depression and eating disorders

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Casper AND ANXIETY, VOLUME 8, SUPPLEMENT 1:96–104 (1998) DEPRESSION

DEPRESSION AND EATING DISORDERS Regina C. Casper, M.D.* Both depressive disorders and eating disorders are multidimensional and heterogeneous disorders. This paper examines the nature of their relationship by reviewing clinical descriptive, family-genetic, treatment, and biological studies that relate to the issue. The studies confirm the prominence of depressive symptoms and depressive disorders in eating disorders. Other psychiatric syndromes which occur with less frequency, such as anxiety disorders and obsessive-compulsive disorders in anorexia nervosa, or personality disorders, anxiety disorders, and substance abuse in bulimia nervosa, also play an important role in the development and maintenance of eating disorders. Since few studies have controlled for starvation-induced physical, endocrine, or psychological changes which mimic the symptoms considered diagnostic for depression, further research will be needed. The evidence for a shared etiology is not compelling for anorexia nervosa and is at most suggestive for bulimia nervosa. Since in contemporary cases dieting-induced weight loss is the principal trigger, women with self-critical or depressive features will be disproportionately recruited into eating disorders. The model that fits the data best would accommodate a relationship between eating disorders and the full spectrum of depressive disorders from no depression to severe depression, with somewhat higher rates of depression in bulimic anorectic and bulimia nervosa patients than in restricting anorexia nervosa patients, but the model would admit a specific pathophysiology and psychopathology in each eating disorder. Depression and Anxiety, Volume 8, Supplement 1:96–104, 1998. © 1998 Wiley-Liss, Inc. Key words: depression; anorexia nervosa; bulimia nervosa; endocrine changes; sleep studies; family studies; relationship

INTRODUCTION

Eating disorders—the term now encompasses anor-

exia nervosa (AN) and bulimia nervosa (BN)—are classified as psychiatric disorders, yet there is no consensus about the nature of the underlying psychopathology. Patients experience difficulties in a broad range of psychological domains. Consistently documented throughout history are a low self-esteem, body dissatisfaction, and a self-critical attitude (Janet, 1903; Casper et al., 1981; Bell, 1985) which, considering the age of onset in adolescence in AN and the bias for females, have led to suggestions, starting with Freud (1950), that eating disorders manifest a variant of depression. Connections between the two disorders could not be scrutinized, however, until Feighner’s research criteria (RDC) (1972) were amended with the introduction of the DSM III criteria. The RDC criteria did not permit a diagnosis of AN in the presence of an affective disorder. Since then, several theories (see Fig. 1) have been offered: (1) an inherent depressive disposition might pave the way for the eating disorder,

© 1998 WILEY-LISS, INC.

(2) both disorders might arise from a common foundation and, conversely, (3) the eating disorder process may expose and set into motion a genetic or biologic vulnerability for depression. Numerous studies have been devoted to examining these theories from a descriptive-diagnostic viewpoint, through family genetic studies and through biological studies and several articles (Strober and Katz, 1987; Szmuckler, 1987; Pope and Hudson, 1988) have discussed the relationship between eating disorders and depressive disorders. Few studies have taken note of the fact that both depressive disorders and eating disorders are multidimensional and seem to be heterogeneous disorders. For instance, in phenomenology and treatment response, depressive disorders associated with atypical

Stanford University, School of Medicine, Stanford, California *Correspondence to: Regina C. Casper, M.D., Stanford University, School of Medicine, Room 2365, Stanford, CA 94305-5546. Received for publication 8 August 1997; Accepted 2 September 1997

Research Article: Depression and Eating Disorders

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appetite, but in anorexia nervosa, hunger is felt, unless the emaciation has become life-threatening. Another example would be “early morning awakening,” a symptom presumably indicative of melancholia, which is commonly observed in underweight AN patients, in whom it reflects a different state of mind and mood than in the depressed patient. Instead of feeling immobilized by hopeless ruminations, as depressives do, AN patients awake early full of energy, sprightly, and active. Methodologically it would be most appropriate to reevaluate the patient in positive metabolic balance after a significant amount of weight gain (10%); unfortunately, few studies have attempted to control for undernutrition.

DISTURBED EATING ATTITUDES AND BEHAVIOR AND DEPRESSED MOOD IN NORMAL ADOLESCENTS Figure 1. Hypothetical relationships between depression and anorexia nervosa.

physical symptoms, such as hypersomnia and hyperphagia, can be easily distinguished from classical endogenous depressions, associated with insomnia and appetite loss. Similarly, in the eating disorders evidence from descriptive (Casper et al., 1980; Garfinkel et al., 1980; Strober et al., 1982; Casper, 1990) and outcome studies (Strober et al., 1996) supports a distinction between the restricting and the bulimic type of anorexia nervosa. Few studies have investigated the full affective disorder spectrum in relation to the full spectrum of eating disorders. Another problem which has received little attention is to what extent depression ratings measure signs of starvation. We will first discuss some of the methodological problems of validating a diagnosis of depression in eating disorders and then review the evidence for a role of depression in AN, separately from that in BN.

PROBLEMS WITH ASSESSING DEPRESSION IN EATING DISORDERS The use of physical symptoms as criteria for the diagnosis of depression (physical symptoms which overlap with the physiological signs of starvation or excess food intake, such as weight loss, insomnia, or hypersomnia) raises questions about the validity of depression rating scales for diagnosing depression—or even anxiety—in eating disorders. Even more problematic is the tacit assumption that physical symptoms named alike carry the same meaning (for a more detailed discussion, see Casper, 1987). It is well known that the designation anorexia in AN is a misnomer. “Anorexia” denotes loss of

Cross-sectional surveys of normal adolescent populations have shown positive correlations between mood disturbances and eating and weight concerns, not only for females but also for males (Casper et al., 1981; Richards et al., 1990). Steiger et al. (1992) found in adolescent girls with concurrent mood and eating symptoms more self-criticism and family problems along with body image concerns. Girls with abnormal eating patterns, but no mood changes, expressed body concerns but they had a normal psychological profile.

ANOREXIA NERVOSA DESCRIPTIVE AND DIAGNOSTIC STUDIES Self-concept and body concept. If we consider features related to depression, the most consistent findings reported by AN patients of different ages are disturbances in self-concept, including self-critical attitudes which extend to the body and undermine self-esteem (Casper et al., 1981). These findings have been replicated across independent samples (Swift et al., 1986) and across countries (Steinhausen and Vollrath, 1993), suggesting a specific transcultural self-image profile in AN. Indeed, Laessle et al. (1988) found that the negative self- and body-valuation explained between 34 and 45% of the variance in the depression score of eating disorder patients. It is important to remember that self-esteem has genetic components (Roy et al., 1995). Another risk factor for depression, parental loss, was found not to be a risk factor for eating disorders (Kendler et al., 1992). Symptoms of depression within the clinical range are common in hospitalized AN patients, with restricting patients scoring as less depressed on traditional self- and observer-rating scales than bulimic AN patients (Casper et al., 1980; Eckert et al., 1982; Rosen et al., 1989). DEPRESSIVE DISORDERS Table 1 lists the concurrent and lifetime diagnoses of affective disorders by frequency in, for the most

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TABLE 1. Prevalence of affective disorders in patients with anorexia nervosa Authors

Diagnosis

Number

Age in years

Cantwell et al., 1977

AN

26

19.7

Feighner

Not

Hendren et al., 1983

AN

84

24

Hudson et al., 1983

AN-R

16*

25

Criteria DMS-III DIS

Reported Not Reported 19%

Herzog et al., 1984 Walsh et al., 1985

AN-B AN AN-B

25 27 9

25.8 22.6 25.4

DSM-III SADC DSM III SADS

Laessle et al., 1987

AN-R AN-B AN-R

14 33 13

22.4 22.2 21.5

SADS DSM-III SCID

Fornari et al., 1992

AN-B AN-R

26 63**

22.1 ?

DSM-III-R SADS-L

Piran et al., 1985

Instruments

AN-B

Dysthymia

MDD

Bipolar D Comments

46.1%

0

56%

0

50%

13%

58% of mothers MDD Retrospective case study 13%

80% 55.6% 74.1% Life 56% Co: 33% 43% 37% 15%

12% 0 0

44% kleptomania Rater reliabilitiy? 33% alcohol abuse

42% Not

46% 54.2%

12% ?

Reported

72.2%

Not Reported Life 44% Control:0 Life 92% 73% 31%

0 0 0

Bulimic 9% Cyclo-thymic Lifetime rates comparable to depression 45.8% anxiety disorder

*One male. **Nine males.

part, hospitalized AN patients. Patients were on average in their early twenties, suggesting a more severe and chronically ill and perhaps treatment-resistant sample, since the age of onset for AN is close to middle adolescence (Casper, 1996). Prevalence rates ranged from 46–74% (Cantwell et al., 1977; Hendren, 1983; Hudson et al., 1983a; Herzog, 1984; Piran et al., 1985; Walsh et al., 1985; Laessle et al., 1987; Fornari et al., 1992). In the studies which subtyped patients, prevalence rates tended to be lower in restricters, from 15–50%, than they were in bulimic AN patients, from 46–80%. In the few studies that recorded dysthymia, rates showed a wide spread from 19–93 %. A lifetime diagnosis of depression did not rule out anxiety disorders, such as panic disorder or social phobia, which, if they were recorded, were diagnosed with some frequency in the studies. Comorbidity not only with major depression but also with phobias and alcoholism has been found in a population-based twin study of AN patients who met definite or probable criteria; unfortunately, the data were not analyzed by subtype (Walters and Kendler, 1995). The high percentage of AN patients fulfilling criteria for a major depressive episode could be taken to support an association between the two disorders, yet such a conclusion seems premature without knowing how many of the symptoms recorded as signs of depression were really epiphenomena of starvation.

pared to relatives of control populations. Strober et al. (1990) and Biederman et al. (1985) examined whether this familial aggregation might be related to the presence of a depressive disorder in the anorectic proband. Strober et al. (1990) also argued that if affective disorders and AN were expressions of a common biological pathology, then cross-transmission of both disorders should occur. Both studies (Biederman et al., 1985b; Strober et al., 1990), did find significant clustering of affective disorders in first- and second-degree relatives of AN patients with coexisting depression, observations which disagreed with an earlier study by Gershon et al. (1984), who observed similar rates of familial affective disorder in depressed and nondepressed AN patients. In answer to the second question, Strober et al. (1990) observed strong evidence for familial transmission of AN and a slightly elevated risk of BN in female first-degree relatives of anorectic patients compared to relatives of healthy controls; in fact, relatives of patients with affective disorders reported no case of anorexia nervosa. Strober et al. (1990) concluded that the data supported independent transmission with a subset of patients carrying familial traits for both disorders. Piran et al. (1985) and Hudson et al. (1982) did not interview most families directly, but both noted two to three times the rate of a family history of depression in relatives of bulimic AN patients compared to families of restricting patients.

FAMILY STUDIES Family studies have identified markedly elevated rates of major affective disorders in relatives of AN patients (Gershon et al., 1984; Biederman et al., 1985b; Piran et al., 1985; Strober et al., 1990) com-

AFFECTIVE DISORDERS IN OUTCOME STUDIES Follow-up studies conducted between 8 to 12 years after illness onset have shown two to three times the normal rate of any affective disorders in former AN


patients, mostly major depression and dysthymia (Halmi et al., 1991; Herpertz-Dahlmann et al., 1996). If the rates are analyzed by outcome, between 65–80% of the chronically ill qualify for a lifetime diagnosis of major depression, with higher rates in older samples, who show high rates of concurrent anxiety disorders and higher than normal rates of obsessive-compulsive disorder. In good outcome (fully physically recovered) and intermediate outcome patients, the lifetime morbidity for major depression (23%) and dysthymia (11%) was similar to the rate reported by Weismann et al. (1996) for normal populations. Physically healthy patients free of symptoms of AN had no or very low lifetime rates of affective disorders on follow-up (Casper and Jabine, 1996; Rastam et al., 1996). BIOLOGICAL STUDIES The biological findings in the two areas which have major bearing on the relationship to depression will be briefly reviewed here. Sleep studies. Sleep in depressive disorders is characterized by sleep continuity disruption, decreased slow wave sleep (SWS) and REM abnormalities, the most specific being reduced REM latency (Kupfer, 1976). In studies of patients with AN, as summarized in Benca and Casper (1994), sleep parameters were either indistinguishable from age-matched controls or a minority exhibited reductions in REM latency, sleep efficiency, SWS, total sleep time, and REM density. Hence, the changes resembled those in depressed controls, except for a decrease in REM density. Some studies observed significant relationships between abnormal sleep parameters in AN patients and weight loss, and others observed improvement in total sleep time, SWS, and sleep efficiency with weight gain. Studies of the hypothalamic-pituitary-adrenal (HPA) axis. Patients with severe major depressive disorders frequently show hypercortisolemia and/or nonsuppression of plasma cortisol levels after dexamethasone administration (Carroll et al., 1976). Once more, the results are difficult to interpret in AN, because fasting and weight loss have been shown to influence functioning of the HPA axis, not only in normal subjects (Fichter et al., 1986) but also in patients with major depression (Casper et al., 1988). When ten studies are combined which tested altogether 200 AN patients (between 51–85% of their ideal body weight), on average 65% of patients failed to suppress plasma cortisol levels after administration of dexamethasone (DM) (Doerr et al., 1980; Gerner and Gwirtsman, 1981; Piran et al., 1985; Abou-Saleh et al., 1986; Schweitzer et al., 1986; Maguire et al., 1987; Walsh et al., 1987; Estour et al., 1990; Herpertz-Dahlmann and Remschmidt, 1990; Tamai et al., 1990). In two studies (Doerr et al., 1980; Gerner and Gwirtsman, 1981), 90% of AN patients showed nonsuppression. Those studies that assessed depression found no relationship between endocrine changes and the presence of depressive symptoms or a diagnosis of depression (Schweitzer et al., 1986;

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Maguire et al., 1987; Herpertz-Dahlmann and Remschmidt, 1990). Hypercortisolemia, along with changes in the circadian rhythm, are frequently found in underweight AN patients, but both normalize with weight gain (Walsh et al., 1978; Casper et al., 1979). TREATMENT STUDIES Given the reports of a greater than normal prevalence of major depressive disorder in AN, antidepressant drugs would be expected to benefit AN, yet the results of placebo-controlled treatment studies with antidepressants have been disappointing. The studies could not document, either, a significant effect on weight gain, the major outcome variable in AN, or a significant effect on depressive symptoms (Lacey and Crisp, 1981; Biederman et al., 1985a; Halmi et al., 1986). To our knowledge, drug studies have not explored the question whether the subset of AN patients who, following metabolic stabilization, qualify for a diagnosis of major depression, would improve with antidepressants.

BULIMIA NERVOSA DEPRESSIVE SYMPTOMS Symptoms of depression and anxiety are commonly reported by BN patients who apply to specialty clinics, with 56% of women scoring 20 on the Beck Depression Inventory (BDI) (Hatsukami et al., 1984; Rosen et al., 1989). Research protocols seem to recruit different BN patient populations, as demonstrated by the large Fluoxetine Study (Fluoxetine Bulimia Nervosa Collaborative Study Group, 1992), where mean Hamilton Depression ratings were in the high normal range. Even though in BN patients vomiting induces an intermittent caloric deficit, starvation effects would be expected to be less severe and, hence, to cause less distortion of depression rating scales. AFFECTIVE DISORDERS IN BULIMIA NERVOSA POPULATIONS In studies which employed standardized interviews in clinic populations, a high prevalence (up to 90%) of any affective disorder, along with somewhat lower rates for anxiety disorders (Hudson et al., 1987b; Brewerton et al., 1995) and alcohol abuse (from 9–19%) (Hudson et al., 1983a; Hatsukami et al., 1984; Walsh et al., 1985) have been found. Table 2 displays studies that evaluated more than ten patients; between 30–60% qualified for a coexisting major depressive disorder and 50–65% for a lifetime major depression (Stern et al., 1984; Fornari et al., 1992). Retrospective analyses suggest that in a third of the cases the affective disorder was present before the onset of BN (Walsh et al., 1985; Hudson et al. 1987). AFFECTIVE DISORDERS IN FAMILIES OF BULIMIA NERVOSA PATIENTS Studies in which the families of bulimic probands were interviewed, and one (Wilson and Lindholm,

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TABLE 2. Prevalence of affective disorders in patients with anorexia nervosa* Authors Hatsukami et al., 1984

Diagnosis

Number

Age in years

BN

108

23.6

Instruments Interview

Dysthymia

MDD

c: 21%

C: 11%

DSM-III

p: 0.9%

p: 13%

c: 95% p: 18%

c: 21% p: 71% 80%

Walsh et al., 1985

BN

34

25.7

Cooper et al., 1986

BN

35

23.5

SADS DMS-III Interview

Hudson et al., 1987

BN

44 dep. pts 51

37.9 26.3

PSE DIS

Laessle et al., 1987

BN

+19 remitted 13

25.1 24.9

Keck et al., 1990

BN

67

28

Fornari et al., 1992

BN

18

?

DMS-III CID DSM-III-R SCID DSM-III-R SADS-L DSM-III-R

Bipolar D Comments 0

18.5% alcohol and drug abuse

p: 0.9% 0

Cyclothymia 9% alcohol abuse

32%

0

100% 59%

7.5% M 12%

11% p: 31%

47% 46%

11% 0

c: 6% p: 0 –

23% 42% c: 29% p: 52%

c: 4% p: 1%

Symptomatic differences MDD 32% in control subjects

* c = current; p = past.

1985) in which patients’ recollections were used, reported higher rates of familial affective disorder in probands with BN, from 35–55%, than in families of psychiatric control populations (Hudson et al., 1983b; Lee et al., 1985; Mitchell et al., 1986; Hudson et al., 1987b). Stern et al. (1984) is an exception. The authors found similar prevalence rates for primary affective disorders in relatives (including mothers) of bulimic probands as in relatives of controls who had no eating disorder (8% and 9%, respectively), despite the fact that about half of the patients reported a lifetime history of affective disorder, including minor depressive disorder. The discrepancies between the studies might be due to differences in the sample and to differing degrees of the severity in the depressive disorder. This interpretation receives support from observations by Wilson and Lindholm (1985), who noted that patients with lower ratings on the BDI showed less familial penetration than bulimic patients whose BDI exceeded 24. Furthermore, Kendler (1997) recently reported that in female twins with a lifetime history of major depression melancholia was not associated with BN. SLEEP STUDIES In view of the young adult age of most bulimic patients, it would be worthwhile to think about the most suitable comparison group for sleep studies, young adult depressives with hypersomnia—and sometimes hyperphagia (Hawkins et al., 1985)—or young adults with melancholic depression. Polysomnographic studies have found few abnormalities in BN—at most a tendency toward decreased slow-wave sleep and, in only one study, reduced REM latency. There are several reports of parasomnias, sleep-walking, and sleep-

related eating in BN patients, which require further investigation (Benca and Casper, 1994). HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS By and large, BN patients tend to have normal circadian rhythm secretory patterns of plasma cortisol. When the results of 13 studies which tested dexamethasone suppression in a total of 244 patients with BN are combined, 43% of the sample did not suppress morning or afternoon plasma cortisol levels (Hudson et al., 1982, 1987a; Gwirtsman et al., 1983; Mitchell and Bantle 1983; Lindy et al., 1985; Musisi and Garfinkel 1985; Kiriike et al., 1986; Levy and Dixon 1987; Walsh et al., 1987; O’Brien et al., 1988; Perez et al., 1988; Kaplan et al., 1989; Byrne et al., 1990). The patients mean age was in the early to mid-twenties (range 16–59 years) and their weight was from 83– 111% of ideal body weight, suggesting undernutrition in some cases. DST nonsuppression (NS) was not related to depression severity or to a diagnosis of depression, but in two studies NS was related to low weights (Levy and Dixon 1987; Kaplan et al., 1989). In two studies (Walsh et al. 1987; Hudson et al. 1987), all BN patients showed normal DST suppression, virtually identical to that of controls. When one considers the frequency of HPA axis and sleep changes, several points must be borne in mind. The sensitivity and specificity of the DST and the sleep parameters show considerable variability in different age groups, within major depressive disorder and in moderate depressions. DST suppression is the rule in depressions with atypical physical symptoms ((Hawkins et al., 1985; Casper et al., 1988). The data also suggest that in some patients the results might


have been influenced by the physiological changes of episodic caloric deficiency through vomiting. OUTCOME OF BULIMIA NERVOSA Although several short-term outcome studies are now available, comorbidity with affective disorders has not been the main focus (Collings and King, 1994; Fairburn et al., 1995; Reiss and Johnson-Sabine, 1995). A recent review of outcome in BN reported a 50% recovery rate after 5–10 years and noted that comorbid depression at presentation was not predictive of outcome in the majority of studies, albeit few studies had conducted reliable depression ratings at intake (Keel and Mitchell, 1997). Fichter and Quadflieg (1996) found at a two-year follow-up that 38% of BN patients had a lifetime diagnosis of affective disorder, with 33% qualifying for a current diagnosis. Rates for anxiety, obsessive-compulsive disorders, and substance abuse were about half the rates for affective disorders. PHARMACOLOGICAL TREATMENT OF BULIMIA Numerous well-designed placebo-controlled trials have shown that bulimic symptoms respond well to all classes of antidepressant drugs—tricyclics, monoamine oxidase inhibitors, and serotonin reuptake inhibitors, as well as other drugs such as phenytoin and naltrexone (Mitchell and Groat 1984; Walsh et al., 1984; Hughes et al., 1986; Kennedy et al., 1988; Mitchell, 1989; Fluoxetine Bulimia Nervosa Collaborative Study Group, 1992). Although measures of depression and anxiety frequently show improvement, the beneficial effects on bulimic symptoms are not dependent on the antidepressant effect. With time it has become apparent that antidepressant drugs rarely lead to remission and that their effects may not be sustained. When Mitchell et al. (1990) demonstrated in controlled studies that psychological treatments added significantly to the therapeutic benefit of antidepressants, the standard treatment changed and various forms of psychological therapies, either alone or in combination with antidepressants, began to be used (Walsh et al., 1997). A similar trend can be observed in the treatment of depressions (Thase et al., 1996), where mild to moderate depressions have been shown to respond well to psychological therapies.

CONCLUSIONS The reviewed clinical descriptive, family, genetic, and outcome studies confirm the prominence of depressive symptoms and depressive disorders in eating disorders. Other psychiatric syndromes which occur with less frequency, such as anxiety disorders and obsessive-compulsive disorders in AN and BN personality disorders, anxiety disorders, and substance abuse, probably play an equally important role in the development and maintenance of eating disorders, but those data could not be reviewed here in detail.

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Eating disorders present unique problems for diagnosing depression because they are regularly accompanied by a variety of physical changes. It is well documented that starvation—and, less commonly, hyperphagia—can produce physiological and psychological symptoms which resemble those considered diagnostic for depression. Inevitably, therefore, if symptom ratings and diagnostic interviews are performed when the patient is severely underweight and in negative metabolic balance the evaluation will be confounded by starvation effects. Similarly, there is strong evidence that starvation interferes with sleep and triggers endocrine changes. For the HPA axis, and less so for sleep, the interpretation is equally complicated because the changes induced by caloric restriction are similar to the ones observed in depression, although their underlying mechanism might not be the same. It certainly would have been methodologically more sound to postpone any evaluation or testing until patients were nutritionally and metabolically stabilized at a healthier weight. Virtually no studies controlled for the effects of caloric restriction. Since, for obvious reasons, comparison groups matched for body weight and nutritional or metabolic status were not included, some of the psychological data, and certainly the biological data, cannot be considered as specific for depression as they would be in a person of normal weight. Keeping these considerations in mind, the model that fits the data best would allow for the full range of no depression to severe depressive disturbances and depressive disorders to be associated with eating disorders, with somewhat higher rates of depression in bulimic anorectic and bulimia nervosa patients than in restricting anorexia nervosa patients. Additionally, clinical studies and recent twin studies suggest that BN patients have more moderate forms of depression. Finally, turning to the question of the nature of the relationship between depression and anorexia nervosa, we know clinically that a depressive disorder can, but infrequently does, trigger anorexia nervosa. Typically, if depressive features, symptoms, or a disorder are present, the depression eventually becomes intertwined with the anorexia nervosa, but this interaction cannot be considered evidence of a shared etiology. The lack of efficacy of antidepressants in AN and findings from family studies which have reported low rates of affective disorder in nondepressed anorectic probands would, in effect, argue against a common abnormality. In regard to BN, it is tempting to interpret the effectiveness of antidepressant drugs and the benefit from psychological treatments in BN as evidence for a common abnormality, but this conclusion would not be consistent with evidence from treatment studies which indicate that depressive symptoms or a lifetime history of a depressive disorder are not infrequently absent in BN. The most parsimonious model would posit a vulnerability for the entire spectrum of depressive distur-

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bances as one of several risk factors which, in combination with other psychological and environmental risk factors—notably food restriction and weight loss—would lead in the genetically predisposed to either the restricting or bulimic form of anorexia nervosa or to bulimia nervosa.

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