Disentangling the links between gastric emptying and binge eating v. purging in eating disorders using a case-control design.

BACKGROUND: Prior work supports delayed gastric emptying in anorexia nervosa and bulimia nervosa (BN) but not binge-eating disorder, suggesting that neither low body weight nor binge eating fully accounts for slowed gastric motility. Specifying a link between delayed gastric emptying and self-induced vomiting could offer new insights into the pathophysiology of purging disorder (PD). METHODS: Women (N = 95) recruited from the community meeting criteria for DSM-5 BN who purged (n = 26), BN with nonpurging compensatory behaviors (n = 18), PD (n = 25), or healthy control women (n = 26) completed assessments of gastric emptying, gut peptides, and subjective responses over the course of a standardized test meal under two conditions administered in a double-blind, crossover sequence: placebo and 10 mg of metoclopramide. RESULTS: Delayed gastric emptying was associated with purging with no main or moderating effects of binge eating in the placebo condition. Medication eliminated group differences in gastric emptying but did not alter group differences in reported gastrointestinal distress. Exploratory analyses revealed that medication caused increased postprandial PYY release, which predicted elevated gastrointestinal distress. CONCLUSIONS: Delayed gastric emptying demonstrates a specific association with purging behaviors. However, correcting disruptions in gastric emptying may exacerbate disruptions in gut peptide responses specifically linked to the presence of purging after normal amounts of food.

Satiation deficits and binge eating: Probing differences between bulimia nervosa and purging disorder using an ad lib test meal.

Purging disorder (PD) has been included as a named condition within the DSM-5 category of Other Specified Feeding or Eating Disorder and differs from bulimia nervosa (BN) in the absence of binge-eating episodes. The current study evaluated satiation through behavioral and self-report measures to understand how this construct may explain distinct symptom presentations for bulimia nervosa (BN) and purging disorder (PD). Women (N = 119) were recruited from the community if they met DSM-5 criteria for BN (n = 57), PD (n = 31), or were free of eating pathology (n = 31 controls). Participants completed structured clinical interviews and questionnaires and an ad lib test meal during which they provided reports of subjective states. Significant group differences were found on self-reported symptoms, ad lib test meal intake, and subjective responses to food intake between individuals with eating disorders and controls and between BN and PD. Further, ad lib intake was associated with self-reported frequency and size of binge episodes. In a multivariable model, the amount of food consumed during binges as reported during clinical interviews predicted amount of food consumed during the ad lib test meal, controlling for other binge-related variables. Satiation deficits distinguish BN from PD and appear to be specifically linked to the size of binge episodes. Future work should expand exploration of physiological bases of these differences to contribute to novel interventions.

Disturbance of gut satiety peptide in purging disorder.

OBJECTIVE: Little is known about biological factors that contribute to purging after normal amounts of food-the central feature of purging disorder (PD). This study comes from a series of nested studies examining ingestive behaviors in bulimic syndromes and specifically evaluated the satiety peptide YY (PYY) and the hunger peptide ghrelin in women with PD (n = 25), bulimia nervosa-purging (BNp) (n = 26), and controls (n = 26). Based on distinct subjective responses to a fixed meal in PD (Keel, Wolfe, Liddle, DeYoung, & Jimerson, ), we tested whether postprandial PYY response was significantly greater and ghrelin levels significantly lower in women with PD compared to controls and women with BNp. METHOD: Participants completed structured clinical interviews, self-report questionnaires, and laboratory assessments of gut peptide and subjective responses to a fixed meal. RESULTS: Women with PD demonstrated a significantly greater postprandial PYY response compared to women with BNp and controls, who did not differ significantly. PD women also endorsed significantly greater gastrointestinal distress, and PYY predicted gastrointestinal intestinal distress. Ghrelin levels were significantly greater in PD and BNp compared to controls, but did not differ significantly between eating disorders. Women with BNp endorsed significantly greater postprandial hunger, and ghrelin predicted hunger. DISCUSSION: PD is associated with a unique disturbance in PYY response. Findings contribute to growing evidence of physiological distinctions between PD and BNp. Future research should examine whether these distinctions account for differences in clinical presentation as this could inform the development of specific interventions for patients with PD.

Impaired reversal learning in an animal model of anorexia nervosa.

BACKGROUND: Clinical investigations indicate that anorexia nervosa (AN) is associated with impaired cognitive flexibility. Activity-based anorexia (ABA), a rodent behavioral model of AN, is characterized by compulsive wheel running associated with voluntary food restriction and progressive weight loss. The goal of this study was to test whether ABA is associated with impaired cognitive flexibility. METHODS: Female Sprague-Dawley rats were trained to perform the attentional set-shifting test (ASST) to assess cognitive flexibility, including capacity for set-shifting and reversal learning. Rats were assigned to ABA or weight-loss paired control (WPC) conditions. Following baseline testing, the ABA group had access to food for 1h/d and access to running wheels 23h/d until 20% weight loss was voluntarily achieved. For the WPC group, running wheels were locked and access to food was restricted to reduce body weight at the same rate as the ABA group. ASST performance was assessed after weight loss, and again following weight recovery. RESULTS: Compared to baseline, the ABA group (but not the WPC group) showed a significant decrement in reversal learning at low weight, with return to baseline performance following weight restoration. The other components of ASST were not affected. CONCLUSIONS: Impaired reversal learning, indicative of increased perseverative responding, in the ABA model reveals its potential to recapitulate selective components of cortical dysfunction in AN. This finding supports the utility of the ABA model for investigations of the neural mechanisms underlying such deficits. Reversal learning relies on neural circuits involving the orbitofrontal cortex and thus the results implicate orbitofrontal abnormalities in AN-like state.

Plasma BDNF levels following weight recovery in anorexia nervosa.

OBJECTIVE: Preclinical studies have implicated brain-derived neurotrophic factor (BDNF) in the regulation of eating behavior and body weight. As reviewed in this report, prior studies of BDNF levels in anorexia nervosa have yielded variable results, perhaps reflecting effects of malnutrition and psychiatric comorbidity. The goal of the current report was to assess plasma BDNF as a biomarker in weight-recovered individuals with a history of anorexia nervosa (ANWR). METHODS: Study groups included women meeting criteria for ANWR and healthy female controls. Participants were in a normal weight range, free of current major psychiatric disorder, and free of medication. Self-ratings included eating disorder symptoms, depression and anxiety. Plasma BDNF levels were measured by enzyme linked immunoassay. RESULTS: Plasma BDNF levels were not significantly different for ANWR and control groups. Plasma BDNF levels were inversely correlated with anxiety ratings in controls (p<0.02) but not in the ANWR group. DISCUSSION: This report provides new evidence that circulating BDNF concentrations do not differ in healthy controls and ANWR free of psychiatric comorbidity. Additionally, the data provide new information on the relationship between plasma BDNF and anxiety in these two study groups.

Initial evaluation, diagnosis, and treatment of anorexia nervosa and bulimia nervosa.

Eating disorders are life-threatening conditions that are challenging to address; however, the primary care setting provides an important opportunity for critical medical and psychosocial intervention. The recently published Diagnostic and Statistical Manual of Mental Disorders, 5th ed., includes updated diagnostic criteria for anorexia nervosa (e.g., elimination of amenorrhea as a diagnostic criterion) and for bulimia nervosa (e.g., criterion for frequency of binge episodes decreased to an average of once per week). In addition to the role of environmental triggers and societal expectations of body size and shape, research has suggested that genes and discrete biochemical signals contribute to the development of eating disorders. Anorexia nervosa and bulimia nervosa occur most often in adolescent females and are often accompanied by depression and other comorbid psychiatric disorders. For low-weight patients with anorexia nervosa, virtually all physiologic systems are affected, ranging from hypotension and osteopenia to life-threatening arrhythmias, often requiring emergent assessment and hospitalization for metabolic stabilization. In patients with frequent purging or laxative abuse, the presence of electrolyte abnormalities requires prompt intervention. Family-based treatment is helpful for adolescents with anorexia nervosa, whereas short-term psychotherapy, such as cognitive behavior therapy, is effective for most patients with bulimia nervosa. The use of psychotropic medications is limited for anorexia nervosa, whereas treatment studies have shown a benefit of antidepressant medications for patients with bulimia nervosa. Treatment is most effective when it includes a multidisciplinary, teambased approach.

Emotion contagion moderates the relationship between emotionally-negative families and abnormal eating behavior.

OBJECTIVE: To reconcile empirical inconsistencies in the relationship between emotionally-negative families and daughters' abnormal eating, we hypothesized a critical moderating variable: daughters' vulnerability to emotion contagion. METHOD: A nonclinical sample of undergraduate females (N = 92) was recruited via an advertisement and completed self-report measures validated for assessing: families' expressive negativity, daughters' susceptibility to emotion contagion, dietary restraint, and disinhibition, eating attitudes, and several control variables (interpersonal orientation, alexithymia, and the big five personality traits: extraversion, conscientiousness, openness, neuroticism, and agreeableness). RESULTS: All variables and interactions were entered as predictors in a multistep multiple regression equation. Only an emotion contagion by family expressivity interaction term significantly predicted unhealthy eating attitudes (ß = .29, p = .02) and dietary restraint (ß = .27, p = .03). Negatively expressive families significantly induced unhealthy eating and restraint but only among young women susceptible to emotion contagion (ps < .05). DISCUSSION: Young women susceptible to emotion contagion may be at increased risk for eating disorders.

Serum amylase in bulimia nervosa and purging disorder: differentiating the association with binge eating versus purging behavior.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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). CONCLUSION: 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.

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.

State self-esteem ratings in women with bulimia nervosa and bulimia nervosa in remission.

OBJECTIVE: Bulimia nervosa (BN) is associated with low self-esteem. This study was designed to assess whether low self-esteem persists in nondepressed individuals who have recovered from BN (BN-R). METHOD: Study groups included BN (n = 22), BN-R (n = 20), and healthy controls (n = 42). Participants were medication-free, and none met criteria for current major depression. Assessment instruments included the State Self-Esteem Scale (SSES), a self-rating scale designed to measure state-related changes in self-esteem. RESULTS: Consistent with previous reports, SSES scores for BN were lower than for controls (p < .001). For BN-R, SSES scores were higher than for BN (p < .001), but lower than for controls (p < .025). For BN-R, scores on the SSES Appearance subscale were inversely correlated with ratings of dietary restraint (p < .005). CONCLUSION: This study provides new evidence for persistent low self-esteem following recovery from BN. Follow-up studies are needed to assess whether low self-esteem contributes to recurrent dieting and risk for relapse.

Clinical features and physiological response to a test meal in purging disorder and bulimia nervosa.

CONTEXT: Recent data suggest that purging disorder, a recently characterized form of eating disorder not otherwise specified, may be worthy of specific delineation in nosological schemes. However, more data are needed to determine how purging disorder differs from bulimia nervosa. OBJECTIVE: To examine clinical features and subjective as well as objective physiological responses to a standardized test meal in purging disorder compared with bulimia nervosa and controls. DESIGN: Study visit 1 included psychological assessments with structured clinical interviews and questionnaires. Study visit 2 included assessment of test-meal responses. SETTING: Participants recruited from the community completed test-meal studies in a General Clinical Research Center. PARTICIPANTS: Women with DSM-IV bulimia nervosa-purging subtype (n = 37) and purging disorder (n = 20) and non-eating disorder controls (n = 33) with a body mass index (calculated as weight in kilograms divided by height in meters squared) between 18.5 and 26.5 who were free of psychotropic medications. MAIN OUTCOME MEASURES: Assessments of eating disorder severity, postprandial cholecystokinin response, and subjective responses to test meals. RESULTS: Eating abnormalities were significantly elevated in participants with purging disorder and bulimia nervosa compared with controls but did not differ between eating disorder groups. Participants with purging disorder demonstrated significantly greater postprandial cholecystokinin release compared with participants with bulimia nervosa (t(76.44) = 2.51; P = .01) and did not differ significantly from controls (t(75.93) = 0.03; P = .98). Participants with purging disorder reported significantly greater postprandial fullness and gastrointestinal distress compared with participants with bulimia nervosa and controls. CONCLUSIONS: Purging disorder is a clinically significant disorder of eating that appears to be distinct from bulimia nervosa on subjective and physiological responses to a test meal. Findings support further consideration of purging disorder for inclusion in the classification of eating disorders. Future studies on the psychobiology of purging disorder are needed to understand the propensity to purge in the absence of binge eating.

Obsessive-compulsive characteristics in women who have recovered from bulimia nervosa.

OBJECTIVE: The goal of this study was to follow up on reports that obsessive-compulsive characteristics, which are commonly elevated in bulimia nervosa (BN), may also be elevated in individuals who have recovered from BN (BN-R). METHOD: Self-ratings on the Maudsley Obsessional-Compulsive Inventory (MOCI), the Restraint Scale (a measure of dieting behavior related to weight concerns), and questionnaires reflecting eating disorder-related symptoms were evaluated for women who met criteria for BN (n = 25) or BN-R (n = 21) and were free of obsessive-compulsive disorder, and for healthy female controls (n = 28). RESULTS: MOCI scores for the BN-R group (5.5 +/- 5.4) were similar to those for the BN group (5.4 +/- 4.4) and were significantly elevated (p < 0.05, p < 0.02, respectively) in comparison to controls (2.5 +/- 1.9). Of note, MOCI scores for the BN-R group were significantly correlated with scores on the Restraint Scale (r = 0.60, p < 0.02). CONCLUSION: Further studies are needed to assess the relationship between elevated obsessive-compulsive characteristics and eating patterns in individuals recovered from BN.

Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry.

The effects of type 1 diabetes and key metabolic variables on brain structure are not well understood. Sensitive methods of assessing brain structure, such as voxel-based morphometry (VBM), have not previously been used to investigate central nervous system changes in a diabetic population. Using VBM, we compared type 1 diabetic patients aged 25-40 years with disease duration of 15-25 years and minimal diabetes complications with an age-matched, nondiabetic control group. We investigated whether lower than expected gray matter densities were present, and if so, whether they were associated with glycemic control and history of severe hypoglycemic events. In comparison with control subjects, diabetic patients showed lower density of gray matter in several brain regions. Moreover, in the patient group, higher HbA(1c) levels and severe hypoglycemic events were associated with lower density of gray matter in brain regions responsible for language processing and memory. Our study represents the first comprehensive study of gray matter density changes in type 1 diabetes and suggests that persistent hyperglycemia and acute severe hypoglycemia have an impact on brain structure.

Effect of dieting on plasma leptin, soluble leptin receptor, adiponectin and resistin levels in healthy volunteers.

OBJECTIVE: Recent findings demonstrating important effects of the adipokines on metabolism, energy homeostasis and body weight regulation have prompted research on the possible role of negative energy balance in altering adipocytokine regulation. The goal of this study was to evaluate the effects of a hypocaloric diet in healthy normal-weight volunteers. An additional goal was to help clarify the contribution of restricted caloric intake to altered plasma adipokine levels in the eating disorders anorexia nervosa and bulimia nervosa. DESIGN: Participants were studied before and after a 4-week reduced-calorie diet (1000-12000 kcal/day). patients Subjects included 15 healthy, normal-weight women (age 22 +/- 3 years). MEASUREMENTS: Plasma concentrations of leptin, soluble leptin receptor protein (sOB-R), adiponectin, resistin, thyroid hormones and beta-hydroxybutyrate were determined following overnight fast before and after the 4-week reduced-calorie diet. RESULTS: Subjects lost a mean of 3.4 +/- 2.1 kg in response to the reduced-calorie diet. The weight loss phase was associated with a 60.3% decrease in plasma leptin levels (P < 0.001), a 43.5% increase in sOB-R levels (P < 0.002) and a 16.2% decrease in plasma adiponectin levels (P < 0.04). There was no significant change in plasma resistin levels. CONCLUSIONS: These results demonstrate that a modest decrease in energy intake sustained over several weeks may play an important role in altering levels of plasma leptin and sOB-R. The findings also provide preliminary evidence that, in contrast to previous results in obese subjects, caloric restriction with accompanying weight loss in healthy, normal-weight volunteers may lead to decreased circulating adiponectin levels. Additional studies will be needed to clarify the contribution of altered energy intake to abnormalities in cytokine levels in the eating disorders.

Neuropeptides in eating disorders.

The past decade has witnessed a dramatic acceleration in research on the role of the neuropeptides in the regulation of eating behavior and body weight homeostasis. This expanding research focus has been driven in part by increasing public health concerns related to obesity and the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN). Preclinical advances have been facilitated by the development of new molecular and behavioral research methodologies. With a focus on clinical investigations in AN and BN, this article reviews research on selected hypothalamic and gut-related peptide systems with prominent effects on eating behavior. Studies of the orexigenic peptides neuropeptide Y and the opioid peptides have shown state-related abnormalities in patients with eating disorders. With respect to gut-related peptides, there appears to be substantial evidence for blunting in the meal-related release of the satiety promoting peptide cholecystokinin in BN. Fasting plasma levels of the orexigenic peptide ghrelin have been found to be elevated in patients with AN. As discussed in this review, additional studies will be needed to assess the role of nutritional and body weight changes in neuropeptide alterations observed in symptomatic eating disorder patients, and to identify stable trait-related abnormalities in neuropeptide regulation that persist in individuals who have recovered from an eating disorder.

Report of the National Institutes of Health workshop on overcoming barriers to treatment research in anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is associated with serious medical morbidity and has the highest mortality rate of all psychiatric disorders. The National Institutes of Health (NIH) Workshop on Overcoming Barriers to Treatment Research in Anorexia Nervosa convened on September 26-27, 2002 to address the dearth of treatment research in this area. The goals of this workshop were to discuss the stages of illness and illness severity, pharmacologic interventions, psychological interventions, and methodologic considerations. METHOD: The program consisted of a series of brief presentations by moderators, each followed by a discussion of the topic by workshop participants, facilitated by the session chair. RESULTS: This report summarizes the major discussions of these sessions and concludes with a set of recommendations related to the development of treatment research in AN based on these findings. DISCUSSION: It is crucial that treatment research in this area be prioritized.