Opposite modifications in circulating leptin and soluble leptin receptor across the eating disorder spectrum

Leptin is thought to modulate feeding behaviour, body weight and energy metabolism by acting through specific cellular receptors. Derangements of leptin production have been repeatedly reported in patients with anorexia nervosa (AN) or bulimia nervosa (BN), but no information has been provided on the functional status of leptin receptors in these disorders. Therefore, we measured plasma levels of leptin and its soluble receptor (Ob-Re) in a total of 130 women, including 22 patients with AN, 45 patients with BN, 18 patients with the binge-eating disorder (BED), 12 non-binge eating obese women and 33 healthy women. Circulating leptin was drastically reduced in underweight anorexics and normal-weight bulimics, but increased in overweight BED patients and non-binge-eating obese women. Conversely, plasma levels of Ob-Re were significantly increased in patients with AN or BN, but decreased in BED and non-binge-eating obese women. Significant inverse correlations were detected between plasma levels of leptin and those of Ob-Re in all the subject groups, except in non-binge-eating obese subjects. These results show, for the first time, that opposite modifications occur in circulating levels of leptin and Ob-Re across the eating-disorder spectrum. The relevance of these findings to the pathophysiology and treatment of eating disorders remains to be elucidated.     

Immunoendocrine findings in patients with eating disorders.

Immune changes may occur in patients with anorexia nervosa (AN) or bulimia nervosa (BN), and a role for proinflammatory cytokines has been proposed in the pathogenesis of both disorders. We measured plasma levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), soluble forms of the cytokine receptor proteins gp130 and leukemia inhibitory factor receptor (LIF-R), the anti-inflammatory Clara cell 16-kD protein (CC16), prolactin (PRL), cortisol and 17beta-estradiol in 21 anorexic women, 21 bulimic women and 21 healthy females. As compared to healthy subjects, anorexics exhibited significantly increased plasma levels of gp130 and LIF-R, whereas bulimics had significantly decreased blood concentrations of CC16. No significant differences emerged in the blood levels of the remaining immune parameters. Both patient groups manifested higher plasma levels of cortisol and reduced plasma concentrations of PRL and 17beta-estradiol. In anorexics, a significant negative correlation was found between plasma levels of gp130 or LIF-R and the body mass index. These findings do not support the hypothesis that proinflammatory cytokines may play a pathogenetic role in eating disorders.     

Hormonal and metabolic responses to acute ghrelin administration in patients with bulimia nervosa

Ghrelin is generally influenced by energy balance status and is inversely associated with body mass index (BMI), being reduced in simple obesity, notable exception being Prader Willi syndrome, and elevated in several conditions of undernutrition, including anorexia nervosa (AN). Interestingly, ghrelin levels have also been found elevated in patients with bulimia nervosa (BN) in spite of normal BMI. In humans, intravenous (iv) ghrelin administration induces endocrine (increase in GH, PRL, ACTH and cortisol) and metabolic (increase in glucose and decrease in insulin) effects as well as an increase in appetite and food intake. In AN, ghrelin administration surprisingly leads to a decreased GH response and absence of glycemic variations but normal PRL, ACTH and insulin response. This pattern would reflect a decrease in sensitivity to ghrelin or, alternatively, the metabolic status of AN. To further clarify the function of ghrelin in eating disorders, the endocrine and metabolic response to acute iv ghrelin (1.0 microg/kg) was studied in seven young women with purging BN (BW, BMI, mean+/-SEM: 20.3+/-0.5 kg/m2). Circulating total ghrelin levels were also measured. The results in BW were compared to those recorded in a group of nine healthy women (HW; BMI 22.3+/-2.5 kg/m2). The GH response to ghrelin in BW overlapped with that in HW. Ghrelin administration also led to a similar increase in PRL, ACTH, cortisol and glucose levels in the two groups. Insulin levels were not significantly modified by ghrelin administration in either group. The overlapping endocrine and metabolic response to ghrelin in the two groups occurred with regard to circulating total ghrelin levels which were higher in BW than in HW. In conclusion, BN, a condition of ghrelin hypersecretion, is connoted by a normal endocrine and metabolic response to exogenous ghrelin administration.     

Circulating ghrelin is decreased in non-obese and obese women with binge eating disorder as well as in obese non-binge eating women, but not in patients with bulimia nervosa

Ghrelin is a peripheral gastric peptide involved in the regulation of eating behavior and energy homeostasis. While changes in ghrelin plasma levels have been found in anorexia nervosa, bulimia nervosa (BN) and obesity, no study has assessed circulating ghrelin in binge eating disorder (BED). Therefore, we measured plasma levels of this peptide in women with BED as compared to women with BN, obesity and healthy controls. One hundred and eighty-two drug-free women (56 bulimics, 13 non-obese and 34 obese BED subjects, 28 obese non-binge eating women and 51 non-obese healthy women) underwent psychopathological and nutritional assessments and blood sample collection for glucose and ghrelin assays in the morning. As compared to non-obese healthy women, both non-obese and obese BED women as well as obese non-binge eating women had significantly increased values of body weight, body mass index and body fat mass. Moreover, plasma ghrelin concentrations were significantly decreased in both non-obese (P<0.01) and obese (P<0.0001) BED women as well as in obese non-binge eating women (P<0.001) but not in women with BN. No significant correlations emerged between plasma ghrelin values and the frequency of binge/vomiting in BN subjects or the frequency of bingeing in BED individuals. The reduction of plasma ghrelin in non-obese and obese binge eaters as well as in obese non-binge eaters may represent a secondary change aiming to counteract their positive energy imbalance.     

Reduced plasma leptin concentrations in bulimia nervosa

Leptin is a protein produced by the ob-ob gene which inhibits food intake. Plasma levels have previously been reported to be altered in obesity and anorexia nervosa (AN) but not bulimia nervosa (BN). We measured fasting plasma leptin levels by radioimmunoassay in 53 subjects carefully studied at NIMH, including 37 women meeting DSM-III-R criteria for BN [10 with concurrent AN (body mass index (BMI)=14.1+/-1.4), 27 without AN (BMI=20.4+/-1.6)] and 16 normal control women (NCs) (BMI=21.1+/-2.0). Patients were medication-free and abstinent from bingeing and purging for three to four weeks prior to study. Plasma leptin levels were significantly correlated to BMI (r=0.41, P<0.002), weight (kg, r=0.43, P<0.001), and percent average body weight (%ABW, r=0.45, P<0.001) in the total group. Plasma leptin levels were lower in the BN subjects (3.4+/-2.5 ng/ml) compared to the NCs (6.1+/-2.6 ng/ml, P<0.001, ANCOVA) even after controlling for BMI and weight. There was no significant difference between BN subjects with AN (n=10, 2.6+/-2.6 ng/ml) and those without AN (n=27, 3.8+/-2.4 ng/ml), despite lower BMI in BN with AN. Furthermore, leptin levels were decreased in BN without AN compared with healthy controls, even though BMI was comparable in these two subgroups. Plasma leptin concentrations were negatively correlated with baseline plasma cortisol levels (n=49, r=-0.49, P<0.001) and positively correlated with prolactin responses following L-tryptophan (n=49, r=0.37, P<0.009) and m-chlorophenylpiperazine (n=52, r=0.24, P<0.09). This is the first known report of decreased plasma leptin levels in BN. The decrement in leptin concentration is not related to BMI, body weight, or the presence or absence of BN. HPA axis activation as well as serotonin dysregulation may be related to decreased leptin levels, which may in turn contribute to disinhibited eating in BN. Although current leptin levels were not correlated with self-reported previous binge frequency, the role of leptin in the pathophysiology of BN deserves further study.     

Anxiety disorders in anorexia nervosa and bulimia nervosa: co-morbidity and chronology of appearance.

The objectives of the study were to assess lifetime prevalence of specific anxiety disorders, and their age of onset relative to that of eating disorders (ED), in a French sample of patients with anorexia nervosa (AN) or bulimia nervosa (BN). We assessed frequencies of seven anxiety disorders and childhood histories of separation anxiety disorder among 63 subjects with a current DSM-IV diagnosis of an ED, using the Composite International Diagnostic Interview (CIDI). Eighty-three percent of subjects with AN and 71% of those with BN had at least one lifetime diagnosis of an anxiety disorder. By far, the most frequent was social phobia (55% of the anorexics and 59% of the bulimics). When present, the co-morbid anxiety disorder had predated the onset of the ED in 75% of subjects with AN, and 88% of subjects with BN. Our results are consistent with those of studies conducted in other countries, and show that an anxiety disorder frequently exists before an ED. This has to be taken in consideration for successful treatment of patients with AN or BN.     

Aggressive behavioral characteristics and endogenous hormones in women with Bulimia nervosa

Increased aggressiveness frequently occurs in patients with bulimia nervosa (BN), but its neurobiological correlates have been poorly investigated. In this study, we investigated possible relationships between such clinical measure and blood levels of endogenous hormones in patients with BN. Morning plasma levels of testosterone, 17beta-estradiol, prolactin (PRL) and cortisol were measured in 33 bulimic women and 22 healthy female controls. The eating-related psychopathology, depression and aggressiveness were rated by specific psychometric scales. Bulimic patients showed decreased plasma levels of PRL and 17beta-estradiol, and increased concentrations of cortisol and testosterone. Moreover, patients scored higher than healthy controls on rating scales assessing eating-related psychopathology, depressive symptoms and aggressiveness. A significant positive correlation was found between testosterone plasma levels and aggressiveness in patients but not in controls. These findings suggest that in BN, increased plasma levels of testosterone may play a role in the modulation of aggressiveness.     

Compulsive and impulsive traits in individuals with obese binge eating disorder and bulimia nervosa

Many researchers have questioned whether patients with bulimia nervosa (BN) have more prominent impulsive or compulsive traits and whether eating disorders should be considered to be obsessivel compulsive (OC) spectrum disorders. It this paper we compare the extent to which individuals with BN and binge eating disorder (BED) exhibit both OC and impulsive traits. Thirty-one women with BN and 39 women with BED were enrolled in this study. Psychiatric diagnoses were made using the Structured Clinical Interview for DSM-III-R and participants completed a number of questionnaires (including one developed by the authors) to assess impulsive and OC traints. Compared to the BED group, the BN group reported spending significantly more time being preoccupied     

Emotional eating in anorexia nervosa and bulimia nervosa

ObjectivesThe relationship between emotional states and eating behaviors is complex, and emotional eating has been identified as a possible factor triggering binge eating in bulimia nervosa (BN) and binge eating disorder. Few studies considered emotional eating in patients with anorexia nervosa.MethodsThe present study evaluated the clinical correlates of emotional eating in 251 eating-disordered (EDs) subjects (70 AN restricting type, 71 AN binge eating/purging type, 110 BN purging type) and in a group of 89 healthy control subjects. Subjects were assessed by means of a clinical interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and several self-reported questionnaires, including the Emotional Eating Scale (EES).ResultsNo significant differences were found between the 3 EDs groups in terms of EES total score, and all patients with ED showed higher EES scores compared with control subjects. Emotional eating was associated with subjective binge eating in AN binge eating/purging type and with objective binge eating in patients with BN. Among patients with AN restricting type, emotional eating was associated with restraint, but this association was lost when controlling for fear of loss of control over eating, which was the principal determinant of restraint.ConclusionEmotional eating and fear of loss of control over eating are significantly associated with specific eating attitudes and behaviors, according to the different diagnoses. Emotional eating is a relevant psychopathologic dimension that deserves a careful investigation in both anorectic and bulimic patients.     

Teasing history and eating disorder features: an age- and body mass index-matched comparison of bulimia nervosa and binge-eating disorder

The study examined whether a history of being teased about physical appearance is associated with differential patterns of current symptomatology in patients with bulimia nervosa (BN) as compared to patients with binge-eating disorder (BED). Thirty-two adult female patients with BN were compared with an age- and body mass index (BMI)-matched group of 32 adult female patients with BED. A battery of established instruments were used to assess physical appearance-related teasing history, current eating disorder features, body dissatisfaction, and psychological functioning (depression and self-esteem). BN patients reported a significantly higher frequency of having been teased about weight and size (WST) but a similar frequency of having been teased about general appearance (GAT) as the age- and BMI-matched BED patients. The two study groups did not differ significantly on current eating disorder features, body dissatisfaction, or psychological functioning, with the one exception that BN patients were characterized by significantly greater dietary restraint. Correlational analyses conducted separately within the BN and BED study groups revealed few significant associations between teasing history and eating disorder features in either study group. For the BN group, neither WST nor GAT was significantly associated with eating disorder features or body dissatisfaction, but both were significantly associated with lower self-esteem. For the age- and BMI-matched BED group, WST was not associated with eating disorder features, body dissatisfaction, or psychological functioning, but GAT was associated with higher dietary restraint and depression. Although physical appearance related teasing history was not associated with most eating disorder features for either study group, it appears that the association of different forms of teasing with psychological functioning may vary depending on the type of eating disorder symptomatology.     

Effectiveness of individualized,integrative outpatient treatment for females with anorexia nervosa and bulimia nervosa

ABSTRACT

The effectiveness of an individualized outpatient program was investigated in the treatment of bulimia nervosa (BN) and anorexia nervosa (AN). Participants included 151 females who received outpatient eating disorder treatment in the partial hospitalization program, the intensive outpatient program, or a combination of the two programs. Outcome measures included the Eating Disorder Inventory (EDI-2), Beck Depression Inventory (BDI-II), frequency of binge eating and purging, and mean body weight. Findings included significant increases in weight for the AN group, reductions in binge eating frequency for the BN group, and reductions in EDI-2 and BDI-II scores and purging frequency for both groups. This study provides preliminary support for the efficacy of a multimodal program for the treatment of both anorexia nervosa and bulimia nervosa.     

Abnormal serum prolactin responses to luteinizing hormone-releasing hormone (LHRH) in patients with anorexia nervosa and bulimia

Abnormal responses of serum prolactin (PRL) to luteinizing hormone-releasing hormone (LHRH) stimulation have been observed in anovulatory women and in hypogonadal patients. Various endocrinological abnormalities have been demonstrated in patients with anorexia nervosa (AN). The present study was undertaken to further investigate responses of serum PRL, growth hormone (GH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) to LHRH stimulation in 65 patients with AN and in 12 patients with bulimia before therapy and in the AN patients after several months of treatment, and in comparison to 12 normal women of the same age. Serum PRL responses to LHRH were positive (peak PRL levels greater than 25 ng/ml and delta increase in PRL greater than 10 ng/ml) in 16.9% of AN and 16.6% of bulimic patients; they were negative (absent) in all controls. Following restoration of the AN patients to normal body weight, the PRL responses to LHRH became normalized in those patients whose eating disorder behavior also returned to normal. However, in those patients whose eating disorder patterns continued to be abnormal, abnormal PRL responses persisted. The bulimic patients were of normal body weight, and yet had abnormal PRL responses. Thus, the responses of PRL correlated more closely with the behavior of the underlying eating disorder rather than with body weight gain or normal body weight.     

Suicidal behavior in adolescents and adults with bulimia nervosa

Background

Recent evidence suggests increased risk for mortality in bulimia nervosa (BN). However, little is yet known about suicidal behavior in BN.

Aims

To examine frequency and correlates of suicidal ideation and attempts in adolescents and adults with BN in two population-based samples.

Method

A total of 10,123 adolescents and 2980 adults in two nationally representative surveys of mental disorder were queried regarding eating disorder symptoms and suicidal ideation and attempts.

Results

Less than 1 percent (0.9%) of adolescents and 1.0% of adults met the criteria for BN. Suicidal ideation was more common among adolescents with BN (53.0%) compared with those with binge eating disorder (BED) (34.4%), other psychopathology (21.3%) or no psychopathology (3.8%). Similar trends emerged for the association between BN and self-reported suicidal plans or attempts. Among adults, suicidality was more common in BN than in the no psychopathology group, but not significantly different from the anorexia nervosa (AN), BED, or other psychopathology subgroups.

Conclusion

There is a high risk of suicidal ideation and behavior among those with BN. These results underscore the importance of addressing suicide risk in adolescents and adults with eating disorder symptoms.     

Comparison of patients with bulimia nervosa, obese patients with binge eating disorder, and nonobese patients with binge eating disorder

This study compared patients with bulimia nervosa (BN), obese patients with binge eating disorder (BED), and nonobese patients with BED. One hundred sixty-two adult women consecutively evaluated for outpatient clinical trials who met DSM-IV criteria for BN, purging type (N = 46) or for BED (N = 79 obese and N = 37 nonobese) were compared using the Eating Disorder Inventory (EDI). The three groups differed significantly on two (drive for thinness and body dissatisfaction) of the three eating-related scales and on all five of the general personality scales of the EDI. When age and depression level were controlled, findings for the eating-related scales did not change, whereas four of the five general personality scales were no longer significant. Post hoc analyses revealed that the BN group and the nonobese BED group had significantly higher drive for thinness than the obese BED group. The nonobese and the obese BED groups did not differ from each other in any area (other than drive for thinness), including body dissatisfaction. The nonobese and the obese BED groups had significantly lower maturity features than the BN group. Our findings suggest that when the effects of age and depression levels are controlled, treatment-seeking women with BN and BED are generally similar. Certain differences that do exist between women with BN and BED are associated with obesity status (drive for thinness), whereas others are associated with diagnosis (body dissatisfaction, maturity fears).     

Cognitive-behavioral psychotherapy for adolescents with eating disorders

Anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) are grouped together under the term eating disorders. Due to its typical onset in adolescence, AN in particular represents a frequent disorder with often an unfavourable course in this age range (Steinhausen 2002). The mental, social and physical consequences are serious. Research has shown that cognitive-behavioral treatment (CBT) has good effectiveness in adult patients with AN, BN and BED and that it is superior to other treatments. However, there have been few studies on children and adolescents. The effectiveness in adolescence can thus be judged only when the results in adulthood are taken into account. At present, there is limited evidence for the effectiveness of CBT in adolescence.     

Advances in diagnosis and treatment of anorexia nervosa and bulimia nervosa.

This paper reviews four areas of research into anorexia nervosa (AN) and bulimia nervosa (BN). First, in terms of diagnosis, the psychological concerns about weight and shape are now addressed in BN, bringing it more in line with the related disorder, anorexia nervosa. Second, studies of psychiatric comorbidity confirm the overlap between eating disorders and depression, obsessive compulsive disorder, substance abuse, and personality disorder. Nevertheless, there are reasons to accept the distinct qualities of each syndrome, and eating disorders are not merely a variant of these other conditions. Third, treatment advances in BN involve mainly cognitive-behavioural or interpersonal psychotherapies and pharmacotherapies primarily with antidepressants. The effect of combining more than one approach is beginning to be addressed. Finally, outcome studies involving people with both AN and BN have shown that the disorders "cross over" and that both conditions have a high rate of relapse. A renewed interest in the treatment of AN is needed.     

Effects of emotional acceptance and rumination on media-induced body dissatisfaction in anorexia and bulimia nervosa

IntroductionBody dissatisfaction is an important risk and maintaining factor for eating disorders. The aim of the present study was to experimentally test the effects of two emotion regulation strategies - acceptance and rumination - on media-induced body dissatisfaction in eating disorders.MethodAfter watching pictures of thin models, women with anorexia nervosa (AN; n = 39) and bulimia nervosa (BN; n = 39) were encouraged to either use emotional acceptance or rumination to cope with their feelings. Body dissatisfaction and mood were repeatedly assessed.ResultsAcceptance significantly improved body dissatisfaction in women with BN. Rumination led to a significant increase of body dissatisfaction in both eating disorder groups. Results were independent from mood changes.DiscussionFindings highlight the importance ruminative thinking may have in the aggravation of dissatisfaction with the own body in AN and BN. Results suggest that emotional acceptance is a useful strategy to regulate body dissatisfaction after exposure to thin-ideal media in BN.     

On the role of sadness in the psychopathology of anorexia nervosa

Recent models on the development and maintenance of eating disorders propose negative emotions to be important precursors for the occurrence of eating disorder symptomatology. In fact, previous research on bulimia nervosa (BN) and binge eating disorder provides evidence that negative emotions are an antecedent condition for binge eating. However, there is a lack of research examining the influence of negative emotions on restrictive eating and exercising in individuals with anorexia nervosa (AN). In an experimental study, women with AN (n=39) and BN (n=34) as well as a non-eating disordered control group (CG; n=34) watched a sadness-inducing film clip. Before and after the film clip participants rated their current desire to engage in dietary restriction (DTR) and desire to exercise (DTE). Main results reveal that DTR significantly increased after the film clip in women with AN only, while DTE decreased over time in all groups. Results are in line with the notion that negative emotions have a prominent influence on the core eating pathology in AN.     

Normal brain tissue volumes after long-term recovery in anorexia and bulimia nervosa.

BACKGROUND: Individuals who are ill with anorexia (AN) and bulimia nervosa (BN) often have increased cerebrospinal fluid (CSF) volumes and decreased total gray and white matter volumes. It is unclear whether such disturbances persist after recovery from an eating disorder. METHODS: Magnetic resonance imaging was performed on 40 women who were long-term recovered (>1 year no binging, purging, or restricting behaviors, normal weight, and menstrual cycles, not on medication) from restricting or binge/purging type AN or BN and 31 healthy control women (CW). Voxel-based morphometry (VBM) was used for data analysis. RESULTS: Recovered AN and BN subgroups were similar to CW in terms of cerebrospinal fluid (CSF) volume as well as total or regional gray or white matter volume. CONCLUSIONS: These findings suggest that structural brain abnormalities are reversible in individuals with eating disorders after long-term recovery.     

Central and peripheral ACTH and cortisol levels in anorexia nervosa and bulimia

To explore the relationship of central and peripheral adrenocorticotropic hormone (ACTH, or corticotropin) levels to hypothalamo-pituitary-adrenal axis dysfunction in patients with eating disorders, levels of cerebrospinal fluid (CSF) and plasma ACTH, cortisol, and 24-hour urinary free cortisol were measured in 16 patients with anorexia nervosa (60% +/- 1.1% of ideal body weight), 14 patients with bulimia (93.2% +/- 4.6% of ideal body weight), and 11 healthy age-matched women volunteers. The CSF, plasma, and urinary free cortisol levels were elevated in underweight anorexic patients and showed declines following weight recovery. Cortisol-binding globulin levels were similar in anorexics and controls. In contrast, underweight anorexics showed low CSF ACTH levels that returned to normal following weight recovery, and their plasma ACTH levels were normal. On hospital admission, bulimic patients demonstrated normal ACTH and cortisol levels. After their abstinence from binge-purge episodes, the CSF ACTH levels decreased significantly. Positive relationships were found among CSF, plasma, and urinary cortisol levels, and inverse relationships were seen between cortisol measures and CSF ACTH levels in patients with eating disorders. Secretion of ACTH into the CSF may respond to feedback by cortisol or, alternatively, may be suppressed by the hypersecretion of corticotropin-releasing hormone, leading to the depletion of the pro-opiomelanocortin molecule.