Feeding and Eating Disorders

Satiety

Serotonin has long been a focus of attention for its possible role in disrupted satiety. There is substantial evidence that altered 5-hydroxytryptamine (5-HT, serotonin) functioning contributes to dysregulated appetite, mood, and impulse control in EDs and that such alteration persists after recovery from AN and BN, possibly reflecting premorbid vulnerability. There also is evidence that CCK levels are altered in ED populations. Findings for AN are inconsistent. Although there is some evidence that young women with AN have high levels of pre- and postprandial CCK that may impede treatment progress by contributing to postprandial nausea and vomiting, other reports have shown decreased CCK compared with controls. In patients with BN, there is consistent evidence for an impaired satiety response, characterized by a blunted postprandial CCK response as well as delayed gastric emptying. In contrast, individuals with BED and obesity do not differ in postprandial CCK responses from those with obesity but no BED. The relationships between CCK, binge eating, and BMI warrant further clarification.

Peptide tyrosine (PYY), the intestinally derived anorexigen that elicits satiety, appears to be dysregulated in individuals with AN and BN, but not in those with BED. Young women with AN have higher levels of PYY compared with controls, perhaps contributing to reduced food intake. In individuals with BN, expected elevations in PYY after meals are blunted, possibly playing a role in impaired satiety. A recent report found no differences between BED and non-BED groups in fasting levels and postprandial changes in PYY. Women with BN have been found to secrete abnormally low levels of the GI satiety peptides glucagon-like peptide 1 and pancreatic polypeptide, which is thought to be a consequence of the adaptation to large meals in the form of enlarged gastric capacity and reduced muscle tone in the gastric wall. Attenuated secretion of these GI satiety polypeptides may play a role in maintaining bulimic behavior.

Appetite

The orexigenic peptide ghrelin is of interest in EDs because it is the only known GI hormone that stimulates appetite and promotes food intake. Ghrelin influences secretion of growth hormone, induces adiposity, and is implicated in signaling the hypothalamic nuclei involved in energy homeostasis. Gastric secretion of ghrelin is stimulated by a combination of neural (vagus nerve), mechanical (distension), chemical (osmolarity; caloric content and macronutrient composition of the meal) and hormonal (insulin) factors with unknown priority. Consistent findings in the literature examining ghrelin in patients with AN have shown that (1) circulating basal levels of ghrelin are elevated, a likely consequence of prolonged starvation ; (2) growth hormone and appetite responses to ghrelin are blunted, suggesting ghrelin resistance or altered ghrelin sensitivity ; and (3) ghrelin levels return to normal after partial weight recovery, suggesting a physiologic effect to compensate for lack of nutritional intake and energy stores. More recently, a randomized, double-blind, placebo-controlled trial using a ghrelin agonist in 22 outpatients with AN revealed that those treated with a ghrelin agonist demonstrated significantly decreased gastric emptying time, and a trend of greater weight gain after 4 weeks.

Plasma levels of ghrelin are normal or elevated in individuals with BN, which suggests that abnormal eating behaviors, including binge eating and purging, may influence ghrelin secretion ; there is a postprandial blunted response (i.e., reduced suppression of ghrelin) in these patients. The relationship between elevated ghrelin and binge eating in patients with BN requires further exploration. Investigations of ghrelin functioning in individuals with BED have reported lower circulating levels of pre- and postprandial ghrelin, possibly reflecting down-regulation in response to chronic overeating and smaller decreases in ghrelin after eating.

Energy Storage

Leptin and adiponectin are hormonal signals associated with longer-term regulation of body fat stores. Leptin is also directly implicated in satiety through its binding to the ventral medial nucleus of the hypothalamus, an area termed the satiety center . Leptin and adiponectin are both altered in patients with EDs. A number of studies have found evidence for hyperadiponectinemia and hypoleptinemia in populations of underweight AN with reversal following restoration of weight ; increased adiponectin levels may act protectively to support energy homeostasis during food deprivation. Individuals with BN also exhibit decreased plasma levels of leptin and increased levels of total plasma-adiponectin which are inversely correlated with longer duration of illness and increased severity of symptoms. The mechanism of altered leptin functioning in BN is unclear because blunted postprandial leptin levels are not observed in individuals with BED.

There are other mechanisms of interest including neuropeptide Y, peptides glucagon-like peptide-2, orexins A and B, the endocannabinoids, resistin (adipose tissue-specific secretory factor), and brain-derived neurotrophic factor, but more research is necessary to elucidate their roles in the pathophysiology of EDs. One high priority for research is clarifying whether observed psychobiological abnormalities are antecedents or consequences of disturbed eating behavior that return to normal after recovery; this information could shed light on cause and possible treatment targets. Patients often report intense discomfort after eating as a reason they continue to restrict intake. The discomfort may be dismissed as perceptual or psychological in the absence of any medical findings to support the symptoms, but there may be disruptions in CNS or peripheral signals contributing to this and other reported symptoms.

Anorexia Nervosa

AN is characterized by a significantly low weight (the weight that is less than minimally normal), fear of gaining weight (despite being thin), and a disturbance in the way body shape or weight is perceived (e.g., a denial of the medical seriousness of being underweight or feeling fat despite emaciation). It is not uncommon for an individual with AN to deny or minimize fear of weight gain at initial evaluation (and sometimes an apparent absence of this fear persists). Even if a patient does not admit or disclose an intense fear of weight gain, evidence of continuing behaviors that undermine weight gain (e.g., restrictive eating, purging, excessive exercising) may be used to establish this criterion. Individuals with AN typically restrict their food selections and caloric intake, but about half of those with AN also routinely binge eat and/or engage in inappropriate purging behaviors like self-induced vomiting or laxative use to prevent weight gain ( Box. 9.1 ). AN is further divided into 2 subtypes: restricting type (those who primarily control their weight through dieting, fasting, or exercising) and binge-eating/purging type (those who routinely purge calories to control weight and/or routinely binge eat). In middle-aged and older women new-onset AN may present in conjunction with difficulty making life transitions and fear of aging. The diagnosis of AN may be delayed when patients present to a GI specialty practice without disclosing their concerns and behaviors relating to weight. Presentation with GI complaints, even if related to real symptoms or disease, can sometimes prove to be a “red herring,” drawing attention away from and delaying diagnosis of an ED. One study of 20 consecutive patients who presented to a GI practice and ultimately were diagnosed with an ED found the diagnosis of an ED was delayed for an average of 13 months after presentation. Notably, all patients stated a desire to gain weight and denied attempts to lose weight via exercise, purging, or dietary restriction. Individuals with AN are not always able or willing to frame their difficulty maintaining a healthy weight as intentional, so diagnosis may initially be unsuspected and delayed.

Bulimia Nervosa

The clinical hallmark of BN is recurrent binge eating accompanied by inappropriate compensatory behaviors to control weight or to purge calories consumed during a binge (see Box 9.1 ). On average, these behaviors must occur once each week for at least 3 months to meet diagnostic criteria. Also intrinsic to the diagnosis of BN is the excessive influence of weight and/or shape on self-image. Individuals with BN have poor self-image that is often anchored to their weight. It is not unusual for individuals with AN or BN to weigh themselves daily, even several times each day, and to experience fluctuations in self-esteem and mood based on the result.

By definition, binge eating is consumption of an unusually large amount of food during a “discrete period of time” (i.e., not overeating or “grazing” all day), accompanied by the feeling that the eating cannot be controlled. Many patients describe an emotional numbing during the period of eating; for some, this state appears to motivate the bingeing. Most clinicians are familiar with self-induced vomiting as the primary purging behavior, but individuals with BN may also use alternative or additional means to prevent weight gain, including abuse of laxatives and/or enemas, diuretics, stimulants (including methylphenidate, cocaine, over-the-counter “natural” supplements, and caffeine), under-dosing of insulin (for those with diabetes mellitus), fasting or restrictive eating, and excessive exercise (see Box 9.1 ). In adolescents with celiac disease, intentional consumption of gluten to promote weight loss has also been reported. Whereas most individuals with BN use compensatory behaviors that include purging, those who only use excessive physical activity or fasting are more challenging to identify. As with overeating and dieting, it is frequently difficult to determine the line between culturally normative and pathologic behavior with excessive exercise. Generally, clinical suspicion should be raised when an individual continues to exercise despite an injury or illness, or if he or she is exercising routinely in excess of what a coach is advising for the team.

It is recommended that clinicians ask about purging behaviors if an ED is suspected. Although it is not certain that a patient will respond candidly, individuals are more likely than not to eventually disclose information about symptoms when asked. Some patients report feeling relieved when clinicians pose such questions if they previously had not been able to discuss their symptoms. On occasion, however, patients report learning about techniques from clinicians’ questions, so it is advisable for clinicians to provide a psychoeducational context for the questions (e.g., by conveying serious physical consequences associated with the behavior) and to avoid introducing information about a dangerous behavior (e.g., under-dosing insulin), using appropriate discretion based upon the clinical context. Patients also benefit from learning that treatment is available and effective, and from feeling understood by their clinicians.

Whereas purging and other behaviors aimed at neutralizing or decreasing calorie intake and modifying weight can pose medical risks when chronic, some of them pose more immediate and potentially lethal consequences. Patients should be educated about these acute life-threatening risks, and steps should be taken to eradicate such behaviors immediately. For example, because of the serious neurotoxicity, cardiotoxicity, and risk of death associated with repeated ingestion of syrup of ipecac, its ongoing use is a clinical emergency and may require immediate hospitalization. Many patients are unaware of the serious risk associated with syrup of ipecac use. Similarly, ephedra, now banned in the US, poses risk of stroke or adverse cardiac events even in young adults. Some ephedra-free supplements marketed as weight-loss agents may also be pro-arrhythmic and pose medical risks. Although patients find it difficult to abstain from purging behaviors, they may be willing to substitute less immediately harmful behaviors while treatment is initiated.

Binge-Eating Disorder

BED is characterized by recurrent and persistent binge eating. To meet diagnostic criteria, binge episodes should occur at least weekly, on average, over a duration of 3 or more months. Unlike BN, BED is not associated with recurrent inappropriate compensatory behaviors to prevent weight gain. BED is distinguished from non-pathologic overeating by several possible associated symptoms including rapid eating, eating irrespective of hunger or satiety eating alone because of shame, and negative feelings after a binge. Apart from overweight or obesity, which is common in BED, BED patients frequently present without any specifically associated physical findings. Although in some cases binge eating associated with BED may cause or perpetuate weight gain, many with BED develop symptoms only after they have become overweight. Individuals with BED are frequently distressed enough about their symptoms to seek medical help, although they may present seeking a solution to their weight gain rather than their binge eating. A substantial percentage of patients who seek weight loss treatment will have comorbid BED. Therefore, medical subspecialists are likely to encounter these patients before they have been diagnosed with BED.