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Phenomenologic relationship of eating disorders to major affective disorder
Psychiatry Research, 9, 345-354 Elsevier
Phenomenologic Major Affective James I. Hudson, Yurgelun-Todd Received
345
Relationship Disorder
Harrison
of
Eating
G. Pope, Jr., Jeffrey
Disorders
M. Jonas,
to
and Deborah
April 6, 1983; revised version received July 19. 1983; accepted July 25, 1983.
Abstract. We administered the National Institute of Mental Health Diagnostic Interview Schedule to 41 patients with a lifetime history of anorexia nervosa (25 with and 16 without bulimia) and to 49 patients with bulimia alone. Results showed that 77% of the patients with eating disorders had a lifetime diagnosis of DSM-III major affective disorder, a rate significantly higher than that found in comparison groups composed of the first-degree relatives of probands with schizophrenia and bipolar disorder. High lifetime rates of anxiety disorders, substance use disorders, and kleptomania were also observed. By contrast, few cases of personality disorders and no cases of schizophrenia were found. These findings combine with the results of studies of family history, long-term outcome, response to biological tests, and treatment response to suggest that anorexia nervosa and bulimia may be closely related to major affective disorder. Key Words. Affective
disorders,
anorexia
nervosa,
appetite
disorders,
bulimia.
Anorexia nervosa and bulimia are disorders characterized by disturbed eating behavior. Anorexia nervosa has been well described, but only recently has bulimia been recognized as a distinct diagnostic entity (Russell, 1979; American Psychiatric Association, 1980). Bulimia appears to be closely related to anorexia nervosa because about
half of anorexic patients have had bulimia (Hsu et al., 1979; Casper et al., 1980; Crisp et al., 1980; Garfinkel et al., 1980). Conversely, about half of bulimic patients seeking treatment are reported to have displayed anorexia nervosa (Russell, 1979; Fairburn, 1981; Pyle et al., 1981). Although the etiology of these disorders remains unknown, several lines of evidence suggest that they may be related to major affective disorder. First, both depressive symptoms (Halmi, 1974; Morgan and Russell, 1975; Cantwell et al., 1977; Crisp et al., 1980; Eckert et al., 1982; Gershon et al., 1983; Hendren, 1983; Herzog and Osuna, 1983) and manic-like symptoms (Barcai, 1977; Kron et al., 1978) are commonly described in anorexia nervosa; depressive symptomatology has also been reported in bulimics of normal weight (Nogami and Yabana, 1977; Russell, 1979; Pyle et al., 1981; Hudson et al., 1982; Johnsonand Larsen, 1982; Herzogand Osuna, 1983; Walshet al., 1983). Second, family studies have found a high prevalence of affective disorder in the relatives of patients with anorexia nervosa (Cantwell et al., 1977; Winokur et al., 1980;
James I. Hudson, M.D., Harrison G. Pope, Jr., M.D., Jeffrey M. Jonas, M.D., and Deborah YurgelunTodd, M.S., are at the Mailman Research Center, McLean Hospital, Belmont, MA, and Harvard Medical School, Boston, MA. (Reprint requests to Dr. J.I. Hudson, McLean Hospital, I15 Mill St., Belmont, MA 02178, USA.) 01651781/83/$03.00
0 1983 Elsevier Science Publishers
B.V.
346 Gershon et al., 1983; Hudson et al., 19836; Strober, 1983) and bulimia (Pyle et al., 1981; Hudson et al., 1982, 1983b). Third, outcome studies have found that patients with anorexia nervosa often exhibit depressive symptoms at followup (Halmi, 1974; Cantwell et al., 1977; Hsu et al., 1979). Studies on the course of bulimia have not as yet appeared. Fourth, abnormal responses to the dexamethasone suppression test (DST) and thyrotropin-releasing hormone stimulation test, similar to those reported in patients with major depression (Carroll et al., 1981; Loosen and Prange, 1982), have been found in patients with eating disorders. In anorexia nervosa, weight loss alone could account for these abnormalities (Boyar et al., 1977; Walsh et al., 1978; Gerner and Gwirtsman, 1980; Loosen and Prange, 1982; Walsh, 1982), but in bulimic patients above 80% of ideal body weight, the effects of weight loss on the tests are much less (Hudson et al., 1982, 1983a; Gwirtsman et al., 1983; Mendels, 1983). Fifth, controlled and uncontrolled reports suggest that antidepressant medications and lithium carbonate may be effective in both anorexia nervosa (Needleman and Waber, 1976; Mills, 1976; Barcai, 1977; Moore, 1977; White and Schnaultz, 1977; Gross et al., 1981; Stein et al., 1982; Halmi et al., 1983) and bulimia (Pope and Hudson, 1982; Walsh et al., 1982; Glassman and Walsh, 1983; Jonas et al., 1983; Mendels, 1983; Pope et al., 1983; Roy-Byrne et al., 1983; Pope et al., in press). This evidence, although inconclusive, encourages further investigation of the relationship between the eating disorders and major affective disorder. Therefore, we performed a systematic study of the phenomenology of anorexia nervosa and bulimia. Methods Subjects were 90 consecutive individuals who met DSM-III criteria (American Psychiatric Association, 1980) for anorexia nervosa, bulimia, or both disorders at any point in their lifetimes. Sixteen had anorexia nervosa but not bulimia (group AN: 15 women, mean age 25, SD 7, range 17-37; one man, age 24), 25 had displayed both anorexia nervosa and bulimia during their lifetimes (group AN/B: 24 women, mean age 25.8, SD 7.3, range 13-43; one man, age 28) and 49 had bulimia alone (group B: 46 women, mean age 28.4, SD 8, range 17-49; three men, ages 26, 41, and 56). Nine of the subjects had active anorexia nervosa, 59 had active bulimia, and five had active anorexia nervosa and bulimia concurrently. Subjects were drawn from four sources: (I) patients with eating disorders admitted to McLean Hospital (AN q 5, AN/B q 15, B = 10); (2) outpatients with eating disorders referred to the authors for treatment or consultation (AN = IO, AN/ B=5, B=23); (3) research subjects with anorexia nervosa or bulimia who responded to our advertisement in the newsletter of a local self-help organization for eating disorders (AN q 1, AN/B q 4, B = 12) (Pope et al., 1983); and (4) respondents to a similar advertisement for subjects with bulimia, stating only that we were seeking “subjects with uncontrolled eating binges for a treatment study,” which was placed in a weekly metropolitan newspaper (AN = 0, AN/B = 1, B = 4) (Pope et al., 1983). For purposes of subsequent analysis, subjects in group 1 are termed inpatients and those in groups 2-4 are termed outpatients. Although groups 3 and 4 were initially research subjects, most continued as outpatients in treatment at our center after completion of the study. There were no significant differences between group 2 and groups 3 and 4 on demographic indices, severity of eating disorder symptoms, or prevalence of major affective disorder. Psychiatric information on the subjects’ first-degree relatives was elicited from the subjects and available family members using methods previously described (Hudson et al., 1982, 19836). Family history data on 69 of these subjects plus 20 other subjects have been reported elsewhere (Hudson et al., 19836); the most striking finding was that 53% of the 89 subjects studied had at least one first-degree relative with a major affective disorder.
347 All subjects were administered the National Institute of Mental Health Diagnostic Interview Schedule (DIS) (Robins et al., 1980), an instrument of demonstrated reliability (Helzer et al., 1977a, 19776; Robins et al., 1979), and the Eating Disorder Supplement (EDS), a questionnaire designed by us to elicit symptoms of eating disorders. Questions on the DIS pertaining to tobacco use disorders and psychosexual dysfunction were omitted. The diagnosis of dysthymic disorder was not made when major depression was also present, since we could not easily diagnose the former in the presence of the latter using the DIS questions. Diagnoses of personality disorders other than antisocial personality disorder, which are not generated by the DIS, were based on additional unstructured interview questions and available clinical data. The DIS interviews were administered by one of the first three authors (JIH, HGP, or JMJ); there were no significant differences among the three interviewers in the rates of diagnosing any DSM-III disorder. Two comparison groups, also interviewed with the DIS, were generated from the data of an ongoing family interview study: (1) 41 first-degree relatives of 17 probands with DSM-III schizophrenia and (2) 50 first-degree relatives of 15 probands with DSM-III bipolar disorder. These relatives were interviewed by two of the authors (HGP and DYT) who were unaware of the diagnosis of the proband. The first group would not be expected to have a higher prevalence of major affective disorder than might be found in the general population, whereas the second
group would be expected to have an increased prevalence of major affective disorder (Slater and Cowie, 1971; Tsuang et al., 1980; Gershon et al., 1982). Several DSM-III diagnoses are hierarchical, carrying exclusion criteria which prohibit the diagnosis of one disorder when the criteria for another disorder are fulfilled. This convention applies, for example, to the diagnosis of anxiety disorders when a major affective disorder is also present and the diagnosis of bulimia when anorexia nervosa is present. Because there are data which question the validity of these exclusion criteria for both anxiety disorders (Sheehan and Sheehan, 1982a, 19826; Leckman et al., 1983, and in press) and eating disorders (Garner and Garfinkel, 1983; Yager et al., 1983) we have presented diagnoses nonhierarchically; that is, we did not exclude a diagnosis if another, normally preemptive, diagnosis was also present. Comparisons for statistical significance were made using Fisher’s exact test, two-tailed.
Results DSM-III diagnoses found in the study groups are displayed in Table 1. There were no statistically significant differences among any of the three study groups in lifetime rates of any noneating disorder or group of disorders with one exception: kleptomania was significantly more common in subjects with bulimia plus anorexia (44% of cases) than among pure anorexics (6%; p < 0.02). Most striking were the high lifetime rates of affective disorder in all groups of patients. Affective disorder occurred both in the presence and in the absence of eating disorder symptoms. Of the 69 patients with a lifetime diagnosis of major affective disorder, the onset of the affective disorder preceded the onset of the eating disorder by at least 1 year in 34 (49%) occurred within the same year in 21(30%), and postdated the onset of the eating disorder by at least 1 year in 14 (28%). Of the 73 patients with an active eating disorder on evaluation, 50 (68%) had concurrent major affective disorder; of the remaining 17 patients whose eating disorder was in remission, 10 (59%) met criteria for a major affective disorder. An additional finding from the DIS responses was that 3 1 (34%) of patients had made at least one suicide attempt (AN = 4, AN/B = 11, B 16). Significantly higher lifetime rates of major affective disorder were found among inpatients compared to outpatients (Table 2); inpatients and outpatients did not differ significantly in the lifetime rates of other disorders. q
348 Table 1. Lifetime DSM-III
diagnoses
in 90 patients with eating disorders
AN
n=16
Diagnosis1 Substance
AN/B
B
Total
n=25
n=49
n=90
n
O/O
n
O/O
n
O/O
n
1
6
9
36
11
22
21
23 13
%
use disorders
Alcohol abuse or dependence Amphetamine
abuse or
dependence Other substance use2 Total3
2
13
7
28
3
6
12
3
19
6
24
4
8
13
14
3
19
11
44
15
31
29
32
Affective disorders Bipolar
2
13
3
12
7
14
12
13
Major depression
8
50
20
80
29
59
57
63
10
63
23
92
77
Total major affective disorders Cyclothymic
0
Dysthymic
3
Atypical
0
Totals
13
36
73
69
0
1
2
1
1
19
0
5
10
8
9
1
2
1
1
81
23
92
43
88
79
88
14
0
Anxiety disorders Agoraphobia
2
13
6
24
5
10
13
Simple phobia
4
25
1
4
6
12
11
12
Panic
6
38
11
44
19
39
36
40
11
69
11
44
12
24
34
38
12
75
14
56
23
47
49
54
13
11
44
12
24
25
28
1
4
1
2
2
2
12
48
13
26
27
30
Histrionic
3
12
4
8
7
8
Antisocial
0
1
2
1
1
Borderline
5
20
5
10
IO
11
Total3
5
20
6
12
11
12
Obsessive-compulsive Total3 Impulse control disorders Kleptomania Intermittent
explosive 13
Total3 Personality
disorders
AN=anorexia nervosa without bulimia; AN/B=anorexia nervosa with bulimia; B=bulimia alone. 1. In addition, there were two cases of schizoaffective disorder iAN=l, B=l), three cases of factitious disorder with psychological symptoms [AN/B=l, B=2), and one case each of conduct drsorder, socialized, nonaggressive (in group BJ and zoophilia (in group AN/B). There were no cases of schizophrenia, schizoid personality disorder, schizotypal personality disorder, or somatization disorder. 2. Include cases of sedative-hypnotic abuse or dependence IAN=l, AN/B=3), opioid abuse or dependence (AN=l, AN/B=1 ), cocaine abuse [B=l), cannabis abuse or dependence (AN=l, AN/B=2, B=l ), and mixed substance abuse (AN/B=l. B=3). 3. Totals represent the number of patients who had at least one diagnosis wtthrn the group of disorders, Some patients had more than one diagnosis; hence, the total number of diagnoses within a group of disorders may exceed the number of patients affected.
349 Table 2. Lifetime DSM-III diagnoses: outpatients by diagnostic group
Diagnoses Substance
use disorders
Major affective Anxiety
disorders
disorders2
Kleptomania Personality
disorders
Inpatients
compared
to
Inpatients
Outpatients
n=30
n=60
n
%
n
%
12
40
17
28
28
93
41
681
20
67
29
48
11
37
14
23
3
10
a
13
1.p
2.
The lifetime rates of major affective disorder were significantly higher in the eating disorders subjects than in either of the comparison groups (Table 3). Table 3. Comparison of lifetime rates of major affective disorder among various groups Bipolar disorder Grows
Major depression
n
n
%
30
10
33
n
Total %
n
%
la
60
28
931
Eating disorders inpatients Eating disorders outpatients
60
2
3
39
65
41
682
Total
90
12
13
57
63
69
772
41
0
5
12
5
50
3
13
26
16
Relatives phrenic Relatives bioolar
of schizoprobands
123
of orobands
6
32
1. p=O.OZ compared to eating disorders outpatients; p
Discussion Using the DIS, we found that 77% of 90 patients with anorexia nervosa, bulimia, or both displayed a lifetime diagnosis of a major affective disorder, and that an additional 13% displayed cyclothymic disorder, dysthymic disorder, atypical affective disorder, or schizoaffective disorder. The lifetime rates of major affective disorder did not differ significantly among the eating disorders subgroups but were significantly greater in inpatients compared to outpatients. Previous studies using the Research
350 Diagnostic Criteria (RDC) (Spitzer et al., 1978) have also reported a high prevalence of major affective disorder in anorexia nervosa (Gershon et al., 1983; Hendren, 1983; Herzog and Osuna, 1983) and bulimia (Herzog and Osuna, 1983; Walsh et al., 1983). The lifetime rate of major affective disorder in subjects with eating disorders (both inpatient and outpatient subgroups) significantly exceeded that found in the comparison groups of the first-degree relatives of schizophrenic probands and even the first-degree relatives of bipolar probands-despite the fact that the latter group presumably shows a prevalence of major affective disorder already higher than would be expected in the general population (Slater and Cowie, 1971; Tsuang et al., 1980; Gershon et al., 1982). In our sample of patients, anxiety disorders were second to affective disorders in prevalence; 54% had a lifetime diagnosis of panic disorder, agoraphobia, obsessivecompulsive disorder, or a combination thereof. This finding is consistent with several reports of a high level of anxiety and obsessive-compulsive symptoms in patients with anorexia nervosa (Halmi, 1974; Cantwell et al., 1977; Crisp et al., 1980; Strober, 1980) and bulimia (Nogami and Yabana, 1977; Pyle et al., 1981). Kleptomania was observed in 27% of our patients. The high prevalence of kleptomania has been noted by others, particularly in association with bulimia (Casper et al., 1980; Crisp et al., 1980; Garfinkel et al., 1980; Pyle et al., 1981). Substance use disorders were common among all eating disorder groups. This finding is consistent with two reports of frequent alcoholism, use of illicit drugs, or both in patients with anorexia nervosa, particularly those with concomitant bulimia (Eckert et al., 1979; Garfinkel et al., 1980). We found a low prevalence of personality disorders in all eating disorder groups. Because diagnoses of most personality disorders were made using unstructured questions and clinical data, we may have underestimated the prevalence of personality disorders in these patients. We found no cases of schizophrenia among our subjects. This observation is consistent with findings from several large studies which have shown schizophrenia to be rare or absent in patients with eating disorders (Theander, 1970; Morgan and Russell, 1975; Cantwell et al., 1977; Grounds, 1982). Although Hsu et al. (198 1) found six cases of schizophrenia among 105 anorexic patients, five of the six cases had clear symptoms of depression, three had rapid remissions, and two had a strong family history of affective disorder. Thus, perhaps only one case would meet DSM-III criteria for schizophrenia. Two alternative explanations for the findings should be considered. First, could our sample have been biased to include a disproportionate number of patients with concomitant major affective disorder? Although this explanation cannot be excluded, it seems unlikely because (1) subjects were consecutive patients with eating disorders drawn from four separate sources and (2) the study population was similar, both in demographic characteristics and prevalence of affective symptomatology, to other large series of patients with anorexia nervosa, bulimia, or both reported previously (Russell, 1979; Casper et al., 1980; Crisp et al., 1980; Garfinkel et al., 1980; Pyle et al., 1981; Gershon et al., 1983; Hendren, 1983; Herzog and Osuna, 1983; Walsh et al., 1983). Of course, the inpatients in our sample, because of their need for hospital
351 treatment, might be expected to exhibit significant psychopathology in addition to their eating disorder. Even if we restrict our consideration to the outpatient portion of the sample, however, the lifetime prevalence rates of affective and anxiety disorders among outpatients are still significantly higher than in the comparison groups. A second alternative explanation is that the affective symptoms in patients with eating disorders might be attributable to weight loss, or represent a reaction to the eating disorder itself. For example, Crisp and Stonehill (1973) report that weight loss was associated with sleep disturbance and other depressive symptoms in psychiatric patients without severe depression. Several studies report that depressive symptoms, present in anorexia nervosa patients at low weight, improve with weight gain (Gerner and Gwirtsman, 1980; Strober, 1980; Eckert et al., 1982). However, these studies do not exclude the possibility that weight gain and concomitant reduction in depressive symptoms might both be due to improvement in an underlying affective disorder. In addition, since a majority of our anorexic patients exhibited major affective disorder at times when they were of normal weight and because the nonanorexic patients with bulimia had a similar lifetime rate of DSM-III major affective disorder, it is clear that weight loss alone could not have accounted for the high prevalence of major affective disorder observed. It also appears unlikely that the affective symptoms in our patients represented a reaction to having an eating disorder, since major affective disorder developed before the eating disorder in 49% of the 69 cases in which major affective disorder occurred, and was present in 59% of the 17 patients whose eating disorder symptoms were in remission on evaluation. It should be noted, however, that retrospective assessment of age of onset of both eating disorders and affective disorders is difficult, and should be considered tentative. Finally, the bipolar disorder diagnosed in 13% of patients could not easily be attributable to either weight loss or reaction to illness. In summary, among 90 patients with anorexia nervosa, bulimia, or both, we found a lifetime rate of major affective disorder much higher than that found in two comparison populations. This high rate appears unlikely to be due to idiosyncratic patient selection or to be explainable as a reaction to weight loss or eating disorder symptoms. This finding, combined with the results of studies of family history, long-term outcome, response to biological tests, and response to antidepressant medications, favors the hypothesis that anorexia nervosa and bulimia may be closely related to major affective disorder. The research reported was supported in part by a Medical Foundation Research Fellowship (Dr. Hudson); by a Biomedical Research Support Grant RR05484 awarded by Biomedical Research Support Program, Division of Research Resources, National Institute of Mental Health; by a grant from the MacArthur Foundation; and by a grant from the Abigail Adams Atchley Fund, Lincoln, MA. The authors thank the Anorexia Nervosa Aid Society of Massachusetts for assistance in recruiting subjects.
Acknowledgments.
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L.N.,
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(1982a).
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Slater, E., and Cowie, V. The Genetics of Mental Illness. Oxford University Press, London (1971). Spitzer, R.L., Endicott, J., and Robins, E. Research Diagnostic Criteria: Rationale and reliability. Archives of General Psychiatry, 35, 773 (1978). Stein, G.S., Hartshorn, S. Jones, J., and Steinberg, D. Lithium in a case of severe anorexia nervosa. British Journal of Psychiatry, 140, 526 (1982). Strober, M. Personality and symptomatic features in young, nonchronic anorexia nervosa patients. Journal of Psychosomatic Research, 24, 353 (1980). Strober, M. Familial depression in anorexia nervosa. Presented at the Annual Meeting of the American Psychiatric Association, New York, May 4 (1983). Theander, S. Anorexia nervosa. Acta Psychiatrica Scandinavica, Suppl. 214 (1970). Tsuang, M.T., Winokur, G., and Crowe, R.R. Morbidity risks of schizophrenia and affective disorders among first-degree relatives of patients with schizophrenia, mania, depression, and surgical conditions. British Journal of Psychiatry, 137,497 (1980). Walsh, B.T. Endocrine disturbances in anorexia nervosa and depression. Psychosomatic Medicine,
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Walsh, B.T., Katz, J.L., Levin, J., Kream, J., Fukushima, and Zumoff, B. Adrenal activity in anorexia nervosa.
D.K., Hellman,
L.D., Weiber,
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H.,
40, 499
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Winokur, A., March, V., and Mendels, J. Primary affective disorder in relatives of patients with anorexia nervosa. American Journal of Psychiatry. 137, 695 (1980). Yager, J., Lee-Benner, K., Landsverk, J., and Johnson, C. Bulimic spectrum disorder: The Glamour survey. Presented at the Annual Meeting of the American Psychiatric Association, New York, May 4 (1983).
Phenomenologic Major Affective James I. Hudson, Yurgelun-Todd Received
345
Relationship Disorder
Harrison
of
Eating
G. Pope, Jr., Jeffrey
Disorders
M. Jonas,
to
and Deborah
April 6, 1983; revised version received July 19. 1983; accepted July 25, 1983.
Abstract. We administered the National Institute of Mental Health Diagnostic Interview Schedule to 41 patients with a lifetime history of anorexia nervosa (25 with and 16 without bulimia) and to 49 patients with bulimia alone. Results showed that 77% of the patients with eating disorders had a lifetime diagnosis of DSM-III major affective disorder, a rate significantly higher than that found in comparison groups composed of the first-degree relatives of probands with schizophrenia and bipolar disorder. High lifetime rates of anxiety disorders, substance use disorders, and kleptomania were also observed. By contrast, few cases of personality disorders and no cases of schizophrenia were found. These findings combine with the results of studies of family history, long-term outcome, response to biological tests, and treatment response to suggest that anorexia nervosa and bulimia may be closely related to major affective disorder. Key Words. Affective
disorders,
anorexia
nervosa,
appetite
disorders,
bulimia.
Anorexia nervosa and bulimia are disorders characterized by disturbed eating behavior. Anorexia nervosa has been well described, but only recently has bulimia been recognized as a distinct diagnostic entity (Russell, 1979; American Psychiatric Association, 1980). Bulimia appears to be closely related to anorexia nervosa because about
half of anorexic patients have had bulimia (Hsu et al., 1979; Casper et al., 1980; Crisp et al., 1980; Garfinkel et al., 1980). Conversely, about half of bulimic patients seeking treatment are reported to have displayed anorexia nervosa (Russell, 1979; Fairburn, 1981; Pyle et al., 1981). Although the etiology of these disorders remains unknown, several lines of evidence suggest that they may be related to major affective disorder. First, both depressive symptoms (Halmi, 1974; Morgan and Russell, 1975; Cantwell et al., 1977; Crisp et al., 1980; Eckert et al., 1982; Gershon et al., 1983; Hendren, 1983; Herzog and Osuna, 1983) and manic-like symptoms (Barcai, 1977; Kron et al., 1978) are commonly described in anorexia nervosa; depressive symptomatology has also been reported in bulimics of normal weight (Nogami and Yabana, 1977; Russell, 1979; Pyle et al., 1981; Hudson et al., 1982; Johnsonand Larsen, 1982; Herzogand Osuna, 1983; Walshet al., 1983). Second, family studies have found a high prevalence of affective disorder in the relatives of patients with anorexia nervosa (Cantwell et al., 1977; Winokur et al., 1980;
James I. Hudson, M.D., Harrison G. Pope, Jr., M.D., Jeffrey M. Jonas, M.D., and Deborah YurgelunTodd, M.S., are at the Mailman Research Center, McLean Hospital, Belmont, MA, and Harvard Medical School, Boston, MA. (Reprint requests to Dr. J.I. Hudson, McLean Hospital, I15 Mill St., Belmont, MA 02178, USA.) 01651781/83/$03.00
0 1983 Elsevier Science Publishers
B.V.
346 Gershon et al., 1983; Hudson et al., 19836; Strober, 1983) and bulimia (Pyle et al., 1981; Hudson et al., 1982, 1983b). Third, outcome studies have found that patients with anorexia nervosa often exhibit depressive symptoms at followup (Halmi, 1974; Cantwell et al., 1977; Hsu et al., 1979). Studies on the course of bulimia have not as yet appeared. Fourth, abnormal responses to the dexamethasone suppression test (DST) and thyrotropin-releasing hormone stimulation test, similar to those reported in patients with major depression (Carroll et al., 1981; Loosen and Prange, 1982), have been found in patients with eating disorders. In anorexia nervosa, weight loss alone could account for these abnormalities (Boyar et al., 1977; Walsh et al., 1978; Gerner and Gwirtsman, 1980; Loosen and Prange, 1982; Walsh, 1982), but in bulimic patients above 80% of ideal body weight, the effects of weight loss on the tests are much less (Hudson et al., 1982, 1983a; Gwirtsman et al., 1983; Mendels, 1983). Fifth, controlled and uncontrolled reports suggest that antidepressant medications and lithium carbonate may be effective in both anorexia nervosa (Needleman and Waber, 1976; Mills, 1976; Barcai, 1977; Moore, 1977; White and Schnaultz, 1977; Gross et al., 1981; Stein et al., 1982; Halmi et al., 1983) and bulimia (Pope and Hudson, 1982; Walsh et al., 1982; Glassman and Walsh, 1983; Jonas et al., 1983; Mendels, 1983; Pope et al., 1983; Roy-Byrne et al., 1983; Pope et al., in press). This evidence, although inconclusive, encourages further investigation of the relationship between the eating disorders and major affective disorder. Therefore, we performed a systematic study of the phenomenology of anorexia nervosa and bulimia. Methods Subjects were 90 consecutive individuals who met DSM-III criteria (American Psychiatric Association, 1980) for anorexia nervosa, bulimia, or both disorders at any point in their lifetimes. Sixteen had anorexia nervosa but not bulimia (group AN: 15 women, mean age 25, SD 7, range 17-37; one man, age 24), 25 had displayed both anorexia nervosa and bulimia during their lifetimes (group AN/B: 24 women, mean age 25.8, SD 7.3, range 13-43; one man, age 28) and 49 had bulimia alone (group B: 46 women, mean age 28.4, SD 8, range 17-49; three men, ages 26, 41, and 56). Nine of the subjects had active anorexia nervosa, 59 had active bulimia, and five had active anorexia nervosa and bulimia concurrently. Subjects were drawn from four sources: (I) patients with eating disorders admitted to McLean Hospital (AN q 5, AN/B q 15, B = 10); (2) outpatients with eating disorders referred to the authors for treatment or consultation (AN = IO, AN/ B=5, B=23); (3) research subjects with anorexia nervosa or bulimia who responded to our advertisement in the newsletter of a local self-help organization for eating disorders (AN q 1, AN/B q 4, B = 12) (Pope et al., 1983); and (4) respondents to a similar advertisement for subjects with bulimia, stating only that we were seeking “subjects with uncontrolled eating binges for a treatment study,” which was placed in a weekly metropolitan newspaper (AN = 0, AN/B = 1, B = 4) (Pope et al., 1983). For purposes of subsequent analysis, subjects in group 1 are termed inpatients and those in groups 2-4 are termed outpatients. Although groups 3 and 4 were initially research subjects, most continued as outpatients in treatment at our center after completion of the study. There were no significant differences between group 2 and groups 3 and 4 on demographic indices, severity of eating disorder symptoms, or prevalence of major affective disorder. Psychiatric information on the subjects’ first-degree relatives was elicited from the subjects and available family members using methods previously described (Hudson et al., 1982, 19836). Family history data on 69 of these subjects plus 20 other subjects have been reported elsewhere (Hudson et al., 19836); the most striking finding was that 53% of the 89 subjects studied had at least one first-degree relative with a major affective disorder.
347 All subjects were administered the National Institute of Mental Health Diagnostic Interview Schedule (DIS) (Robins et al., 1980), an instrument of demonstrated reliability (Helzer et al., 1977a, 19776; Robins et al., 1979), and the Eating Disorder Supplement (EDS), a questionnaire designed by us to elicit symptoms of eating disorders. Questions on the DIS pertaining to tobacco use disorders and psychosexual dysfunction were omitted. The diagnosis of dysthymic disorder was not made when major depression was also present, since we could not easily diagnose the former in the presence of the latter using the DIS questions. Diagnoses of personality disorders other than antisocial personality disorder, which are not generated by the DIS, were based on additional unstructured interview questions and available clinical data. The DIS interviews were administered by one of the first three authors (JIH, HGP, or JMJ); there were no significant differences among the three interviewers in the rates of diagnosing any DSM-III disorder. Two comparison groups, also interviewed with the DIS, were generated from the data of an ongoing family interview study: (1) 41 first-degree relatives of 17 probands with DSM-III schizophrenia and (2) 50 first-degree relatives of 15 probands with DSM-III bipolar disorder. These relatives were interviewed by two of the authors (HGP and DYT) who were unaware of the diagnosis of the proband. The first group would not be expected to have a higher prevalence of major affective disorder than might be found in the general population, whereas the second
group would be expected to have an increased prevalence of major affective disorder (Slater and Cowie, 1971; Tsuang et al., 1980; Gershon et al., 1982). Several DSM-III diagnoses are hierarchical, carrying exclusion criteria which prohibit the diagnosis of one disorder when the criteria for another disorder are fulfilled. This convention applies, for example, to the diagnosis of anxiety disorders when a major affective disorder is also present and the diagnosis of bulimia when anorexia nervosa is present. Because there are data which question the validity of these exclusion criteria for both anxiety disorders (Sheehan and Sheehan, 1982a, 19826; Leckman et al., 1983, and in press) and eating disorders (Garner and Garfinkel, 1983; Yager et al., 1983) we have presented diagnoses nonhierarchically; that is, we did not exclude a diagnosis if another, normally preemptive, diagnosis was also present. Comparisons for statistical significance were made using Fisher’s exact test, two-tailed.
Results DSM-III diagnoses found in the study groups are displayed in Table 1. There were no statistically significant differences among any of the three study groups in lifetime rates of any noneating disorder or group of disorders with one exception: kleptomania was significantly more common in subjects with bulimia plus anorexia (44% of cases) than among pure anorexics (6%; p < 0.02). Most striking were the high lifetime rates of affective disorder in all groups of patients. Affective disorder occurred both in the presence and in the absence of eating disorder symptoms. Of the 69 patients with a lifetime diagnosis of major affective disorder, the onset of the affective disorder preceded the onset of the eating disorder by at least 1 year in 34 (49%) occurred within the same year in 21(30%), and postdated the onset of the eating disorder by at least 1 year in 14 (28%). Of the 73 patients with an active eating disorder on evaluation, 50 (68%) had concurrent major affective disorder; of the remaining 17 patients whose eating disorder was in remission, 10 (59%) met criteria for a major affective disorder. An additional finding from the DIS responses was that 3 1 (34%) of patients had made at least one suicide attempt (AN = 4, AN/B = 11, B 16). Significantly higher lifetime rates of major affective disorder were found among inpatients compared to outpatients (Table 2); inpatients and outpatients did not differ significantly in the lifetime rates of other disorders. q
348 Table 1. Lifetime DSM-III
diagnoses
in 90 patients with eating disorders
AN
n=16
Diagnosis1 Substance
AN/B
B
Total
n=25
n=49
n=90
n
O/O
n
O/O
n
O/O
n
1
6
9
36
11
22
21
23 13
%
use disorders
Alcohol abuse or dependence Amphetamine
abuse or
dependence Other substance use2 Total3
2
13
7
28
3
6
12
3
19
6
24
4
8
13
14
3
19
11
44
15
31
29
32
Affective disorders Bipolar
2
13
3
12
7
14
12
13
Major depression
8
50
20
80
29
59
57
63
10
63
23
92
77
Total major affective disorders Cyclothymic
0
Dysthymic
3
Atypical
0
Totals
13
36
73
69
0
1
2
1
1
19
0
5
10
8
9
1
2
1
1
81
23
92
43
88
79
88
14
0
Anxiety disorders Agoraphobia
2
13
6
24
5
10
13
Simple phobia
4
25
1
4
6
12
11
12
Panic
6
38
11
44
19
39
36
40
11
69
11
44
12
24
34
38
12
75
14
56
23
47
49
54
13
11
44
12
24
25
28
1
4
1
2
2
2
12
48
13
26
27
30
Histrionic
3
12
4
8
7
8
Antisocial
0
1
2
1
1
Borderline
5
20
5
10
IO
11
Total3
5
20
6
12
11
12
Obsessive-compulsive Total3 Impulse control disorders Kleptomania Intermittent
explosive 13
Total3 Personality
disorders
AN=anorexia nervosa without bulimia; AN/B=anorexia nervosa with bulimia; B=bulimia alone. 1. In addition, there were two cases of schizoaffective disorder iAN=l, B=l), three cases of factitious disorder with psychological symptoms [AN/B=l, B=2), and one case each of conduct drsorder, socialized, nonaggressive (in group BJ and zoophilia (in group AN/B). There were no cases of schizophrenia, schizoid personality disorder, schizotypal personality disorder, or somatization disorder. 2. Include cases of sedative-hypnotic abuse or dependence IAN=l, AN/B=3), opioid abuse or dependence (AN=l, AN/B=1 ), cocaine abuse [B=l), cannabis abuse or dependence (AN=l, AN/B=2, B=l ), and mixed substance abuse (AN/B=l. B=3). 3. Totals represent the number of patients who had at least one diagnosis wtthrn the group of disorders, Some patients had more than one diagnosis; hence, the total number of diagnoses within a group of disorders may exceed the number of patients affected.
349 Table 2. Lifetime DSM-III diagnoses: outpatients by diagnostic group
Diagnoses Substance
use disorders
Major affective Anxiety
disorders
disorders2
Kleptomania Personality
disorders
Inpatients
compared
to
Inpatients
Outpatients
n=30
n=60
n
%
n
%
12
40
17
28
28
93
41
681
20
67
29
48
11
37
14
23
3
10
a
13
1.p
2.
The lifetime rates of major affective disorder were significantly higher in the eating disorders subjects than in either of the comparison groups (Table 3). Table 3. Comparison of lifetime rates of major affective disorder among various groups Bipolar disorder Grows
Major depression
n
n
%
30
10
33
n
Total %
n
%
la
60
28
931
Eating disorders inpatients Eating disorders outpatients
60
2
3
39
65
41
682
Total
90
12
13
57
63
69
772
41
0
5
12
5
50
3
13
26
16
Relatives phrenic Relatives bioolar
of schizoprobands
123
of orobands
6
32
1. p=O.OZ compared to eating disorders outpatients; p
Discussion Using the DIS, we found that 77% of 90 patients with anorexia nervosa, bulimia, or both displayed a lifetime diagnosis of a major affective disorder, and that an additional 13% displayed cyclothymic disorder, dysthymic disorder, atypical affective disorder, or schizoaffective disorder. The lifetime rates of major affective disorder did not differ significantly among the eating disorders subgroups but were significantly greater in inpatients compared to outpatients. Previous studies using the Research
350 Diagnostic Criteria (RDC) (Spitzer et al., 1978) have also reported a high prevalence of major affective disorder in anorexia nervosa (Gershon et al., 1983; Hendren, 1983; Herzog and Osuna, 1983) and bulimia (Herzog and Osuna, 1983; Walsh et al., 1983). The lifetime rate of major affective disorder in subjects with eating disorders (both inpatient and outpatient subgroups) significantly exceeded that found in the comparison groups of the first-degree relatives of schizophrenic probands and even the first-degree relatives of bipolar probands-despite the fact that the latter group presumably shows a prevalence of major affective disorder already higher than would be expected in the general population (Slater and Cowie, 1971; Tsuang et al., 1980; Gershon et al., 1982). In our sample of patients, anxiety disorders were second to affective disorders in prevalence; 54% had a lifetime diagnosis of panic disorder, agoraphobia, obsessivecompulsive disorder, or a combination thereof. This finding is consistent with several reports of a high level of anxiety and obsessive-compulsive symptoms in patients with anorexia nervosa (Halmi, 1974; Cantwell et al., 1977; Crisp et al., 1980; Strober, 1980) and bulimia (Nogami and Yabana, 1977; Pyle et al., 1981). Kleptomania was observed in 27% of our patients. The high prevalence of kleptomania has been noted by others, particularly in association with bulimia (Casper et al., 1980; Crisp et al., 1980; Garfinkel et al., 1980; Pyle et al., 1981). Substance use disorders were common among all eating disorder groups. This finding is consistent with two reports of frequent alcoholism, use of illicit drugs, or both in patients with anorexia nervosa, particularly those with concomitant bulimia (Eckert et al., 1979; Garfinkel et al., 1980). We found a low prevalence of personality disorders in all eating disorder groups. Because diagnoses of most personality disorders were made using unstructured questions and clinical data, we may have underestimated the prevalence of personality disorders in these patients. We found no cases of schizophrenia among our subjects. This observation is consistent with findings from several large studies which have shown schizophrenia to be rare or absent in patients with eating disorders (Theander, 1970; Morgan and Russell, 1975; Cantwell et al., 1977; Grounds, 1982). Although Hsu et al. (198 1) found six cases of schizophrenia among 105 anorexic patients, five of the six cases had clear symptoms of depression, three had rapid remissions, and two had a strong family history of affective disorder. Thus, perhaps only one case would meet DSM-III criteria for schizophrenia. Two alternative explanations for the findings should be considered. First, could our sample have been biased to include a disproportionate number of patients with concomitant major affective disorder? Although this explanation cannot be excluded, it seems unlikely because (1) subjects were consecutive patients with eating disorders drawn from four separate sources and (2) the study population was similar, both in demographic characteristics and prevalence of affective symptomatology, to other large series of patients with anorexia nervosa, bulimia, or both reported previously (Russell, 1979; Casper et al., 1980; Crisp et al., 1980; Garfinkel et al., 1980; Pyle et al., 1981; Gershon et al., 1983; Hendren, 1983; Herzog and Osuna, 1983; Walsh et al., 1983). Of course, the inpatients in our sample, because of their need for hospital
351 treatment, might be expected to exhibit significant psychopathology in addition to their eating disorder. Even if we restrict our consideration to the outpatient portion of the sample, however, the lifetime prevalence rates of affective and anxiety disorders among outpatients are still significantly higher than in the comparison groups. A second alternative explanation is that the affective symptoms in patients with eating disorders might be attributable to weight loss, or represent a reaction to the eating disorder itself. For example, Crisp and Stonehill (1973) report that weight loss was associated with sleep disturbance and other depressive symptoms in psychiatric patients without severe depression. Several studies report that depressive symptoms, present in anorexia nervosa patients at low weight, improve with weight gain (Gerner and Gwirtsman, 1980; Strober, 1980; Eckert et al., 1982). However, these studies do not exclude the possibility that weight gain and concomitant reduction in depressive symptoms might both be due to improvement in an underlying affective disorder. In addition, since a majority of our anorexic patients exhibited major affective disorder at times when they were of normal weight and because the nonanorexic patients with bulimia had a similar lifetime rate of DSM-III major affective disorder, it is clear that weight loss alone could not have accounted for the high prevalence of major affective disorder observed. It also appears unlikely that the affective symptoms in our patients represented a reaction to having an eating disorder, since major affective disorder developed before the eating disorder in 49% of the 69 cases in which major affective disorder occurred, and was present in 59% of the 17 patients whose eating disorder symptoms were in remission on evaluation. It should be noted, however, that retrospective assessment of age of onset of both eating disorders and affective disorders is difficult, and should be considered tentative. Finally, the bipolar disorder diagnosed in 13% of patients could not easily be attributable to either weight loss or reaction to illness. In summary, among 90 patients with anorexia nervosa, bulimia, or both, we found a lifetime rate of major affective disorder much higher than that found in two comparison populations. This high rate appears unlikely to be due to idiosyncratic patient selection or to be explainable as a reaction to weight loss or eating disorder symptoms. This finding, combined with the results of studies of family history, long-term outcome, response to biological tests, and response to antidepressant medications, favors the hypothesis that anorexia nervosa and bulimia may be closely related to major affective disorder. The research reported was supported in part by a Medical Foundation Research Fellowship (Dr. Hudson); by a Biomedical Research Support Grant RR05484 awarded by Biomedical Research Support Program, Division of Research Resources, National Institute of Mental Health; by a grant from the MacArthur Foundation; and by a grant from the Abigail Adams Atchley Fund, Lincoln, MA. The authors thank the Anorexia Nervosa Aid Society of Massachusetts for assistance in recruiting subjects.
Acknowledgments.
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R.L. Depression
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