A Systematic Review and Meta-Analysis Finds Increased Blood Levels of All Forms of Ghrelin in Both Restricting and Binge-Eating/Purging Subtypes of Anorexia Nervosa.

Anorexia nervosa (AN) is a severe psychiatric condition associated with high mortality and chronicity. The hunt for state, trait, subtyping, and prognostic biomarkers is ongoing and the orexigenic hormone ghrelin and its different forms, acyl ghrelin and desacyl ghrelin, have been proposed to be increased in AN, especially in the restrictive subtype. A systematic literature search was performed using established databases up to 30 November 2020. Forty-nine studies met inclusion criteria for cross-sectional and longitudinal meta-analyses on total ghrelin, acyl ghrelin, and desacyl ghrelin. All forms of ghrelin were increased in the acute stage of anorexia nervosa during fasting compared to healthy controls. Previous notions on differences in ghrelin levels between AN subtypes were not supported by current data. In addition, a significant decrease in total ghrelin was observed pre-treatment to follow-up. However, total ghrelin levels at follow-up were still marginally elevated compared to healthy controls, whereas for acyl ghrelin, no overall effect of treatment was observed. Due to heterogeneity in follow-up designs and only few data on long-term recovered patients, longitudinal results should be interpreted with caution. While the first steps towards a biomarker in acute AN have been completed, the value of ghrelin as a potential indicator of treatment success or recovery status or its use in subtype differentiation are yet to be established.

Reward and psychopathological correlates of eating disorders: The explanatory role of leptin.

It has been hypothesized that leptin level alterations in Eating Disorders (EDs) represent a maintaining factor for pathological reward-related ED behaviors, given leptin role in the dopaminergic reward systems. The aim of the present study was to evaluate the role of leptin in EDs as a mediator for the relationship between Body Mass Index (BMI) and several pathological behaviors, such as dietary restraint, compensatory exercise, vomiting, binge eating and emotional eating. Sixty-two patients with EDs and 41 healthy controls (HC) had their blood drawn and completed psychometric tests for the evaluation of general psychopathology, ED psychopathology and emotional eating. Moderated linear regression models showed that, in the presence of high levels of ED psychopathology, leptin levels were negatively associated with dietary restraint and compensatory exercise, and positively with emotional eating and binge eating. Finally, leptin showed an indirect effect on the association between BMI and all these reward-related behaviors. These results suggest that a variation of BMI maintains these pathological ED behaviors through a variation in leptin levels. Considering the role of leptin in reward circuits, the results seem to confirm an aberrant food-related reward mechanism in ED patients.

Meal-Related Acyl and Des-Acyl Ghrelin and Other Appetite-Related Hormones in People with Obesity and Binge Eating.

OBJECTIVE: Potential mechanisms of abnormal food intake, such as dysregulation of meal-related appetite hormones, including acyl ghrelin (AG) and des-acyl ghrelin (DAG), were investigated among men and women with obesity, with and without binge eating (BE). METHODS: Participants (n = 42: 19 female, 23 male) were assigned to a liquid meal and water condition in counterbalanced order, and blood samples for measuring hormones were obtained before and after these conditions. RESULTS: Participants with BE had significantly lower fasting and postingestive AG concentrations than participants without BE in both conditions. During the meal condition, postprandial decreases in AG concentrations were significantly smaller for the BE group than for the non-BE group. There were no significant differences in DAG by BE group. Leptin increased significantly less after meals for those with BE compared with those without BE. There were no differences in other hormones by BE group. Fasting and postmeal hunger ratings were significantly higher for those with BE than for those without BE. CONCLUSIONS: In individuals with BE, lower fasting AG may be due to downregulation by habitual overeating, and a smaller postmeal decline in AG may contribute to overeating. Lower postmeal leptin concentrations may also contribute to overeating.

Association of Nesfatin-1, Acylated Ghrelin and Cortisol with Scores of Compulsion, Food Addiction, and Binge Eating in Adults with Normal Weight and with Obesity.

BACKGROUND/AIMS: The alterations of eating behavior are insufficiently recognized in the clinical attention of adults with obesity. The objective of this study was to examine the characteristics of overeating behavior and its association with depression, perceived stress, acylated ghrelin, nestafin-1, and cortisol. METHODS: This cross-sectional comparative study included 80 participants with obesity and 50 with normal weight. The volunteers completed questionnaires to evaluate symptoms of food addiction (FA), obsessive compulsive, binge eating (BE), depression, and perceived stress. We measured glucose, lipids, acylated ghrelin, nesfatin-1, and insulin in a fasting blood sample as well as urine cortisol. We compared groups with students t test, and analysis of variance, and tested associations by logistic and multiple regression. RESULTS: By multiple regression, the BE total score was positively associated with the FA (p < 0.0001) and depression total score (p < 0.0001). By logistic regression, the positive score of FA was associated with ghrelin (p < 0.02). The perceived stress total score was associated negatively with cortisol (p < 0.0006). CONCLUSION: The BE and FA are strongly associated in agreement with the concept that both conditions have overlapping features. Depressive symptoms are associated with symptoms of disordered eating -behavior. FA positive score was associated with ghrelin. BE total score was associated with nesfatin-1.

Cognitive remediation therapy plus behavioural weight loss compared to behavioural weight loss alone for obesity: study protocol for a randomised controlled trial.

BACKGROUND: Current research indicates that obese individuals have cognitive deficits in executive function, leading to difficulties with planning, impulse control and decision-making. High levels of inflammation have been proposed to contribute to executive function deficits in individuals with obesity. METHODS/DESIGN: One hundred and seventy-six obese participants will be randomly assigned to one of two groups: (1) behavioural weight loss alone (BWL) group = 8 sessions of individual BWL sessions plus 12 group BWL sessions or (2) Cognitive Remediation Therapy for Obesity (CRT-O) plus BWL group (CRT-O + BWL) = 8 sessions of individual CRT-O plus 12 group BWL sessions. The study is double blind - participants will only be told that two weight-loss treatments are being compared and research assistants conducting outcome assessments will not know participants' group allocation. Blood tests will be conducted to measure inflammatory markers. Measurement points will be at baseline, post treatment and 1-year follow-up. The primary outcomes will be differences between treatment groups in percentage weight loss, executive function, binge eating and an examination of whether changes in executive function predict changes in weight and binge eating. Secondary outcome measures will examine changes on inflammation, quality of life, and grazing behaviour and whether these predict changes in executive function and weight. DISCUSSION: If CRT-O + BWL is more effective in assisting people to lose weight long term than BWL alone it should significantly improve treatment outcomes. This study expands upon our recent trial which showed that CRT-O enhanced executive function and weight loss in obese adults. The current study is strengthened by several factors: it is double-blind, it uses an active control, has a larger sample size, and measures inflammation to examine the mechanisms. TRIAL REGISTRATION: The RCT is registered with the Australian New Zealand Registry of Clinical Trial, trial identifier: ACTRN12616000658415 . Registered on 20 May 2016.

Binge eating and biochemical markers of appetite in new users of the contraceptive depot medroxyprogesterone acetate.

PURPOSE: Weight gain has been cited by women as one of the main reasons for discontinuation of the contraceptive depot medroxyprogesterone acetate (DMPA). This study aimed to evaluate binge eating and the biochemical markers of appetite in new DMPA users. METHODS: In this prospective non randomized study with adult healthy women, twenty-eight users of DMPA and twenty-five users of a copper intrauterine device (IUD) were paired for age (±1 year) and body mass index (BMI) (±1 kg/m2). We evaluated binge eating using the Binge Eating Scale (BES), the serum levels of neuropeptide Y, leptin and adiponectin, and the BMI at baseline and after 12 months in both groups. For statistical analysis was used ANOVA for to compare the means of the repeated measurements. RESULTS: Mean age was 29.6 and 28.6 years and BMI was 23.9 and 24.5 kg/m2 for the DMPA and IUD groups, respectively. After 12 months, the frequency of the scores of binge eating remained low in both groups. There were no significant differences between the groups at 12 months with respect to BMI, levels of NPY, leptin, adiponectin, and BES scores. CONCLUSIONS: Healthy adult women did not present with central stimulation of appetite or binge eating disorder in their first year after starting use of DMPA. This study reinforces the use of the contraceptive DPMA and the need for guidance related to living a healthy lifestyle for women who attribute the increase of body weight to the use of the method.

Serum Lipid Levels in Patients with Eating Disorders.

Objective To evaluate some risk factors for cardiovascular diseases in feeding and eating disorders, the degree of lipid abnormalities was investigated in a large Japanese cohort of different groups of feeding and eating disorders, according to the Japan Atherosclerosis Society Guidelines for the Prevention of Atherosclerotic Cardiovascular Diseases 2012 (JAS Guidelines 2012). Methods Participants in the current study included 732 women divided into four groups of feeding and eating disorders: anorexia nervosa, restricting type (AN-R); anorexia nervosa, binge-eating/purging type; bulimia nervosa (BN); and binge-eating disorder (BED). We measured the serum levels of total cholesterol, high-density-lipoprotein (HDL) cholesterol, and triglyceride in these participants. Low-density-lipoprotein (LDL) cholesterol and non-HDL cholesterol levels were also calculated. Results The concentrations of LDL cholesterol and non-HDL cholesterol were widely distributed in all groups. When the LDL cholesterol risk was defined as ≥120 mg/dL and the non-HDL cholesterol risk as ≥150 mg/dL, according to the JAS Guidelines 2012, the proportion of LDL cholesterol risk ranged from 29.6% (BN) to 38.6% (AN-R), and the proportion of non-HDL cholesterol risk ranged from 17.8% (BN) to 30.1% (BED). Conclusion The present findings suggest the existence of LDL cholesterol risk and non-HDL cholesterol risk in all groups of eating disorders. Given the chronicity of this condition, the development of elevated concentrations of LDL cholesterol and non-HDL cholesterol at an early age may increase the risk of cardiovascular diseases.

Disinhibited eating and weight-related insulin mismanagement among individuals with type 1 diabetes.

OBJECTIVE: Withholding insulin for weight control is a dangerous practice among individuals with type 1 diabetes; yet little is known about the factors associated with this behavior. Studies of nondiabetic individuals with weight concerns suggest that eating in a disinhibited manner (e.g., binge eating) predicts the use of maladaptive compensatory strategies (e.g., self-induced vomiting). The purpose of this study was to test whether individuals with type 1 diabetes are less restrained in their eating when they think their blood glucose (BG) is low and whether this contributes to insulin omission for weight control purposes and subsequently higher hemoglobin A1c (HbA1c). METHODS: Two-hundred and seventy-six individuals with type 1 diabetes completed an online survey of eating behaviors, insulin dosing and most recent HbA1c. We used structural equation modeling to test the hypothesis that disinhibited eating when blood sugar is thought to be low predicts weight-related insulin mismanagement, and this, in turn, predicts higher HbA1c. RESULTS: The majority of participants endorsed some degree of disinhibition when they think their blood glucose is low (e.g., eating foods they do not typically allow) and corresponding negative affect (e.g., guilt/shame). The frequency of disinhibited eating was positively associated with weight-related insulin mismanagement. Controlling for age, sex, education, and insulin pump use, the model explained 31.3% of the variance in weight-related insulin mismanagement and 16.8% of the variance in HbA1c. CONCLUSION: Addressing antecedents to disinhibited eating that are unique to type 1 diabetes (e.g., perceived BG level) and associated guilt or shame may reduce weight-related insulin omission.

CCK response in bulimia nervosa and following remission.

The core defining features of bulimia nervosa (BN) are repeated binge eating episodes and inappropriate compensatory (e.g., purging) behavior. Previous studies suggest an abnormal post-prandial response in the satiety-signaling peptide cholecystokinin (CCK) in persons with BN. It is unknown whether this altered response persists following remission or if it may be a potential target for the development of clinical treatment strategies. To examine the nature of this altered response, this study assessed whether CCK normalizes following remission from BN (RBN). This study prospectively evaluated the plasma CCK response and corresponding eating behavior-related ratings (e.g., satiety, fullness, hunger, urge to binge and vomit) in individuals with BN-purging subtype (n=10), RBN-purging subtype (n=14), and healthy controls (CON, n=13) at baseline, +15, +30, and +60 min following the ingestion of a standardized liquid test meal. Subject groups did not significantly differ in CCK response to the test meal. A significant relationship between CCK response and satiety ratings was observed in the RBN group (r=.59, p<.05 two-tailed). A new and unanticipated finding in the BN group was a significant relationship between CCK response and ratings of "urge to vomit" (r=.86, p<.01, two-tailed). Unlike previous investigations, CCK response did not differ in BN and CON groups. Thus the role of symptom severity remains an area of further investigation. Additionally, findings suggest that in this sample, CCK functioning following remission from BN-purging subtype is not different from controls. It remains unknown whether or not CCK functioning may be a protective or liability factor in the stabilization and recovery process. Replication studies utilizing a larger sample size are needed to further elucidate the role of CCK in recovery from BN and its potential target of related novel treatment strategies.

Reduction in total plasma ghrelin levels following catecholamine depletion: relation to bulimic and depressive symptoms.

There is increasing preclinical and clinical evidence of the important role played by the gastric peptide hormone ghrelin in the pathogenesis of symptoms of depression and eating disorders. To investigate the role of ghrelin and its considered counterpart, peptide tyrosine tyrosine (PYY), in the development of bulimic and depressive symptoms induced by catecholamine depletion, we administered the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine (AMPT) in a randomized, double-blind, placebo-controlled crossover, single-site experimental trial to 29 healthy controls and 20 subjects with fully recovered bulimia nervosa (rBN). We found a decrease between preprandial and postprandial plasma ghrelin levels (p<0.0001) and a postprandial rise in plasma PYY levels (p<0.0001) in both conditions in the entire study population. Plasma ghrelin levels decreased in the entire study population after treatment with AMPT compared to placebo (p<0.006). AMPT-induced changes in plasma ghrelin levels were negatively correlated with AMPT-induced depressive symptoms (p<0.004). Plasma ghrelin and plasma PYY levels were also negatively correlated (p<0.05). We did not observe a difference in ghrelin or PYY response to catecholamine depletion between rBN subjects and healthy controls, and there was no correlation between plasma ghrelin and PYY levels and bulimic symptoms induced by catecholamine depletion. These findings suggest a relationship between catecholamines and ghrelin with depressive symptoms.

Short-term exercise combined with Acipimox administration induces an increase in plasma ACTH and its subsequent fall in the recovery phase in bulimic women.

OBJECTIVE: Free fatty acids (FFA)-adrenocorticotropin (ACTH) feedback loop between adipose tissue and the hypothalamic-pituitary centers in the brain has been suggested to be affected by the exercise and by administration of anti-lipolytic drugs. Also leptin may be affected by exercise. Dysfunction of FFA-leptin-ACTH secretion might be involved in binge eating and subsequent purging as is the case in bulimia nervosa (BN). METHODS: In the present single-blind, randomized study, we explored responses of plasma ACTH, leptin and FFA concentrations to exercise (45 min, 2 W/kg of lean body mass [LBM]) with Acipimox (Aci), an anti-lipolytic nicotinic acid analog, or placebo randomly received in nine women with BN and nine healthy women. RESULTS: The exercise with Aci administration resulted in plasma ACTH (p<0.001) and leptin increase higher in BN patients and a decrease in the plasma FFA levels in both groups. The falling of plasma ACTH (p<0.01) levels in the post-exercise recovering phase (90-minute) with Aci administration is more expressed in BN patients. The exercise induced an increase in plasma ACTH (p<0.05) and FFA levels and a decrease in the plasma leptin level in both groups. CONCLUSIONS: We demonstrated that the Aci-induced elevation in plasma ACTH (p<0.001) levels after the exercise higher in BN patients and that the falling of plasma ACTH (p<0.01) levels in the post-exercise recovering phase (90-minute) with Aci administration is suppressed only in BN patients, while Aci increased plasma leptin levels in this recovering phase more in BN patients. Therefore, these observations led us to suggesting that FFA-leptin-ACTH are involved in the dysregulation of neuroendocrine profile in this syndrome and that Aci affects a FFA-independent mechanism. In conclusion, Aci can be considered acceptable in the treatment of eating disorders, and it may also serve as an alternative low-dose dexamethasone suppression test (LDDST) in these patients. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000309886.

Effects of CB1 and CRF1 receptor antagonists on binge-like eating in rats with limited access to a sweet fat diet: lack of withdrawal-like responses.

Positive reinforcement (e.g., appetitive, rewarding properties) has often been hypothesized to maintain excessive intake of palatable foods. Recently, rats receiving intermittent access to high sucrose diets showed binge-like intake with withdrawal-like signs upon cessation of access, suggesting negative reinforcement mechanisms contribute as well. Whether intermittent access to high fat diets also produces withdrawal-like syndromes is controversial. The present study therefore tested the hypothesis that binge-like eating and withdrawal-like anxiety would arise in a novel model of binge eating based on daily 10-min access to a sweet fat diet (35% fat kcal, 31% sucrose kcal). Within 2-3 weeks, female Wistar rats developed binge-like intake comparable to levels seen previously for high sucrose diets (~40% of daily caloric intake within 10 min) plus excess weight gain and adiposity, but absent increased anxiety-like behavior during elevated plus-maze or defensive withdrawal tests after diet withdrawal. Binge-like intake was unaffected by pretreatment with the corticotropin-releasing factor type 1 (CRF(1)) receptor antagonist R121919, and corticosterone responses to restraint stress did not differ between sweet-fat binge rats and chow-fed controls. In contrast, pretreatment with the cannabinoid type 1 (CB(1)) receptor antagonist SR147778 dose-dependently reduced binge-like intake, albeit less effectively than in ad lib chow or sweet fat controls. A priming dose of the sweet fat diet did not precipitate increased anxiety-like behavior, but rather increased plus-maze locomotor activity. The results suggest that CB(1)-dependent positive reinforcement rather than CRF(1)-dependent negative reinforcement mechanisms predominantly maintain excessive intake in this limited access model of sweet-fat diet binges.

Cortisol responses on the dexamethasone suppression test among women with Bulimia-spectrum eating disorders: associations with clinical symptoms.

INTRODUCTION: Evidence associates Bulimia Nervosa (BN) with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but the clinical implications of such alterations need to be better understood. We contrasted cortisol responses to the dexamethasone suppression test (DST) in bulimic and non-eating disordered women and examined relationships among DST cortisol responses, eating symptoms and co-morbid disturbances. METHOD: Sixty women with Bulimia Spectrum (BS) Disorders (either BN or normal weight Eating Disorder NOS with regular binge eating or purging) and 54 non-eating disordered women of similar age and body mass index participated in a 0.5 mg DST, and completed interviews and questionnaires assessing eating symptoms and co-morbid psychopathology. RESULTS: Compared with the normal-eater group, the BS women demonstrated significantly less DST suppression. Among BS women, DST non-suppression was associated with more severe depression, anxiety and eating preoccupations. CONCLUSIONS: Our findings show BS women to show less DST suppression compared to normal eater women, and results link extent of non-suppression, in BS individuals, to severity of depression, anxiety and eating preoccupations.

Orexigenic neuropeptide 26RFa: new evidence for an adaptive profile of appetite regulation in anorexia nervosa.

CONTEXT: Restrictive anorexia nervosa (AN) presents an adaptive appetite regulating profile including mainly high levels of ghrelin. Because this adaptive mechanism is not effective on food intake, other appetite-regulating peptides need to be explored. 26RFa is a hypothalamic neuropeptide that stimulates appetite, gonadotropin release, and bone metabolism. OBJECTIVE: The objective of the study was to evaluate the circadian levels of 26RFa in AN patients compared with healthy subjects, other eating disorders, and constitutional thinness (CT). DESIGN AND SETTINGS: This was a cross-sectional study performed in an endocrine unit and an academic laboratory. INVESTIGATED SUBJECTS: Five groups of age-matched young women were included in the study: 19 restrictive AN, 10 AN with bingeing/purging episodes, 14 with CT, 10 bulimic, and 10 normal-weight controls. MAIN OUTCOME MEASURES: Twelve-point circadian profiles of plasma 26RFa levels were measured in each subject. RESULTS: Significant circadian variations of 26 RFA were noticed in controls with higher values in the morning and abrupt decrease at noon. Twenty-four-hour mean 26RFa levels were significantly increased in restrictive AN and AN with bingeing/purging episodes (P < 0.001), predominantly in the afternoon and evening when compared with controls. Preprandial rises of 26 RFA were noticed in AN patients. Mean 26RFa levels trend to be higher in CT than in controls (P = 0.06) and significantly lower than in AN. The bulimic patients presented a circadian profile of 26RFa similar to that of controls. CONCLUSION: High levels of circulating 26RFa observed in AN patients might reflect an adaptive mechanism of the organism to promote energy intake and to increase fat stores in response to undernutrition.

Meal schedule influences food restriction-induced locomotor sensitization to methamphetamine.

RATIONALE: Traditional protocols for inducing sensitization to psychostimulants use an intermittent or "binge"-like drug administration, and binge eating behavior is comorbid with drug abuse in humans. Food restriction increases the reinforcing properties and self-administration of many drugs of abuse. OBJECTIVE: The present study tested the hypotheses that (1) food restriction induces sensitization to the locomotor stimulation observed in response to methamphetamine and (2) a binge-like feeding schedule during food restriction produces increased sensitization compared to equally restricted mice fed in three daily meals. METHODS: Male DBA/2J mice were fed ad libitum or were food restricted to either an 8% or 16% loss of body weight. Additionally, the food-restricted mice were divided into two groups that were fed in either one meal (binge) or three equal-sized meals (meal). After the reduced body weight was stable, mice were tested for locomotor activity following saline and methamphetamine (1 mg/kg) injections. RESULTS: Both 16% body weight loss groups exhibited sensitization to methamphetamine. Opposite to our hypothesis, the 8% meal but not the 8% binge food-restricted group demonstrated locomotor sensitization. Serum corticosterone levels were significantly higher in the meal-fed groups when compared to the binge- and ad libitum-fed groups. CONCLUSIONS: These results support a role for feeding schedule and plasma corticosterone levels in food restriction-induced enhancement of the effects of methamphetamine.

Enhanced ghrelin secretion in the cephalic phase of food ingestion in women with bulimia nervosa.

In humans, the cephalic phase response to food ingestion consists mostly of vagal efferent activation, which promotes the secretion of entero-pancreatic hormones, including ghrelin. Since symptomatic patients with bulimia nervosa (BN) are characterized by increased vagal tone, we hypothesized an enhanced ghrelin secretion in the cephalic phase of vagal stimulation. Therefore, we investigated ghrelin response to modified sham feeding (MSF) in both BN and healthy women. Six drug-free BN women and 7 age-matched healthy females underwent MSF with initially seeing and smelling a meal, and then chewing the food without swallowing it. Blood samples were drawn immediately before and after MSF for hormone assay. Circulating ghrelin increased after MSF in both groups with BN individuals exhibiting a greater ghrelin increase, which positively correlated with the patients' weekly frequency of binge-purging. These results show for the first time an increased ghrelin secretion in the cephalic phase of vagal stimulation in symptomatic BN patients, likely resulting in a potentiation of the peripheral hunger signal, which might contribute to their aberrant binge-purging behavior.

Psychobiology of purging disorder: reduction in circulating leptin levels in purging disorder in comparison with controls.

OBJECTIVE: Purging disorder (PD), a recently recognized eating disorder syndrome, is differentiated from bulimia nervosa (BN) based on the absence of objectively large binge episodes. BN has been associated with low serum leptin levels. This study examined whether PD is also characterized by low serum leptin. METHOD: Participants included women with PD (n = 20) or BN (n = 37), and non-eating disorder controls (n = 33). Blood samples for measurement of leptin and total ghrelin were obtained after overnight fast. RESULTS: In comparison with control values, leptin levels were significantly decreased in PD (p < .01), as well as in BN (p < .02). Plasma ghrelin levels did not differ significantly across groups. DISCUSSION: These results provide the first evidence that PD is associated with alteration in a neurobiological pathway influencing eating patterns and body weight. Further research is needed to assess whether low leptin levels in PD and BN are associated with restrained eating and weight suppression.

Low serum BDNF and food intake regulation: a possible new explanation of the pathophysiology of eating disorders.

BACKGROUND: Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays an important role in weight regulation and eating behavior, and poorly balanced diets lead to a decrease in blood BDNF levels. However, studies regarding BDNF blood levels in eating disorders (ED) have yielded inconsistent results. We measured serum concentrations of BDNF and assessed behavior and cognition related to eating in ED patients and control subjects. METHODS: Forty female drug-free patients [19 with anorexia nervosa (AN), 21 with bulimia nervosa (BN)], who did not meet the diagnostic criteria for depressive disorder, and 24 age-matched normal control subjects were enrolled in the current study. We evaluated eating-related psychopathology and depressive symptoms using the Eating Disorder Inventory-2 (EDI-2), Eating Attitude Test-26 (EAT-26) and the Hamilton Depression Rating Scale (HDRS), and measured serum BDNF levels by an enzyme-linked immunosorbent assay. RESULTS: Compared to normal controls, serum levels of BDNF were significantly reduced in AN, but not in BN. There was a significant positive correlation between serum BDNF levels and BMI in both AN patients (r=.649, p=.003) and BN patients (r=.626, p=.002). However, no correlation between serum BDNF levels and BMI was detected in the controls. Furthermore, there was a significant negative correlation between serum BDNF levels and the oral control subscale scores of EAT in both AN patients (r=-.506, p=.027) and BN patients (r=-.511, p=.018); whereas, no correlation was detected in normal controls. CONCLUSION: Our study demonstrated that individuals showing more extreme food intake regulation were those with lower serum BDNF levels. This finding is contrary to that in mice where mice with reduced BDNF levels showed aberrant eating behavior. This result suggests that BDNF is no longer functioning appropriately in ED patients, which could be an important factor in the pathophysiological of ED.

Hypercholesterolaemia in anorexia nervosa: frequency and changes during refeeding.

UNLABELLED: High total cholesterol (TC) is common in patients with anorexia nervosa (AN), but its mechanisms remain unclear. PATIENTS AND METHODS: We prospectively studied plasma lipoprotein (LP), haptoglobin, free (f) T3, fT4, TSH, transthyretin and albumin in 120 malnourished adult AN patients (BMI: 13.5+/-1.5 kg/m(2)), 116 non-AN malnourished patients and 119 healthy subjects, matched for age and gender. RESULTS: In 18% of our AN patients, TC was higher than 270 mg/100mL (in non-AN: 5%; P<0.01). TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and HDL2 levels were higher in AN patients than in non-AN patients (P<0.001). Low TC (<150 mg/100mL) and LP levels were observed in 8% of AN patients, but only when BMI was less than 13 kg/m(2). Cholesterol ester transfer protein (CETP) activity was higher in AN patients than in healthy subjects. LP was positively correlated with BMI, albumin, fT3 and haptoglobin levels. In AN patients, there was a biphasic LP profile (low values when BMI was very low, normal values in an intermediate state, and high values when BMI was highest and where bulimia was also present). CONCLUSION: In AN, both high and low cholesterol-rich LP levels were observed. Low T3 and low catabolism allow LP to be maintained, while CETP activity increases cholesterol turnover as an adaptation to its low intake. In severely malnourished AN patients, this fails and LP drops. On the other hand, LP values were higher in the bingeing-purging type of AN than in the restrictive type. Recovery from AN results in the normalization of the LP profile.

Hormonal alteration in obese adolescents with eating disorder: effects of multidisciplinary therapy.

BACKGROUND/AIMS: Ghrelin and leptin play important roles in the physiopathology of eating disorders, starting generally in infancy and adolescence. The aim of this study was to evaluate the effects of multidisciplinary short-term therapy on ghrelin and leptin concentrations, bulimia nervosa symptoms, binge eating disorder symptoms, body composition, and visceral and subcutaneous fat in obese adolescents. METHODS: Twenty obese adolescents with simple obesity (BMI >95th percentile, 36.93 +/- 4.14, CDC) were submitted to multidisciplinary (nutrition, psychology, exercise and clinical) therapy. Plasma ghrelin and leptin concentrations were measured by radioimmunoassay. Bulimic and binge eating behaviors were measured by the Bulimic Investigation Test Edinburgh and the Binge Eating Scale, respectively. Visceral and subcutaneous fat were measured by ultrasonography and body composition by plethysmography. RESULTS: Significant reductions were observed in body weight (101.04 +/- 11.18 to 94.79 +/- 10.94 kg), BMI (36.93 +/- 4.14 to 34.27 +/- 4.78), fat% (41.96 +/- 6.28 to 39.14 +/- 7.62%), visceral fat (4.34 +/- 1.53 to 3.41 +/- 1.12 cm), leptin concentration (20.12 +/- 6.47 to 16.68 +/- 8.08 ng/ml), prevalence of bulimia nervosa (100 to 67%) and binge eating disorder symptoms (40 to 17%). CONCLUSION: Short-term multidisciplinary therapy was effective in improving body composition, visceral fat, leptinemia and eating disorders in obese adolescents.