Biological Aspects of Anorexia Nervosa and Bulimia Nervosa - PsycNET

2 downloads 0 Views 846KB Size Report
Department of Psychiatry, Toronto General Hospital. Toronto, Ontario, Canada. In this article, we review biological factors relevant to the understanding of ...
Journal of Consulting and Clinical Psychology 1987. Vol. 55. No. 5, 645-653

Copyright 1987 by the American Psychological Association, Inc. 0022-006X/87/S00.75

Biological Aspects of Anorexia Nervosa and Bulimia Nervosa Allan S. Kaplan and D. Blake Woodside

This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

Department of Psychiatry, Toronto General Hospital Toronto, Ontario, Canada

In this article, we review biological factors relevant to the understanding of anorexia nervosa and bulimia nervosa. We consider the physical presentation of these disorders; the medical complications of starvation, hinging, and purging; and the cognitive and behavioral effects of starvation. We also review neurophysiotogical and neurochemical aspects of these illnesses and their biological treatments. These biological variables are most prominent in the perpetuation of the eating disorders. Effective treatment approaches must consider psychosocial as well as biological variables to be optimally effective.

the starvation state. Third, we will review the possible biological bases for these changes by examining the current ideas regarding neurophysiological and neurochemical aspects of the illnesses. Finally, we will conclude with a brief review of the recent advances in biological therapies.

Over the past two decades, we have increased our awareness of the eating disorders, anorexia nervosa and bulimia nervosa. During this time, our attention has been focused on biological, psychological, and social variables that affect the predisposition for and the course of these illnesses. This article will focus on some of the biological aspects of these disorders and will emphasize recent research. However, these aspects of the illnesses must be considered in the context of the wider sociological and psychological variables that have been described (Garfinkel & Garner, 1982). Historically, early attention was focused on the hormonal changes observed in anorexia nervosa and bulimia nervosa. Initially, these illnesses were thought to be the clinical manifestation of underlying pathological processes within the pituitary gland (Simmonds, 1914). By the 1940s, it had been established that anorexia nervosa and bulimia nervosa were not a result of pituitary failure, and researchers attempted to explain the illnesses with psychoanalytic thought. Although psychoanalytic thinking provided many valuable insights into some of the predisposing and precipitating factors in the illnesses, the therapies derived from psychoanalytic models proved ineffective, both in altering the core psychopathological disturbances and in normalizing eating behavior. More recent work has begun to examine whether the biological abnormalities found in these disorders are secondary to the effects of starvation or whether they represent some underlying, primary, pathophysiological disturbance that will serve to explain the pathogenesis of the illnesses. This article will focus on the biological abnormalities found in anorexia nervosa and bulimia nervosa. First, we will comment on the medical complications that may arise in the course of the illnesses. Second, we will focus on the cognitive and behavioral changes that are believed to occur as a direct result of

Medical Complications of Anorexia Nervosa and Bulimia Nervosa The medical effects of chronic starvation have been extensively studied. Keys, Brozek, Henschel, Michelsen, and Taylor (1950) studied the effects of carefully monitored semistarvation on a group of volunteers. These individuals, all male, eventually demonstrated most of the physical signs and symptoms of anorexia nervosa. Although many of these signs and symptoms are not pathognomonic to the illness but are secondary to starvation, it is important to be aware of them because they may reflect evidence of serious medical illness. We will discuss (a) the medical complications that are related directly to the starvation state and (b) those that are related more closely to bulimic behavior.

Starvation-Related Complications General Appearance A dramatic description of anorexia nervosa was provided by Allbutt(1910): A young woman thus afflicted, her clothes scarcely hanging together on her anatomy, her pulse slow and slack, her temperature two degrees below the normal mean, her bowels closed, her hair like that of a corpse dry and lustreless, her face and limbs ashy and cold, her hollow eyes the only vivid thing about her (p. 398)

This work was partially supported by the Medical Research Council of Canada, the Ontario Mental Health Foundation, and the National Institute of Nutrition of Canada. The authors would like to thank Linda Westecott for her help in article preparation. Correspondence concerning this article should be addressed to Allan S. Kaplan, Eating Disorder Centre, Toronto General Hospital (CW I, Room 313), 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.

The most striking feature of most patients is their gaunt, emaciated appearance. Many patients will have lost as much as 35% of their premorbid weight, and despite their emaciation, they continue to be excessively active. Additionally, patients often look pale, which may be due to an underlying anemia. 645

646

ALLAN S. KAPLAN AND D. BLAKE WOODSIDE

Dermatological Changes

duced stature and delayed bone maturation, which again is secondary to starvation. Recently, bone abnormalities with osteo-

The skin is extremely sensitive to nutritional change. Most patients have dry, cracking skin, which is probably related both to dehydration and to loss of subcutaneous fat. Scalp hair has

porosis and pathologic fractures have been described in chronically underweight anorexics (Brotman & Stern, 1985; Rigotti, Nussbaum, Herzog, & Neer, 1984).

often thinned and may be dull and lustreless. Axillary and pubic hair is usually unchanged. A fine, downy type of hair, known as lanugo hair, may appear on the face and neck. The fingernails and toenails become brittle. The hands and feet may take on a dusky, bluish color, which is due to cyanosis. Breast tissue is usually reduced. Some patients may show a yellowish discolor-

This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

ation in their skin, known as carotene pigmentation, which may persist for years after weight is restored. This pigmentation is related to a starvation-induced defect in liver carotene metabolism (Russell, 1970).

Medical Complications Related to Singing and Purging Local or Mechanical

Effects

Dermatological changes. In patients who chronically vomit, a callus may be observed on the back of the hand (Russell, 1970). This is due to irritation of the skin by the teeth during repeated attempts to induce vomiting manually. There also may be callus formation below the ribs due to repeated irritation while applying abdominal pressure to facilitate vomiting. The

Cardiovascular Changes Most patients who are starved show bolh bradycardia (heart rate < 60 beats/min) and hypotension. Many patients have orthostatic hypotension, a temporary dizziness upon moving from a sitting to a standing position that may result in blackouts. In addition to the peripheral cyanosis noted previously, many patients have swelling of the feet and ankles, and some patients have arrhythmias, which may result in palpitations, that are detectable by electrocardiography.

Gastrointestinal Changes Patients who are starved have a general reduction in the activity of the bowel. This can cause delays in stomach emptying (thus prolonging a sense of fullness after a meal) and a slowing of other bowel activity. Reduced bowel activity may actually proceed to a total paralysis, or ileus, of the bowel. Patients are usually constipated, as a result both of this condition and of dehydration. Postprandial symptoms, such as the abdominal pain, bloating, and early satiety described by patients with eating disorders, may be a function of this altered physiology. Pancreatic insufficiency, which has been described in extreme cases of malnutrition but has not been studied specifically in eating

skin around the mouth may be red and irritated due to repeated contact with stomach acid. Gastrointestinal changes. Repeated episodes of vomiting tend to cause parotid gland enlargement, which appears as swelling in front of and below the ears. This is probably secondary to the disruption or blockage of salivary ducts leading into the mouth. Accompanying parotid enlargement is often an elevated level of the enzyme amylase in the blood. The source of the amylase is more often salivary than pancreatic (Kaplan, 1987). Tooth enamel is eroded by continual contact with stomach acid, and dental caries are common (Andrews, 1982). Abdominal pain may be directly related to binging and vomiting. Many patients develop hiatus hernia and complain of abdominal pain. Large binges may stress the pancreas and may lead to pancreatitis (Rampling, 1982), which may create a medical emergency. Repeated binging and vomiting may cause esophageal (Schechter, Altemus, & Greenfeld, 1986) or gastric (Mitchell, Pyle, & Miner, 1982) dilatation and even rupture, which may be fatal. Extensive use of laxatives may cause bloody diarrhea. Some patients become laxative-dependent and cannot have bowel movements without them. The extreme result of chronic laxative abuse is a totally flaccid and nonresponsive bowel.

disorders, may interfere with weight gain on refeeding in chronically emaciated anorexics and may perpetuate the illness (Du-

Metabolic

Effects

ne etal., 1985). Some patients complain of generalized muscular weakness.

Endocrine Changes

This is usually due to decreased levels of potassium. Potassium

Female patients who have lost more than 15% of their normal

is lost through repeated episodes of vomiting or laxative abuse. The loss of potassium may become serious enough to cause pal-

body weight tend to develop menstrual irregularities, including

pitations, arrhythmias, and sudden death. Such reductions in

amenorrhea. This is probably related to loss of body fat, but other factors also play a role. Underweight anorexics sometimes

potassium are particularly common in patients who abuse di-

show hypothermia or a reduced body temperature, which is an attempt by the body to reduce energy expenditure.

uretics in an effort to lose weight. Potassium supplements are sometimes required to correct the hypokalemia. Binging and purging may lead to amenorrhea, or irregular menses. This may relate to chaotic nutrient intake, which could

Musculoskelelal Changes A generalized muscular weakness is noted in most emaciated

alter neurotransmitter levels. Patients may also have a reduced sensation to pain, possibly due to elevated endorphin levels (Kaye, Pickar, Ebert, & Naber, 1983).

patients. This can be secondary to the destruction of muscle

The same electrolyte abnormalities that cause arrhythmias

tissue needed for nutrients and also to electrolyte abnormalities due to dehydration and nutritional imbalance. In patients who

may also lead to peripheral edema. There are many possible causes for edema in patients with eating disorders: low protein levels, excessive periods of time spent standing, or even binging

have manifested the illness from an early age, there may be re-

647

SPECIAL SERIES: BIOLOGICAL ASPECTS

This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

on large quantities of salty foods. Patients who abuse ipecac to induce vomiting may develop a cardiomyopathy (Palmer & Quay, 1985). Emetine, the active ingredient in ipecac, destroys heart muscle fibres, and this can lead to heart failure. Finally, abnormalities of serum sodium may lead to convulsions. These are also common in individuals who include large quantities of alcohol in their binges. Patients who fit the high-risk profile for serious medical complications as the result of an eating disorder (a) are chronically ill; (b) are underweight; (c) vomit daily; (d) binge daily; (e) use laxatives, diuretics, ipecac, or amphetamine for weight control; or (f) have coexisting medical conditions such as diabetes or seizure disorder.

copious amounts of coffee and water. Subjects tended to combine foods oddly and to use spices heavily. The men spent hours dawdling over minute meals. All of these behaviors are common in patients with anorexia nervosa and bulimia nervosa, many of whom also attach specific rituals to their eating behavior, such as eating alone or eating in the dark (Garfinkel & Garner, 1982). A significant proportion of subjects in the Keys et al. (1950) study began to binge eat and continued to do so even after the period of experimental starvation had ended. Patients who restrict themselves from eating certain foods tend to develop preoccupations with those foods, and if they binge, they tend to binge on the foods they normally exclude. This usually results in a vicious cycle of repetitive restriction—binging—purging.

Eating Disorders and Other Medical Conditions The concomitant occurrence of eating disorders with other medical conditions can lead to difficult diagnostic and therapeutic problems. There have been reports of diabetes and bulimia nervosa occurring with higher than expected frequency (Rodin, Johnson, Garfinkel, Daneman, & Kenshole, 1986; Szmukler & Russell, 1983). This may be true for other medical conditions as well. Such occurrences often lead to complications and difficulties in the management of both disorders. In such patients, a close liason between therapist and physician is important for optimum care. Cognitive and Behavioral Effects of Starvation The cognitive and behavioral effects of starvation are particularly important because they can mimic symptoms of other serious psychiatric illnesses, such as affective, obsessive, compulsive, and even psychotic disorders. The personality changes accompanying starvation cannot be overemphasized; the diagnosis of personality disorders in starved subjects is particularly unreliable. As with the medical complications of starvation, the changes described here are likely to be seen in an individual who is starved, for any reason, and are not pathognomonic for anorexia nervosa or bulimia nervosa. Bulimic patients are often biologically starved, even when they are at a normal weight, because they are generally under a naturally determined premorbid overweight state (Garfinkel, Moldofsky, & Garner, 1980). The cognitive and behavioral effects of starvation are significant perpetuating factors in anorexia nervosa and bulimia nervosa. Psychodynamic therapies are generally ineffectual in reversing these effects, and refeeding has to occur for patients to be psychologically accessible.

Mood and Personality Keys et al. (1950) noted that subjects became extremely irritable and that quarrels among the men became common. Subjects also demonstrated extreme lability of mood, with rapid changes from depression to exaltation. At times, they demonstrated ambivalence and flat affect. Two subjects suffered clinical "breakdowns," and I subject began to mutilate himself. These men showed clear pathologic changes in mental state. Because of the effects of starvation on mood, diagnosing affective illness in starved patients is almost impossible. Starvation tends to exaggerate premorbid personality traits such as obsessiveness, compulsivity, hypochondriasis, and indecisiveness. Although it has occasionally been suggested that anorexia nervosa and bulimia nervosa are variants of obsessivecompulsive disorders (Rothenberg, 1986), it is more likely that obsessive thoughts and compulsive behaviors are increased in starvation generally. This was noted in the Keys et al. (1950) study when some men became intensely preoccupied with food and chewed up to 60 packs of gum per day, initially to alleviate hunger. However, the behavior continued compulsively even when the goals were not met and when the behavior resulted in severe jaw pain. The hoarding of food and nonfood items was also observed. Cognition Many starved individuals display impaired concentration and alertness. The Keys et al. (1950) subjects were distractable, apathetic, and lethargic. They could think only about food. For many patients, the restriction they practice represents being in control, and the starvation-induced impairment in concentration is so distressing that they further starve to feel more in control, thus worsening the cognitive symptoms.

Food and Eating Behavior Most patients who are starving are extremely preoccupied with food. Keys et al. (1950) noted that his semistarved subjects spent hours planning how they would deal with their day's tiny allotment of food. Many began reading cookbooks and collecting recipes, and several decided to become chefs after the experiment. Food became the exclusive topic of conversation. Subjects demonstrated increased gum chewing, smoking, and nail biting. They attempted to keep their stomachs full by drinking

Sleep and Libido The men in the Keys et al. (1950) study had marked insomnia, despite feelings of tiredness and lethargy. They also reported a marked decrease in sexual interest, activity, and fantasy, and they ceased masturbating. This loss of libido is common in patients with anorexia nervosa. Crisp, Stonehill, and Fenton (1971) noted that sleep changes are regularly observed in starvation, including early morning

This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

648

ALLAN S. KAPLAN AND D. BLAKE WOODSIDE

awakening, and that these changes are not related to affective state. Crisp and Stonehill (1971) noted a decrease in slow-wave sleep that returned to normal upon refeeding. The importance of the cognitive and behavioral changes noted here is primarily related to diagnostic issues and to the perpetuation of the disorder; once established, the disorder develops a life of its own because of these starvation-related symptoms. The most compelling evidence for this has resulted from experiments in which starved subjects have been re-fed. In the Keys et al. (1950) study, many subjects required up to 1 year of rehabilitation prior to recovering. It is well-recognized that, in patients with anorexia nervosa, a return to normal weight and nutritional balance is an essential but not necessarily sufficient condition for long-term recovery. However, psychological treatment aimed at dealing with underlying characterological deficits or conflicts without addressing specific attitudes toward weight, body shape, and eating does not lead to weight gain and the resolution of starvation symptoms. Such psychotherapy used to treat an underweight, starved patient can be supportive but is rarely mutative. Neurophysiological Aspects of Anorexia Nervosa and Bulimia As mentioned previously, many of the hormonal and neuroendocrinological abnormalities noted in anorexia nervosa and bulimia nervosa are thought to be secondary to the effects of starvation, to the altered pattern of macronutrient intake, or to the binge-purge cycle. However, we should examine such abnormalities in the hope of identifying those that are not epiphenomena of these factors but, instead, reflect underlying biological pathogenetic variables. Most recent investigations have focused on five main areas: (a) the hypothalamic pituitary axis, (b) central nervous system amines, (c) central nervous system peptides, (d) carbohydrate metabolism, and (e) gastrointestinal hormones. Hypothalamic-Pituitary Axis The hypothalamus, in concert with the pituitary gland, is responsible for the regulation of most of the body's hormonal activity. The hypothalamus, in response to neural and hormonal activity, releases releasing factors that are carried to the pituitary, where various stimulating factors are synthesized. Two strategies have been used to examine the hypothalamicpituitary axis: first, to study the organ system that is ultimately affected by the axis; second, to study the axis itself. Reproduction and Menstruation The preponderance of women with anorexia nervosa and the occurrence of amenorrhea as an important sign of the illness has led to intense investigation in this area. Amenorrhea is required by several investigators (Feighner et al., 1972; Russell, 1970) for the diagnosis of anorexia nervosa. Only 5%-10% of patients have primary amenorrhea (Garfinkel et al., 1980). The onset of menstruation usually occurs at a normal age, although Crisp (1970) suggested that menarche occurs earlier in patients who develop anorexia nervosa.

Although the amenorrhea present in anorexia nervosa can be substantially explained on the basis of weight loss, some confounding data exist in this regard. It is known (Frisch, 1977) that a critical level of body fat (in the range of 17%) must be present for menarche to occur and that a higher level (approximately 23%) is needed to maintain regular ovulation (Frisch & McArthur, 1974). It is possible that reduced levels of body fat decrease the sensitivity of the hypothalamus to other influences that drive it to produce normal menstruation and ovulation. However, it must be noted that amenorrhea occurs before significant weight loss in about 20% of patients. It is unclear whether this reflects a hypothalamic disturbance or whether it is secondary to some other variable, such as abnormal eating patterns or a general state of emotional upset. The relation between amenorrhea and low body weight has also been demonstrated in normal populations and has been associated with other factors. Sustained and frequent exercise, even in the presence of normal body weight and body fat, has been associated with amenorrhea (McArthur et al., 1980). Patients who have anorexia nervosa or bulimia nervosa do not always resume menstruation once they have returned to their premorbid weights. Between 50%-75% of patients resume menstruation once their weight has been returned to 90% of the average for their age and height (Garfinkel, Moldofsky, & Garner, 1977). There is some evidence (Halmi & Falk, 1983) that individuals who do not resume normal menses are more involved in anorexic behavior as a whole, are more afraid of weight gain, and show more obsessive-compulsive behavior. Menstrual abnormalities also occur in normal-weight bulimics. Perhaps as many as one third of such patients have highly erratic menstruation (Fairburn & Cooper, 1984). The cause for this is not clear; it may be that, although these individuals fall within the statistical weight norms set for their age and height, they are below their biologically determined set-point for weight and thus have borderline levels of body fat. Alternatively, irregular eating patterns may alter brain neurotransmitter levels in some way to change the release of hypothalamic hormones. The pituitary hormones that control menses and ovulation are luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Underweight patients with anorexia nervosa demonstrate patterns of LH and FSH similar to those seen in prepubertal or pubertal girls (Katz, Boyar, Rofrwarg, Hellmans, & Weiner, 1978). These levels occur when amenorrhea is secondary to weight loss for other reasons (Kapen, Sternthal, & Braverman, 1981) but do not occur when amenorrhea is not associated with weight loss (Yen, Tsai, & Naftolin, 1975). Some actively symptomatic anorexic patients who are weight-recovered show persistently immature hormonal patterns that return to normal when clinical recovery has occurred. Two points must be noted here: First, symptomatic patients may persist with amenorrhea despite a return to normal weight; second, these abnormal hormone patterns might be a biological risk factor that predisposes patients to anorexia nervosa (Garfinkel & Garner, 1982). Absolute levels of estrogen and testosterone are reduced in both male and female patients (Russell, 1965). This may explain the observed loss of libido in underweight anorexics; however, it does not indicate a need for treatment with estrogen or

SPECIAL SERIES: BIOLOGICAL ASPECTS

testosterone. No studies examining gonadotropins in normalweight bulimics have been published. In summary, it has been suggested that the process of recovery from anorexia nervosa recapitulates puberty (Donovan & Van Der Werfften Bosch, 1965). As in puberty, the time course of recovery is variable, with a prompt return of menses in some patients and a slower return in others.

649

to this test, including normal (Brown et al., 1977) delayed (Wakeling, DeSouza, Gore, Sabrin, & Kingstone, 1979), and blunted responses (Gwirtsman et al., 1983). The significance of these findings remains unclear. However, simple weight loss has been associated with abnormal TSH responses to TRH (Fichter etal., 1986). Thermoregulation

This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

Cortisol Secretion Cortisol secretion is disturbed in patients with anorexia nervosa and possibly in patients with bulimia nervosa. Most patients with anorexia nervosa have elevated morning plasma cortisol levels (Brown, Garfinkel, Jeuniewic, Moldofsky, & Stancer, 1977), with preservation of (Boyar et al., 1977) or flattening of (Garfinkel, Brown, Stancer, & Moldofsky, 1975) diurnal variation at a higher level. One questionable theory proposes that anorexia nervosa is caused by a state of hypercortisolism and recommends treatment with cortisol antagonists (Sapse & Parsons, 1985). However, the available scientific evidence suggests that hypercortisolism is not a cause of the illness but is probably a result of weight loss (Doerr, Fichter, Pirke, & Lund, 1980). This activation of the hypothalamic pituitary axis (HPA) is probably responsible for abnormalities seen in the dexamethasone suppression test (DST). Considerable material has been written regarding the use of this neuroendocrine test in patients with psychiatric disturbances, including the eating disorders. The majority of patients with anorexia nervosa do not suppress normally (Gerner & Gwirtsman, 1981). Abnormal results seem to be related to weight loss and have also been seen in nondepressed patients who have lost weight for other reasons (Fichter, Pirhe, & Holsboer, 1986). In patients with normal-weight bulimia nervosa, abnormal results on the DST have been reported in 20%-60% of patients (Gwirtsman, Roy-Byrne, Yager, & Gerner, 1983; Kaplan, Garfinkel, Warsh, & Brown, 1986; Musisi & Garfinkel, 1985). The meaning of these abnormal results is unclear but could relate either to abnormal eating patterns or to a biologically underweight state (despite maintenance of normal weight based on average body weight). Thyroid Patients with anorexia nervosa may have low levels of thyroid hormone, especially serum triiodothyronine (serum T3) (Moshang & Utiger, 1977). The same abnormality is found in patients suffering from malnutrition from any cause and in individuals who lose weight rapidly. In starvation states, the reduction in thyroid hormone is a normal adaptation to a condition of low metabolic need due to caloric deprivation (Moshang & Utiger, 1977). Thyroid hormone can be abused by patients to increase their basal metabolic rate and to facilitate weight loss (Binswager, 1944). The hypothalamic-pituitary-thyroid axis has been studied in patients with eating disorders. The pituitary thyroid stimulating hormone (TSH) response to the hypothalamic thyroid releasing hormone (TRH) is an investigative challenge test that examines this axis. Patients with both anorexia nervosa and bulimia nervosa have been found to show a variety of responses

The hypothalamus maintains basal body temperature through a variety of mechanisms. Patients with anorexia nervosa are known to have reduced basal temperatures (Wakeling & Russell, 1970) and show an inability to compensate for changes in temperature. This abnormality is also found in patients who have lost weight for other reasons and is reversible with weight gain. Growth Hormone Some patients with anorexia nervosa have been found to have elevated levels of growth hormone that return to normal upon recovery (Brown et al., 1977). This is common in individuals receiving a reduced caloric intake and does not indicate a need for treatment with synthetic growth hormone.

Summary Hypothalamic-pituitary function is disturbed in patients with eating disorders. This disturbance is mediated by several mechanisms that are generally secondary to the effects of the disordered eating. Some disturbances, such as abnormalities in thermoregulation, TSH response to TRH, and gonadotropin levels, relate directly to weight loss and are seen in other states of emaciation regardless of the cause. Other disturbances, such as abnormalities in resting growth hormone and plasma T3, are secondary to caloric deprivation. Finally, some abnormalities, such as amenorrhea, may reflect the effects of weight loss, disordered eating, or other factors that are not yet understood. Central Nervous System Amines Several central-nervous-system amines act as neurotransmitters, such as serotonin, norepinephrine, and dopamine. The precise manner in which neurotransmitters control the release of hypothalamic and pituitary hormones is complex and is not well-understood. It is reasonable to say that all such hormones are under some neurotransmitter control. There is also significant evidence, especially from animal literature, that neurotransmitters are directly implicated in the control of feeding behavior. Serotonin seems to inhibit feeding by inducing satiety, whereas norepinephrine stimulates feeding by its activity in the medial hypothalamus and paraventricular nucleus and inhibits feeding through its action on the lateral hypothalamus (Liebowitz, 1983). Dopamine may stimulate eating by its activity in the lateral hypothalamus (Ungerstadt, 1971). Neurotransmitters may be affected by the availability of certain nutrients. Serotonin, for example, is partially regulated by the availability of dietary tryptophan (Biggio, Fadda, Fanni, Tagliamonte, & Gessa, 1974). It has been implied that serotonin plays a role in the regulation of mood, pain, sleep, appetite,

This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

650

ALLAN S. KAPLAN AND D. BLAKE WOODSIDE

and the control of some hypothalamic and pituitary hormones. These functions have all been found to be disturbed in patients with eating disorders. Plasma tryptophan has, in fact, been found to be lower in anorexia nervosa patients (Coppen et al., 1976), which indicates a possible reduction in the availability of serotonin in the brain. Although several drugs affecting levels of central serotonin have been tested in the treatment of anorexia nervosa. none have been consistently successful. Monoamine oxidase inhibitors (phenelzine, tranylcypramine) have been used with some success in the treatment of bulimia nervosa (Walsh, Stewart, Roose, Gladis, & Glassman, 1984). These drugs, in addition to their other properties, inhibit the breakdown of serotonin. Several drugs that affect serotonin metabolism are potentially useful in altering hunger and fullness. Examples of such drugs include fenfluramine (Robinson, Checkly, & Russell, 1985) and cyproheptadine (Goldberg, Halmi, Eckert, Casper, & Davis, 1979). Studies of norepinephrine have focused primarily on the products of norepinephrine metabolism, with the rationale being that the levels of these metabolic products reflect, at least in part, the activity of the central norepinephrine systems. The levels of such metabolites have been found to be low in depressed patients (Garfinkel, Warsh, & Stancer, 1979) and in untreated patients with anorexia nervosa (Gross, Lake, Ebert, Ziegler, & Kopin, 1979). However, changes in these levels have been reported to be independent of mood in anorexic patients (Gerner & Gwirtsman, 1981) and to return to normal levels upon refeeding (Gross et al., 1979). Kaye, Ebert, Raleigh, and Lake (1984), however, noted that although cerebrospinal fluid (CSF) norepinephrine levels returned to normal within a few weeks after weight recovery in anorexia, at long-term followup, weight-recovered anorexics were found to have significantly decreased CSF norepinephrine levels compared with control subjects. Norepinephrine systems are also known to interact with endorphins and to be affected by exercise and body-fat levels. There have been reports of weight-related reductions in plasma dopamine (Halmi, Dekirmenjian, Davis, Casper, & Goldberg, 1978), but the significance of these findings is not clear. Central Nervous System Peptides Endorphins and Enkephalins Endorphins and enkephalins play an important role in regulating the pituitary gland. These proteins may act as neurotransmitters and are structurally similar in some ways to opiates. Endorphins have been implicated in pain control, in addictive behaviors, and in the control of eating. There is a considerable body of evidence linking opioids to eating behaviors. Endorphins have been found to be elevated in genetically obese rats (Margules, Moisset, Lewis, Shibuya, & Pert, 1978) and have stimulated food intake when injected into the ventromedial hypothalamus of satiated rats (Grandison & Guidotti, 1977). Naloxone, an opiod antagonist, has been shown to reduce food intake in deprived rats, to abolish the overeating of genetically obese rats (Holtzman, 1974), and to cause loss of weight and appetite when administered to humans

(Hollister, Johnson, Bookhabzer, & Gillespie, 1981). A recent open trial with naltrexone showed significant decreases in binge episodes in bulimic patients (Jonas & Gold, 1986). Starvation has been known to increase opioid release. Kaye, Pickar, Naber, and Eberl (1982) found higher levels of opioids in the spinal fluid of patients with anorexia nervosa who were severely underweight than in the same patients whose weight had been restored or in normal control subjects. Such increased levels lead to increased appetite, which could be responsible for some of the abnormal food-related behavior seen in starved people. Two recent studies have reported conflicting data in this area: Fullerton, Swift, Gerro, and Carlson (1986) reported elevated plasma B-endorphin levels, whereas Waller et al. (1986) reported lowered plasma B-endorphin levels in bulimics compared with control subjects. Faltus (1983) reported that one study found a drop in opioids in anorexics but not in normal subjects after insulin-induced hypoglycemia. This drop could produce dysphoria and may explain the postprandial discomfort experienced by anorexics (Garfinkel & Kaplan, 1985). Argenine Vasopressin Vasopressin, the substance responsible for water balance, may also play a role in memory consolidation (DeWied, 1971). Gold, Kaye, Robertson, and Ebert (1983) found that anorexic patients had erratic patterns of Vasopressin release. It is possible that this abnormality may be responsible for some of the cognitive changes seen in anorexia nervosa and bulimia nervosa patients (Garfinkel & Kaplan, 1985). Carbohydrate Metabolism The distorted perception of food shared by patients with anorexia nervosa usually leads to diets markedly deficient in fats and carbohydrates because they attempt to avoid fat or calorierich foods. As a result, anorexic patients may have abnormally low levels of serum glucose and may be diagnosed as hypoglycemic. However, this condition is directly related to starvation and reverts back to normal on refeeding (Russell & Bruce, 1964). In states of extreme starvation, the body may become so glucosedeficient that a change will occur in the body's metabolism. Instead of using sugar as the preferred fuel source, the body may switch to ketone bodies, a by-product of fat metabolism. This can markedly effect cognition and alertness. In some patients, abnormal responses to insulin have been found. These include both insulin resistance (Beumont, George, Pinstone, & Vinik, 1976) and insulin sensitivity (Mecklenburg, Loriaux, Thompson, Anderson, & Lipsett, 1974). Some of these effects may be secondary to starvation (Waschlicht-Rodbard. Gross, Rodbard, Ebert, & Roth, 1979). Gastrointestinal Hormones The gastrointestinal tract is much more active in secreting hormones than has previously been known. Although the function of many of these hormones is poorly understood, some, such as cholecystokinin (CCK), are located both in the gut and the brain. Cholecystokinin has been found to be involved in satiety regulation (Bennett & McMartin, 1979). As mentioned

651

SPECIAL SERIES: BIOLOGICAL ASPECTS

previously, gut motility is often impaired in patients with eating disorders. Clinically, this is evidenced by complaints of bloating, dyspepsia, and early satiety. Agents that speed gastric emptying, such as domperidone or metoclopramide, may be useful in providing some symptomatic relief and may assist in the refeeding process (Russell et al., 1983).

This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

Biologic Treatment of Anorexia Nervosa and Bulimia Nervosa Medical therapies for anorexia nervosa and bulimia nervosa include both generally accepted and more experimental treatments. The generally accepted therapeutic modalities include (a) nutritional rehabilitation, with the use of supplemental liquid feeding, nasogastric tube feeding or total perenteral nutrition if the condition is life-threatening, and (b) pharmacotherapy. Pharmacotherapy can be used to facilitate eating through the reduction of anxiety with anxiolytics or neuroleptics (chlorpromazine 10-25 mg before meals); to reduce postprandial symptoms with prokinetic agents (Russell et al., 1983) (domperidone 10-20 mg before meals); to correct electrolyte imbalance (potassium supplementation); to treat comorbidity such as depression (antidepressants); and to reduce bulimic behavior (tricyclics or monoamine oxidase inhibitors). Experimental treatments include the use of opiate antagonists such as naltrexone (Jonas & Gold, 1986) or serotonergic agonists such as fenfluoramine or fluoxitene (Robinson et al., 1985). The rationale for the use of such drugs has been described previously. It must be emphasized that the primary treatment for both anorexia nervosa and bulimia nervosa is the regular intake of an adequate amount of calories. Pharmacologic treatments for anorexia nervosa are utilized as adjuncts to facilitate refeeding; there is no true "antianorexia nervosa" drug. However, for bulimic patients, treatment with antidepressants may reduce the frequency of hinging behaviors (Hughes, Wells, Cunningham, & Ilstrup, 1986; Pope, Hudson, Jonas, & Yurgelun-Todd, 1983; Walsh, Stewart, & Wright, 1981). This effect may occur independently of any antidepressant effect (Brotman, Herzog, & Woods, 1984) and is poorly understood. Further research is needed to identify the subgroup of bulimics who are most likely to respond to antidepressants. Anxiolytics should be used with caution in bulimic patients because of the risk of dependency (Garfinkel & Garner, 1982).

General Conclusion The eating disorders must be viewed from a multidisciplinary perspective if they are to be understood and adequately treated. Currently, the contribution of biology is most evident in the perpetuation of the illness. We know less about possible biological contributions to the predisposition to or the precipitation of these illnesses. It is crucial for clinicians from all disciplines to be familiar with the biological aspects of anorexia nervosa and bulimia nervosa and to know how these aspects interact with psychosocial factors in the pathogenesis and perpetuation of the illnesses. Such knowledge will improve diagnostic acumen and will enhance the efficacy of therapeutic interventions.

References Allbutt, T. C. (1910). Neuroses of the stomach and of other pans of the abdomen. In T. C. Allbut & H. D. Rolleston (Eds.), A system of medicine (Vol. 3, pp. 386-409). London: MacMillan. Andrews, F. F. H. (1982). Dental erosion due to anorexia nervosa with bulimia. British Denial Journal, 152, 89-90. Beumont, P. J. V., Geonje, G. C. W., Pinstone, B. L., & Vinik, A. L. (1976). Body weight and the pituitary response to hypothalamic-releasing hormones in patients with anorexia nervosa. Journal of Clinical Endocrinology and Metabolism, 43, 487-496. Bennett, H. P. J., & McMartin, C. (1979). Peptide hormones and their analogues: Distribution, clearance from the circulation, and inactivation in vivo. Pharmacological Review, 31, 247-292. Biggio, G., Fadda, F, Fanni, P., Tagliamonte, A., & Gessa, G. L. (1974). Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxindoleacetic acid by a tryptophan-free diet. Life Science, 14, 1321-1329. Binswager, L. (1944). Der fall Ellen West. Schweiz Archives of Neurology and Psychiatry, 54, 69-117. Boyar, R. M., Hellman, L. D., Romvarg, H., Katz, J., Zumoff, B., O'Connor, J., Bradlow, H. L., & Fukushima, D. K. (1977). Cortisol secretion and metabolism in anorexia nervosa. New England Journal of Medicine. 296, 190-193. Brotman, A. W., Herzog, D. B., & Woods, S. W. (1984). Antidepressant treatment of bulimia: The relationship between bingeing and depressive symptomatology. Journal of Clinical Psychiatry, 45, 7-9. Brotman, A. W., & Stern, T. A. (1985). Osteoporosis and pathologic fractures in anorexia nervosa. American Journal oj Psychiatry, 142, 495-496. Brown, G. M., Garflnkel, P. E., Jeuniewic, N., Moldofsky, H., & Stancer, H. C. (1977). Endocrine profiles in anorexia nervosa. In R. Vigersky (Ed.), Anorexia nervosa (pp. 123-136). New York: Raven Press. Coppen, A. V., Gupta, R. K., Eccleston, E. G., Wood, K. M., Wakeling, A., & DeSousa, V. F. A. (1976). Plasma tryptophan in anorexia nervosa. Lancet, 1, 961. Crisp, A. H. (1970). Anorexia nervosa: "Feeding disorder," "nervous malnutrition," or "weight phobia?" World Review of Nutrition and Diet, 12, 452-504. Crisp, A. H., & Stonehill, E. (1971). Aspects of the relationship between psychiatric status, sleep, nocturnal motility and nutrition. Journal of Psychosomatic Research, 15, 501-509. Crisp, A. H., Stonehill, E.. & Fenton, G. W. (1971). The relationship betwen sleep, nutrition, and mood: A study of patients with anorexia nervosa. Postgraduate Medical Journal. 47, 207-213. DeWied, D. (1971). Long-term effect of vasopressin on the maintenance of a conditioned avoidance response in rats. Nature, 232, 58-60. Doerr, P., Fichter, M., Pirke, K. M., & Lund, R. (1980). Relationship between weight gain and hypothalamic-pituitary-adrenal function in patients with anorexia nervosa. Journal of Steroid Biochemistry, 13, 529-537. Donovan, B. T, & Van Der Werfften Bosch, J. J. (1965). Physiology of puberty (Monographs of the Physiological Society, No. 15). London: Edward Arnold. Durie, P. R., Forstner, G. G., Gaskin, K. J., Weizman. Z.. Kopelman, H. R., Ellis, L., & Longman, C. (1985). Elevated serum immuno reactive pancreatic cationic trypsinogen in acute malnutrition: Evidence of pancreatic damage. Journal of Paediatrics, 106, 233-238. Fairburn, C. G., & Cooper, P. J. (1984). The clinical features of bulimia nervosa. British Journal of Psychiatry, 144. 238-246. Faltus, F. (1983). Biochemical correlates of anorexia nervosa. Activitas Nervosa Superior, 25, 237-239. Feighner, J. P., Robins, E., Guze, S. B., Woodruff, R. A.. Jr., Winocur,

This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

652

ALLAN S. KAPLAN AND D. BLAKE WOODSIDE

G., & Munoz, R. (1972). Diagnostic criteria for use in psychiatric research. Archives of General Psychiatry, 26, 57-63. Fichter, M. M., Pirhe, K. M., & Holsboer, F. (1986). Weight loss causes neuroendocrine disturbances: Experimental study in healthy starving subjects. Psychiatry Research, 17, 61-72. Frisch, R. E. (1977). Re: Food intake, fatness, and reproductive ability. In R. Vigersky (Ed.), Anorexia nervosa (pp. 149-161). New York: Raven Press. Frisch, R. E., & McArthur, J. W. (1974). Menstrual cycles: Fatness as a determinant of minimum weight for height necessary for their maintenance or onset. Science, 185, 949-951. Fullerton, D. X, Swift, W. J., Gerro, C. J., & Carlson, I. H. (1986). Plasma immunoreaction beta-endorphin in bulimics. Psychological Medicine, 16, 59-63. Garfinkel, P. E., Brown, G. M., Stancer, H. C., & Moldofsky, H. (1975). Hypothalamic pituitary function in anorexia nervosa. Archives of General Psychiatry, 32, 739-744. Garfinkel, P. E., & Garner, D. M. (1982). Anorexia nervosa: A multidisciplinary perspective. New York: Brunner/Mazel. Garfinkel, P. E., & Kaplan, A. S. (1985). Starvation based perpetuating factors in anorexia nervosa. International Journal of Eating Disorders, 4,651-665. Garfinkel, P. E., Moldofsky, H., & Garner, D. M. (1977). Prognosis in anorexia nervosa as influenced by clinical features, treatment and self-perception. Canadian Medical Association Journal, 117, 10411045. Garfinkel, P. E., Moldofsky, H., & Garner, D. M. (1980). The heterogeneity of anorexia nervosa. Archives of General Psychiatry, 37, 10361040. Garfinkel, P. E., Warsh, J. J., & Stancer, H. C. (1979). Depression: New evidence in support of biological differentiation. American Journal of Psychiatry. 136, 535-539. Geraer, R. H., & Gwirtsman, H. E. (1981). Abnormalities of dexamethasone suppression test and urinary MHPG in anorexia nervosa. American Journal of Psychiatry, 138, 650-653. Gold, P. W., Kaye, W., Robertson, G. L., & Ebert, M. (1983). Abnormalities in plasma and cerebrospinal fluid argenine vasopress in inpatients with anorexia nervosa. New England Journal of Medicine, 308, 1117-1123. Goldberg, S. C., Halmi, K. A., Eckert, E. D., Casper, R. C., & Davis, J. M. (1979). Cyproheptadine in anorexia nervosa. British Journal of Psychiatry, 134, 67-70. Grandison, L., & Guidotti, L. (1977). Stimulation of food intake by muscinol and b-endorphin. Neuropharmacology, 16, 533-536. Gross, H. A., Lake, C. R., Ebert, M. H., Ziegler, M. G., & Kopin. I. J. (1979). Catecholamine metabolism in primary anorexia nervosa. Journal of Clinical Endocrinology and Metabolism, 48, 805-809. Gwirtsman, H. E., Roy-Byrne, P., Yager, J., & Gerner, R. H. (1983). Neuroendocrine abnormalities in bulimia. American Journal of Psychiatry, 140, 559-563. Halmi, K. A., Dekirmenjian, H., Davis, J. M., Casper, R., & Goldberg, S. (1978). Catecholamine metabolism in anorexia nervosa. Archives of General Psychiatry. 35, 458-460. Halmi, K. A., & Falk, J. R. (1983). Behavioral and dietary discriminators of menstrual function in anorexia nervosa. In P. L. Darby, P. E. Garfinkel, D. M. Garner, & D. V. Coscina (Eds.), Anorexia nervosa: Recent developments in research (pp. 323-329). New York: Alan R. Liss. Hollister, L. E., Johnson, K., Bookhabzer, D., & Gillespie, H. K. (1981). Adverse effects of naloxone in subjects not dependent on opiates. Drug Alcohol Dependence, 8, 37-41. Holtzman, S. C. (1974). Behavioural effects of separate and combined administration of naloxone and d-amphetamine. Journal of Pharmacology and Experimental Therapy, 189, 51-60.

Hughes, P. L., Wells, L. A., Cunningham, C. J., & Ilstrup, D. M. (1986). Treating bulimia with desipramine. Archives of General Psychiatry, 43, 182-186. Jonas, J., & Gold, M. (1986). Naltrexone reverse bulimic symptoms. Lancet, 1, 807. Kapen, S., Sternthal, E., & Braverman, L. (1981). A "pubertal" 24hour luteinizing (LH) secretory pattern following weight loss in the absence of anorexia nervosa. Psychosomatic Medicine, 4, 177-182. Kaplan, A. S. (1987). Hyperamylasemia and bulimia: A clinical review. International Journal of Eating Disorders, 6, 537-543. Kaplan, A. S., Garfinkel, P. E., Warsh, J., & Brown, G. M. (1986). Neuroendocrine responses in bulimia. In E. Ferrari (Ed.), Advances in biosciences (Vol. 60, pp. 241-245). New York: Pergamon Press. Katz, J. L., Boyar, R. M., Roflwarg, H., Hellmans, L., & Weiner, H. (1978). Weight and circadian luteinizing hormone secretory pattern in anorexia nervosa. Psychosomatic Medicine, 40, 549-567. Kaye, W. H., Ebert, M. H., Raleigh, M., & Lake, R. (1984). Abnormalities in CNS monoamine metabolism in anorexia nervosa. Archives of General Psychiatry, 41, 300-355. Kaye, W. H., Pickar, D., Ebert, M. H., & Naber. D. (1983). The opioid system in anorexia nervosa. American Journal of Psychiatry, 140, 371-372. Kaye, W. H., Pickar, D., Naber, D., & Ebert, M. D. (1982). Cerebrospinal fluid opioid activity in anorexia nervosa. American Journal of Psychiatry, 139, 643-645. Keys, A., Brozek, J., Henschel, A., Michelsen, O., & Taylor, H. L. (1950). The biology of human starvation. Minneapolis: University of Minnesota Press. Liebowitz, S. F. (1983). Hypothalamic Catecholamine systems controlling eating behavior: A potential model for anorexia nervosa. In P. L. Darby, P. E. Garfinkel, D. M. Garner, & D. V. Coscina (Eds.), Anorexia nervosa: Recent developments in research (pp. 221 -229). New York: Alan R. Liss. Margules, D. L., Moisset, B., Lewis, M. J., Shibuya, H., & Pert, C. B. (1978). B-endorphin is associated with overeating in genetically obese mice (ob/ob) and rats (fa/fa). Science. 202, 988-991. McArthur, J. W, Bullen, B. A., Beitius, I. Z., Pagano, M., Badger, T. M., & Klibanski, A. (1980). Hypothalamic amenorrhea in runners of normal body composition. Endocrinology Research Communications, 7, 13-25. Mecklenburg, R. S., Loriaux, D. L., Thompson, R. H., & Anderson, A. E., & Lipsett, M. B. (1974). Hypothalamic dysfunction in patients with anorexia nervosa. Medicine, 53, 147-159. Mitchell, J. E., Pyle, R. L., & Miner, R. A. (1982). Gastric dilatation as a complication of bulimia. Psychosomatics, 22, 96-97. Moshang. T, Jr., & Utiger, R. D. (1977). Low triiodothyronine euthyroidism in anorexia nervosa. In R. Vigersky (Ed.), Anorexia nervosa (pp. 265-270). New York: Raven Press. Musisi, S., & Garfinkel, P. E. (1985). Comparative dexamethasone suppression test measurements in bulimia, depression and normal controls. Canadian Journal of Psychiatry, 30, 190-194. Palmer, E. P., & Guay, A. T. (1985). Reversible myopathy secondary to abuse of ipecac in patients with major eating disorders. New England Journal of Medicine, 313. 1457-1459. Pope, H. G., Hudson, J. I., Jonas, J. M., & Yurgelun-Todd, D. (1983). Bulimia treated with imipramine: A placebo controlled double blind study. American Journal of Psychiatry, 140, 554-558. Rampling, D. (1982). Acute pancreatitis in anorexia nervosa. Medical Journal of Australia, 2, 194-195. Rigotti, N. A., Nussbaum, S. R., Herzog, D. B., & Neer, R. M. (1984). Osteoporosis in women with anorexia nervosa. New England Journal of Medicine, 311, 1601. Robinson, P. H., Checkly, S. A., & Russell, G. F. M. (1985). Suppression

This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

SPECIAL SERIES: BIOLOGICAL ASPECTS of eating by fenfluramine in patients with bulimia nervosa. British Journal of Psychiatry, 1446, 169-176. Rodin, G. M., Johnson, L. E., Garfinkel, P. E., Daneman, D., & Kenshole, A. B. (1986). Eating disorders in female adolescents with insulin-dependent diabetes mellitus. International Journal of Psychiatry in Medicine, 16, 49-58. Rothenberg, A. (1986). Eating disorders as a modern obsessive-compulsive syndrome. Psychiatry. 49, 45-53. Russell, G. F. M. (1965). Metabolic aspects of anorexia nervosa. Proceedings of the Royal Society of Medicine, 58, 811-814. Russell, G. F. M. (1970). Anorexia nervosa: Its identity as an illness and its treatment. In J. H. Price (Ed.), Modern trends in psychological medicine (Vol. 2, pp. 131-164). London: Butterworths. Russell, G. F. M., & Bruce, J. T. (1964). Capillary-venous glucose differences in patients with disorders of appetite. Clinical Science, 26, 157-163. Russell, D., Freedman, M. L., Feighlin, D. H. I., Jeejeebhoy, K. N., Swinson, R. P., & Garfinkel, P. E. (1983). Delayed gastric emptying and improvement with domperidone in a patient with anorexia nervosa. American Journal of Psychiatry, 140, 1235-1236. Sapse, A. T., Parsons, J. M. (1985, September). Cortisol, cortisol receptors, and anorexia nervosa. Paper presented at the Eighth World Congress of Psychosomatic Medicine, Chicago. Schechter, J. O., Altemus, M., & Greenfeld, D. G. (1986). Food bingeing and esophageal perforation in anorexia nervosa. Hospital and Community Psychiatry, 37, 507-508. Simmonds, M. (1914). Ueber embolische prozesse in des hypophysis [Concerning embolic phenomena in the hypophysics]. Archives of Pathology and Anatomy. 217,226-239. Szmukler, G. I., & Russell, G. F. M. (1983). Diabetes mellitus, anorexia nervosa and bulimia. British Journal uf Psychiatry, 142, 305-308.

653

Ungerstadt, U. (1971). Adiphasia and aphasia after 6-OHDA induced degeneration of the nigro-striatal dopamine system. Ada Physiologica Scandinavia. 95, 367. Wakeling, A., DeSouza, V. A., Gore, M. B. R., Sabrin, M.. & Kingstone, D. (1979). Amenorrhea, body weight and serum hormone concentrations with particular reference to prolactin and thyroid hormones in anorexia nervosa. Psychologic Medicine, 9, 265-272. Wakeling, A., & Russell, G. F. M. (1970). Disturbances in the regulation of body temperature in anorexia nervosa. Psychologic Medicine. I . 30-39. Waller, D. A., Kiser, R. S., Hardy, B. W., Fuche, I., Feignbaum, L. P., & Uauy, R. (1986). Eating behavior and plasma beta-endorphin in bulimia. American Journal of Clinical Nutrition, 44, 20-23. Walsh, B. T., Stewart, J. W, Roose, S. P., Gladis. M., & Classman, A. H. (1984). Treatment of bulimia with phenelzine. Archives of General Psychiatry, 41, 1105-1109. Walsh, B. T, Stewart, J. W., & Wright, L. (1981). Treatment of bulimia with monoamine oxidase inhibitors. American Journal of Psychiatry, 134, 1629-1630. Waschlicht-Rodbard, H., Gross, H. A., Rodbard, D., Ebert, M. H., & Roth, J. (1979). Increased insulin binding to erythrocytes in anorexia nervosa: Restoration to normal with refeeding. New England Journal of Medicine, 300, 882-887. Yen, S. S. C, Tsai, C. C. Naftolin, F. (1975). Pulsatile patterns ofgonadotropin release in subjects with and without ovarian failure. Journal of Clinical Endocrinology and Metabolism, 30, 671-675.

Received March 4, 1987 Revision received March 25, 1987 Accepted April 20, 1987 •