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Basic Considerations in the Treatment of Obesity
Symposium on Psychiatry in Internal Medicine
Basic Considerations in the Treatment of Obesity Frederick G. Guggenheim, M.D.*
Most people have experienced some of the signs, symptoms, and behaviors of obesity. For example, many have been overweight at some time in their lives and have had another sign of obesity, an excess bulge of fat. Again, most people have experienced a cardinal symptom of obesity, an increase in an appetitive urge for some specific delicious food stuff. Finally, every normal person has probably had at least one episode of a common behavior attributed to obesity: gluttony. For each of us has eaten far too long, or too fast, or too much on some occasions. Common sense would then dictate that obesity is a pathological deviation of commonly understood signs, symptoms, and behaviors that produce morbid corpulence. A frequent problem in adults,34 often adversely affecting health,9,37,43 obesity is usually as poorly understood as it is treated. More than three fourths of a representative polling of American physicians 34 attribute obesity to "a lack of willpower," rather than to psychological or medical ptoblems. Trained in the natural sciences, physicians are all aware that human beings do not defy the second law of thermodynamics: excessive body weight results from a surfeit of caloric intake over caloric expenditures. As such, it should seem that a proper vigorous combination of rational instruction, kindly support, and moral suasion ought to produce weight loss. But such has not been the case. Indeed, Stunkard,66 in surveying the results of treatment outcome for obesity up until the last decade, has stated: "Most obese patients won't even come for treatment. Those who do often drop out. Those who don't drop out, don't lose much weight. Finally, those who do lose weight usually regain it." About 90 per cent of those who lose weight will regain it after a variable period of time. 72 No wonder that 7 of 8 physicians report frustration with their motivational efforts on at least half of their encounters with obese patients. 34 Yet most obese people feel they should be able to lose large amounts of weight in short periods of time with little discomfort. 66
':'Assistant Professor of Psychiatry, Harvard Medical School, Associate Psychiatrist, Massachusetts General Hospital, Boston, Massachusetts
Medical Clinics of North America-Vo!. 61, No. 4, July 1977
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The profusion of nonmedical treatment for obesity (Weight Watchers, Diet Workshop, TOPS, Over-eaters Anonymous) is ample evidence of the nation's increasing interest in conquering obesity. Those "uncooperative" patients still want to lose weight.
THE PLAN This paper will present experimental data relevant to the production of obesity in animals as a background to presenting a series of syndromes seen in human obesity. Although gluttony surely is one cause of obesity, we now know that there are a large variety of other syndromes that lead to obesity. We will then present a system for classifying data relevant to understanding and treating (or not treating) the individual for obesity. Finally, we will briefly review the status of several relatively new and successful treatments in obesity: behavior modification, ileojejunal bypass, self-help groups, and modified protein-sparing diets. For experimental animals and for man, obesity can be defined in a variety of ways. 25 Probably the most uniformly accepted and used standard is that of 20 per cent heavier than mean established optimal weight on a weight-height table. Applying Archimedes principle, body density can be weighed in water. Intrinsic 4°K can be measured with whole body scanning. Triceps skin-fold thickness can be detennined, obesity being defined as a thickness of more than 18 mm for males, 25 mm for females. But probably the most widely used test for obesity is the Eyeball Test. If a person or an animal looks fat, it is. How can experimental obesity in animals best be understood? In a helpful conceptualization, Bray4 has divided the subject into five basic types (see Table 1). The first type of experimental obesity is the hypothalamic type.
Table 1. Experimental Obesity in Animals Neurological Hypothalmic injury to ventromedian nucleus Other central vervous system lesions Endocrinologic Excess glucocorticoids Excess insulin Castration
"Adapted from Bray4
Dietary Single daily feeding High fat diet Gulping-gorging Inactivity Genetic Dominant Recessive Polygenic
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EXPERIMENT AL OBESITY IN ANIMALS Hypothalamic Injury Injury involving the hypothalamic ventromedian nucleus (HVM) has produced a number of profound bodily disturbances, including obesity. Feeding behavior is characterized by hyperphagia when food is freely available and hypophagia when any sort of impediment is placed in the way of eating, a pattern reminiscent of human obesity.56 The weight increase in HVM-injured animals continues until the pre-Iesion weight has been doubled and then remains stable as the hyperphagia recedes. Subsequent fasts in HVM-injured animals are again followed by hyperphagia doubling of pre-Iesion weight. Other observations associated with these HVM-injured animals include: hyperinsulinemic response to feeding, increased storage of unsaturated fatty acids (palmitic acid), and a decrease in motoric behavi~r.4 First electrolytic and surgical ablative, then chemical (gold thioglucose) lesions produced significant obesity, suggesting that a satiety center 71 was being destroyed. In parallel with these studies were ablative studies in the areas of the hypothalamic lateral nucleus (HL). Lesions here produced profound aphagia because of disruption of a postulated feeding center. Although the exact neuroanatomic localizations of these nuclei have recently been called into some doubt,21 the dual mechanism theory has proved heuristic ally useful. More recent neurochemical studies of putative central nervous system neurotransmitters have implicated serotonin as a possible active transmitter in the hypothalamic ventromedian nucleus,5,53 since intracerebroventricular injections of p-chlorophenylalanine can produce obesity by depleting serotonin and disinhibiting feeding behavior. Depletion of norepinephrine apparently produces aphagia. 1 Endocrine Manipulations A second type of experimental obesity in animals is that produced by endocrine manipulations. 4 The degree of obesity, however, is less striking than with hypothalamic obesity. An excess of glucocorticosteroids will produce an excessive amount of fat, although weight gain is not necessarily significant. Steroid administration apparently modifies the metabolism of adipose tissue toward an increased preference for fat storage. 30 Excess insulin treatment temporarily increases body weight during the experimental phase by producing a hyperphagia, presumably through stimulation of some glucostatic receptors in the hypothalamic lateral nucleus,17 Castration also produces obesity, presumably through alteration of levels of reproductive hormones. 4 Dietary Manipulation Quantity, quality, and frequency of feeding all can influence adipose deposition and weight. It comes as no surprise that caloric intake is
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related to an animal's weight. But results of Fabry and Tepperman's18 important experiments of regulation of frequency of feeding are not well known in the medical community. These investigators worked with genetically identical groups of rats. The control group was allowed chow as usual (frequently, ad libitum), producing a stable weight pattern. A second group of animals were given the same number of calories of chow, but through a stomach tube, with only 2 feedings per day. The latter group accumulated a significantly increased amount of adipose tissue as compared to the control group. A second way in which an alteration of diet can effect adiposity is through an increase in the quantity of dietary fat. Usually rats fed chow ad libitum maintain a stable weight pattern. But given a diet rich in fat, certain strains of rats are unable to reduce total food intake to compensate for increased caloric density, developing gross obesity.57 Finally, another dietary factor amenable to manipulation is the feeding condition. For example, with identical infant rat litters,31 one group was allowed free access to food throughout the 24 hour day, the control group having access only during 2 hours per day. The latter, deprived rats, after weight loss, learned to gulp their food, and soon outgained their litter mates, becoming obese. This abnormal feeding pattern and obesity persisted into adulthood long after free access to food was established. Restrictions on Activity Restriction of physical activity is a simple means of producing obesity in the rat. 33 Usually an increase in physical activity is matched in the experimental animal by an appropriate augmentation of caloric intake, so that weight remains stable. But with very low levels of physical activity, food intake does not match energy needs and the animal has a considerable weight increase. 45 Genetic Obesity A number of obese strains of mice have been carefully studied. 4.11 ,19,34 In many instances, chromosomal mutations are a necessary but not a sufficient cause for the production of obesity. For example, with the dominant yellow strain (AY, AVY, NY) with an aberration on chromosome 2, if there is crowding and a warm cage, obesity develops; but if there is a colder cage without crowding, obesity does not develop despite ad libitum feeding. With the dominant New Zealand obese (NZO) strain, obesity develops with ad libitum feeding unless the female is breeding or has been treated with stilbestrol. Two recessive strains of mice, obese (ob/ob with a mutation on chromosome 6), and diabetes (db/db with its abnormality on chromosome 4) develop identical syndromes of obesity and hyperglycemia, but again only if given ad libitum feeding. Coleman,l1 working with these two strains of mice with identical genetic backgrounds (which allows for parabiotic experimentation), has described two different mechanisms shaping hyperphagic behavior. In the obese (ob/ob) mouse, parabiotic experiments point to a decreased production of a satiety factor. But with
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the diabetic (db/db) mouse, there is a decreased responsiveness to satiety factor. In summary, identical obese, hyperglycemic syndromes in mice with identical genetic backgrounds can be produced by unrelated genes working through a variety of different mechanisms.
OBESITY IN MAN It would be useful to the clinician if the five types of obesity in animals 4 could be used as a classifying principle for obesity in man. However, there are a number of reductionistic difficulties. First of all, the genetic background of human obesity is "a geneticist's nightmare."32 Secondly, there are a variety of environmental, psychological, and medical conditions for which there are currently no experimental analogues. Nonetheless, some useful system of classification is needed to replace the outmoded "endogenous" versus "exogenous" obesity paradigm. This latter term can be applied to a vast majority of patients seen in obesity clinics and bariatric practices. Indeed, Solomon 61 has reported that 90 per cent of patients evaluated at the Johns Hopkins Obesity Clinic had no demonstrable endogenous cause for their obesity. Moreover, the term "exogenous obesity" tends to place the blame for the condition solely on the patient, although surely we would not blame ob/ob or db/db mice with lack of willpower when they ate large meals. Finally, the endogenous-exogenous dichotomy tends to give the clinician a false sense that he understands the condition: which at this phase of our studies, we do not. Wastebasket terms rarely help us with either our understanding or our treatment. Most types of obesity fall into nine categories listed in Table 2. In many instances, several of these factors will be etiologically associated with obesity. Not listed in Table 2 is "essential obesity," a term reserved for those types of obesity, analogous to hypertension, for which no etiologic factors have yet surfaced.
Genetic Obesity Clear-cut genetic obesity in man is rarely if ever encountered by most clinicians. 4 Suffice it to say that people with Prader-Willi syndrome, one genetic type of obesity, are mildly mentally retarded, sexually immature, and have strong cravings for food. Those with the Laurence-MoonBardet-Biedl syndrome are also mentally retarded and also have retinitis pigmentosa. Other rare syndromes include the Morgagni-Morel syndrome and the Alstrom syndrome. Table 2. Types of Human Obesity Genetic NeurologiC Endocrinologic Dietary Inactivity
Socio-occupational Developmental Psychological Pharmacological
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Yet a variety of studies have pointed toward genetic factors, presumably of a polygenic nature, influencing the ability to gain or lose weight. Identical twins even when reared apart, tend to have similar weights. 34 Adopted children resemble their biological parents in body weight more than their adoptive parents. 74 Bruch7 cites a variety of older studies: if one parent is obese, 40 per cent of the offspring will be obese; if both are obese, 80 per cent of the offspring will be obese. As corollary, 90 per cent of obese children have a family history of obesity. 35 Such studies, of course, are not controlled for socioenvironmental and developmental factors. Other studies also raise the specter of genetic influence, although developmental factors can not be ruled out. For example, Sims 60 and Goldman 23 have convincingly demonstrated resistance to fattening in certain of their normal weight volunteers during periods of hyperphagia. Miller4 9 has demonstrated that some people actually do have resistance to slimming. However, lack of any current markers prevent all but speculation on the degree of variance accounted for by genetic factors in human obesity.
Neurologic Causes Most known neurologic causes of obesity are associated with obvious neurologic symptoms. 4 Sources of hypothalamic injury include: craniopharyngiomas, encephalitis, and physical trauma. There are also two types of neurologic obesity without obvious neurologic symptoms or signs. First is the Kleine-Levin syndrome of periodic hyperphagia and hypersomnia. 73 Second, a syndrome of preoccupation with food and electroencephalographic abnormalities has recently been described in a group of patients from a psychiatric clinic. 26 After initiation of therapy with diphenylhydantoin (Dilantin), not only did the preoccupation with food cease, but the hyperphagia stopped promptly and weight went down toward normal parameters. Endocrinologic Causes Endocrinologic causes of obesity include: Cushing's syndrome, diabetes mellitus, insulinoma, castration, and Stein-Levinthal syndrome. They have recently been described in detail elsewhere. 4
Dietary Preferences for high density caloric foods or for large amounts of food can result in obesity. In some instances, this preference may amount to willful gluttony. Unfortunately, our ability to differentiate voluntary gluttony from involuntary succumbing to an-irresistible-urge-from-theappetite-center is limited. Another cause of dietary obesity involves the schedule of eating. It may be that those who eat only once per day and especially those who eat just prior to retiring may be more prone to accumulate adipose tissue. Finally, experimental obesity has been recently studied by college students and prisoners volunteering to overeat. 23.60
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Restricted Activity Physical inactivity is an accompaniment of spontaneous and experimental obesity in man. 4 ,4L46 On some occasions, as in forced bed rest for medical purposes, a modest degree of obesity may develop. For example, a deficit of the physical exercise equivalent to running a mile a day, if not corrected by a decrease in appetite, adds a surfeit of 200 calories a day.27 Over a one year span, such an individual would gain 11 to 22 pounds. The role that decreased physical activity has in the initial genesis or the propagation and maintenance of most cases of obesity is unclear. Exercise, for example, has been shown to increase the synthesis of glucose rather than fat from endogenous lactate,75 whereas inactivity results in decreased glucose utilization with a decreased difference in arteriovenous glucose concentrate which Mayer46 has hypothesized could lead to a stimulation of hypothalamic appetite center.
Sodo-Occupational Factors Mild to moderate obesity is valued and sought for amongst certain groups. For example, Sumo wrestlers and other professional athletes at times aspire toward obesity as an aid in competition. A manly "pot-belly" is esteemed by certain wealth European bourgeoisie. Some African chieftains value fat wives as a sign of financial success. Standards of feminine beauty, as portrayed in the Venetian women of Rubens and Parisiennes of Ingres, required a mild degree of obesity. Obesity also occurs in lower socioeconomic classes. 22 About one third of all lower class American women are obese, compared to 1 in 20 in the upper socioeconomic classes. Although presumably some factors involved may be dietary (foods of lower classes tend to be protein deficient and carbohydrate rich), a variety of other poorly understood factors, including stress, may also be involved.
Developmental Factors During the developmental stages from fetus to infant to adolescent, a number of complex biological and psychological factors play critical roles in the development of adipose tissue, hypothalamic centers, body image, ego and sense of self. Prenatal nutrition, for example, has been demonstrated as an important factor in the subsequent adult body weight in the development of obesity. Ravelli,52 surveying the birthplaces and birthdates of Dutch boys 19 years after an acute catastrophic famine (involving part of the Netherlands in the closing days of World War II), has convincingly demonstrated that those boys whose mothers suffered severe famine in the first trimester have a significantly greater likelihood of being obese than control cohorts. By contrast, those boys whose mothers were afflicted by the famine during the last trimester are now noted to have a significantly increased likelihood of being underweight. By analogy, those American mothers who were severely afflicted with hyperemesis gravidarum, or who were on crash diets during the first trimester might have inadver-
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tently subjected their offspring to conditions which programmed the developing hypothalamus to respond to life as if it were starving. Another demonstration that nutrition during infancy also has potential for producing profound and lasting effects comes from Charney'slO follow-up of infants weighed at 6 months of age. On follow-up 20 years later, he found a significant increase in obesity in those infants in the upper quartile (75 to 100 per cent) by weight as compared to their peers in the lower quartile (1 to 25 per cent). Obesity of infancy and childhood induces not only the usual hypertrophy of adipocytes, but hyperplasia of these cells with an increase in their absolute cell number. Knittle,38 studying the size and number of adipocytes in children has concluded that a critical period for adipose tissue development occurs somewhere between birth and age two. This time frame has important consequences for future development of the size of the fat depot in the adult. A second period appears to be the prepubescent and adolescent period when cellular proliferation may occur again in these subjects. Thus, whether the baby fat "melts away" or continues to increase in amount during prepubescence may be determined by the adipose cell count. Intrapsychic determinants of "obesogenic mothers" vary widely. Some developmental obesity results from simple, misguided maternal feeding practices. Some mothers vaguely believe: "A fat baby is a healthy baby!" But the behavior of other mothers may be more complex, using the children's eating behaviors as a means of undoing: "My family lived in grinding poverty in the Old Country. That will never happen to you!" Still other mothers have convoluted, troubled, and tenaciously held convictions about feeding that relates to their own conflicted upbringings: "I'll show them what a good mother I am. You'll eat everything I cook for you!" Maternal psychogenic factors in developmental obesity have been described extensively by Hilda Bruch 7 and others.36 Bruch 6 noted that mothers of obese children often are unusually concerned, anxious, and extraordinarily domineering. Many relate to their children as if they were possessions, without respect for individuality or particular needs. Often the children are used to compensate for overwhelming frustration or disappointment. 48 Much ofthe emotional interchange of mother and obese child is ambiguous and ambivalent, especially the giving and accepting of food. Kalucy36 notes four features peculiar to these families: (1) these mothers use food as a primary means of giving comfort, relieving distress, and rewarding desired behavior, often to the exclusion of holding, encouraging, or nursing; (2) these mothers often respond to the children because of their own anxieties or needs, leading to further confusion between internally felt stimuli and external actions; (3) such mothers tend to come from families and cultures where "all food served has to be eaten," further diminishing the relationship between internal cues and external behaviors relating to physiologic needs; (4) finally, obese children come to expect that all their distress and positive feeling will be responded to by the giving of food. Consequent to these mixed and distorted cue signals the child develops:36
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(1) a decreased capacity to discriminate between internal cues such as anger, depression and hunger, coupled with a tendency to respond to non-hunger cues by eating; (2) an inappropriately heightened, often fragile acceptance of one's essential rightness, coupled with an insecurity about personal effectiveness. Here narcissism, buttressed with denial, reaction formation, and a dissociation of the impact of eating on weight and behavior occur; (3) an inability to develop personal skills leading to independence coupled with a hypersensitivity, immaturity, and diminished objectivity; (4) the capacity to distort important relationships especially during dieting and intense emotional interchange. Added to these internal difficulties is the harsh societal rejection of the obese child and adolescent.2.8.15.29 These rebuffs often result in a sense of self-loathing and a negative sense of body image.29.36.67 Having said all this, we must still not lose sight of the fact that not all children of obesogenic families are overweight, nor are all obese children treated by the families in the same way.36 It remains unclear why certain children of these obesogenic families escape pernicious infiuence. Indeed, in actual practice, it is often difficult to know whether emotional factors contributed to the genesis of developmental obesity or whether psychological problems are secondary to social rejection these youngsters encounter, since the two factors are often so closely intertwined. 7 In making a prognosis, no single medical or psychological factor has permitted a definite prediction of the course of developmental obesity. 7 Long-term predictive studies following fat cell counts show great promise, and are now under way.38 Assessment of problems within the family and the emotional maturity of the child so far has been of greater importance for prediction than physical factors. Bruch 7 has summarized the poor prognostic signs in developmental obesity: 1. early onset (although there are exceptions); 2. lack of physical activity, especially if coupled with social isolation and withdrawal; 3. lack of familial stability, warmth, and support; 4. the presence of familial anxiety and discord, preventing the child's striving for independence; 5. inadequate achievement in the Draw-A-Person test, and to a lesser extent, a discrepancy between performance and verbal on the IQ test; 6. paradoxically, the more medical treatment, the worse the prognosis. By contrast, those efforts at weight reduction that are prompted by the obese child or adolescent are much more likely to end in success than those prompted by others.
Psychological Factors In the previous section on developmental obesity, we detailed ways in which obesity itself can cause emotional confiict. Harsh societal judgments about obesity, for example, can warp an individual's sense of self, with a distortion of body image and self-loathing. We also detailed
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how obesity can be associatively linked with psychological turmoil by a common etiologic link, the obesogenic mother. In this section, we shall discuss those types of adult-onset obesity that are strongly related to psychological factors. No clear estimate exists for the proportion of adult-onset obesity that is the end-product of coping with emotional problems. Nor is there any particular personality type in obesity.36 Attempts to link obesity with neuroticism and neurotic conflicts have yielded some paradoxical results. For example, Graff.!4 and others have shown that the obese, particularly the obese male who is not under any medical or psychiatric treatment, has fewer neurotic lifestyle characteristics than occur in the normal population. The "superstability" of the obese may indicate that they are unusually mentally healthy. Or this super-stability may indicate that the obese are, as a group, protected against the experience of neurotic symptomatology.36 Clinic populations of obese individuals, however, have a higher than normal level of neuroticism.1 2 This may be because: (1) eating and obesity are no longer adequate defenses, and (2) the development of a neurotic illness, however independent of obesity, may lead to an increasing need for seeking out comfort, relief, and security. 36 Two types of psychological obesity are often seen and easily identified. These are reactive hyperphagia and symbolic obesity. Whereas some patients with developmental and other types of obesity may profess a desire to lose weight for locomotion, health, or cosmetic reasons, people with reactive hyperphagia and symbolic obesity may be disinterested in or ambivalent about weight reduction through dieting. Reactive hyperphagia, which includes binge eating, usually develops in a setting of emotional trauma such as death of a close family member, the break-up of a love affair, or separation from home. At times even threat of separation, rejection, or injury may trigger reactive hyperphagia. For example, some of the weight gain in pregnant women or even in expectant fathers revolves around issues of fear of not being adequately supported after the birth of the child. Another issue might be fear of being drained by the baby. Eating wards off feelings of anxiety, depression, and loneliness. Here, not the obesity, but the oral gratification and the sense oftranquilization from being "stuffed" are important. Another type of obesity with a strong psychogenic component is symbolic obesity. Here the size or the appearance of the obese person is not a problem, but rather a solution. One example is a woman who fears that she will again resume sexual promiscuity should her weight and appearance return to normal; she continues to invest in being fat. Other examples: the financially successful industrialist who sees his giant size as reflecting the degree of his absolute power to control, and the ghetto matriarch with the bouffant hair-do and bright, flowing robes who sees her size as a sign of dominance over others in her realm. Despite physicians' diligence at pushing weight reduction regimens, some patients will not want to cooperate until obesity presents problems with locomotion or severe health hazards. Those with symbolic obesity see their overweight as an asset, not as a liability.
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Obesity and overeating can defend against the development of feelings of anger, depression or anxiety triggered by unresolved, underlying conflicts. Disruption of (compensatory) eating habits on the other hand, can lead to significant emotional distress. Emerging psychological symptoms can vary from mild depression to transient though severe anxiety, depersonalization, and even transient delusions. 3 However, the emergence of severe psychopathology seems to be more the exception than the rule. 69 Those obese people most at risk have developmental obesity. To a lesser extent, those with acute ongoing stress may also be prone to develop psychological symptoms during dieting or starvation. Another syndrome of potential psychological vulnerability while dieting is the night eating syndrome. 65 Prognostic ally, this is also a useful indicator of little chance for substantial weight loss. A transient syndrome, it is characterized by initial insomnia, the induction of sleep or tranquilization by massive caloric ingestion, and morning anorexia. It may account for 10 per cent of patients seen in an obesity clinic. Neither the underlying dynamics nor the pathophysiology of this syndrome have been completely elaborated.
Pharmacologic Causes The advent of antipsychotic, antidepressant, antihistaminic, antiserotonergic, and anti-inflammatory agents have produced a variety of iatrogenic obesities. As of this time, no body of knowledge has yet been generated that adequately accounts for this phenomenon, one that has perplexed physicians and bedeviled their patients. Pediatricians have observed that cyproheptadine (Periactin) produces considerable obesity in normal, underweight children, as well as children with psychological problems. 28 Nonsystematic observations that other antihistamines are not as potent a stimulus to hyperphagia have not been carried out yet, nor have the responsible mechanisms been defined. But interestingly, interventricular injections in rats of a blocker of serotonin synthesis, p-chlorophenylalanine, has produced experimental hyperphagia and obesity.5 Concomitant depletion of serotonin and norepinephrine 53 does not produce hyperphagia. Selective depletion of norepinephrine itself produces hyperphagia in some studies. 1 The clinically useful anorexigenic agents often have effects on brain norepinephrine, dopamine, and serotonin brain tissue levels and turnover. Amphetamines release and deplete norepinephrine,28 yet selective depletion of norepinephrine itself produces not aphagia but hyperphagia.! The resolution of these seemingly paradoxical results may hinge on the pivotal roles of central serotonin levels and norepinephrine's regulation and stimulation of central serotonin synthesis storage and release. Serotonergic systems in the brain are very interesting in regard to control of feeding because they depend on dietary factors. They can be readily influenced by dietary tryptophan. How central serotonergic and noradrenergic mechanisms relate to the considerable obesity seen in many patients on antipsychotic agents such as chlorpromazine and haloperidol and the antidepressant amitriptyline is unclear. For example, whether the differential effects on block-
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ade of serotonergic and nor adrenergic uptake found amongst the tricyclic antidepressants can prove of use has not yet been clarified. Currently, many patients are in a considerable bind: abandoning tricyclic therapy predisposes to devastating depression. But taking medication (which produces a "sweet-tooth" for carbohydrates) produces an unwanted increase in weight. In some patients this pharmacologic obesity can induce a serious blow to self-esteem.
TREATMENT Obesity in humans and in rats have a number of clinical features in common: (1) hyperphagia in certain settings where tasty food is readily available; (2) a failure of satiety mechanisms; (3) finickiness about food; (4) unwillingness to work for food; (5) a reduction in hunger drive; (6) a decrease in spontaneous physical activity; (7) a consistent increase in weight to a certain set point. 50 All effective strategies for dealing with the syndrome of obesity must relate to these manifest behaviors. The anorexigenic medications such as chlortermine, fenfiuramine, and mazindol all try to inhibit the appetitive urges. Their efficacy has recently been reviewed. I6 The bulk replacers, through working on these satiety mechanisms 44 also try to turn off appetite mechanisms, but this time by stimulating the satiation-tranquilization response. Most of those agents do not expand in the stomach, but rather in the small intestine, thus acting as a cathartic agent. Acute intermittent fasts, especially during two weeks of hospitalization has proven to be quite successful and easily tolerated. I4 Perhaps some endogenous anorexigenic agent suppresses hunger and appetitive cravings or increases the sense of satiation. Unfortunately, not many insurance companies will pay for this or any other form of hospital treatment for obesity (save for ileojejunal bypass). Outpatient proteinsparing diets and modified fasts have recently been advocated 20 ,40 and, when coupled with a comprehensive program, have produced a mean loss of more than 40 pounds of weight in a group of 67 subjects, many maintaining that loss at one and two years post treatment. Some medical problems may be precipitated by fasting regimens however (hyperuricemia, cholecystitis, hypotension, etc.). Another approach to weight control involves primarily group support for modification of eating habits. TOPS70 and Overeaters Anonymous 39 have proven themselves to be very effective for some patients, perhaps helping the individual to deal strictly with standards for satiety mechanisms while avoiding situations in which hyperphagia becomes nearly inevitable. Behavior modification makes use of clinical behavior common to the HVM rat as well as the super-obese human, attempting and often succeeding in extinguishing certain dysfunctional behaviors leading to the increasing hyperphagic state. A significant detail in the behavior modification scheme is that the patient participates in the design of his treat-
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ment by observing his own eating behavior to produce a set of experimental conditions that can be shaped, reinforced, or extinguished. 64 The patient keeps daily records of his eating behaviors, noting the amount, time, and circumstances associated with his eating (what room, what body position, what other concomitant activity, what emotional state). Next, the patient shapes his behavior, agreeing only to eat in a certain place, for example, the kitchen, but never in the living room or in front of the television. Then he agrees only to eat in a sitting position, at mealtimes in the kitchen, and if the table is set. Later, he agrees to chew his food a certain number of times or put his utensils down on the plate in between bites, and to pause one or two minutes in the middle of the meal. These useful behaviors are promptly rewarded in ways meaningful to the patient (money, points, privileges, and so forth). Results from the mildly overweight and the severely overweight51 are good,68 proving that effective weight reduction could occur if behavioral principles are enunciated, even in a manual without physician support. One of the significant features about behavior modification is that individuals continue to lose weight even after they are no longer actively working in behavior modification, whereas most studies of people attending diet clinics, etc., show on follow-up that their weight does not stabilize or continue to go down but rather goes up. The relevance of getting the patient to focus upon environmental variables in the treatment of his obesity is based on Schachter's showing56 that much eating behavior of the obese is under environmental rather than internalized control. What is encouraging about the current behavior modification approach (as exemplified in Stuart and Davis' book, "Slim Chance in a Fat World: Behavioral Control of Obesity"63) is both the greater weight loss during treatment and the superior weight loss after treatment in comparison to traditional management of dietary instructions given to the patients, or the medication-encouragement approach. Finally, ileojejunal bypass operations, short-circuiting absorption areas for fat, have now been refined to a considerable degree. Both morbidity and mortality rates are considerably lower than a decade ago. 13 ,54,55 Criteria for selection, by an interdisciplinary team of internists, psychiatrists, surgeons, patients and spouse 42 include the following criteria: (1) weight of more than 100 pounds in excess or twice ideal body weight; (2) failure of all reasonable available alternative treatments to control the continued weight gain; (3) absence of a history of alcoholism, severe reactive anorexia, or ongoing pregnancy; (4) high persistent motivation by the patient for the procedure; (5) ability to be treated for any severe concomitant medical and/or psychiatric condition prior to operation if these might interfere with immediate or longer-term immediate postoperative course (unstabilized psychosis, moderatesevere depressive reaction); (6) ability to maintain good doctor-patient follow-up; (7) absence of severe masochistic or immature personality traits; (8) absence of consistently unreasonable expectations. Through such vehicles of new hope, family and medical team encouragement, and the immediate aversive consequences of a diarrheal
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bowel movement or abdominal cramps, many super-obese patients have been able to correct their weight and their lives toward normal. 62 Interestingly, we have noted that bypass patients spontaneously begin ingesting smaller meals, develop a lack of frequent binge-eating, and suspend eating as a replacement for other gratifications. Yet at a time when Blue Cross (in certain states) has acknowledged this procedure as the only reimbursible treatment for morbid obesity, some clinics no longer perform the procedure because of morbidity with it in their hands. 47
SUMMARY The recognition and treatment of obesity has undergone marked changes in the past two decades. Along with the abandoning of the concept of exogenous obesity, the physician has discovered a variety of developmental, psychological, pharmacologic, socioeconomic, neurological, and genetic roots for the syndrome. The clinician has also found medical treatment modalities (fasting and behavior modification) that hold much more prOInise than traditional supportive relationships with dietary consultation and anorexogenic medications. Surgical treatment also, ileojejunal bypass, is gradually emerging as a treatment of choice for certain well-motivated, super-obese people for whom all other treatment modalities have failed. Future research into central serotonergic mechanisms offers hope that we can begin to know what it is that turns on hunger, turns off appetite, and regulates weight in such a stable manner over such a long period of time.
REFERENCES 1. Ahlskog, J. E., and Hoebel, B. G.: Overeating and obesity from damage to a noradrenergic system in the brain. Science, 182: 166-168, 1973. 2. Allon, N.: The stigma of overweight in everyday life. In Bray, G. A., ed.: Obesity in Perspective, Part 2, New York, Harper and Row, 1975, pp. 83-102. 3. Atkinson, R. M., and Ringuette, E. L.: A survey of biographicaI' and psychological features in extraordinary fatness. Psychosom. Med., 29:121-133, 1967. 4. Bray, G. A.: The varieties of obesity. In Bray, G. A., and Bethune, J. E., eds.: Treatment and Management of Obesity. New York, Harper and Row, 1974, pp. 61-76. 5. Breisch, S. T., Zemlan, E. P., Hoebel, B. G.: Hyperphagia and obesity following serotonin depletion by intraventricular p-chlorophenylalanine. Science, 192 :382-384, 1976. 6. Bruch, H., and Touraine, G.: Obesity in childhood: V. The family frame of obese children. Psychosom. Med., 2 :141-206, 1940. 7. Bru"ch, H.: Eating Disorders. New York, Basic Books, 1973. 8. Bruch, H.: The psychological handicaps of the obese. In Bray, G. A., ed.: Obesity in Perspective, Part 2, New York, Harper and Row, 1975, pp. 111-114. 9. Buskirk, E. R., and Bartlett, H. L.: Obesity and pulmonary function. In Bray, G. A., ed.: Obesity in Perspective, Part 2, New York, Harper and Row, 1975, pp. 225-232. 10. Charney, E., Goodman, H. C., McBride, M., et al.: Childhood antecedents of adult obesity. New Eng. J. Med., 295:6-9,1976. 11. Coleman, D. C., and Hummel, K. P.: Effects of parabiosis of normal and genetically diabetic mice. Amer. J. Physiol., 217:1298-1304,1969. 12. Crup, A. H.: The possible significance of some behavioral correlates of weight and carbohydrate intake. J. Psychosom. Res., 11 :117-131, 1967. 13. DeWind, L. T., and Payne, J. H.: Intestinal bypass surgery for morbid obesity. J.A.M.A., 236:2298-2301, 1976.
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14. Duncan. G. G., Hunscher, M. A., Cristofori, F. C., et al.: The control of obesity by intermittent fasts. Med. Clin. N. Amer., 48:1359-1372, 1964. 15. Dwyer, J., and Mayer, J.: The dismal condition: Problems faced by obese adolescent girls in American society. In Bray, G. A., ed.: Obesity in Perspective, Part 2, New York, Harper and Row, 1975, pp. 103-110. 16. Dykes, M. H.: Evaluation of three anorexiants. J.A.M.A., 230:270-272, 1974. 17. Epstein, A. N., and Teitelbaum, P.: Specific loss of the hypoglycemic control of feeding in recovered lateral rats. Amer. J. PhysioI., 213 :1159-1167, 1967. 18. Fabry, P., and Tepperman, J.: Meal frequency-A possible factor in human pathology. Amer. J. Clin. Nutr., 23:1059-1068,1970. 19. Fuller, J. L.: Genetic aspects of regulation of food intake. Advances Psychosom. Med., 7:2-24, 1972. 20. Genuth, S. M., Castro, J. H., and Vertes, V.: Weight reduction in obesity by outpatient semistarvation. J.A.M.A., 230:987-991, 1974. 21. Gold, R. M.: Hypothalamic obesity: The myth of the ventromedial nucleus. Science, 182:488-489, 1973. 22. Goldblatt, P. B., Moore, M. E., and Stunkard, A. J.: Social factors in obesity. J.A.M.A., 192:1039-1044, 1965. 23. Goldman, R. F., Haisman, M. F., Bynum, G., et al.: Experimental obesity in man. Metabolic rate in relation to dietary intake. In Bray, G. A., ed.: Obesity in Perspective, Part 2, New York, Harper and Row, 1975, pp. 165-186. 24. Graff, F. H.: Overweight and emotions in an obesity clinic. Psychosomatics, 6:89-94, 1965. 25. Grande, F.: Assessment of Body Fat in Man. In Bray, G. A., ed.: Obesity in Perspective, Part 2, New York, Harper and Row, 1975, pp. 189-204. 26. Green, R. S., and Rau, J. H.: Treatment of compulsive eating disturbances with anticonvulsant medication. Amer. J. Psychiat., 131 :428-432, 1974. 27. Harger, B.S., Miller, J. B., and Thomas, J. C.: The caloric cost of running. J.A.M.A., 228:482-483, 1974. 28. Heil, G. C., and Ross, S. T.: Chemical agents affecting appetite. In Bray, G. A., ed.: Obesity in Perspective, Part 2, New York, Harper and Row, 1975, pp. 409-418. 29. Hirsch, J.: The Psychological Consequences of Obesity. In Bray, G. A .. ed.: Obesity in Perspective, Part 2, New York, Harper and Row, 1975, pp. 81-82. 30. Hollifield, G., and Parson, W.: Metabolic adaptations to a "stuff and starve" feeding program. J. Clin. Invest., 41 :245-250, 1962. 31. Hollifield, G.: Glucocorticoid-induced obesity: A model and a challenge. Amer. J. Clin. Nutr., 21 :1471-1474, 1968. 32. Hunt, E. E.: Epidemiologic considerations. Advances Psychosom. Med., 7:148-172, 1972. 33. Ingle, P. J.: A simple means of producing obesity in the rat. Proc. Soc. Exper. BioI. Med., 72 :605, 1949. 34. James, W. P. T., and Traybum, P.: An integrated view of metabolic and genetic basis for obesity. Lancet, 2 :770-773, October 9, 1976. 35. Johnson, M., Burke, B., and Mayer, J.: Relative importance of inactivity and overeating in the energy balance of obese high school girls. Amer. J. Clin. Nutr .. 4 :37-44, 1956. 36. Kalucy, R. S.: Obesity: An attempt to find a common ground among some of the biological, psychological and sociological phenomena of the obesity/overeating syndromes. Modem Trends Psychosom. Med., 3:404-429, 1976. 37. Keys, A.: Overweight and the risk of heart attack and sudden death. In Bray, G. A., ed.: Obesity in Perspective, Part 2, New York, Harper and Row, 1975, pp. 215-224. 38. Knittle, J. L.: Early influences on development of adipose tissue. In Bray, G. A., ed.: Obesity in Perspective, Part 2, 1975, pp. 241-244. 39. Lindner, P. G.: Overeaters anonymous-Report on a self-help group. Obesity/Bariatrics Med., 3: 134-137, 1974. 40. Lindner, P. G., and Blackbum, G. L.: Multidisciplinary approach to obesity utilizing fasting modified by protein-sparing therapy. Obesity/Bariatric Med., 5:198-216, 1976. 41. Lutwak, L., and Coulston, A.: Activity and Obesity. In Bray, G. A., ed.: Obesity in Perspective, Part 2, New York, Harper and Row, 1975, pp. 393-396. 42. Malt, R. A., and Guggenheim, F. G.: Surgery for Obesity. New Eng. J. Med., 293 :43-44, 1976. 43. Mann, G. V.: The influence of obesity on health. New Eng. J. Med., 291 :178-232,1974. 44. Marquette, C. J.: Effects of bulk-producing tablets on hunger intensity in dieting patient. Obesity/Bariatric Med., 5:84-88, 1976. 45. Mayer, J., Marshall, N. B., et al.: Exercise, food intake, and body weight in normal rats and genetically obese adult mice. Amer. J. PhysioI. 177:544-548, 1954. 46. Mayer, J.: Obesity. Ann. Rev. Med., 14:111-132,1963.
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47. Medical News: Bypass operation loses favor in obesity treatment. J.A.M.A., 236:2729, 1976. 48. Mendelson, M.: Psychological aspects of obesity. Med. Clin. N. Amer., 48:1373-1385, 1964. 49. Miller, D. S., and Parsonage, S.: Resistance to slimming. Lancet, 1 :773-775, 1975. 50. Nisbett, R. E.: Starvation and the behavior of the obese. In Bray, G. A., and Bethune, J. E., eds.: Treatment and Management of Obesity. New York, Harper and Row, 1974, pp. 45-57. 51. Penick, S. B., Filion, R., Fox, S., et al.: Behavior modification in the treatment of obesity. Psychosom. Med., 33 :49-55, 1971. 52. Ravelli, G. P., Stein, Z. A., Susser, M. W.: Obesity in young men after famine exposure in utero and early infancy. New Eng. J. Med., 295 :349--353, 1976. 53. Saller, C., and Strickler, E.: Hyperphagia and increased growth in rats after intraventricular injection of 5, 7-dihydroxytryptamine. Science, 192 :385--387, 1976. 54. Salmon, P. A.: Intestinal bypass: Clinical experience and experimental results. In Bray, G. A., ed.: Obesity in Perspective, Part 2. New York, Harper and Row, 1975, pp. 473496. 55. Sandstead, H. H.: Jejunoileal shunt in morbid obesity. In Bray, G. A., ed.: Obesity in Perspective, Part 2. New York, Harper and Row, 1975, pp. 459-472. 56. Schachter, S.: Obesity and eating. Science, 161 :751-756, 1968. 57. Schemmel, R., Mickelsen, 0., and Gill, J. L.: Dietary obesity in rats: Body weight and fat accretion in seven strains of rats. J. Nutr., 100:1041-1048, 1970. 58. Scott, B. T.: How doctors help motivate patients to shed pounds. Medical Opinion, 1974, pp. 36-41. 59. Seltzer, C. C.: Genetics and obesity. Physiolopathology of Adipose Tissue, Report of 3rd International Meeting of Endocrinology Excerpta Medica, 1968, pp. 325--334. 60. Sims, E. H.: Studies in human hyperphagia in treatment and management of obesity. In Bray, G. A., and Bethune, J. E., eds.: Treatment and Management of Obesity. New York, Harper and Row, 1974, pp. 28-44. 61. Solomon, N.: The study and treatment of the obese patient. Hospital Practice, 1969, pp. 90-94. 62. Solow, C, Silberfarb, P. M., and Swift, K.: Psychosocial effects of intestinal bypass surgery for severe obesity. New Eng. J. Med., 290:300--304, 1974. 63. Stuart, R. B., and Davis, B.: Slim Chance in a Fat World: Behavioral Control of Obesity. Illinois, Research Press, 1972. 64. Stuart, R. B.: Behavioral control of overeating: A status report. In Bray, G. A., ed.: Obesity in Perspective, Part 2. New York, Harper and Row, 1975, pp. 367-385. 65. Stunkard, A. J., Grace, W. J., and Wolff, H. G.: The night-eating syndrome. Amer. J. Med., 19:78-86,1955. 66. Stunkard, A., and McLaren-Hume, M.: The results of treatment for obesity. Arch. Intern. Med., 103:79-85, 1959. 67. Stunkard, A., a Stunkard, A., and McLaren-Hume, M.: The results oftreand Mendelson, M.: Obesity and body image. Amer. J. Psychiat., 123 :134-138, 1967. 68. Stunkard, A.: New therapies for the eating disorders. Arch. Gen. Psychiat., 26:391-398, 1972. 69. Stunkard, A. J., and Rush, J.: Dieting and depression reexamined. Ann. Intern. Med., 81 :526-532, 1974. 70. Stunkard, A.: Studies on TOPS: A self-help group for obesity. In Bray, G. A., ed.: Obesity in Perspective, Part 2. New York, Harper and Row, 1975, pp. 387--392. 71. Sutin, J.: Neural factors in the control of food intake. In Bray, G. A., ed.: Obesity in Perspective, Part 2. New York, Harper and Row, 1975, pp. 1-12. 72. Vaisrub, S.: Psychoneurosis and obesity-The hen and egg dilemma. J.A.M.A., 230:591, 1974. 73. Williams, R. L., Karacass, 1.: Kleine-Levine syndrome. In Reises, M. F., ed.: American Handbook of Psychiatry, Vol. 4. New York, Basic Books, 1974, pp. 863-868. 74. Withers, R. J.: Problems in the genetics of human obesity. Eugen. Rev., 56:81--90,1964. 75. Young, D. R., Pelligra, R., et al.: Glucose oxidation and replacement during prolonged exercise in man. J. Applied Physiol., 23:734-741,1967. Warren 6 Massachusetts General Hospital Boston, Massachusetts 02114
Basic Considerations in the Treatment of Obesity Frederick G. Guggenheim, M.D.*
Most people have experienced some of the signs, symptoms, and behaviors of obesity. For example, many have been overweight at some time in their lives and have had another sign of obesity, an excess bulge of fat. Again, most people have experienced a cardinal symptom of obesity, an increase in an appetitive urge for some specific delicious food stuff. Finally, every normal person has probably had at least one episode of a common behavior attributed to obesity: gluttony. For each of us has eaten far too long, or too fast, or too much on some occasions. Common sense would then dictate that obesity is a pathological deviation of commonly understood signs, symptoms, and behaviors that produce morbid corpulence. A frequent problem in adults,34 often adversely affecting health,9,37,43 obesity is usually as poorly understood as it is treated. More than three fourths of a representative polling of American physicians 34 attribute obesity to "a lack of willpower," rather than to psychological or medical ptoblems. Trained in the natural sciences, physicians are all aware that human beings do not defy the second law of thermodynamics: excessive body weight results from a surfeit of caloric intake over caloric expenditures. As such, it should seem that a proper vigorous combination of rational instruction, kindly support, and moral suasion ought to produce weight loss. But such has not been the case. Indeed, Stunkard,66 in surveying the results of treatment outcome for obesity up until the last decade, has stated: "Most obese patients won't even come for treatment. Those who do often drop out. Those who don't drop out, don't lose much weight. Finally, those who do lose weight usually regain it." About 90 per cent of those who lose weight will regain it after a variable period of time. 72 No wonder that 7 of 8 physicians report frustration with their motivational efforts on at least half of their encounters with obese patients. 34 Yet most obese people feel they should be able to lose large amounts of weight in short periods of time with little discomfort. 66
':'Assistant Professor of Psychiatry, Harvard Medical School, Associate Psychiatrist, Massachusetts General Hospital, Boston, Massachusetts
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The profusion of nonmedical treatment for obesity (Weight Watchers, Diet Workshop, TOPS, Over-eaters Anonymous) is ample evidence of the nation's increasing interest in conquering obesity. Those "uncooperative" patients still want to lose weight.
THE PLAN This paper will present experimental data relevant to the production of obesity in animals as a background to presenting a series of syndromes seen in human obesity. Although gluttony surely is one cause of obesity, we now know that there are a large variety of other syndromes that lead to obesity. We will then present a system for classifying data relevant to understanding and treating (or not treating) the individual for obesity. Finally, we will briefly review the status of several relatively new and successful treatments in obesity: behavior modification, ileojejunal bypass, self-help groups, and modified protein-sparing diets. For experimental animals and for man, obesity can be defined in a variety of ways. 25 Probably the most uniformly accepted and used standard is that of 20 per cent heavier than mean established optimal weight on a weight-height table. Applying Archimedes principle, body density can be weighed in water. Intrinsic 4°K can be measured with whole body scanning. Triceps skin-fold thickness can be detennined, obesity being defined as a thickness of more than 18 mm for males, 25 mm for females. But probably the most widely used test for obesity is the Eyeball Test. If a person or an animal looks fat, it is. How can experimental obesity in animals best be understood? In a helpful conceptualization, Bray4 has divided the subject into five basic types (see Table 1). The first type of experimental obesity is the hypothalamic type.
Table 1. Experimental Obesity in Animals Neurological Hypothalmic injury to ventromedian nucleus Other central vervous system lesions Endocrinologic Excess glucocorticoids Excess insulin Castration
"Adapted from Bray4
Dietary Single daily feeding High fat diet Gulping-gorging Inactivity Genetic Dominant Recessive Polygenic
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EXPERIMENT AL OBESITY IN ANIMALS Hypothalamic Injury Injury involving the hypothalamic ventromedian nucleus (HVM) has produced a number of profound bodily disturbances, including obesity. Feeding behavior is characterized by hyperphagia when food is freely available and hypophagia when any sort of impediment is placed in the way of eating, a pattern reminiscent of human obesity.56 The weight increase in HVM-injured animals continues until the pre-Iesion weight has been doubled and then remains stable as the hyperphagia recedes. Subsequent fasts in HVM-injured animals are again followed by hyperphagia doubling of pre-Iesion weight. Other observations associated with these HVM-injured animals include: hyperinsulinemic response to feeding, increased storage of unsaturated fatty acids (palmitic acid), and a decrease in motoric behavi~r.4 First electrolytic and surgical ablative, then chemical (gold thioglucose) lesions produced significant obesity, suggesting that a satiety center 71 was being destroyed. In parallel with these studies were ablative studies in the areas of the hypothalamic lateral nucleus (HL). Lesions here produced profound aphagia because of disruption of a postulated feeding center. Although the exact neuroanatomic localizations of these nuclei have recently been called into some doubt,21 the dual mechanism theory has proved heuristic ally useful. More recent neurochemical studies of putative central nervous system neurotransmitters have implicated serotonin as a possible active transmitter in the hypothalamic ventromedian nucleus,5,53 since intracerebroventricular injections of p-chlorophenylalanine can produce obesity by depleting serotonin and disinhibiting feeding behavior. Depletion of norepinephrine apparently produces aphagia. 1 Endocrine Manipulations A second type of experimental obesity in animals is that produced by endocrine manipulations. 4 The degree of obesity, however, is less striking than with hypothalamic obesity. An excess of glucocorticosteroids will produce an excessive amount of fat, although weight gain is not necessarily significant. Steroid administration apparently modifies the metabolism of adipose tissue toward an increased preference for fat storage. 30 Excess insulin treatment temporarily increases body weight during the experimental phase by producing a hyperphagia, presumably through stimulation of some glucostatic receptors in the hypothalamic lateral nucleus,17 Castration also produces obesity, presumably through alteration of levels of reproductive hormones. 4 Dietary Manipulation Quantity, quality, and frequency of feeding all can influence adipose deposition and weight. It comes as no surprise that caloric intake is
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related to an animal's weight. But results of Fabry and Tepperman's18 important experiments of regulation of frequency of feeding are not well known in the medical community. These investigators worked with genetically identical groups of rats. The control group was allowed chow as usual (frequently, ad libitum), producing a stable weight pattern. A second group of animals were given the same number of calories of chow, but through a stomach tube, with only 2 feedings per day. The latter group accumulated a significantly increased amount of adipose tissue as compared to the control group. A second way in which an alteration of diet can effect adiposity is through an increase in the quantity of dietary fat. Usually rats fed chow ad libitum maintain a stable weight pattern. But given a diet rich in fat, certain strains of rats are unable to reduce total food intake to compensate for increased caloric density, developing gross obesity.57 Finally, another dietary factor amenable to manipulation is the feeding condition. For example, with identical infant rat litters,31 one group was allowed free access to food throughout the 24 hour day, the control group having access only during 2 hours per day. The latter, deprived rats, after weight loss, learned to gulp their food, and soon outgained their litter mates, becoming obese. This abnormal feeding pattern and obesity persisted into adulthood long after free access to food was established. Restrictions on Activity Restriction of physical activity is a simple means of producing obesity in the rat. 33 Usually an increase in physical activity is matched in the experimental animal by an appropriate augmentation of caloric intake, so that weight remains stable. But with very low levels of physical activity, food intake does not match energy needs and the animal has a considerable weight increase. 45 Genetic Obesity A number of obese strains of mice have been carefully studied. 4.11 ,19,34 In many instances, chromosomal mutations are a necessary but not a sufficient cause for the production of obesity. For example, with the dominant yellow strain (AY, AVY, NY) with an aberration on chromosome 2, if there is crowding and a warm cage, obesity develops; but if there is a colder cage without crowding, obesity does not develop despite ad libitum feeding. With the dominant New Zealand obese (NZO) strain, obesity develops with ad libitum feeding unless the female is breeding or has been treated with stilbestrol. Two recessive strains of mice, obese (ob/ob with a mutation on chromosome 6), and diabetes (db/db with its abnormality on chromosome 4) develop identical syndromes of obesity and hyperglycemia, but again only if given ad libitum feeding. Coleman,l1 working with these two strains of mice with identical genetic backgrounds (which allows for parabiotic experimentation), has described two different mechanisms shaping hyperphagic behavior. In the obese (ob/ob) mouse, parabiotic experiments point to a decreased production of a satiety factor. But with
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the diabetic (db/db) mouse, there is a decreased responsiveness to satiety factor. In summary, identical obese, hyperglycemic syndromes in mice with identical genetic backgrounds can be produced by unrelated genes working through a variety of different mechanisms.
OBESITY IN MAN It would be useful to the clinician if the five types of obesity in animals 4 could be used as a classifying principle for obesity in man. However, there are a number of reductionistic difficulties. First of all, the genetic background of human obesity is "a geneticist's nightmare."32 Secondly, there are a variety of environmental, psychological, and medical conditions for which there are currently no experimental analogues. Nonetheless, some useful system of classification is needed to replace the outmoded "endogenous" versus "exogenous" obesity paradigm. This latter term can be applied to a vast majority of patients seen in obesity clinics and bariatric practices. Indeed, Solomon 61 has reported that 90 per cent of patients evaluated at the Johns Hopkins Obesity Clinic had no demonstrable endogenous cause for their obesity. Moreover, the term "exogenous obesity" tends to place the blame for the condition solely on the patient, although surely we would not blame ob/ob or db/db mice with lack of willpower when they ate large meals. Finally, the endogenous-exogenous dichotomy tends to give the clinician a false sense that he understands the condition: which at this phase of our studies, we do not. Wastebasket terms rarely help us with either our understanding or our treatment. Most types of obesity fall into nine categories listed in Table 2. In many instances, several of these factors will be etiologically associated with obesity. Not listed in Table 2 is "essential obesity," a term reserved for those types of obesity, analogous to hypertension, for which no etiologic factors have yet surfaced.
Genetic Obesity Clear-cut genetic obesity in man is rarely if ever encountered by most clinicians. 4 Suffice it to say that people with Prader-Willi syndrome, one genetic type of obesity, are mildly mentally retarded, sexually immature, and have strong cravings for food. Those with the Laurence-MoonBardet-Biedl syndrome are also mentally retarded and also have retinitis pigmentosa. Other rare syndromes include the Morgagni-Morel syndrome and the Alstrom syndrome. Table 2. Types of Human Obesity Genetic NeurologiC Endocrinologic Dietary Inactivity
Socio-occupational Developmental Psychological Pharmacological
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Yet a variety of studies have pointed toward genetic factors, presumably of a polygenic nature, influencing the ability to gain or lose weight. Identical twins even when reared apart, tend to have similar weights. 34 Adopted children resemble their biological parents in body weight more than their adoptive parents. 74 Bruch7 cites a variety of older studies: if one parent is obese, 40 per cent of the offspring will be obese; if both are obese, 80 per cent of the offspring will be obese. As corollary, 90 per cent of obese children have a family history of obesity. 35 Such studies, of course, are not controlled for socioenvironmental and developmental factors. Other studies also raise the specter of genetic influence, although developmental factors can not be ruled out. For example, Sims 60 and Goldman 23 have convincingly demonstrated resistance to fattening in certain of their normal weight volunteers during periods of hyperphagia. Miller4 9 has demonstrated that some people actually do have resistance to slimming. However, lack of any current markers prevent all but speculation on the degree of variance accounted for by genetic factors in human obesity.
Neurologic Causes Most known neurologic causes of obesity are associated with obvious neurologic symptoms. 4 Sources of hypothalamic injury include: craniopharyngiomas, encephalitis, and physical trauma. There are also two types of neurologic obesity without obvious neurologic symptoms or signs. First is the Kleine-Levin syndrome of periodic hyperphagia and hypersomnia. 73 Second, a syndrome of preoccupation with food and electroencephalographic abnormalities has recently been described in a group of patients from a psychiatric clinic. 26 After initiation of therapy with diphenylhydantoin (Dilantin), not only did the preoccupation with food cease, but the hyperphagia stopped promptly and weight went down toward normal parameters. Endocrinologic Causes Endocrinologic causes of obesity include: Cushing's syndrome, diabetes mellitus, insulinoma, castration, and Stein-Levinthal syndrome. They have recently been described in detail elsewhere. 4
Dietary Preferences for high density caloric foods or for large amounts of food can result in obesity. In some instances, this preference may amount to willful gluttony. Unfortunately, our ability to differentiate voluntary gluttony from involuntary succumbing to an-irresistible-urge-from-theappetite-center is limited. Another cause of dietary obesity involves the schedule of eating. It may be that those who eat only once per day and especially those who eat just prior to retiring may be more prone to accumulate adipose tissue. Finally, experimental obesity has been recently studied by college students and prisoners volunteering to overeat. 23.60
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Restricted Activity Physical inactivity is an accompaniment of spontaneous and experimental obesity in man. 4 ,4L46 On some occasions, as in forced bed rest for medical purposes, a modest degree of obesity may develop. For example, a deficit of the physical exercise equivalent to running a mile a day, if not corrected by a decrease in appetite, adds a surfeit of 200 calories a day.27 Over a one year span, such an individual would gain 11 to 22 pounds. The role that decreased physical activity has in the initial genesis or the propagation and maintenance of most cases of obesity is unclear. Exercise, for example, has been shown to increase the synthesis of glucose rather than fat from endogenous lactate,75 whereas inactivity results in decreased glucose utilization with a decreased difference in arteriovenous glucose concentrate which Mayer46 has hypothesized could lead to a stimulation of hypothalamic appetite center.
Sodo-Occupational Factors Mild to moderate obesity is valued and sought for amongst certain groups. For example, Sumo wrestlers and other professional athletes at times aspire toward obesity as an aid in competition. A manly "pot-belly" is esteemed by certain wealth European bourgeoisie. Some African chieftains value fat wives as a sign of financial success. Standards of feminine beauty, as portrayed in the Venetian women of Rubens and Parisiennes of Ingres, required a mild degree of obesity. Obesity also occurs in lower socioeconomic classes. 22 About one third of all lower class American women are obese, compared to 1 in 20 in the upper socioeconomic classes. Although presumably some factors involved may be dietary (foods of lower classes tend to be protein deficient and carbohydrate rich), a variety of other poorly understood factors, including stress, may also be involved.
Developmental Factors During the developmental stages from fetus to infant to adolescent, a number of complex biological and psychological factors play critical roles in the development of adipose tissue, hypothalamic centers, body image, ego and sense of self. Prenatal nutrition, for example, has been demonstrated as an important factor in the subsequent adult body weight in the development of obesity. Ravelli,52 surveying the birthplaces and birthdates of Dutch boys 19 years after an acute catastrophic famine (involving part of the Netherlands in the closing days of World War II), has convincingly demonstrated that those boys whose mothers suffered severe famine in the first trimester have a significantly greater likelihood of being obese than control cohorts. By contrast, those boys whose mothers were afflicted by the famine during the last trimester are now noted to have a significantly increased likelihood of being underweight. By analogy, those American mothers who were severely afflicted with hyperemesis gravidarum, or who were on crash diets during the first trimester might have inadver-
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tently subjected their offspring to conditions which programmed the developing hypothalamus to respond to life as if it were starving. Another demonstration that nutrition during infancy also has potential for producing profound and lasting effects comes from Charney'slO follow-up of infants weighed at 6 months of age. On follow-up 20 years later, he found a significant increase in obesity in those infants in the upper quartile (75 to 100 per cent) by weight as compared to their peers in the lower quartile (1 to 25 per cent). Obesity of infancy and childhood induces not only the usual hypertrophy of adipocytes, but hyperplasia of these cells with an increase in their absolute cell number. Knittle,38 studying the size and number of adipocytes in children has concluded that a critical period for adipose tissue development occurs somewhere between birth and age two. This time frame has important consequences for future development of the size of the fat depot in the adult. A second period appears to be the prepubescent and adolescent period when cellular proliferation may occur again in these subjects. Thus, whether the baby fat "melts away" or continues to increase in amount during prepubescence may be determined by the adipose cell count. Intrapsychic determinants of "obesogenic mothers" vary widely. Some developmental obesity results from simple, misguided maternal feeding practices. Some mothers vaguely believe: "A fat baby is a healthy baby!" But the behavior of other mothers may be more complex, using the children's eating behaviors as a means of undoing: "My family lived in grinding poverty in the Old Country. That will never happen to you!" Still other mothers have convoluted, troubled, and tenaciously held convictions about feeding that relates to their own conflicted upbringings: "I'll show them what a good mother I am. You'll eat everything I cook for you!" Maternal psychogenic factors in developmental obesity have been described extensively by Hilda Bruch 7 and others.36 Bruch 6 noted that mothers of obese children often are unusually concerned, anxious, and extraordinarily domineering. Many relate to their children as if they were possessions, without respect for individuality or particular needs. Often the children are used to compensate for overwhelming frustration or disappointment. 48 Much ofthe emotional interchange of mother and obese child is ambiguous and ambivalent, especially the giving and accepting of food. Kalucy36 notes four features peculiar to these families: (1) these mothers use food as a primary means of giving comfort, relieving distress, and rewarding desired behavior, often to the exclusion of holding, encouraging, or nursing; (2) these mothers often respond to the children because of their own anxieties or needs, leading to further confusion between internally felt stimuli and external actions; (3) such mothers tend to come from families and cultures where "all food served has to be eaten," further diminishing the relationship between internal cues and external behaviors relating to physiologic needs; (4) finally, obese children come to expect that all their distress and positive feeling will be responded to by the giving of food. Consequent to these mixed and distorted cue signals the child develops:36
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(1) a decreased capacity to discriminate between internal cues such as anger, depression and hunger, coupled with a tendency to respond to non-hunger cues by eating; (2) an inappropriately heightened, often fragile acceptance of one's essential rightness, coupled with an insecurity about personal effectiveness. Here narcissism, buttressed with denial, reaction formation, and a dissociation of the impact of eating on weight and behavior occur; (3) an inability to develop personal skills leading to independence coupled with a hypersensitivity, immaturity, and diminished objectivity; (4) the capacity to distort important relationships especially during dieting and intense emotional interchange. Added to these internal difficulties is the harsh societal rejection of the obese child and adolescent.2.8.15.29 These rebuffs often result in a sense of self-loathing and a negative sense of body image.29.36.67 Having said all this, we must still not lose sight of the fact that not all children of obesogenic families are overweight, nor are all obese children treated by the families in the same way.36 It remains unclear why certain children of these obesogenic families escape pernicious infiuence. Indeed, in actual practice, it is often difficult to know whether emotional factors contributed to the genesis of developmental obesity or whether psychological problems are secondary to social rejection these youngsters encounter, since the two factors are often so closely intertwined. 7 In making a prognosis, no single medical or psychological factor has permitted a definite prediction of the course of developmental obesity. 7 Long-term predictive studies following fat cell counts show great promise, and are now under way.38 Assessment of problems within the family and the emotional maturity of the child so far has been of greater importance for prediction than physical factors. Bruch 7 has summarized the poor prognostic signs in developmental obesity: 1. early onset (although there are exceptions); 2. lack of physical activity, especially if coupled with social isolation and withdrawal; 3. lack of familial stability, warmth, and support; 4. the presence of familial anxiety and discord, preventing the child's striving for independence; 5. inadequate achievement in the Draw-A-Person test, and to a lesser extent, a discrepancy between performance and verbal on the IQ test; 6. paradoxically, the more medical treatment, the worse the prognosis. By contrast, those efforts at weight reduction that are prompted by the obese child or adolescent are much more likely to end in success than those prompted by others.
Psychological Factors In the previous section on developmental obesity, we detailed ways in which obesity itself can cause emotional confiict. Harsh societal judgments about obesity, for example, can warp an individual's sense of self, with a distortion of body image and self-loathing. We also detailed
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how obesity can be associatively linked with psychological turmoil by a common etiologic link, the obesogenic mother. In this section, we shall discuss those types of adult-onset obesity that are strongly related to psychological factors. No clear estimate exists for the proportion of adult-onset obesity that is the end-product of coping with emotional problems. Nor is there any particular personality type in obesity.36 Attempts to link obesity with neuroticism and neurotic conflicts have yielded some paradoxical results. For example, Graff.!4 and others have shown that the obese, particularly the obese male who is not under any medical or psychiatric treatment, has fewer neurotic lifestyle characteristics than occur in the normal population. The "superstability" of the obese may indicate that they are unusually mentally healthy. Or this super-stability may indicate that the obese are, as a group, protected against the experience of neurotic symptomatology.36 Clinic populations of obese individuals, however, have a higher than normal level of neuroticism.1 2 This may be because: (1) eating and obesity are no longer adequate defenses, and (2) the development of a neurotic illness, however independent of obesity, may lead to an increasing need for seeking out comfort, relief, and security. 36 Two types of psychological obesity are often seen and easily identified. These are reactive hyperphagia and symbolic obesity. Whereas some patients with developmental and other types of obesity may profess a desire to lose weight for locomotion, health, or cosmetic reasons, people with reactive hyperphagia and symbolic obesity may be disinterested in or ambivalent about weight reduction through dieting. Reactive hyperphagia, which includes binge eating, usually develops in a setting of emotional trauma such as death of a close family member, the break-up of a love affair, or separation from home. At times even threat of separation, rejection, or injury may trigger reactive hyperphagia. For example, some of the weight gain in pregnant women or even in expectant fathers revolves around issues of fear of not being adequately supported after the birth of the child. Another issue might be fear of being drained by the baby. Eating wards off feelings of anxiety, depression, and loneliness. Here, not the obesity, but the oral gratification and the sense oftranquilization from being "stuffed" are important. Another type of obesity with a strong psychogenic component is symbolic obesity. Here the size or the appearance of the obese person is not a problem, but rather a solution. One example is a woman who fears that she will again resume sexual promiscuity should her weight and appearance return to normal; she continues to invest in being fat. Other examples: the financially successful industrialist who sees his giant size as reflecting the degree of his absolute power to control, and the ghetto matriarch with the bouffant hair-do and bright, flowing robes who sees her size as a sign of dominance over others in her realm. Despite physicians' diligence at pushing weight reduction regimens, some patients will not want to cooperate until obesity presents problems with locomotion or severe health hazards. Those with symbolic obesity see their overweight as an asset, not as a liability.
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Obesity and overeating can defend against the development of feelings of anger, depression or anxiety triggered by unresolved, underlying conflicts. Disruption of (compensatory) eating habits on the other hand, can lead to significant emotional distress. Emerging psychological symptoms can vary from mild depression to transient though severe anxiety, depersonalization, and even transient delusions. 3 However, the emergence of severe psychopathology seems to be more the exception than the rule. 69 Those obese people most at risk have developmental obesity. To a lesser extent, those with acute ongoing stress may also be prone to develop psychological symptoms during dieting or starvation. Another syndrome of potential psychological vulnerability while dieting is the night eating syndrome. 65 Prognostic ally, this is also a useful indicator of little chance for substantial weight loss. A transient syndrome, it is characterized by initial insomnia, the induction of sleep or tranquilization by massive caloric ingestion, and morning anorexia. It may account for 10 per cent of patients seen in an obesity clinic. Neither the underlying dynamics nor the pathophysiology of this syndrome have been completely elaborated.
Pharmacologic Causes The advent of antipsychotic, antidepressant, antihistaminic, antiserotonergic, and anti-inflammatory agents have produced a variety of iatrogenic obesities. As of this time, no body of knowledge has yet been generated that adequately accounts for this phenomenon, one that has perplexed physicians and bedeviled their patients. Pediatricians have observed that cyproheptadine (Periactin) produces considerable obesity in normal, underweight children, as well as children with psychological problems. 28 Nonsystematic observations that other antihistamines are not as potent a stimulus to hyperphagia have not been carried out yet, nor have the responsible mechanisms been defined. But interestingly, interventricular injections in rats of a blocker of serotonin synthesis, p-chlorophenylalanine, has produced experimental hyperphagia and obesity.5 Concomitant depletion of serotonin and norepinephrine 53 does not produce hyperphagia. Selective depletion of norepinephrine itself produces hyperphagia in some studies. 1 The clinically useful anorexigenic agents often have effects on brain norepinephrine, dopamine, and serotonin brain tissue levels and turnover. Amphetamines release and deplete norepinephrine,28 yet selective depletion of norepinephrine itself produces not aphagia but hyperphagia.! The resolution of these seemingly paradoxical results may hinge on the pivotal roles of central serotonin levels and norepinephrine's regulation and stimulation of central serotonin synthesis storage and release. Serotonergic systems in the brain are very interesting in regard to control of feeding because they depend on dietary factors. They can be readily influenced by dietary tryptophan. How central serotonergic and noradrenergic mechanisms relate to the considerable obesity seen in many patients on antipsychotic agents such as chlorpromazine and haloperidol and the antidepressant amitriptyline is unclear. For example, whether the differential effects on block-
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ade of serotonergic and nor adrenergic uptake found amongst the tricyclic antidepressants can prove of use has not yet been clarified. Currently, many patients are in a considerable bind: abandoning tricyclic therapy predisposes to devastating depression. But taking medication (which produces a "sweet-tooth" for carbohydrates) produces an unwanted increase in weight. In some patients this pharmacologic obesity can induce a serious blow to self-esteem.
TREATMENT Obesity in humans and in rats have a number of clinical features in common: (1) hyperphagia in certain settings where tasty food is readily available; (2) a failure of satiety mechanisms; (3) finickiness about food; (4) unwillingness to work for food; (5) a reduction in hunger drive; (6) a decrease in spontaneous physical activity; (7) a consistent increase in weight to a certain set point. 50 All effective strategies for dealing with the syndrome of obesity must relate to these manifest behaviors. The anorexigenic medications such as chlortermine, fenfiuramine, and mazindol all try to inhibit the appetitive urges. Their efficacy has recently been reviewed. I6 The bulk replacers, through working on these satiety mechanisms 44 also try to turn off appetite mechanisms, but this time by stimulating the satiation-tranquilization response. Most of those agents do not expand in the stomach, but rather in the small intestine, thus acting as a cathartic agent. Acute intermittent fasts, especially during two weeks of hospitalization has proven to be quite successful and easily tolerated. I4 Perhaps some endogenous anorexigenic agent suppresses hunger and appetitive cravings or increases the sense of satiation. Unfortunately, not many insurance companies will pay for this or any other form of hospital treatment for obesity (save for ileojejunal bypass). Outpatient proteinsparing diets and modified fasts have recently been advocated 20 ,40 and, when coupled with a comprehensive program, have produced a mean loss of more than 40 pounds of weight in a group of 67 subjects, many maintaining that loss at one and two years post treatment. Some medical problems may be precipitated by fasting regimens however (hyperuricemia, cholecystitis, hypotension, etc.). Another approach to weight control involves primarily group support for modification of eating habits. TOPS70 and Overeaters Anonymous 39 have proven themselves to be very effective for some patients, perhaps helping the individual to deal strictly with standards for satiety mechanisms while avoiding situations in which hyperphagia becomes nearly inevitable. Behavior modification makes use of clinical behavior common to the HVM rat as well as the super-obese human, attempting and often succeeding in extinguishing certain dysfunctional behaviors leading to the increasing hyperphagic state. A significant detail in the behavior modification scheme is that the patient participates in the design of his treat-
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ment by observing his own eating behavior to produce a set of experimental conditions that can be shaped, reinforced, or extinguished. 64 The patient keeps daily records of his eating behaviors, noting the amount, time, and circumstances associated with his eating (what room, what body position, what other concomitant activity, what emotional state). Next, the patient shapes his behavior, agreeing only to eat in a certain place, for example, the kitchen, but never in the living room or in front of the television. Then he agrees only to eat in a sitting position, at mealtimes in the kitchen, and if the table is set. Later, he agrees to chew his food a certain number of times or put his utensils down on the plate in between bites, and to pause one or two minutes in the middle of the meal. These useful behaviors are promptly rewarded in ways meaningful to the patient (money, points, privileges, and so forth). Results from the mildly overweight and the severely overweight51 are good,68 proving that effective weight reduction could occur if behavioral principles are enunciated, even in a manual without physician support. One of the significant features about behavior modification is that individuals continue to lose weight even after they are no longer actively working in behavior modification, whereas most studies of people attending diet clinics, etc., show on follow-up that their weight does not stabilize or continue to go down but rather goes up. The relevance of getting the patient to focus upon environmental variables in the treatment of his obesity is based on Schachter's showing56 that much eating behavior of the obese is under environmental rather than internalized control. What is encouraging about the current behavior modification approach (as exemplified in Stuart and Davis' book, "Slim Chance in a Fat World: Behavioral Control of Obesity"63) is both the greater weight loss during treatment and the superior weight loss after treatment in comparison to traditional management of dietary instructions given to the patients, or the medication-encouragement approach. Finally, ileojejunal bypass operations, short-circuiting absorption areas for fat, have now been refined to a considerable degree. Both morbidity and mortality rates are considerably lower than a decade ago. 13 ,54,55 Criteria for selection, by an interdisciplinary team of internists, psychiatrists, surgeons, patients and spouse 42 include the following criteria: (1) weight of more than 100 pounds in excess or twice ideal body weight; (2) failure of all reasonable available alternative treatments to control the continued weight gain; (3) absence of a history of alcoholism, severe reactive anorexia, or ongoing pregnancy; (4) high persistent motivation by the patient for the procedure; (5) ability to be treated for any severe concomitant medical and/or psychiatric condition prior to operation if these might interfere with immediate or longer-term immediate postoperative course (unstabilized psychosis, moderatesevere depressive reaction); (6) ability to maintain good doctor-patient follow-up; (7) absence of severe masochistic or immature personality traits; (8) absence of consistently unreasonable expectations. Through such vehicles of new hope, family and medical team encouragement, and the immediate aversive consequences of a diarrheal
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bowel movement or abdominal cramps, many super-obese patients have been able to correct their weight and their lives toward normal. 62 Interestingly, we have noted that bypass patients spontaneously begin ingesting smaller meals, develop a lack of frequent binge-eating, and suspend eating as a replacement for other gratifications. Yet at a time when Blue Cross (in certain states) has acknowledged this procedure as the only reimbursible treatment for morbid obesity, some clinics no longer perform the procedure because of morbidity with it in their hands. 47
SUMMARY The recognition and treatment of obesity has undergone marked changes in the past two decades. Along with the abandoning of the concept of exogenous obesity, the physician has discovered a variety of developmental, psychological, pharmacologic, socioeconomic, neurological, and genetic roots for the syndrome. The clinician has also found medical treatment modalities (fasting and behavior modification) that hold much more prOInise than traditional supportive relationships with dietary consultation and anorexogenic medications. Surgical treatment also, ileojejunal bypass, is gradually emerging as a treatment of choice for certain well-motivated, super-obese people for whom all other treatment modalities have failed. Future research into central serotonergic mechanisms offers hope that we can begin to know what it is that turns on hunger, turns off appetite, and regulates weight in such a stable manner over such a long period of time.
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47. Medical News: Bypass operation loses favor in obesity treatment. J.A.M.A., 236:2729, 1976. 48. Mendelson, M.: Psychological aspects of obesity. Med. Clin. N. Amer., 48:1373-1385, 1964. 49. Miller, D. S., and Parsonage, S.: Resistance to slimming. Lancet, 1 :773-775, 1975. 50. Nisbett, R. E.: Starvation and the behavior of the obese. In Bray, G. A., and Bethune, J. E., eds.: Treatment and Management of Obesity. New York, Harper and Row, 1974, pp. 45-57. 51. Penick, S. B., Filion, R., Fox, S., et al.: Behavior modification in the treatment of obesity. Psychosom. Med., 33 :49-55, 1971. 52. Ravelli, G. P., Stein, Z. A., Susser, M. W.: Obesity in young men after famine exposure in utero and early infancy. New Eng. J. Med., 295 :349--353, 1976. 53. Saller, C., and Strickler, E.: Hyperphagia and increased growth in rats after intraventricular injection of 5, 7-dihydroxytryptamine. Science, 192 :385--387, 1976. 54. Salmon, P. A.: Intestinal bypass: Clinical experience and experimental results. In Bray, G. A., ed.: Obesity in Perspective, Part 2. New York, Harper and Row, 1975, pp. 473496. 55. Sandstead, H. H.: Jejunoileal shunt in morbid obesity. In Bray, G. A., ed.: Obesity in Perspective, Part 2. New York, Harper and Row, 1975, pp. 459-472. 56. Schachter, S.: Obesity and eating. Science, 161 :751-756, 1968. 57. Schemmel, R., Mickelsen, 0., and Gill, J. L.: Dietary obesity in rats: Body weight and fat accretion in seven strains of rats. J. Nutr., 100:1041-1048, 1970. 58. Scott, B. T.: How doctors help motivate patients to shed pounds. Medical Opinion, 1974, pp. 36-41. 59. Seltzer, C. C.: Genetics and obesity. Physiolopathology of Adipose Tissue, Report of 3rd International Meeting of Endocrinology Excerpta Medica, 1968, pp. 325--334. 60. Sims, E. H.: Studies in human hyperphagia in treatment and management of obesity. In Bray, G. A., and Bethune, J. E., eds.: Treatment and Management of Obesity. New York, Harper and Row, 1974, pp. 28-44. 61. Solomon, N.: The study and treatment of the obese patient. Hospital Practice, 1969, pp. 90-94. 62. Solow, C, Silberfarb, P. M., and Swift, K.: Psychosocial effects of intestinal bypass surgery for severe obesity. New Eng. J. Med., 290:300--304, 1974. 63. Stuart, R. B., and Davis, B.: Slim Chance in a Fat World: Behavioral Control of Obesity. Illinois, Research Press, 1972. 64. Stuart, R. B.: Behavioral control of overeating: A status report. In Bray, G. A., ed.: Obesity in Perspective, Part 2. New York, Harper and Row, 1975, pp. 367-385. 65. Stunkard, A. J., Grace, W. J., and Wolff, H. G.: The night-eating syndrome. Amer. J. Med., 19:78-86,1955. 66. Stunkard, A., and McLaren-Hume, M.: The results of treatment for obesity. Arch. Intern. Med., 103:79-85, 1959. 67. Stunkard, A., a Stunkard, A., and McLaren-Hume, M.: The results oftreand Mendelson, M.: Obesity and body image. Amer. J. Psychiat., 123 :134-138, 1967. 68. Stunkard, A.: New therapies for the eating disorders. Arch. Gen. Psychiat., 26:391-398, 1972. 69. Stunkard, A. J., and Rush, J.: Dieting and depression reexamined. Ann. Intern. Med., 81 :526-532, 1974. 70. Stunkard, A.: Studies on TOPS: A self-help group for obesity. In Bray, G. A., ed.: Obesity in Perspective, Part 2. New York, Harper and Row, 1975, pp. 387--392. 71. Sutin, J.: Neural factors in the control of food intake. In Bray, G. A., ed.: Obesity in Perspective, Part 2. New York, Harper and Row, 1975, pp. 1-12. 72. Vaisrub, S.: Psychoneurosis and obesity-The hen and egg dilemma. J.A.M.A., 230:591, 1974. 73. Williams, R. L., Karacass, 1.: Kleine-Levine syndrome. In Reises, M. F., ed.: American Handbook of Psychiatry, Vol. 4. New York, Basic Books, 1974, pp. 863-868. 74. Withers, R. J.: Problems in the genetics of human obesity. Eugen. Rev., 56:81--90,1964. 75. Young, D. R., Pelligra, R., et al.: Glucose oxidation and replacement during prolonged exercise in man. J. Applied Physiol., 23:734-741,1967. Warren 6 Massachusetts General Hospital Boston, Massachusetts 02114