeks, separated by a 4-week wash-out period. Primary outcome was the mean change in body weight. Secondary outcome was score changes on the Eating Disorder Inventory-2 (EDI-2). Data were analyzed for the 24 patients who completed the trial. RESULTS During dronabinol treatment, participants gained 0.73 kg (t = 2.86, df = 22, p < 0.01) above placebo without significant psychotropic adverse events. Dronabinol significantly predicted weight gain in a multiple linear regression including EDI-2 body dissatisfaction score and leptin. EDI-2 subscale scores showed no significant changes over time. DISCUSSION Dronabinol therapy was well tolerated. During four weeks of exposure it induced a small but significant weight gain in the absence of severe adverse events.

Leptin, ghrelin, and endocannabinoids: potential therapeutic targets in anorexia nervosa.

Anorexia nervosa (AN) has the highest mortality rate between psychiatric disorders, and evidence for managing it is still very limited. So far, pharmacological treatment has focused on a narrow range of drugs and only a few controlled studies have been performed. Furthermore, the studies have been of short duration and included a limited number of subjects, often heterogenic with regard to stage and acute nutritive status. Thus, novel approaches are urgently needed. Body weight homeostasis is tightly regulated throughout life. With the discovery of orexigenic and anorectic signals, an array of new molecular targets to control eating behavior has emerged. This review focuses on recent advances in three important signal systems: leptin, ghrelin, and endocannabinoids toward the identification of potential therapeutical breakthroughs in AN. Our review of the current literature shows that leptin may have therapeutic potentials in promoting restoration of menstrual cycles in weight restored patients, reducing motor restlessness in severely hyperactive patients, and preventing osteoporosis in chronic patients. Ghrelin and endocannabinoids exert orexigenic effects which may facilitate nutritional restoration. Leptin and endocannabinoids may exert antidepressive and anxiolytic effects. Finally, monitoring serum concentration of leptin may be useful in order to prevent refeeding syndrome.

Purging behavior in anorexia nervosa and eating disorder not otherwise specified: A retrospective cohort study

Purging behavior in eating disorders is associated with medical risks. We aimed to compare remission rates in purging and non-purging females with anorexia nervosa (AN) and eating disorder not otherwise specified (EDNOS) in a large retrospective single center cohort. A total of 339 patients with AN and 266 patients with EDNOS were included in the study. The proportion of subjects with purging behavior at least once a week during the last 3 months was similar in the two groups: 22% in AN and 24% in EDNOS. Remission was defined by a goal weight ≥85% of ideal body weight and no reported purging behavior in the last 6 months. The median time from onset to remission for patients with AN was 7 years for the non-purging vs. 11 years for the purging patients. The purging AN patients with both vomiting and laxative abuse displayed the poorest course. Among EDNOS patients, the time to remission was also significantly longer for purging patients compared to non-purging patients. Thus, in line with previous studies, we found that purging behavior is associated with delayed time to remission in treatment-seeking AN and EDNOS patients. This study provides evidence to support the retention of the diagnostic sub-typing in AN.

Reflections on involuntary treatment in the prevention of fatal anorexia nervosa: A review of five cases†

OBJECTIVE Involuntary treatment in the prevention of fatal anorexia nervosa (AN) is still controversial. METHOD Five fatal cases of AN were identified out of 1,160 patients who attended a specialized eating disorder unit between 1994 and 2006. Information on inpatient, ambulatory, and emergency room treatment was extracted from a population-based registration system. RESULTS Personality disorders were diagnosed in all five patients and substance abuse in three patients. In all cases, illness duration was more than 10 years and late onset was seen in two cases. None of the deaths were due to suicide. Involuntary hospital admission was instituted for three patients, but only one patient was compulsory detained more than once. Four patients died after having discontinued treatment. DISCUSSION Compulsory treatment may be of crucial importance in the prevention of fatalities in patients with long-standing AN and psychiatric comorbidity who discontinue treatment.

Is glycyrrhizin sensitivity increased in anorexia nervosa and should licorice be avoided? Case report and review of the literature

OBJECTIVE Hypokalemia is a potentially life-threatening electrolyte disturbance in anorexia nervosa and is most frequently caused by purging behavior. We report a case of severe hypokalemia in anorexia nervosa induced by daily ingestion of approximately 20 g of licorice. METHODS To confirm the diagnosis of licorice-induced pseudohyperaldosteronism, a re-exposure trial was performed. RESULTS Cessation of the licorice intake normalized plasma potassium, renin, and aldosterone levels and the urine cortisol/cortisone ratio. Re-exposure confirmed the diagnosis. The pronounced response to a relatively low daily dose of licorice suggests high glycyrrhizin sensitivity. CONCLUSION Patients with anorexia nervosa not only have decreased food intake but also selective and sometimes bizarre eating habits that, in association with increased sensitivity to glycyrrhizin, may cause severe hypokalemia.

Changes in IGF-I, urinary free cortisol and adipokines during dronabinol therapy in anorexia nervosa: Results from a randomised, controlled trial.

OBJECTIVE Anorexia nervosa (AN) is characterised by complex neuroendocrine disturbances due to severe underweight, physical hyperactivity and purging behaviour. Cannabinoid agonists are used to palliate cachexia of various causes, but their interactions with the hormonal systems that are involved in energy metabolism have not been previously described in humans. Therefore we found it of interest to assess interactions between the synthetic cannabinoid agonist dronabinol and insulin-like growth factor I (IGF-I), urinary free cortisol (UFC) and adipokines in patients with chronic AN. DESIGN This was a prospective, double-blind randomised crossover study, conducted at a specialised care centre for eating disorders. The results are based on twenty-four adult women with chronic AN, who completed the study. The participants received dronabinol (oral capsules, 5mg daily) and matching placebo over four weeks, separated by a four-week washout period. Bioactive IGF was determined by a cell-based bioassay, whereas total IGF-I, IGFBP-2 and -3 and the two adipokines leptin and adiponectines were measured by immunoassays. The UFC excretion was determined by mass spectrometry. RESULTS As previously reported, dronabinol treatment caused a small, yet significant increase in BMI as compared to placebo (+0.23 kg/m(2); P = 0.04). This modest weight gain predicted a corresponding increase in bioactive IGF-I, while the amount of daily energy expenditure due to physical activity had a comparable but opposite effect. Nevertheless, neither IGF-I, bioactive IGF nor the IGFBPs levels changed significantly during dronabinol intervention as compared to placebo. Adiponectin also remained unaffected by the weight gain, whereas plasma leptin showed a transient increase at three weeks (P < 0.05). UFC levels were decreased during dronabinol intervention. CONCLUSION Our results showed that low-dosage therapy with the synthetic cannabinoid agonist dronabinol affected neither the concentration nor the activity of the circulating IGF-system in women with severe and chronic AN. However, our results suggest that such treatment may alleviate the increased hypothalamic-pituitary-adrenal axis activity seen in these patients.

Exercise addiction in men is associated with lower fat-adjusted leptin levels.

Objective:To test a hypothesized association between resting leptin levels (adjusted for body fat percentage) and symptoms of primary exercise addiction. Design:Cross-sectional design. Setting:Habitual amateur exercisers participating in running, fitness, weight training, and biking. Participants:Twenty men with exercise addiction as defined by the Exercise Addiction Inventory (EAI scores 24-30) and 20 men in an exercise control group (EAI scores 6-16) matched on body mass index. Main Outcome Measures:Plasma leptin and sex hormones were measured in blood samples collected under fasting and resting conditions. Body composition was assessed by dual-energy x-ray absorptiometry. Eating disorder symptoms were identified by the Eating Disorder Inventory 2. Results:The exercise addiction group had significantly (P < 0.001) lower leptin levels (1.1 &mgr;g/L, SD = 1.3) than controls (4.3 &mgr;g/L, SD = 2.9). Even when adjusted for body fat percentage, the addiction group had significantly (P < 0.001) lower leptin levels (0.1 &mgr;g/L, SD = 0.1) than the controls (0.2 &mgr;g/L, SD = 0.1). Body fat–adjusted leptin correlated with free bioavailable testosterone, but it was only significant in nonaddictive exercisers. None of the exercisers seemed to suffer from an eating disorder. Conclusions:This is the first study showing that excessive training in exercise addiction is associated with low levels of body fat–adjusted leptin levels. Clinical relevance:Hypoleptinemia could be involved in the pathogenesis of exercise addiction. However, further studies are needed to explore the potential causal relationship.

The BODY-Q Stretch Marks Scale: A Development and Validation Study

Background Stretch marks are common permanent dermal lesions that can cause psychosocial distress. A number of treatment modalities are available, with the majority targeted towards collagen production. Objectives To develop and field test a new BODY-Q scale to measure appearance of stretch marks in order to provide a means to incorporate the patient perspective into future treatment studies. Methods We previously described the development of the BODY-Q conceptual framework, which involved a literature review, 63 patient interviews, 22 cognitive interviews and input from 9 experts, and the international field-test study that involved 403 weight loss and 331 body contouring patients. To develop the Stretch Marks scale, we reexamined appearance codes from the original interviews. The scale was field tested in an international study. Rasch measurement theory (RMT) analysis was used to refine the scale and examine measurement properties. Results The Stretch Marks scale was completed by 630 participants, who provided 774 assessments. After dropping 3 items, the data fit the Rasch model (P = 0.56). Items (eg, length, width, amount, location, up close) mapped out a well-targeted clinical hierarchy. All items had ordered thresholds and good item fit. There was no evidence of differential item functioning (bias) by gender, age group or language (English vs Danish). The scale evidenced high reliability (ie, person separation index = 0.94, Cronbachs alpha = 0.97). For construct validity, the mean score correlated with the total number of body areas with stretch marks, higher BMI before bariatric surgery, and other BODY-Q scales. Conclusions This scale could be used to measure the impact of innovative treatments for stretch marks. Level of Evidence 4

Serum Levels of Fetal Antigen 1 in Extreme Nutritional States

Objective. Recent data suggest that fetal antigen (FA1) is linked to disorders of body weight. Thus, we measured FA1 serum levels in two extreme nutritional states of morbid obesity (MO) and anorexia nervosa (AN) and monitored its response to weight changes. Design. FA1 and insulin serum concentrations were assessed in a cross-sectional study design at defined time points after gastric restrictive surgery for 25 MO patients and 15 women with AN. Results. Absolute FA1 serum levels were within the assay normal range and were not different between the groups at baseline. However, the ratio of FA1/BMI was significantly higher in AN. FA1 was inversely correlated with BMI before and after weight change in AN, but not in MO patients. In addition, MO patients displayed a significant concomitant decrease of FA1 and insulin with the first 25% of EWL, while in AN patients a significant increase of FA1 was observed in association with weight gain. Conclusion. FA1 is a sensitive indicator of metabolic adaptation during weight change. While FA1 serum levels in humans generally do not correlate with BMI, our results suggest that changes in FA1 serum levels reflect changes in adipose tissue turnover.