Fibroblast growth factor (FGF)23 is a novel phosphaturic factor associated with inorganic phosphate homeostasis. Previous human studies have shown that serum FGF23 levels increase in response to a high phosphate diet. For anorexia nervosa (AN) patients, inorganic phosphate homeostasis is important in the clinical course, such as in refeeding syndrome. The purpose of this study was to determine plasma levels of intact FGF23 (iFGF23) in restricting-type AN (AN-R) patients, binge-eating/purging-type AN (AN-BP) patients, and healthy controls.
The subjects consisted of 6 female AN-R patients, 6 female AN-BP patients, and 11 healthy female controls; both inpatients and outpatients were included. Plasma iFGF23, 1,25-dihydroxyvitamin D (1,25-(OH)2D), and 25-hydroxyvitamin D (25-OHD) levels were measured. Data are presented as the median and the range. A two-tailed Mann-Whitney U-test with Bonferroni correction was used to assess differences among the three groups, and a value of p < 0.017 was considered statistically significant.
There were no differences between AN-R patients and controls in the iFGF23 and 1,25-(OH)2D levels. In AN-BP patients, the iFGF23 level (41.3 pg/ml; range, 6.1–155.5 pg/ml) was significantly higher than in controls (3.8 pg/ml; range, not detected-21.3 pg/ml; p = 0.001), and the 1,25-(OH)2D was significantly lower in AN-BP patients (7.0 pg/ml; range, 4.2–33.7 pg/ml) than in controls (39.7 pg/ml; range, 6.3–58.5 pg/ml; p = 0.015). No differences in plasma 25-OHD levels were observed among the groups.
This preliminary study is the first to show that plasma iFGF23 levels are increased in AN-BP patients, and that these elevated plasma FGF23 levels might be related to the decrease in plasma 1,25-(OH)2D levels.
Patients with anorexia nervosa-restricting type (AN-R) sometimes develop accompanying bulimic symptoms or the full syndrome of bulimia nervosa (BN). If clinicians could predict who might change into the bulimic sub-type or BN, preventative steps could be taken. Therefore, we investigated anthropometric and psychological factors possibly associated with such changes.
All participants were from a study by the Japanese Genetic Research Group for Eating Disorders. Of 80 patients initially diagnosed with AN-R, 22 changed to the AN-Binge Eating/Purging Type (AN-BP) and 14 to BN for some period of time. The remaining 44 patients remained AN-R only from the onset to the investigation period. Variables compared by ANOVA included anthropometric measures, personality traits such as Multiple Perfectionism Scale scores and Temperament and Character Inventory scores, and Beck Depression Inventory-II scores.
In comparison with AN-R only patients, those who developed BN had significantly higher current BMI (p < 0.05) and maximum BMI in the past (p < 0.05). They also scored significantly higher for the psychological characteristic of parental criticism (p < 0.05) and lower in self-directedness (p < 0.05), which confirms previous reports, but these differences disappeared when the depression score was used as a co-variant. No significant differences were obtained for personality traits or depression among the AN-R only patients irrespective of their duration of illness.
The present findings suggest a tendency toward obesity among patients who cross over from AN-R to BN. Low self-directedness and high parental criticism may be associated with the development of BN by patients with AN-R, although the differences may also be associated with depression.
Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is secreted from bone and serum level increases as renal function declines. Higher levels of FGF23 are associated with increased mortality in hemodialysis-patients and in patients with chronic kidney disease (CKD) stage 2-4. The use of active vitamin D and phosphate binders as recommended in international guidelines, may affect the level of FGF23 and thereby clinical outcome. We investigated the effects of a phosphate binder and active vitamin D on the serum levels of intact FGF23 (iFGF23) and intact parathyroid hormone (iPTH) in patients with CKD stage 3b (glomerular filtration rate (GFR) 30–44 ml/min/1.73 m2).
Seven women and 14 men were included, mean age 65.6 ± 12.2 years. They were randomized in a 1:1 ratio to receive one of two treatment sequences. Group-1 (the alphacalcidol-sevelamer carbonate group): alphacalcidol 0.25 μg once daily for two weeks followed by sevelamer carbonate 800 mg TID with meals for two weeks after a two-week washout period. Group-2 (the sevelamer carbonate-alphacalcidol group): vice versa. Nineteen patients completed the study. The 25-hydroxyvitamin D level at baseline was 97.6 ± 25.0 nmol/l.
There were no treatment effects on the iFGF23 and iPTH levels overall. In group-1 the iFGF23 level was higher after treatment with alphacalcidol compared with sevelamer carbonate (mean 105.8 ± 41.6 vs. 79.1 ± 36.5 pg/ml, p = 0.047 (CI: 0.4-52.9), and the iPTH level was lower (median: 26.5, range: 14.6-55.2 vs. median 36.1, range 13.4-106.9 pg/ml, p = 0.011). In group-2 the iFGF23 level increased non-significantly after treatment with sevelamer carbonate and throughout the washout period.
In this crossover trial with alphacalcidol and sevelamer carbonate in patients with CKD stage 3b, the levels of iFGF23 were not significantly different after the two treatments. However, in the group of patients initiating therapy with sevelamer carbonate the iFGF23 levels seemed to increase while this response was mitigated in the group of patients given alphacalcidol followed by sevelamer carbonate. This may have therapeutic implications on choice of first line therapy. The number of patients is small and this conclusion is in part based on subgroup analysis. It is therefore important that these results are confirmed in larger studies.
Trial Registration Number: European Clinical Trial Database (EudraCT) 2010-020415-36 and Clinical Trials.gov NCT01231438
Active vitamin D; Chronic kidney disease; Fibroblast growth factor 23; FGF23; Phosphate-binder; Parathyroid hormone; PTH; Sevelamer carbonate
Food intake is mediated, in part, through brain pathways for motivation and reinforcement. Dysregulation of these pathways may underlay some of the behaviors exhibited by patients with eating disorders. Research using animal models of eating disorders has greatly contributed to the detailed study of potential brain mechanisms that many underlie the causes or consequences of aberrant eating behaviors. This review focuses on neurochemical evidence of reward-related brain dysfunctions obtained through animal models of binge eating, bulimia nervosa, or anorexia nervosa. The findings suggest that alterations in dopamine (DA), acetylcholine (ACh) and opioid systems in reward-related brain areas occur in response to binge eating of palatable foods. Moreover, animal models of bulimia nervosa suggest that while bingeing on palatable food releases DA, purging attenuates the release of ACh that might otherwise signal satiety. Animal models of anorexia nervosa suggest that restricted access to food enhances the reinforcing effects of DA when the animal does eat. The activity-based anorexia model suggests alterations in mesolimbic DA and serotonin occur as a result of starvation coupled with excessive wheel running. These findings with animal models complement data obtained through neuroimaging and pharmacotherapy studies of clinical populations. Finally, information on the neurochemical consequences of the behaviors associated with these eating disorders will be useful in understanding these complex disorders and may inform future therapeutic approaches, as discussed here.
acetylcholine; binge eating; clinical studies; dopamine; eating disorders; opioids; rat; serotonin
The Intracellular Fibroblast Growth Factor (iFGF) subfamily includes four members (FGFs 11–14) of the structurally related FGF superfamily. Previous studies showed that the iFGFs interact directly with the pore-forming (α) subunits of voltage-gated sodium (Nav) channels and regulate the functional properties of sodium channel currents. Sequence heterogeneity among the iFGFs is thought to confer specificity to this regulation. Here, we demonstrate that the two N-terminal alternatively spliced FGF14 variants, FGF14-1a and FGF14-1b, differentially regulate currents produced by Nav1.2-and Nav1.6 channels. FGF14-1b, but not FGF14-1a, attenuates both Nav1.2 and Nav1.6 current densities. In contrast, co-expression of an FGF14 mutant, lacking the N-terminus, increased Nav1.6 current densities. In neurons, both FGF14-1a and FGF14-1b localized at the axonal initial segment, and deletion of the N-terminus abolished this localization. Thus, the FGF14 N-terminus is required for targeting and functional regulation of Nav channels, suggesting an important function for FGF14 alternative splicing in regulating neuronal excitability.
Neuropeptide Y (NPY) is an important central orexigenic hormone predominantly produced by the hypothalamus, and recently found to be secreted in adipose tissue (AT). Acipimox (Aci) inhibits lipolysis in AT and reduces plasma glycerol and free fatty acid (FFA) levels. Exercise and Aci are enhancers of growth hormone (GH) and NPY secretion and exercise may alter leptin levels. We expect to find abnormal neuropeptidergic response in plasma and AT in patients with bulimia nervosa (BN). We hypothesize that Aci influences these peptides via a FFA-independent mechanism and that Aci inhibits lipolysis through a cyclic adenosine monophosphate (cAMP)-dependent pathway. Dysregulations of the AT-brain axis peptides might be involved in binge eating as is the case in BN.
The objective of this study was to determine the responses of plasma NPY, GH, leptin, FFA and glycerol levels to exercise in BN patients and healthy women (C) given the anti-lipolytic drug Aci or placebo. The secondary objective of this study was to compare the responses of extracellular glycerol levels and plasma glycerol levels to exercise alone or together with Aci administration in BN patients and C women. Extracellular glycerol was measured in vivo in subcutaneous (sc) abdominal AT using microdialysis. Eight BN and eight C women were recruited for this single-blind, randomized study. Aci or placebo was given 1 hour before the exercise (45 min, 2 W/kg of lean body mass [LBM]). NPY, GH, leptin, FFA, glycerol plasma and AT glycerol levels were measured using commercial kits.
The primary outcome of this study was that the exercise with Aci administration resulted in plasma NPY and GH increase (after a 45-minute exercise) and leptin (after a 90-minute post-exercise recovering phase) increased more in BN patients. The secondary outcomes of this study were that the exercise with Aci administration induced a higher decrease of extracellular glycerol in BN patients compared to the C group, while the exercise induced a higher increase of glycerol concentrations in sc abdominal AT of BN patients. Plasma glycerol levels decreased more in BN patients and plasma FFA levels were depressed in both groups after the exercise with Aci administration. The exercise induced similar increases in plasma NPY, GH, FFA and glycerol levels, and a similar decrease in the plasma leptin level in both groups.
We confirm the results of a single-blind, randomized, microdialysis study, i.e. that the Aci-induced elevation in plasma NPY and GH levels during the exercise is higher in BN patients and that Aci increased plasma leptin levels in the post-exercise recovering phase (90-minute) more in BN patients. The post-exercise rise (45-minute) in AT glycerol is much more attenuated by acute Aci treatment in BN patients. Simultaneously, we found facilitated turnover of plasma glycerol after the exercise together with Aci administration in BN. Our results support the hypotheses that Aci exerts an effect on the FFA-independent and cAMP-dependent mechanism.
Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000955910
Neuropeptide Y; Growth hormone; Leptin; Bulimia nervosa; Acipimox; Exercise; Adipose tissue; Free fatty acids; Glycerol; Microdialysis
Elevated serum amylase levels in bulimia nervosa (BN), associated with increased salivary gland size and self-induced vomiting in some patients, provide a possible marker of symptom severity. The goal of this study was to assess whether serum hyperamylasemia in BN is more closely associated with binge eating episodes involving consumption of large amounts of food or with purging behavior.
Participants included women with BN (n=26); women with “purging disorder” (PD), a subtype of EDNOS characterized by recurrent purging in the absence of objectively large binge eating episodes (n=14); and healthy non-eating disorder female controls (n=32). There were no significant differences in age or body mass index (BMI) across groups. The clinical groups reported similar frequency of self-induced vomiting behavior and were free of psychotropic medications. Serum samples were obtained after overnight fast and were assayed for alpha-amylase by enzymatic method.
Serum amylase levels were significantly elevated in BN (60.7 ± 25.4 international units [IU]/liter, mean ± sd) in comparison to PD (44.7 ± 17.1 IU/L, p < 02) and to Controls (49.3 ± 15.8, p < .05).
These findings provide evidence to suggest that it is recurrent binge eating involving large amounts of food, rather than self-induced vomiting, which contributes to elevated serum amylase values in BN.
bulimia nervosa; purging disorder; self-induced vomiting; binge eating; serum amylase; hyperamylasemia
The present study investigated plasma levels of gut-brain axis peptides ghrelin, obestatin, NPY and PYY after consumption of a high-carbohydrate (HC) and high-protein (HP) breakfast in patients with anorexia nervosa, bulimia nervosa and in healthy controls. These peptides play an important role in regulation of energy homeostasis and their secretion is disturbed under condition of eating disorders. As various types of consumed macronutrients may induce different plasma hormone responses, so we examined these responses in women patients with eating disorders and compared them with those of healthy controls.
We examined plasma hormone responses to HC and HP breakfast in patients with AN (n = 14; age: 24.6 ± 1.8 years, BMI: 15.3 ± 0.7), BN (n = 15; age: 23.2 ± 1.7 years, BMI: 20.5 ± 0.9) and healthy controls (n = 14; age: 24.9 ± 1.4 years, BMI: 21.1 ± 0.8). Blood samples were drawn from the cubital vein, the first blood drawn was collected before meal, and then 30, 60, 90, 120 and 150 min after breakfast consumption. Plasma hormone levels were determined by commercially available RIA kits.
Fasting and postprandial plasma obestatin levels were significantly increased in both AN and BN patients, while plasma ghrelin levels were significantly increased in AN patients only. After breakfast consumption, plasma levels of ghrelin and obestatin decreased, although they were still above the range of values of healthy controls. Fasting NPY plasma levels were significantly increased in AN and BN patients and did not change postprandially. Fasting PYY levels were comparable in AN, BN and healthy controls, but postprandially significantly increased after HP breakfast in AN and BN patients. Different reactions to breakfast consumption was found for ghrelin and PYY among investigated groups, while for obestatin and NPY these reactions were similar in all groups.
Significant increase of obestatin and NPY in AN and BN patients may indicate their important role as the markers of eating disorders. Different reactions of ghrelin and PYY to breakfast consumption among groups suggest that role of these hormones in regulation of energy homeostasis can be adjusted in dependence to acute status of eating disorder.
Ghrelin; Obestatin; NPY; PYY; Anorexia nervosa; Bulimia nervosa; High-carbohydrate breakfast; High-protein breakfast
We examined prevalence of substance use disorders (SUD) in women with: (1) anorexia nervosa (AN) restricting type (RAN); (2) AN with purging only (PAN); (3) AN with binge eating only (BAN); and (4) lifetime AN and bulimia nervosa (ANBN). Secondary analyses examined SUD related to lifetime purging behavior and lifetime binge eating.
Participants (N = 731) were drawn from the International Price Foundation Genetic Studies.
The prevalence of SUD differed across AN subtypes, with more in the ANBN group reporting SUD than those in the RAN and PAN groups. Individuals who purged were more likely to report substance use than those who did not purge. Prevalence of SUD differed across lifetime binge eating status.
SUD are common in AN and are associated with bulimic symptomatology. Results underscore the heterogeneity in AN, highlighting the importance of screening for SUD across AN subtypes.
eating disorders; anorexia nervosa; bulimia nervosa; drug use; alcohol related disorders; cannabis
The aim of our study was to determine the central and peripheral autonomic nervous system profiles underlying anorexia nervosa (AN) syndrome, given that affected patients present with the opposite clinical profile to that seen in the hyperinsulinism syndrome.
We measured blood pressure and heart rate, as well as circulating neurotransmitters (noradrenaline, adrenaline, dopamine, plasma serotonin, and platelet serotonin), using high-performance liquid chromatography with electrochemical detection, during supine resting, one minute of orthostasis, and after five minutes of exercise. In total, 22 AN patients (12 binge-eating/purging type and 10 restricting type) and age-, gender-, and race-matched controls (70 ± 10.1% versus 98 ± 3.0% of ideal body weight) were recruited.
We found that patients with AN had adrenal sympathetic overactivity and neural sympathetic underactivity, demonstrated by a predominance of circulating adrenaline over noradrenaline levels, not only during the supine resting state (52 ± 2 versus 29 ± 1 pg/mL) but also during orthostasis (67 ± 3 versus 32 ± 2 pg/mL, P < 0.05) and after exercise challenge (84 ± 4 versus 30 ± 3 pg/mL, P < 0.01).
Considering that this peripheral autonomic nervous system disorder depends on the absolute predominance of adrenomedullary C1 adrenergic nuclei over A5 noradrenergic pontine nucleus, let us ratify the abovementioned findings. The AN syndrome depends on the predominance of overwhelming adrenal sympathetic activity over neural sympathetic activity. This combined central and autonomic nervous system profile contrasts with that registered in patients affected by hyperinsulinism, hypoglycemia, and bulimia syndrome which depends on the absolute predominance of neural sympathetic activity.
anorexia nervosa; adrenal sympathetic activity; adrenaline; noradrenaline; eating disorders
Fibroblast growth factor 23 (FGF-23) is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD). Circulating intact FGF-23 (iFGF-23) and C-terminal (CtFGF-23) concentrations (ELISA) were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1); and in association with fat mass and bone mineral density (DEXA) and atherosclerosis (intima media thickness, IMT) in 78 subjects (52 women) with a wide range of adiposity (Cohort 2). Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine) contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance.
Plasma FGF-23 concentrations and its relationship with calcium-phosphate homeostasis were evaluated in 48 perimenopausal obese women and in 29 nonobese controls. Serum parathyroid hormone, 25-hydroxyvitamin D3, CTX1, osteocalcin, total calcium, phosphorus, creatinine, and plasma intact FGF-23 concentrations were assessed. DXA of lumbar spine and femoral neck was performed to determine bone mineral density (BMD). Plasma iFGF-23 concentration was significantly higher in obese patients (by 42%) and correlated with age and BMD of proximal femur (R = −0.346; R = 0.285, resp.) but not with markers of bone turnover. However, serum phosphorus level in obese subjects was significantly lower. iFGF-23 concentration correlated significantly with body mass index (R = 0.292) and fat content (R = 0.259) in all study subjects. Moreover, a significant correlation between iFGF-23 and iPTH (R = 0.254) was found. No correlation between serum phosphorus or eGFR and plasma iFGF-23 and between eGFR and serum phosphorus was found. Elevated serum iFGF-23 concentration may partially explain lower phosphorus levels in the obese and seems not to reflect bone turnover.
Increasing empirical evidence supports the validity of binge eating disorder (BED), a research diagnosis in the appendix of DSM-IV, and its inclusion as a distinct and formal diagnosis in the DSM-V. A pressing question regarding the specific criteria for BED diagnosis is whether, like bulimia nervosa (BN), it should be characterized by overvaluation of shape and weight. This study compared features of eating disorders in 436 treatment-seeking women comprising four groups: 195 BED participants who overvalue their shape/weight, 129 BED participants with subclinical levels of overvaluation, 61 BN participants, and 51 participants with sub-threshold BN. The BED clinical overvaluation group had significantly higher levels of specific eating disorder psychopathology than the three other groups which did not differ significantly from each other. Findings suggest that overvaluation of shape and weight should not be considered as a required criterion for BED because this would exclude a substantial proportion of BED patients with clinically significant problems. Rather, overvaluation of shape and weight warrants consideration either as a diagnostic specifier or as a dimensional severity rating as it provides important information about severity within BED.
shape and weight concerns; binge eating disorder; bulimia nervosa; obesity; body image
The purpose of this paper is to review the available literature that addresses the predictive validity and utility of subtyping anorexia nervosa patients into binge/purge and restrictor subtypes.
Literature was reviewed including studies that compared individuals with subtype diagnoses on clinical and outcome variables as well as more recent research examining the frequency of diagnostic crossover.
Several studies found that in general the binge/purge subtype patients have more psychopathology, tend to be older and tend to have a worse outcome. More recent studies which have examined diagnostic crossover suggest that the rate of crossover from the restrictor subtype to the binge/purge subtype is substantial. Crossover from the binge/purge to the restrictor subtype appears to occur less commonly. There is also literature documenting crossover from anorexia nervosa to bulimia nervosa and a small literature looking at crossover from bulimia nervosa to anorexia nervosa.
The results of this review suggest that although there is generally progression from restrictor anorexia nervosa to binge/purge anorexia nervosa to bulimia nervosa in a sizeable number of patients, other crossover patterns can be seen as well, and the amount of crossover is quite large. This suggests a lack of predictive validity for subtypes. Validity and Utility of Subtyping Anorexia Nervosa
Individuals who suffer from Anorexia Nervosa refuse to maintain a minimally normal body weight, are intensely afraid of gaining weight and exhibit a significant disturbance in the perception of the shape and size of their body. Postmenarchal females with this disorder are amenorrohic. In the Binge-Eating/Purging subtype individuals regularly engage in binge eating and purging behaviour (i.e self-induced vomiting or misuse of laxatives, diuretics, or enemas).
Hypokalaemia is often seen in chronic Anorexia Nervosa, especially that of the purging type (ANp), and, as well as electrocardiographic anomalies, this can lead to tubulointerstitial nephritis (hypokalaemic nephropathy) with typical histological characteristics. The physiopathological mechanisms behind this damage are linked to altered stimulation of vasoactive mediators, and to the ammonium-mediated activation of the alternative complement pathway. However, it has not yet been ascertained whether a variant of the pathway specific for ANp , exists.
We describe herein a case of hypokalaemic nephropathy in a patient affected by chronic ANp who presented to our Centre for Eating Disorders.
Hypokalaemia can provoke cardiovascular alterations as well as muscular and renal complications, and thus potential renal damage needs to be investigated in patients suffering from long-term purgative anorexia.
Pharmacotherapy for anorexia nervosa is considered to be of limited efficacy. However, many studies suffer methodological limitations, and the utility of newer drugs in the treatment of anorexia has not been examined yet. Although there have been more fruitful investigations on the efficacy of medication in the management of bulimia nervosa, there are still many unresolved issues regarding the optimal management of partial remission during the acute treatment phase and the intensity and duration of pharmacotherapy to achieve optimal prophylaxis. Selective serotonin reuptake inhibitors (SSRIs) control the binge urges in binge-eating disorder, but more trials are required to investigate the utility of SSRIs and other agents in maintenance treatment. We review the current status of psychopharmacotherapy for anorexia nervosa, bulimia nervosa and binge-eating disorder and evaluate the merits of newer agents in the treatment of these disorders.
Although it is thought that eating disorders result from the interplay of personal and sociocultural factors, a comprehensive model of eating disorders remains to be established. The aim of this study was to determine the extent to which the childhood factors and deficit in visuoperceptual ability contribute to eating disorders.
A total of 76 participants - 22 women with anorexia nervosa (AN), 28 women with bulimia nervosa (BN), and 26 healthy women of comparable age, IQ, and years of education - were examined. Neuropsychological tasks were applied to measure the visuoperceptual deficits, viz. the Rey-Osterrieth complex figure test and the group embedded figures test (GEFT). A questionnaire designed to obtain retrospective assessments of the childhood risk factors was administered to the participants.
The women with both AN and BN were less likely to report having supportive figures in their childhood and poor copy accuracy in the Rey-Osterrieth test. The women with AN were more likely to report premorbid anxiety, childhood emotional undereating and showed poor performances in the GEFT. In the final model, the factors independently contributing to the case status were less social support in childhood as a common factor for both AN and BN, and childhood emotional undereating and poor ability in the low-level visuospatial processing for AN.
Our results suggest the disturbance in the food-emotion relationship and the deficit in low-level visuospatial processing in people with AN. Lower social support appears to contribute to an increase in vulnerability to both AN and BN.
Childhood risk factors; Emotional eating; Visuospatial ability; Anorexia nervosa; Bulimia nervosa
Disordered eating behavior and body dissatisfaction affect a large proportion of the Dutch population and account for severe psychological, physical and social morbidity. Yet, the threshold for seeking professional care is still high. In the Netherlands, only 7.5% of patients with bulimia nervosa and 33% of patients with anorexia nervosa are treated within the mental health care system. Easily accessible and low-threshold interventions, therefore, are needed urgently. The internet has great potential to offer such interventions. The aim of this study is to determine whether a web-based treatment program for patients with eating disorders can improve eating disorder psychopathology among female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified.
This randomized controlled trial will compare the outcomes of an experimental treatment group to a waiting list control group. In the web-based treatment program, participants will communicate personally and asynchronously with their therapists exclusively via the internet. The first part of the program will focus on analyzing eating attitudes and behaviors. In the second part of the program participants will learn how to change their attitudes and behaviors. Participants assigned to the waiting list control group will receive no-reply email messages once every two weeks during the waiting period of 15 weeks, after which they can start the program. The primary outcome measure is an improvement in eating disorder psychopathology as determined by the Eating Disorder Examination Questionnaire. Secondary outcomes include improvements in body image, physical and mental health, body weight, self-esteem, quality of life, and social contacts. In addition, the participants’ motivation for treatment and their acceptability of the program and the therapeutic alliance will be measured. The study will follow the recommendations in the CONSORT statement relating to designing and reporting on RCTs.
This study protocol presents the design of a RCT for evaluating the effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified.
The protocol for this study is registered with the Netherlands Trial Registry NTR2415.
Eating disorders; Bulimia nervosa; Binge eating disorder; Eating disorders not otherwise specified; Randomized controlled trial; Web-based treatment program; e-health; Intensive therapeutic support; Asynchronous support
Eating disorders such as anorexia (AN) and bulimia nervosa (BN) are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT) peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY), peptide YY (PYY), cholecystokinin (CCK), leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE), serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice.
Women with bulimia nervosa undergoing treatment with the reversible monoamine oxidase type A inhibitor, brofaromine, were rated for mood and eating behaviour and their plasma and urine were assessed for phenylacetic acid (unconjugated and total) and unconjugated phenylethylamine prior to and after four weeks of drug treatment. Changes in plasma unconjugated phenylacetic acid concentrations were significantly and negatively correlated with the corresponding changes in Hamilton Depression scores but not with eating behavior measures. There were no significant correlations between changes in phenylethylamine levels and changes in rating scores. Patients diagnosed as suffering concurrently from severe depression (Hamilton Depression score of 17 or higher) had lower plasma and urinary phenylacetic acid levels than did those whose depression was not severe (Hamilton score less than 17). Phenylethylamine concentrations were not different between the severely and mildly depressed subgroups. The results confirm earlier studies on the relationship between phenylacetic acid and depression while showing that a similar relationship does not pertain to phenylacetic acid and eating behavior in bulimia nervosa.
Effect of eating rate on binge size in bulimia nervosa. Bulimia Nervosa (BN) is an eating disorder characterized by recurrent episodes of binge eating. During binge eating episodes, patients often describe the rapid consumption of food, and laboratory studies have shown that during binges patients with BN eat faster than normal controls (NC), but the hypothesis that a rapid rate of eating contributes to the excessive intake of binge meals has not yet been experimentally tested. The aim of this study was to assess the effect of eating rate on binge size in BN, in order to determine whether binge size is mediated, in part, by rate of eating. Thirteen BN and 14 NC subjects were asked to binge eat a yogurt shake that was served at a fast rate (140g/min) on one occasion and at a slow rate (70g/min) on another. NC subjects consumed 169 g more when eating at the fast rate than when eating at the slow rate. In contrast, consumption rates failed to influence binge size in patients with BN (fast: 1205 g; slow: 1195 g). Consequently, there was a significant group by rate interaction. As expected, patients with BN consumed more overall than NC subjects (1200 g vs. 740 g). When instructed to binge in the eating laboratory, patients with BN ate equally large amounts of food at a slow rate as at a fast rate. NC subjects ate less at a slow rate. These findings indicate that in a structured laboratory meal paradigm binge size is not affected by rate of eating.
bulimia nervosa; eating laboratory; eating rate; binge eating; eating disorders
Anorexia nervosa is regarded a s a typical culture bound syndrome, and its existence is negligible in nonwestern countries due to protective biological and socio-cultural factors. Most of the cases reported from nonwestern countries are atypical in presentation with lack of body image disturbances. Recent studies showed that anorexia nervosa is no more culture bound, in fact it is a "culture change syndrome" due to westernization and no differences are seen in the phenomenology of anorexia nervosa between the two cultures. We report a typical case of anorexia nervosa of binge eating and purging type associated with body dysmorphophobia in an adolescent girl.
Anorexia Nervosa; Culture bound syndrome; binge eating
We report two patients with anorexia nervosa and Graves' disease who received subtotal thyroidectomy for Graves' disease and concomitantly experienced remission from anorexia nervosa. Both were young women (aged 20 and 26) at the time of surgery. Both had well controlled thyroid function and eating behavior at the time of surgery. Both were followed for over five years without relapse of anorexia nervosa or hyperthyroidism. These cases suggest the existence of an endocrine factor originating from the thyroid gland that is involved in the pathogenesis of anorexia nervosa. Since patients of thyroidectomy can remain in good health with supplement of thyroxine alone, it can be hypothesized that this anorexigenic endocrine factor is an evolutionary relic not necessary for the normal function of humans and does not have physiological effects unless secreted beyond normal levels. Given that, it implies the existence of a creature in the animal kingdom for which such an anorexigenic hormone is essential for survival. Migrating birds eat beyond their caloric expenditure before migration and become anorexic for the duration of their flight. It is also known that their thyroid function is elevated during migration. The normal physiology of migration is a complex mechanism involving the hypothalamic, pituitary, thyroid, adrenal and reproductive hormones. The mechanism of disease, however, can be simpler. A review of the literature is presented that suggest a heretofore unreported thyroid hormone, which is involved in the regulation of migration behavior, may be the responsible factor behind anorexia nervosa.
thyroid; anorexia nervosa; thyroidectomy; avian migration
Elucidation of clinically relevant subtypes has been proposed as a means of advancing treatment research, but classifying anorexia nervosa (AN) patients into restricting and binge-eating/purging types has demonstrated limited predictive validity. This study aimed to evaluate whether an approach to classifying eating disorder patients based on comorbid personality psychopathology has utility in predicting treatment response and readmission in patients with AN.
Data were collected from 154 AN patients (M[SD] age = 25.6[9.4] years; 95.5% female; 96.8% Caucasian) at admission, discharge, and three months post-discharge from intensive treatment. Latent profile analysis of personality traits assessed at admission was performed to classify participants into personality subtypes, which were then used to predict outcomes at discharge and risk of readmission.
The best-fitting model identified three personality subtypes (undercontrolled, overcontrolled, low psychopathology) that contributed significantly to multivariate models predicting study outcomes. Undercontrolled patients were more likely to have a poor outcome at discharge than overcontrolled (OR = 3.56, p = .01) and low psychopathology patients (OR = 11.23, p <.001). Undercontrolled patients also had a greater risk of discharge against medical advice (HR = 2.08, p = .02) and readmission than overcontrolled patients (HR = 3.76, p = .009). Binge-eating/purging versus restricting subtypes did not predict discharge against medical advice or readmission in the multivariate models.
Findings support the clinical utility of personality subtypes in AN. Future work is needed to identify mechanisms that explain diminished treatment response in undercontrolled patients and to develop interventions for this high-risk group.
anorexia nervosa; subtypes; personality; latent profile analysis; treatment
A woman with severe, refractory bulimia nervosa (BN) underwent treatment for comorbid depression using repetitive transcranial magnetic stimulation (rTMS) of the dorsomedial prefrontal cortex (DMPFC) using a novel technique. Unexpectedly, she showed a rapid, dramatic remission from BN. For 5 months pre-treatment, she had reported two 5-h binge-purge episodes per day. After rTMS session 2 the episodes stopped entirely for 1 week; after session 10 there were no further recurrences. Depression scores improved more gradually to remission at session 10. Full remission from depression and binge-eating/purging episodes was sustained more than 2 months after treatment completion. In neuroimaging studies, the DMPFC is important in impulse control, and is underactive in BN. DMPFC–rTMS may have enhanced the patient’s ability to deploy previously acquired strategies to avoid binge-eating and purging via a reduction in her impulsivity. A larger sham-controlled trial of DMPFC–rTMS for binge-eating and purging behavior may be warranted.
rTMS; transcranial; bulimia; anorexia; depression; dorsomedial; prefrontal; impulsivity