Polysomnographic findings and dexamethasone nonsuppression in unipolar depression: A replication and extension

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BIOL PSYCHIATRY 1987:22:872-.X82

_

Polysomnographic Findings and Dexamethasone Nonsuppression in Unipolar Depression: A Replication and Extension Donna E. Giles, Michael A. Schlesser, A. John Rush, Paul J. Orsulak, Carl L. Fulton, and Howard P. Roffwarg

To evaluate the replicability of our previous findings of increased incidence of biological dysregulation in endogenous depression, we have studied a new series of patients with major depressive disorder, unipolar type (n = 103). The subtypes compared were defined by Research Diagnostic Criteria and were endogenouslnonendogenous, primatyl secondary, and Winokur’s family history classification. As an extension of the research, we evaluated the endogenous subtype more precisely by distinguishing those patients who met criteria for probable endogenous, comparing them to both endogenous and nonendogenous depressed patients. The findings of the replication study were consistent with our earlier report; the incidence of both dexamethasone nonsuppression and reduced rapid eye movement (REM) latency was higher in those with endogenous depression. Findings for each of the other subtypes revealed no differences. The probable endogenous depressed patients were comparable to the nonendogenous depressed patients in all variables measured.

Introduction Replication is central to evaluating the validity of a scientific finding. Therefore, we have studied a series of patients meeting Research Diagnostic Criteria (RDC) (Spitzer et al. 1978) for major depressive disorder with the purposes of evaluating (A) the replicability of our previous findings concerning the relationship between dexamethasone response and rapid eye movement (REM) latency (Rush et al. 1982) and (B) the RDC category “probable endogenous depression.” Earlier reports (e.g., Kupfer 1976) suggested that reduced REM latency discriminated

From the Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburph, PA (D.E.G.); the Affective Disorders Unit, Department of Psychiatry, University of Texas Health Science Center, Dallas, TX (H.P.R., A.J.R); and Dallas Neuropsychiatry Associates, Dallas, TX (M.A.S.. C.L.F.). Presented in part at the annual meeting of the Society of Biological Psychiatry, Dallas, TX, May 1985. Supported in part by NIMH Grant MH-35370 (A.J.R.). Address reprint requests to Dr. Donna E. Giles, Department of Psychiatry, Western Psychiattic Institate and Clinic, University of Pittsburgh, 3811 O’Hara Street, Pittsburgh, PA 15213. Received June 25, 1986: revised November 6. 1986

0 1987 Society of Biological

Psychiatry

ooo6-3223/87/$03.50

REM

Latency and DST in Unipolar Depression

BIOL PSYCHIATRY 1987:22:872-882

873

primary from secondary depression. In our laboratory, we compared the RDC primary/secondary and endogenousfnonendogenous descriptive classifications to determine the system better validated by the incidence of reduced REM latency (Rush et al. 1982). Consistent with RDC, we defined secondary depression as major depression preceded in time by a major psychiatric disorder and excluded all subjects with major medical illnesses. The only personality disorder resulting in a diagnosis of “secondary depression” by RDC was antisocial ~rsonality disorder. Our findings for the p~m~/second~ distinction did not confirm those of Kupfer (1976). Both reduced REM latency and dexamethasone nonsuppression occurred more frequently in endogenous than in nonendogenous depressions. More recent research by colleagues of Kupfer (Thase et al. 1984) supported the endogenous/nonendogenous classification as more valid than the primary/secondary subdivision. Others (Feinberg et al. 1982; Mendlewicz et al. 1984) also reported that REM latency diffe~ntiated endogenous from nonendogenous depression. Dexamethasone nonsuppression response has amassed considerable controversy in the literature. There are multiple studies supporting the relative specificity of the nonsuppression response to depression and, in particular, to endogenous or melancholic depression (e.g., Carroll et al. 1976; Giles and Rush 1982; Rush et al. 1982). Several studies present data at variance with these findings, however (e.g., Stokes et al. 1983). One factor influencing discrepancies in various investigations is descriptive diagnosis and group assignment for depressed patients. Some studies classify patients as “endogenous depression” if they meet criteria for “probable endogenous depression,” whereas other studies include this same category of patients as “nonendogenous.” Previously, we have assigned probable endogenous depressions to the nonendogenous group. We specifically compared definite endogenous, probable endogenous, and nonendogenous RDC subtypes to evaluate the relationship of these diagnoses to REM latency and dexamethasone suppression status.

Methods One hundred and three adult women and men patients (87 outpatients and 16 inpatients), presenting at the Affective Disorders Unit with a chief complaint of depression, were evaluated by the Schedule for Affective Disorders and Schizophrenia-Life-time Version (SADS-L) (Endicott and Spitzer 1978). All subjects included in this study met RDC for unipolar major depressive disorder, and all were in a definite episode at the time of study. Patients with bipolar depression, psychotic depression, organic affective disorders, and/or medical illnesses that could interfere with interpretation of dexamethasone response or polysomnographic measures were excluded. All patients underwent a blood screen, including complete blood count, chemistry screen, urinalysis, and thyroid function tests. The Ill-item Hamilton Rating Scale for Depression (HRSD) (Hamilton 1960, 1967) was used to measure symptom severity. All patients had a minimum single-rater HRSD score of 14. Diagnostic classification was masked to both polysomnographic (PSG) and Dexamethasone Suppression Test (DST) findings. Primary/secondary and endogenous/probable endogenous/nonendogenous distinctions were made according to RDC (Spitzer et al. 1978). Family history subtypes-familial pure depressive disease (FPDD), depressed spectrum disease (DSD), and sporadic depressive disorder (SDD) (Winok~ et al. 1978)-were derived from the patient’s report of clearly recognizable and/or treated illnesses in

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BIOL PSYCHIATRY 1987:22:X72-88?

first-degree relatives. Only those with primary depression and with no history of bipolar disorder in first-degree relatives were included in the family history classification. Subjects were medication-free for a minimum of 14 days prior to sleep laboratory assessment. Polysomnographic recordings were obtained for 2 consecutive nights with electroencephalogram (EEG), horizontal electrooculogram (EOG), and submental electromyogram (EMG) lead placements and were scored manually according to the criteria of Rechtschaffen and Kales f 1968). Sleep onset was defined as the first half~m~nuteleading 10 consecutive minutes of Stage I or deeper polygraphic sleep, interrupted by no more than 2 min of awake or movement time. REM latency was calculated from sleep onset to the first half-minute occurrence of Stage REM. A mean REM latency of 65.0 min or less was defined as a meaningful reduction in REM latency based on studies of normals (Williams et al. 1974) and by normal control data collected in our laboratory (Roffwarg et al. 1984). REM latency and time in Stages REM 1, 2, 3, and 4 were calculated in minutes. REM activity (phasic activity per REM period) was scored on a O-4-point scale for each 30-set epoch of REM sleep for each REM period. Mean REM activity in a REM period was calculated by dividing the sum of each 30-set epoch by the number of 30-see epochs in the REM period. Within 7-10 days of the polysomnog~phic assessment, each subject took 1.O mg p.o. dexamethasone at I 1:OOnh$ ( t60 min). At 4:00 PM ( tr60 min), the following day, a serum cortisol sample was drawn. A nonsuppression response was defined as a serum cortisol value greater than 4.0 p,g/dl. This threshold value was chosen for two reasons. Carroll et al. ( 1981) indicated that a single 4:OOPM postdexamethasone sample will detect 80%~88% of DST nonsuppressors identified by three serum cortisol samples postdexamethasone (8:00 AM, 4:00 PM, and f ~:~OPM).Our own normal control study revealed that 95.0% of normal controls produce values <4.0 pg/dl after 1.O mg dexamethasone using all three postdexamethasone cortisol samples (Rush et al. 1982). Serum cortisol was quantified by radioimmunoassay (RIA) in all samples. The intraassay coefficient of variation is 8.3% at 6.0 pg/dl. and the interassay coefficient variation is 9.73% (Orsulak and Rush 1983).

Results Results are presented in a manner comparable to our previous report in order to facilitate comparison. Table 1 summarizes the demog~phi~, severity, and diagnostic data for this sample. As in our initial report, subjects tended to range between 25 and 50 years of age; the female:male ratio was maintained at approximately 2:1, and the severity of depressive symptoms tended to be moderate to severe. Mean length of episode (over a year) for this sample was comparable to the initial group. At the time of assessment, those patients with FPDD has been in an episode longer. The prounion of subjects within each diagnostic subtype category was similar also; approximately 40% (411103) of the sample met criteria for endogenous depression, 85% (881103) were considered primary, and 41% (35/85) met criteria for FPDD. Variables included in the Analyses of Variance performed for each of the three subclassifications included demographic variables (age, sex), dexamethasone response [both post-DST serum cortisol level and designation of normal (<4.0 pgldl) or abnormal (>4.0 @g/d])], and ~lysomnographic measures. Polysomnograph~~ parameters measured ineluded sleep continuity (sleep latency, time in bed, total sleep period, total sleep time.

BiOLPSYCHIATRY

REM Latency and DST in Unipolar Depression

Table 1, Demographic

Means (Standard Deviations)

Characteristics:

Sex F:M

Episode length (months)

HRSD

36.1 (10.7)

2.0

17.0 (26.7)

21.8 (5.3)

35.2 (10.4) 35.9 (10.4)

1.6

15.1 (20.1) 22.5 (34.4)

24.2” (5.5) 20.2 (4.7)

19.2 (31.2) 21.7 (20.9)

21.9 (5.5) 21.1 (4.2)

3O.P (43.8) 13.2 (17.9) 12.3 (14.3)

21.2 (5.7) 22.3 (5.4) 22.5 (5.6)

Age n

(years)

Total sample

103

Endogenous

41

Nonendogenous

62

Primary

88

Secondary

15

Familial pure depressive disease Depressed spectrum disease Sporadic depressive disorder

35

Variable

875

1987;22:872-882

27 23

2.4

34.4” (9.7) 42.8 (11.8)

2.3

34.1 (10.8) 36.5 (10.7) 32.6 (8.4)

1.9

1.0

2.4 2.3

awake plus movement time); REM sleep (REM latency, RE?Mtime, REM density, REM periods’), and non-REM sleep (Stages l-4 and total non-REM time). Results of the primary/secondary analyses are presented in Table 2. As in the 1982 study, no differences in severity or in dex~eth~one nonsuppression were noted. In our 1982 study, REM latency was reduced, and REM time and REM densities were increased, Table 2. Primary Versus Secondary Depressions Primary (n = 88) Variable Previous study HRSD DS’P TSTb DST REM latency REM time REM density I REM density 2 REM density 3 Replication study Age

Mean

SD

21.9 5.5 25.0% 384.4 48.2 3.2 3.9 69.1 27.4 90.0 27.3 1.4 0.5 1.6 0.5 1.8 0.5 34.4

9.7

Secondary (n = 15) Mean

so

21.1 4.2 26.7% 362.5 58.4 3.1 3.1 67.2 26.7 91.4 15.9 1.5 0.6 1.6 0.4 1.7 0.5 42.8

11.8

F

P

0.32 2.5 0.01 0.06 0.00 0.11 0.98 0.57

NS NS NS NS NS NS NS NS NS

9.1

0.003

kj = 0.02. TST, total sleep time.

‘Only the first three REM periods me

period.

used, as in our 1982

sample, because of the

decrementin REMperiods after the thii

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BIOLPSYCHIATRI 19X1:22:872 -8X2

Table 3. Family History Subtypes

~__

Variable Previous study HRSD DST”

TST REM latency NREM time Stage 4 DST mean Replication study REM density I REM density 2 REM density 3

__

1X51)

FPDD

SDD

(11 = 2.5) -_-___

(n = 27) -___

Ill -__

Mean

Sl)

Mean

SD

Mean

21.2

5.7

22.3

5.4

22.5 5.6 38.1%’ 387.9 51.2 74. I 26.6 305.1 43.7 10.8 17.8 4. I 4.6

2.5.8s 373.4 so.2 64.X 27.3 290.3 39.6 6.9 14.2 3.5 4.7

8.0% 395.5 42.6 70.7 30.7 309.8 35.3 9.9 20.5 2. I 1.7

I.3

0.5

I .2

I .4 I .6

0.3 0.5

1.7 I .6

0.4 0.4 0.5

1.x 2.0 2.1

23)

51)

fi 0.47

0.6 0.6 0.7

I) NS 0.05 NS

1.7 0.84 2.08 0.41 I .54

NS

6.96 12.30 5.06

0.002 O.Oill 0.009

NS NS NS

in secondary compared to primary depression. These differences were not found in this sample. Primary and secondary depressions showed equivalent polysomnographic and DST findings. The secondary group was older in this series of patients, although not in the initial sample. Family history comparisons in the 1982 series indicated that the FPDD subgroup had a higher incidence of DST nonsuppression, and the SDD subgroup produced more Stage 4 sleep. These findings were not replicated in this study; patients in the SDD group had a higher incidence of dexamethasone nonsuppression and no differences were found in Stage 4 sleep (Table 3). Differences were found in REM activity, however, with the FPDD subgroup producing uniformly less active REM periods than the SDD subgroup. REM activity in the DSD subgroup was equivalent to the FPDD subgroup (Table 3). Table 4 compares the endogenous and nonendogenous groups. Originally, we found differences between these groups in severity of depression, incidence of dexamethasone nonsuppression, total sleep time, non-REM time, Stage 2 time, and REM latency. In the current series of patients, mean HRSD scores continued to be higher for the endogenous group compared to the nonendogenous group. Pearson product-moment correlation coefTable 4. Endogenous

Versus Nonendogenous

Nonendogenous (n = 62)

Endogenous (n = 41) Variable HRSD REM latency TST” NREM time Stage 2 Serum cortisol Wdl) TST,

total

sleep time

Analysis of Covariance

F

P

4.7 28.2 40.6 36.0 31.3

15.9 15.16 0.13 0.24 0.1 I

O.ooOl O.G#l NS NS NS

2.5

8.58

0.025

Mean

SD

Mean

SD

24.2 56.5 311.5 290.2 228.7

5.5 20.4 62.2 49.7 48.9

20.2 76.9 383.7 302.3 233.0

4.6

5.0

2.3

877

BIOL PSYCHIATRY 1987;22:872-882

REM Latency and DST in Unipolar Depression

Table 5. Estimates of Logistic Regression Parameters Dependent variables Dexamethasone

Reduced REM

Independent variables Endogenous HRSD

nonsuppression

latency (1) 0.58” (0.21) -

(2) 0.506 (0.22) - 0.03 (0.04)

(1) 0.66” (0.25)

(2) 0.54* (0.26) -0.06 (0.05)

Estimated coefficient is significantly different from 0 at ‘Tl.005 level and 9.05 level Standard errors appear in parentheses.

ficients were indicative of a significant, positive association between HRSD and postdexamethasone serum cortisol levels (r = 0.23, p = 0.03). The correlation between REM latency and HRSD scores was nonsignificant (r = - 0.15, p = 0.13). We used Analysis of Covariance with HRSD as the covariate as a conservative strategy to partial out the effect of severity statistically. Even when accounting for severity, the mean dexamethasone response and mean REM latency were different for endogenous and nonendogenous depression. Sleep continuity measures (total sleep time, non-REM time, Stage 2 time) did not differentiate the two groups. Categorical measures of REM latency (reduced/nonreduced) and dexamethasone response (normal/abnormal) were also evaluated. Logistic Regression Analysis was used because it is a procedure designed to accommodate these binary dependent variables, while allowing evaluation of the effect of severity on the dependent variables. The effect of severity was evaluated by first excluding (column 1, Table 5) and, second, including (column 2, Table 5) HRSD scores in the equation. With logistic regression, the effect of subtype of depression on reduced REM latency and dexamethasone nonsuppression is estimated in comparison with a reference group. Thus, in Table 5, the estimates for endogenous depression reflect a comparison with nonendogenous depression. Although severity contributes to the strength of the differences, coefficients associated with incidence of both reduced REM latency and dexamethasone nonsuppression are significant even with severity considered.

Relationship of Polysomnographic Parameters to Dexamethasone Suppression Test Response The relationship between DST status and REM latency reduction was examined in this series of patients to compare findings with our initial report. Subjects were identified by endogenous/nonendogenous subtype, by DST response (suppressor/nonsuppressor), and by REM latency (reduced/nonreduced). Table 6 presents these data as frequency counts. The sample size in this comparison is 95 (8 patients could not be discontinued from medications contraindicated for a valid DST, most often birth control pills). Of the total sample, 15.8% (n = 15) showed both DST nonsuppression and reduced REM latency, 51.6% (n = 49) showed reduced REM latency (with or without DST nonsuppression), 35.8% (n = 34) showed reduced REM latency and normal DST suppression, and 9.5% (n = 9) showed DST nonsuppression with nonreduced REM latency. Thirty-nine percent

878

BIOL PSYCHIATR)’ 19X7:22:872-882

D.E. Giles et al

Table 6. REM Latency in Relation to Dexamethasone

Suppression

Suppressor Nonreduced latency Endogenoua Nonendogenous Reduced latencyb Endogenous Nonendogenous Total Endogenous Nonendogenous

Test Response

Nonsuppressof’

Total

7 30

5 4

I2 34

15 19

10 5

25 74

22 49

I5 9

37 5x

“Nonsuppressor defined as 34.0

pg/dl. ‘Reduced latency defined as S65.0 min.

(n = 37) of this sample had neither abnormality. These findings are virtually identical to our initial series. Of the endogenous group, 81.1% (n = 30) showed either reduced REM latency, DST nonsuppression, or both; 48.3% (n = 28) of the nonendogenous group showed one or both of the abnormalities. Of the endogenous patients, 67.6% (n = 25) had reduced REM latencies, whereas 41.4% (n = 24) of the nonendogenous patients had similar reductions. DST nonsuppression was present in 40.5% (n = 15) of the endogenous group and in 15.5% (n = 9) of the nonendogenous group. We evaluated the relative predictive utility of DST and “reduced’ REM latency values. Sensitivity, specificity, and confidence intervals were calculated for varying thresholds of REM latency and for DST nonsuppression, defined as B4.0 pg/dl (Table 7). In the current patient series, some sensitivity and specificity was lost at 60.0 and 62.0 min REM latency threshold values compared to the 1982 study, where the sensitivity was 63% and 66%, respectively. The 65.0-min threshold value continued to identify approximately 7 of 10 endogenous patients and to exclude 3 of 5 nonendogenous patients. Although DST nonsuppression continued to be much higher in the endogenous group, some specificity was lost (95% to 85%) in this patient series compared to our initial sample. Characterization

of Probable Endogenous Depression

In comparisons among endogenous, probable, and nonendogenous depression, the sample size has increased from 103 to 128 patients. As we replicated our findings of increased Table 7. REM Latency or DST Response in Endogenous

Depression

Factor

Sensitivity W)

Specificity W)

Confidence interval (So)

REM latency d 40 50 60 62 65 DST >4.0

17 39 54 56 68 41

94 90 71 66 58 85

64 73 55 52 52 63

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BIOL PSYCHIATRY 1987;22:872-882

REM Latency and DST in Unipolar Depression

Table 8. Definite, Probable, and Nonendogenous Descriptive Variables: Mean (Standard Deviations) Definite endogenous (n = 55)

Probable endogenous (n = 38)

Nonendogenous (n = 35)

Percent women Age

56.4 35.9 (11.4)

73.0 37.7 (12.7)

65.7 33.4 (6.8)

HRSD” Episode

25.1

21.6

(4.7)

19.1 (4.8)

1.8 (0.8) 1.7 (2.5) 9.2 (10.0)

2.7 (1.9) 1.6 (3.0) 7.1 (5.6)

Variable

(5.5)

5.0 (11.0)

Number

1.3 (1.9) 9.4 (9.5)

Length (years) Time ill (years) Percent primary Percent FPD

89.1

79.0

85.7

47.9

46.4

32.3

‘%*,,la= 15.3, p < 0.001.

incidence of reduced REM latency and DST nonsuppression in the endogenous classification, we believed it was justified to include those subjects from our 1982 sample in

whom we could determine by individual symptom tabulation whether the individual was “definite endogenous,” “probable endogenous”, or “nonendogenous.” This process added 25 subjects to the comparison and provided a more powerful examination of the biological characteristics of probable endogenous in relation to both definite endogenous and nonendogenous depression. Table 8 presents the descriptive characteristics of this sample. There were no differences among sex distribution, age, number or length of episodes, time ill, percentage of patients meeting criteria for primary depression, or patients with depression in relatives among the three subtypes. Severity of depression discriminated the three subgroups (F2,rz6 = 15.3, p < 0.0001). Those patients with definite endogenous depression were more severely depressed than either the probable or nonendogenous groups. Probable endogenous depressed patients were more depressed than nonendogenous patients (Duncan’s post hoc test). Because of the potential role of severity in incidence of both endogenous depression and biological abnormalities, and given that those with endogenous depression were more Table 9. Estimates of Logistic Regression Parameters Dependent variables Reduced REM latency

Dexamethasone nonsuppression

Independent variables

(1)

(2)

(1)

Definite endogenous Probable endogenous HRSD

0.71” (0.23) 0.01 (0.24) -

0.606 (0.25) -0.05 (0.25) -0.03 (0.04)

0.94” (0.34) - 0.46 (0.36) -

Estimated coefficient is significantly different from 0 at: “0.005 level and bo.02 level. Standard enws appear in parentheses.

(2) o.79b (0.36) 0.39 (0.37) -0.05 (0.04)

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BIOLPSYCHIATKY 1987:22:872-X8?

Ilk.

C;llcs et

ri:

severely depressed, we evaluated the relationship of severity to dexamethasone response and to REM latency in minutes using a Pearson product-moment correlation procedure. Severity by HRSD scores was weakly and inversely related to REM latency (Y = - 0.17, p = 0.056); the relationship of severity to dexamethasone response was positive and significant (r = 0.30, p = 0.001). To accommodate this finding, logistic regression analyses were performed on each of REM latency and dexamethasone nonsuppression a:, defined categorically (reduced REM latency ~65.0 min, nonreduced REM latency B65.0 min; dexamethasone nonsuppression >4.0 pg/dl, dexamethasone suppression ~4.0 kg/dl). In Table 9, we have presented the results of logistic regression analyses excluding (column 1) and including (column 2) HRSD scores to evaluate the influence of severity. Estimates for definite endogenous and probable endogenous groups each reflect a comparison with the nonendogenous group. Findings for reduced REM latency provided clear evidence for the influence of group membership, independent of severity. Those patients with endogenous depression have a higher probability of reduced REM latency compared to the nonendogenous group. Nonendogenous and probable endogenous depressed patients are associated with similar probabilities of reduced REM latency. This pattern held with dexamethasone nonsuppression. Examining the influence of group membership without accounting for severity of depression is compatible with our previous findings, (i.e., a higher probability of dexamethasone nonsuppression is noted in endogenous depression). This case is supported even when the effect of severity is considered. As shown in Table 9, endogenous patients have a higher estimate of dexamethasone nonsuppression when compared to nonendogenous patients when severity of depression is held constant. Probable endogenous patients are similar to the nonendogenous patients in estimates of nonsuppression. An analysis of covariance procedure using HRSD scores as the covariate was performed to evaluate continuous data (i.e., mean differences in sleep and dexamethasone parameters) among definite, probable, and nonendogenous depressions. Differences are summarized in Table 10. REM latency was reduced significantly in the endogenous group compared to both probable and nonendogenous groups. Probable and nonendogenous depressed groups were equivalent (Duncan’s post hoc). Similarly, mean serum cortisol levels were higher in the endogenous group compared to both the probable and nonendogenous groups. Again, probable and nonendogenous groups were comparable (Duncan’s post hoc). The effect of severity was nonsignificant for REM latency (F.J,l~3 = 0.01, p = 0.91), but was significant for dexamethasone response (F3,116 = 3.8, p = 0.054). Only the length of the second REM period also discriminated the three groups (F3,,22 = 5.8, p = 0.002). Nonendogenous patients had a longer REM period (27.7 +- 9.9 min) compared to endogenous (21.3 + 9.4 min) and probable endogenous (21.8 t 8.2 min) patients, who were equivalent. No other polygraphic measures discriminated among the three subtypes.

Table 10. Major Biological Variable REM latency Dexamethasone response

Variables in Endogenous Subdivisions: Means (Standard Deviations)

Definite endogenous

Probable endogenous

Nonendogenous

I-

P

55.5 (55.4) 5.0

74.7 (74.8) 2.x (2.‘))

79.6 (79.8) 1.9 (2.4)

12.4

0.0001

1.2

0.0413

(4.7)

REM Latency and DST in Unipolar Depression

BIOLPSYCHlATRY

881

~~7;2~87~-882

bssion Two major

findings proceeded from this research. The first is that the essential findings of our original study (Rush et al. 1982) were replicated and conned. Those patients with endogenous depression show higher incidences of both reduced REM latency and dexamethasone nonsuppression compared to the nonendogenous group. These findings were maintained when severity was partialled out. Moreover, primary and secondary depressed groups showed equivalent biological findings. Despite the greater age of the secondary group, findings are essentially equivalent to our initial report. The second major finding was that those patients who meet RDC for “probable endogenous depression” were comparable to the nonendogenous group relative to age, sex distribution, and familial association of depression. Probable endogenous depressed patients were less depressed than definite endogenous and more depressed than nonendogenous patients. Even when the difference in severity among the endogenous, probable, and nonendogenous groups is controlled, both mean REM latency and incidence of reduced REM latency were equivalent between probable and nonendogenous depression. The probable endogenous and nonendogenous groups were equivalent with regard to mean postdexamethasone serum cortisol levels and were lower than the endogenous group. The definite endogenous group clearly had a higher mean dexamethasone value than either of the other two groups. Of particular note, when dexame~asone response is treated in a no~~abno~al fashion, severity influenced the effect of group membership yet did not override it. That is, the probability of an abnormal dexamethasone response was higher when endogenous patients were compared to nonendogenous patients. Probable and nonendogenous patients had similar estimates of nonsuppression. This study assessed the impact of “probable” endogenous patient inclusion in the “nonendogenous” or the “endogenous” classification. These data are suggestive of a potential mitigating influence of probable endogenous patients on the Dexamethasone Suppression Test controversy. When these patients are included in the endogenous group, a substantially lower mean serum cortisol and a potentially lower incidence of DST nonsuppression will ensue. Conversely, if the probable endogenous patients are added to the nonendogenous group, a higher proportion with evidence of hypothalamic-pituita~-adrenal axis dysfunction will result. Similarly, if probable endogenous are included in the endogenous group, a lower frequency of reduced REM latency will result. Taken together, these findings suggest the critical role clinical descriptive diagnosis plays in evaluating

laboratory

tests.

The authors wish to express their appreciation to David Savage for his secretarial support; to Jerry Currie, AtiqueKhan, Damian May, and Brad Witte for their technical assistance; and to Kenneth Z. Altshuler,M.D., Stanton Sharp professor and Chairman, and to the Psychiatric Clinical Diagnostic Laboratory at Dallas Veterans Administration Medical Center.

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BIOL PSYCHIATRY 1987:22:872- 882

D.E.

Cites cl ;II

Endicott J, Spitzer RL (1978): A diagnostic interview. The Schedule for Affective Disorders and Schizophrenia. Arch Gen ~,s~~~~ur~ 35:837-844 Feinberg M, Gillin JD. Carroll BJ, Greden JF, Zis AP (1982): EEG studies of sleep in the diagnosis of depression. Biol Psychiatry 17:305-3 16. Giles DE, Rush AJ ( 1982): Relationship of dysfunctional attitudes and dexamethasone response in endogenous and nonendogenous depression. Biol Psychiat~ 17: 1303-I 3 14. Hamilton M (1960): A rating scale for depression. J Neural Neurosurg Psychiatry 1256-62. Hamilton M (1967): Development of a rating scale for primary depressive illness. Br J Sot C’lin Psycho1 6:278-296.

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