Psychiarry Research, 16, 45-50 Elsevier

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Iowa Discriminant Index for Endogenous Depression: Family History Correlates

Mark Zimmerman, William Coryell, and Dalene Stangl

Received February 27, 1985; revised version received May 13, 198.5; accepted June 10. 198.5.

Abstract. We examined the risk of psychiatric illness in the first-degree relatives of the 257 depressed inpatients upon whom we constructed the Iowa Discriminant Index (IDI) for endogenous depression. Nonendogenous depressives had a higher rate of alcoholism and antisocial personality in their families. 1DI endogenous subtyping was not associated with a family history of depression. These results provide additional support for the validity of the empirically derived IDI.

Key Words. Depression, endogenous subtyping, family history.

The endogenous] nonendogenous distinction within the depressive disorders has been discussed, debated, and researched for more than 60 years. At least 10 operational definitions of endogenous depression have been published, with most only studied by the authors who proposed them (Carney et al., 1965; Forrest et al., 1965; Leff et al., 1970; Spitzer et al., 1977; American Psychiatric Association, 1980; Kirkegaard, 1981; Feinberg and Carroll, 1982; Beth et al., 1983; Paykel et al., 1983; Thase et al., 1983). The majority of these criteria were apparently distilled from clinical intuition, although the authors never discussed their choice of symptoms. Two groups of investigators used an empirical approach toward developing an operational definition for endogenous depression (Carney et al., 1965; Feinberg and Carroll, 1982). Both rated a collection of signs and symptoms of depression, and also classified the patients as endogenous or nonendogenous based on clinical experience. They then used multivariate statistical analyses on their symptom ratings to derive criteria that operationalized their clinical diagnoses. The problem with this approach is the potential unreliability of the clinical diagnosis. Perhaps because of unreliability, several of the items included on each respective scale differ, and two recent studies found only modest overlap between the patients diagnosed endogenous by each definition (Davidson et al., 1984; Zimmerman et al., in press).

To overcome the problem of diagnostic unreliability, we used the dexamethasone suppression test (DST) as the independent variable in a discriminant function analysis (Zimmerman et al., 1985b). The use of the DST as the external criterion to construct an empirical symptom-based definition of endogenous depression may be criticized in light of the recent studies questioning the DST’s specificity for depression. It is

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

0165-1781, X5 $03.30 c 1985 Elsevier Science Publishers B.V.

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therefore important to present additional evidence for the validity of such an empirically derived diagnostic index. In the present report we examine the familial correlates of the Iowa Discriminant Index for endogenous depression.

Methods

Two hundred and fifty-seven inpatients 18 years of age or older with DSM-lllmajor depressive disorder were diagnosed according to the Iowa Discriminant Index (IDI) for endogenous depression. The ID1 was constructed from a discriminant function analysis on the 10 Research Diagnostic Criteria (RDC) (Spitzer et al., 1977) endogenous criteria with DST results as the independent variable. The diagnostic algorithm was derived on 127 of the 257 patients, and cross-validated on the remaining 130 patients. See Table 1 for the five ID1 items and their weights. Patients scoring 2 9 on the ID1 are diagnosed endogenous, whereas patients scoring < 8 are diagnosed nonendogenous. Further details about patient selection and diagnosis are given in our prior publication (Zimmerman et al. 19856).

Family history diagnoses were based on information collected from the patients. The interview followed the guide provided in the Family History Research Diagnostic Criteria (FH-RDC) (Endicott et al., 1978) and assessed the presence or absence of alcohol problems, legal problems, periods of depression, etc., for all first-degree family members. We recorded specific details about hospitalization, types of treatment received, and functional impairment. Each relative was diagnosed twice-according to both a high and low diagnostic threshold. The results of several studies suggest that a low diagnostic threshold reduces the relationship between proband and familial psychopathology (Weissman et al., 1982; Winokur, 1983; Zimmerman et al., 1985~). Our low threshold diagnoses were based on a strict interpretation of the FH-RDC. For example, we would diagnose as alcoholic someone who had alcohol-related marital problems even if these did not lead to a separation or divorce, and we would diagnose as depressed someone who had a full depressive syndrome for 2 weeks or more following a divorce, even if they did not seek treatment or manifest gross functional impairment. Our high threshold diagnoses required hospitalization for depression and treatment for alcoholism.

Table 1. Iowa Discriminant Index (IDI) for endogneous depression

Symptom Weight

Mood worse in morning (SADS item 351 = 3 or 4) +5

Middle or terminal insomnia (HRSD item 5 or 6 2 1) +6

Psychomotor disturbance (HRSD item 8 or 9 2 1) +4

Poor appetite (HRSD item 12 2 1) +4

Pervasive or nonpervasive anhedonia (SADS item 326 2 3) -4

SADS = Schedule for Affective Disorders and Schizophrenia (Spitzer et al., 19771; HRSD = Hamilton Rating ScaleforDepression (Hamilton, 1967i.ThecutoffsontheSADSorHRSDthatweused toratethe symptoms present follow each item. The IDI total score is computed by summing the weights of the symptoms rated as present.

Data Analysis. Morbid risks were calculated with age-corrected denominators or bezugsziffers (BZ) by the Weinberg shorter method. Thus, relatives over the age of risk for the particular illness were given a value of 1; those within the age of risk were given a value of i/2; and those below it were given a value of 0. Limits for these ages of risk for depression, alcoholism, and antisocial personality were 15-59, 20-39, and 20-39 years, respectively (Tsuang et al. 1984). Morbid risks were compared according to the method proposed by Breborowicz and Trzebiatowska-Trzeciak (1976). This comparison modifies the x* statistic to accommodate the statistical artifacts introduced by age correction in the denominators of the morbid risk calculations.

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Results

Table 2 shows that the majority of the 257 patients were female, high school graduates, and had one or more prior psychiatric hospitalizations. Slightly more than one- quarter of the sample were separated or divorced. The mean scores on the rating scales completed during the first week of hospitalization reflected a moderate to severe level of symptoms. One hundred and forty (54.5%) patients were endogenous according to the IDI, and 117 (45.5%) were nonendogenous. The two groups did not differ in sex ratio, marital status, or years of education. The endogenous patients were non- significantly older (40.5 * 16.8 vs. 37.1 + 14.1, t = 1.77, p > 0.10).

Table 2. Demographic and clinical characteristics in 257 deoressed inoatients

Sex

Male (n)

Female (n)

Marital status

Single (n)

Married (n)

Separated (n) Divorced (n) Widowed (n)

Education

Mean years (SD)

High school graduate (n)

College graduate (ni

Age Mean years (SD)

Prior hospitalizations

Mean (SD)

No prior hospitalization (n)

Rating scales during week 1 of hospitalization

Mean 17-item HRSD (SD)

Mean 24-item HRSD (SD)1

Mean Beck Depression Inventory (SD)2

32.3%

67.7%

24.9%

42.4%

6.2%

20.2%

6.2%

12.5

78.0%

16.5%

39.0

3.0

18.7%

( 83) (174)

( 641

(169)

( 161 c 52) c 16)

( 2.5) (201)

( 45)

( 15.5)

i 3.61

( 48)

( 6.1) ( 8.6) ( 11.1)

( 8.2) - Mean Global Assessment Scale (SD)

22.5

29.3

28.4

38.8 - 1. The full 24-item Hamilton Rating Scale for Depression (HRSD) was not completed on 5 patients. 2. Eight patients were unable to complete the Beck Depression Inventory (Beck et al., 1961 ).

The morbid risks for alcoholism and antisocial personality were significantly lower in the endogenous group (Table 3). There was no association between the morbid risk for depression and ID1 endogenous subtyping.

Discussion

The early writers on the characteristics of endogenous subtyping suggested that endogenous depressives were more likely to have a family history of depression, whereas nonendogenous (neurotic) patients were more likely to have a higher rate of

Table 3. IDI subtyping and family history morbid risks in first- degree relatives of 251 depressed inpatients

Nonendogenous Endogenous (n = 113) (n = 138)

Morbid Morbid BZ risk (%) BZ risk (W)

FH-RDC depression 464 17.7 607 16.8

Hospitalized depression 449.5 10.2 589.5 9.8

FH-RDC alcoholism 517 15.3 674 9.51

Treated alcoholism 507 5.7 667 2.41

Antisocial personality 609.5 3.1 794 1.42

Note. Family history information was missing for 6 patients. BZ = bezugsziffer; FH-RDC = Family History Research Diagnostic Criteria. 1. p < 0.005. 2. p < 0.05.

psychopathic states in their families (Gillespie, 1926, 1929; Buzzard, 1930; Strauss, 1930). Recent research has confirmed only the latter of these two predictions. Three studies found that a clinical diagnosis of reactive/neurotic depression was signifi- cantly associated with a family history of alcoholism but not depression (Winokur and Pitts, 1964; Perris et al., 1982; Winokur, 1983). In a cluster analysis, Andreasen and Grove (1982) found a significantly higher frequency of alcoholism, but not depression, in the families of patients in the nonendogenous than in those of patients in the endogenous clusters. Finally, two studies of DSM-III (American Psychiatric Association, 1980) melancholia also found higher rates of alcoholism in non- melancholic families (Price et al., 1984; Zimmerman et al., in press). The present results on the validity of the IDI are consistent with these studies-the nonendogenous subtype is associated with increased familial rates of alcoholism and antisocial personality but not depression.

Perhaps the conventional wisdom that endogenous depression is more genetic than neurotic depression is incorrect. Just as there are genetic components to antisocial personality (Crowe, 1974) and anxiety disorders (Torgersen, 1983), the etiology of neurotic depression probably involves an inherited component. It would be interesting to examine whether these depressive subtypes breed true. Unfortunately, the family history method is not sensitive enough to subtype the depressive relatives.

The validity of the ID1 is supported by its association with a proposed laboratory measure of endogenous depression, and a specific family history of psychiatric illness. The utility of the ID1 will rest with its prognostic significance. We have conducted a 6-month prospective followup of the patients, and will examine the predictive validity of ID1 diagnoses in a subsequent report.

References

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

Andreasen, N.C.. and Grove, W.M. The classification of depression: Traditional versus mathematical approaches. American Journal of Psychiatry, 139,45 (1982).

49

Beth, P., Gjerris, A., Anderson, J., Bojholm, S., Kramp, P., Bolwig, T.G., Kastrup, M., Clemmensen, L., and Rafaelsen, O.J. The melancholia scale and the Newcastle scales: Item- combinations and inter-observer reliability. British Journal of Psychiatry, 143, 58 (1983).

Beck, A.T., Ward, C.H., Mendelson, M., Mock, J., and Erbaugh, J. An inventory for measuring depression. Archives of General Psychiatry, 4, 561 (1961).

Breborowicz, G., and Trzebiatowska-Trzeciak, 0. A method for testing differences in morbidity risk for affective psychoses. Acta Psychiatrica Scandinavica, 54, 353 (1976).

Buzzard, E.F. Discussion on the diagnosis and treatment of the milder forms of the manic- depressive psychosis. Proceedings of the Royal Society of Medicine, 23, 88 1 (1930).

Carney, M.W.P., Roth, M., and Garside, R.F. The diagnosis of depressive syndromes and the prediction of ECT response. British Journal of Psychiatry, 111, 659 (1965).

Crowe, R.R. An adoption study of antisocial personality. Archives of General Psychiatry. 31, 785 (1974).

Davidson, J., Turnbull, C., Strickland, R., and Belyea, M. Comparative diagnostic criteria for melancholia and endogenous depression. Archives of General Psychiatry, 41, 506 (1984).

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

Feinberg, M., and Carroll, B.J. Separation of subtypes of depression using discriminant analysis. British Journal of Psychiatry, 140 384 (1982).

Forrest, A.D., Fraser, R.H., and Priest, R.G. Environmental factors in depressive illness. British Journal of Psychiatry, 111, 243 (1965).

Gillespie, R.D. Discussion on manic-depressive psychosis. British Medical Journal, II, 878 (1926).

Gillespie, R.D. The clinical differentiation of types of depression. Guy’s Hospital Reports, 9, 306 (1929).

Hamilton, M. Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6, 278 (1967).

Kirkegaard, C. The thyrotropin response to thyrotropin-releasing hormone in endogenous depression. Psychoneuroendocrinology, 6, 189 (1981).

Leff, M.J., Roatch, J.F., and Bunney, W.E., Jr. Environmental factors preceding the onset of severe depressions. Psychiatry, 30, 293 (1970).

Paykel, E.S., Parker, R.R., Rowan, P.R., Rao, B.M., and Taylor, C.N. Nosology of atypical depression. Psychological Medicine, 13, 13 1 (1983).

Perris, H., von Knorring, L., and Perris, C. Genetic vulnerability for depression and life events. Neuropsychobiology, 8,241 (1982).

Price, L.H., Nelson, J.C., Charney, D.S., and Quinlan, D.M. The clinical utility of family history for the diagnosis of melancholia. Journal of Nervous and Mental Disease, 172,5 (1984).

Spitzer, R.L., Endicott, J., and Robins, E. Research Diagnostic Criteriafora Selected Group of Functional Disorders. 3rd ed. New York State Psychiatric Institute, New York (1977).

Strauss, E.B. Discussion on the diagnosis and treatment of the milder forms of the manic- depressive psychosis. Proceedings of the Royal Society of Medicine, 23, 894 (1930).

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

Torgersen, S. Genetic factors in anxiety disorders. Archives of General Psychiatry, 40, 1085 (1983).

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

Weissman, M.M., Kidd, K.K., and Prusoff, B.A. Variability in rates of affective disorders in relatives of depressed and normal probands. Archives of General Psychiatry, 39, 1397 (1982).

Winokur, G. Controversies in depression, or do clinicians know something after all? In: Clayton, P.J., and Barrett, J.E., eds. Treatment of Depression: Old Controversies and New Approaches. Raven Press, New York, p. 153 (1983).

Winokur, G., and Pitts, F.N. Affective disorder: I. Is reactive depression an entity? Journal of Nervous and Mental Disease, 138, 541 (1964).

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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 of General Psychiatry, 42,300 (1985a).

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 (in press).

Zimmerman, M., Stangl, D., and Coryell, W. The Research Diagnostic Criteria for endogenous depression and the dexamethasone suppression test: A discriminant function analysis. Psychiatry Research, 14, 197 (1985b).