P.s.rchiarr.r Rrseurc h, 18, 209-2 I5 Elsevier

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Validity of the Hamilton Endogenous Subscale: An Independent Replication -

Mark Zimmerman, William Coryell, Bruce Pfohl, and Dalene Stangl

Received Oc,ioher 30, 198.5; revised version received January 21. 1986.

1986; accepted January, 28,

Abstract. We calculated scores on the Hamilton Endogenous Subscale (HES) (Thase et al.. 1983) for 252 depressed inpatients. The HES scores were bimodally distributed. and HES classification was significantly associated with endogenous (Research Diagnostic Criteria) and melancholic (DSM-II/) subtyping. Based on a cutoff score of 8, HES classification was not associated with either family history of specific psychiatric illness or abnormal dexamethasone suppression test (DST) results. When the cutoff was raised to IO. DST nonsuppressi,on was more frequent in HES endogenous depressives, although we again failed to find an association with a family history of psychiatric disorders.

Key Words. Endogenous depression, Hamilton Rating Scale for Depression, melancholia.

The distinction between endogenous and nonendogenous depression has a rich history, characterized by debates, research, and ultimately confusion (Kendell, 1976). During the past decade, the two most frequently studied sets of diagnostic criteria for endogenous depression have been the Research Diagnostic Criteria(RDC) (Spitzer et al., 1978) and DSM-IIIdefinitions (American Psychiatric Association, 1980). During the 1960s. before the publication of these criteria sets, endogenous subtyping was based primarily on the clinician’s overall impression. Because the Hamilton Rating Scale for Depression (H RSD) (Hamilton, 1967) was widely used in these studies, an HRSD analog to the presently used diagnostic systems would help researchers to interpret earlier findings within a contemporary diagnostic framework. Thase et al. (1983) examined the validity of a subscale for endogenous classification derived from the HRSD. and found a significant association with RDC and DSM-f/I subtyping.

The purpose of the present analysis is twofold: (1) We attempted to replicate the finding by Thase et al. (1983) of a significant association between the Hamilton Endogenous Subscale (HES) and the DSM-III and RDC endogenous criteria. (2) We examined the validity of the HES in terms of its association with results of the dexamethasone suppression test (DST) and family history of specific psychiatric disorders.

Mark Zimmerman, B.A.. William Coryell. M.D.. Bruce Pfohl. M.D., and Dalene Stangl. M.A., are m the Department of Psychiatry. University of Iowa College of Medicine. 500 Newton Rd.. Iowa City. IA 52242, USA. (Reprint requests to M. Zimmerman.)

0 I65- I78 I 86 $03.50 @ 1986 Elsevier Science Publishers B.V: .

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Methods

Over a 2-year period, we recruited a consecutive series of 257 inpatients with DSM-III major depressive disorder. We did not require a minimum level of symptom severity on a measure such as the H RSD, nor did we exclude severely depressed patients who were unable to complete some of our measures. Our only criteria for inclusion were that the patient be I8 years of age or older, and not have any of the medical or pharmacological conditions reported to invalidate the DST (Carroll et al., 1981; Privitera et al., 1982; Cameron et al., 1984).

Two of the researchers completed the Beck Depression Inventory (Beck et al., 1979) Global Assessment Scale (Endicott et al., 1976) and 24-item HRSD within I week of admission (mean = 2.5 days). We supplemented the HRSD with questions from the Schedule for Affective Disorders and Schizophrenia (SADS) (Spitzer and Endicott, 1978) on distinct quality of mood (item 236) reactivity to pleasurable environmental stimuli (item 350) diurnal variation of mood (item 35 I), and loss of interest or pleasure in usual activities (item 326). The cutoffs that we used on the HRSD and SADS items to determine the presence or absence of the endogenous symptoms are described by Zimmerman et al. (1985b).

The HES is the sum of HRSD items 5-9, 16. 18, and 23 (middle insomnia, terminal insomnia, work and activities, retardation, agitation, weight loss, diurnal variation, and hopelessness). Thase et al. (1983) found that HES scores were bimodally distributed around a score of 7 (the range of HES scores is O-22) and classified patients scoring > 8 as endogenous. Because they also found that a cutoff of IO maximized the concordance between HES classification and DSM-III melancholic subtyping, we examined the validity of both HES cutoffs.

Family history diagnoses were based on information collected from the patient, and are described in greater detail by Zimmerman et al. (1985~). Briefly, each relative was diagnosed two times-according to both a low and high diagnostic threshold. Our low threshold diagnoses used a strict interpretation of the Family History Research Diagnostic Criteria (FH-RDC) (Endicott et al., 1978). Our high threshold diagnoses for depression and alcoholism required hospitalization and treatment, respectively. Morbid risks were calculated with age-corrected denominators by the Weinberg short method. Relatives over the age of risk for a particular illness received a value of I; those within the age of risk, a value of r/2, and those below, a value of 0. Limits for these ages of risk were 15-59 for depression and 20-39 for alcoholism and antisocial personality (Tsuang et al., 1984).

The DST was completed during the first week of hospitalization. Patients took I mg of dexamethasone at I I p.m. and had blood drawn the next day at 8 a.m. and 4 p.m. Serum cortisol was measured by radioimmunoassay. Thirty-three normal controls also completed the 1 mg DST with 8 a.m. and 4 p.m. blood sampling. The test’s specificity was 97% with a cutoff of 5 pg/dl, and 91% with a cutoff of 4 pg/dl. Nonsuppression was therefore defined as a serum cortisol level > 5.0 pg/dl at either sampling.

Results

We could not classify five patients on the HES because of missing data; thus, our analyses are based on 252 patients. Table 1 shows that most patients were female high school graduates, with at least one prior psychiatric hospitalization. More than half of the sample met RDC endogenous criteria (n q 169), and only 14.3% were non- endogenous depressives. The remaining 47 patients were probable endogenous depressives according to the RDC. One hundred and four patients (41.3%) were DSM-III melancholic. The mean HES score was 9.5 (SD = 3.4), and 184 patients (73.0%) scored > 8. The distribution of HES scores significantly departed from normality (Kolmogorov-Smirnoff goodness of fit,p < 0.05). with a point of rarity at 7 (Fig. I), yielding a bimodal distribution of scores.

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Table 1. Demographic and clinical characteristics in 252 depressed inoatients

Sex (n)

Male 32.5% ( 82)

Female 67.5% I 170)

Marital status

Single 24.6% ( 62)

Married 42.1% (106)

Separated 6.3% i 16)

Divorced 20.6% ( 52)

Widowed 6.3% i 16)

Education

Mean years (SD) 12.5 (2.51

High school graduate [n) 77.5% (196)

College graduate (n) 16.9% I 42)

Age Mean years (SD) 39.0 115.3)

Prior hospitalizations

Mean (SD) 3.0 (3.71

No prior hospitalization (ni 19.0% ( 48)

Rating scales during week 1 of hospitalization

Mean 17-item Hamilton Rating Scale for Depression (SD)

Mean 24-item Hamilton Rating Scale for Depression (SD)

Mean Beck Depression Inventory (SD)1

22.4 ( 6.1)

29.3 ( 8.6)

28.4 (11.1)

Mean Global Assessment Scale (SD) 39.0 ( 8.0)

1. Eight patients were unable to complete the Beck Depression Inventory.

Fig. 1. Distribution of Hamilton Endogenous Subscale (HES) scores in 257 depressed inpatients

35 1

30-

2 25-

5 5 2 20-

b

$ IS-

f

= lo-

S-

o- i i S i S

HE’S Score

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HES Subtyping with a Cutoff of 8. HES-8 classification was significantly associated with both RDC endogenous (~2 q 60.1, df’= 2, p < 0.0001) and DSM-III

melancholic subtyping (~2 q 44.2, df = 1, p < 0.000 1) (Table 2~). The sensitivity of the HES-8 was good, but specificity was low (Table 3~).

Table 2. Relationship between Hamilton Endogenous Subscale (HES) classification and Research Diagnostic Criteria and DSM-//I subtyping in 252 depressed inpatients

a. HES classification based on a cutoff of 8

RDC diagnosis

Nonendogenous !n = 361

Probable endogenous in = 47)

Definite endogenous (n = 169)

DSM-//I diagnosis

Nonmelancholic in = 148)

Melancholic in = 1041

b. HES classification based on a cutoff of 10

RDC diagnosis

Nonendogenous cn = 361

Probable endogenous in = 471

Definite endogenous (n = 1691

DSM-//I diagnosis

Nonmelancholic In = 1481

Melancholic (n = 104)

HES classification

Nonendogenous Endogenous (n = 88) (n = 184)

22 14

26 21

20 149

63 85

5 99

HES classification

Nonendogenous Endogenous (n = 119) (n = 133)

27 9

32 15

60 109

95 53

24 80

One third of the patients were DST nonsuppressors. HES-8 classification did not predict nonsuppression (endogenous 34.8%; nonendogenous 29.4%; x2 = 0.6, NS). Similarly, HES-8 classification was not significantly associated with the morbid risk of depression, alcoholism, or antisocial personality as calculated by using either a low or high threshold for diagnosis (Table 4~). HES Classification With a Cutoff of 10. Raising the HES cutoff from 8 to 10 reduced the concordance with RDC subtyping, although the agreement with DSM-III

melancholia was slightly greater (Table 3b). As expected, the higher cutoff reduced sensitivity but increased specificity.

HES-IO classification was significantly, albeit *weakly, associated with DST nonsuppression (endogenous 39.1 Ye; nonendogenous 26.9%; x2 = 4.2 1, p < 0.05).

There was no association between HES-10 subtyping and the morbid risk of specific psychiatric disorders in the proband’s first-degree relatives (Table 46).

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Table 3. Diagnostic performance of the Hamilton Endogenous Subscale (HES) compared to Research Diagnostic Criteria (RDC) and DSM-III subtyping

Positive Negative predictive predictive

Criterion Sensitivity1 Specificity2 values value4 Kappa P

a. HES classification based on a cutoff of 8 RDC definite

endogenous 80.2% 57.8%

RDC definite &

probable endogenous 78.2% 61.1%

DSM-//I melancholia 95.2% 42.6%

b. HES classification based on a cutoff of 10 RDC definite

endogenous 64.5% 7 1 1% RDC definite &

probable endogenous 57.4% 75.0%

DSM-//I melancholia 76.9% 64.2%

80.9% 32.4%

92.4% 70.6%

53.6% 92.6%

82.0% 22.7%

93.2% 49.6%

60.2% 79.8%

0.48 < 0.001

0.29 < 0.001

0.34 < 0.001

0.32 < 0.001

0.17 < 0.01

0.39 < 0.001

1. Sensitivity = number of patients with endogenous depression correctly identified by the HES number of patients with endogenous depression.

2. Specrfrcity = number of patients with nonendogenous depression correctly identified by the HES number of patients with nonendogenous depression.

3. Positive predictive value = number of patients with endogenous depression correctly identified by the HES number of patients classified endogenous by HES.

4. Negative predicbve value = number of patients wtth nonendogenousdepressron correctly identified by the HES number of patients classified nonendogenous by the HES.

Table 4. Hamilton Endogenous Subscale (HES) classification and family history morbid risks in first degree relatives of 246 depressed inpatients

a. HES classification based on a cutoff of 8 Endogenous (n = 179) Nonendogenous (n = 87)

BZ Morbid Risk (%) BZ Morbid Risk (%)

FH-RDC depression 778.5 16.7 276 18.7

Hospitalized depression 756.5 9.9 268 10.1

FH-RDC alcoholism 873.5 11.2 300.5 17.3

Treated alcoholism 862.5 3.3 294.5 5.8

Antisocial personality 1027.5 2.0 357.5 2.8

b. HES classification based on a cutoff of 10 Endogenous (n = 130) Nonendogenous (n = 116)

BZ Morbid Risk I%) BZ Morbid Risk (%)

FH-RDC depression 571.0 17.7 485.5 16.7

Hospitalized depression 553.0 10.0 471.5 10.0

FH-RDC alcoholism 634.5 11.7 539.5 12.8

Treated alcoholism 626.5 3.4 530.5 4.5

Antisocial personality 748.5 2.1 636.5 2.2

Note-Family history informatron was missrng for 6 patients. BZ indicates bezugzlffer: FH-RDC = Family History Research Diagnostic Critena

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Discussion

Thase et al. (1983) applied RDC and DSM-III diagnostic criteria to the case summaries of 149 depressed outpatients. Despite differences in sample (we studied more severely ill inpatients) and methodology (we used a structured interview to make RDC and DSM-IIZendogenous diagnoses), our results were similar to their findings. In both studies, the distribution of HES scores was bimodal, with a point of rarity at a score of 7. Our kappa coefficients for classification (Table 3) were similar to those of Thase et al. (1983) for DSM-I// melancholia (Thase et al., K = 0.30), although their kappa for RDC definite/probable endogenous depression was higher (K = 0.62).

Although the HES is significantly associated with these operational criteria, between a fourth and a third of the patients are misclassified by the HES. This high rate of misclassification apparently reduces the construct validity of the HES. We previously reported that both the RDC and DSM-III endogenous criteria are significantly associated with a family history of alcoholism, and that the DSM-III

definition is associated with DST results (Zimmerman et al., 19856, 1986). In the present report, HES classification was not associated with a family history of specific psychiatric illness and only weakly associated with DST nonsuppression. Thus, the high rate of HES misclassification may limit its usefulness in retrospective diagnoses.

We studied an inpatient sample in which the vast majority of patients met RDC for probable or definite endogenous depression. Thase et al. (1983) derived the HES on a less severely ill outpatient sample. Perhaps the HES has greater validity in an outpatient population. Independent replication of the results of Thase et al. (1983) in an outpatient population is needed to evaluate more fully the utility of the HES.

References

American Psychiatric Association. DSM-III: Diagnostic and Statistical Manual of’ Menral Disorders. 3rd ed. APA, Washington, DC (1980).

Beck, A.T., Rush, A.J.. Shaw, B.F., and Emery, G. Cognitive Therapy for Depression. Guilford Press, New York ( 1979).

Cameron, O.G.. Kronfol, Z., &eden. J.. and Carroll. B.J. Hypothalamic-pituitary- adrenocortical activity in patients with diabetes mellitus. Archives qfGenera/ Psychiarrr,, 41, 1090 (1984).

Carroll, B.J., Feinberg, M., Greden, J.F.. Tarika. J., Albala, A.A.. Haskett, R.F., James. N.Mcl., Kronfol, Z.. Lohr. N., Steiner, M.. de Vigne, J.P., and Young, E. A specific laboratory test for the diagnosis of melancholia: Standardization, validation, and clinical utility. Archives of’Guzera/ P.s_whiarry, 38, I5 (198 I).

Endicott. J., Andreasen. N., and Spitzer. R.L. Fami1.p History Researc,h Diagnostic, Criteria. 3rd ed. New York State Psychiatric Institute, New York (1978).

Endicott, J., Spitzer, R.J., Fleiss. J.. and Cohen, J. The Global Assessment Scale: A procedure for measuring overall severity of psychiatric disturbance. Archives cf General Ps_whiatr.\~, 33, 766 ( 1976).

Hamilton, M. Development of a rating scale for primary depressive illness. British Journalqf Social and Clinical Ps~~cholog~~, 6, 278 (1967).

Kendell. R.E. The classification of depressions: A review of contemporary confusion. British Journal c~/’ Psj,c,hia/rj,, 129, 15 ( 1976).

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Privitera, M.R., Greden, J.F.. Gardner, R.W., Ritchie, J.C., and Carroll, B.J. Interference by carbamazepine with the dexamethasone suppression test. Biological Psychiatry, 17,61 I (1982).

Spitzer, R.L., and Endicott, J. Schedule for Affective Disorders and Schizophrenia. New York State Psychiatric Institute. New York (1978).

Spitzer, R.L., Endicott, J., and Robins, E. Research Diagnostic Criteria: Rationale and reliability. Archives of Genera/ Ps.vchintry, 35, 773 (1978).

Thase, M.E., Hersen, M., and Bellack, A.S. Validation of a Hamilton subscale for endogenomorphic depression. Journal of Affecrive Disorders, 5, 267 (1983).

Tsuang. M.T., Winokur, G., and Crowe, R.R. Psychiatric disorders among relatives of surgical controls. Journal qf Clinical Psychiatry, 45, 420 (1984).

Zimmerman. M., Coryell, W., and Pfohl, B.M. The importance of diagnostic thresholds in familial classification: The dexamethasone suppression test and familial subtypes of depression. Archives qf General Ps.vchiarry, 42, 300 (1985~).

Zimmerman, M.. Coryell. W., Pfohl, B., and Stangl, D. Four definitions of endogenous depression and the dexamethasone suppression test. Journal of A.ffective Disorders, 8, 37 (1985b).

Zimmerman. M.. Coryell. W., Pfohl, B., and Stangl, D. The validity of four definitions of endogenous depression: II. Clinical, demographic, familial and psychosocial correlates. Archives of General Psychiatry, 43, 234 ( 1986).