HPA axis disturbance in obsessive-compulsive disorder

243

Psychiatry Research. 30:243-25I Elsevier

HPA Axis Disturbance

in Obsessive-Compulsive

William H. Coryell, Donald W. Black, Michael Russell Noyes, Jr. Received 1989.

March 13. 1989; revised version received

Disorder

W. Kelly, and

August 28, 1989; accepted

October 24.

Abstract. Twenty nondepressed outpatients with DSM-III obsessive-compulsive disorder entered a IO-week placebo-controlled study of clomipramine and underwent a I-mg dexamethasone suppression test (DST) at baseline; I I had a repeat DST at the end of treatment. Nonsuppression was rare. When compared to 82 previously described outpatients with panic disorder studied in a similar fashion, OCD patients had postdexamethasone cortisol values that were substantially lower and more stable over time. Results within the OCD group closely resembled those from a group of never-ill controls. Key Words. Dexamethasone panic disorder.

suppression

test, obsessive-compulsive

disorder,

of the dexamethasone suppression test (DST) described between 1978 and 1982 fostered hopes that an abnormal escape from dexamethasone suppression would prove specific to endogenous depression and that the test would therefore provide a powerful tool for both clinical and research endeavors. Subsequent reports have cited high rates of nonsuppression in a variety of other psychiatric disorders, and enthusiasm toward the DST as a broadly useful clinical procedure has dissipated accordingly. Other disorders clearly associated with an increased risk for hypothalamic-pituitary-adrenal (HPA) axis disturbances are alcohol withdrawal (Willenbreng et al., 1984), anorexia nervosa (Gerner and Gwirtsman, 1981) bulimia (Hudson et al., 1983), and the dementias (Greenwald et al., 1986). The literature is more divided as to panic disorder (Coryell et al., 1989) schizophrenia (Coryell, 1984; Arana et al., 1985; Sharma et al., 1988) mania (Schlesser et al., 1980; Godwin, 1984) nonendogenous depression (Zimmerman et al., 1986) and obsessive-compulsive disorder (Table 1). Therefore, with the exception of bulimia, the nonaffective conditions that are clearly associated with nonsuppression include pathology easily demonstrable at the tissue or metabolic level-a hypermetabolic state for alcohol withdrawal, extreme weight loss for anorexia nervosa, and senile plaques or arterial changes for the common dementias. Bulimia, moreover, has been strongly linked to affective disorder through followup and family studies. What, then, does nonsuppression signify when it occurs in schizophrenia, panic disorder, or obsessivecompulsive disorder? Studies

William H. Coryell, M.D., is Professor of Psychiatry, Donald W. Black, M.D., is Assistant Professor of Psychiatry and Russell Noyes, Jr., M.D., is Professor of Psychiatry, Department of Psychiatry; and Michael W. Kelly, Pharm.D., is Clinical Pharmacology Fellow, Department of Pharmacology, University of Iowa, Iowa City, IA. (Reprint requests to Dr. W.H. 500 Newton Rd., Iowa City, IA 52242, USA.) Ol65-1781/89/$03.50

@ 1989 Elsevier Scientific

Coryell,

University

Publishers Ireland

Ltd.

of Iowa, Dept. of Psychiatry,

7 (25.0)

8 a.m., 4 p.m. & 11 p.m.; 5

28; 11 inpatients

NS vs. 1 (5.9%) outpatient

2 (3.3); ?

5 (17.2); 4 of 5 with major

11 (18.0)

4 p.m.; 5

61; ?

4 (13.8)

4 (30.8)

4 p.m.; 7.125

?; ?

29; outpatients

13; outpatients

Jenike et al. (1987)

Perse et al. (1987)

et al. (1986)

Montiero

?

without major depression

depression were NSs vs. 0 of 24

suppressors

have major depression than

7 (43.8); NSs no more likely to

7 (43.8)

et al. (1986)

4 p.m.; 5

of uncomplicated

-

-

OCD patients were NSs

2 (10%)

illness, 9 (81.8%) were NSs;

anorexia nervosa, or medical

cations of major depression,

11 OCD patients had compli-

-

and postdexamethasone

16; outpatients

major depression, 19 (37.3%) were NSs

Hamilton depression scores cortisol

of 51 control patients with

0; no correlation between

0

Cameron

were

6 (54.5%) inpatients

higher for NS

?; depression scores

-

-

Comments

nonsignificantly

by suppressor status

depression scores did not differ

12 (60.0%) had major depression;

differ by suppressor status

?; depression scores did not

Number with major depression; relaiionship to DST

4 p.m.; 5

18; outpatients

Lieberman et al. (1985)

lnsel et al. (1985)

et al. (1984)

17 outpatients

6 (30.0)

4 p.m.; 5

20; outpatients

Cottraux

7 (41.2)

8 a.m., 4 p.m. & 11 p.m.; 5

et al. (1982)

17; ?

ils

Asberg

-

Study

Number W.)

patients; patient status

DST sampling times; threshold for NS, pg/dl

Number of OCD

Table 1. Dexamethasone suppression test (DST) nonsuppression (NS) in patients with obsessive-compulsive disorder (OCD)

245 The presence of DST nonsuppression among patients with such nonaffective, nonorganic conditions does not necessarily imply misdiagnosis, though this may be a factor. Affective disorders with psychotic features may be confused with schizophrenia, and primary depression may be obscured when complicated by panic attacks or obsessions. In the case of panic disorder, however, DST nonsuppression apparently does not indicate misdiagnosis; in most relevant studies, panic disorder patients who escaped dexamethasone suppression were no more likely to have depression than those who did not (Coryell et al., 1989). Instead, Coryell et al. (1989) found that these patients were more severely ill in general, were less likely to respond to placebo, and were more likely to relapse when withdrawn from somatic therapy than were panic disorder patients with normal DST results. Do DST results have similar implications for patients with other anxiety disorders? We undertook the following study to consider obsessive-compulsive disorder, one of the most distinctive and well-characterized of these disorders. As before, we used repeated DSTs since this procedure has increased sensitivity without compromising specificity in previous studies (Coryell and Schlesser, 1983; Coryell et al., 1983). We also monitored dexamethasone plasma levels since other workers have proposed that control for this variable might improve diagnostic specificity (Carr et al., 1986; Carson et al., 1988). Methods Subjects. Obsessive-compulsive subjects participated in a double-blind, placebo-controlled outpatient trial of clomipramine. Inclusion criteria required that a DSM-III (American Psychiatric Association, 1980) diagnosis of obsessive-compulsive disorder (OCD) be present for at least I year with severity sufficient for scores > 7 on the National lnstitute of Mental Health (NIMH) Global Obsessive-Compulsive Scale (minimum score = I; maximum score = 15) (Murphy et al., 1982) and > I6 on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS; minimum score = 0; maximum score = 40) (Goodman et al., 1986). Among exclusion criteria were the following: major depression which preceded or dominated the clinical picture, DSMIII panic disorder or schizotypal personality, and a score > 22 on the l7-item Hamilton Rating Scale for Depression (HRSD; Hamilton, 1967). Also excluded were patients who had taken psychotropic medications during the preceding 2 weeks or, in the case of monoamine oxidase inhibitors or depot antipsychotics, within the previous 4 weeks. Many medical conditions were precluded as well and, consequently, none of the patients had conditions or were taking medications listed by Carroll et al. (198 I) as potentially complicating the DST. Procedures. A variety of baseline historical, physical, and laboratory evaluations took place during an initial 2-week single-blind placebo period. On the third visit patients were randomly assigned to receive either clomipramine or placebo, given on a double-blind basis. At I I p.m. on the evening before this visit, each patient took I mg of dexamethasone and, on the following day, a single sample was obtained for plasma cortisol and dexamethasone determinations. Though appointment scheduling required some flexibility, we succeeded in confining most visits to the afternoon. The time of sampling therefore varied from I I a.m. to 4 p.m. The dose of clomipramine was then titrated over 4 weeks to 200 mg/day, if tolerated. Clinicians then had the option of a further increase to 300 mg/day over the remaining 6 weeks. Clinical status was monitored throughout this period with the Y-BOCS, the NlMH Global Obsessive-Compulsive Scale, and the Physician’s Global Evaluation. The I-mg DST procedure was repeated after IO weeks of placebo or clomipramine treatment but before any tapering or discontinuation of medication. An earlier report (Coryell et al., 1989) described the composition and assessment of the

246 panic disorder group. Briefly, these were outpatients recruited through advertisement and through a psychiatric clinic, who met DSM-III-R criteria (American Psychiatric Association, 1987) for panic disorder and who had had at least weekly panic attacks during the preceding 3 weeks. They were randomly assigned to 8-week trials of alprazolam, diazepam, or placebo and underwent I-mg DSTs at baseline, 4 weeks later, and at the end of the treatment protocol. Only results for the first and last DSTs are considered here. The control sample has likewise been previously described (Coryell and Zimmerman, 1987). These subjects were acquired through advertisement and underwent a three-stage screen process to exclude any individual with disorders listed in the Research Diagnostic Criteria (Spitzer et al., 1978) or in the DSM-III, Axis 11. These subjects were likewise given I-mg DSTs at baseline, after 4 weeks, and after 8 weeks. Again, only results of the first and last tests are considered here. In all three samples, cortisol was measured using a radioimmunoassay (RIA) with a specific cortisol antiserum obtained from Damon Diagnostics, Needham Heights, MA. This antiserum showed no cross-reactivity with dexamethasone, progesterone, testosterone, or I I-deoxycortisol. Intra-assay and interassay coefficients of variation near 5 pg/dl were I I% and 9.2%, respectively, during the week in which OCD samples were run. While panic disorder and never-ill control samples were run in different years, assay results have been very stable over those years; quality control standards have indicated no assay drift. Plasma dexamethasone was also measured by RlA as described elsewhere (Coryell et al., 1989). A previous report (Coryell et al., 1989) compared panic disorder patients and controls by postdexamethasone cortisols with control for dexamethasone plasma levels. While these subjects were not studied concurrently with the OCD patients, the neuroendocrine testing and assay procedures were identical. The results are reproduced here to give perspective through direct comparison.

Results Twenty patients with OCD completed 2 weeks of placebo and then provided a baseline DST. Compliance with the DST was apparently good since all subjects had detectable dexamethasone plasma levels. Eleven patients provided postdexamethasone blood samples after they had completed 10 weeks of clomipramine or placebo treatment, None of these patients had major depression at intake, though the majority had had prior depressive episodes (Table 2). According to the NIMH Global ObsessiveCompulsive Scale, obsessive-compulsive behavior was “clinical” in I1 (55%) patients, “severe” in 7 (35%) and “very severe” in 2 (10%). Rates of nonsuppression were highly dependent on the threshold used to define nonsuppression (Table 3); these ranged from 5% for values > 6 pg/dl to 15% for values > 4 pg/dl. At the threshold of 4 pg/dl, these rates were significantly lower than those for panic disorder patients and at none of the three thresholds were rates significantly different from those of never-ill controls. Differences between OCD and panic disorder groups became more marked when the higher postdexamethasone cortisol of either the baseline or final DST was considered. Postdexamethasone cortisol values at baseline were positively but nonsignificantly related to obsessive-compulsive severity (Table 4). The correlation between postdexamethasone cortisol and depressive severity approached significance while age and the ratio of weight to height appeared unrelated to cortisol values. Postdexamethasone cortisols did not change substantially between the baseline and final tests. Among patients with both baseline and final DST results, the six given clomipramine showed a drop in Y-BOCS scores from 26.4 (SD = 4.9) to 9.4

247

Table 2. Baseline clinical and demographic features n

20 37.4 (10.6)

Age, mean (SD) # (%) female

13 (65.0)

Duration of illness, years, mean (SD)

13.5 (8.7)

Hamilton depression

score, mean (SD)

13 (65.0)

# (%) with history of major depression Yale-Brown

Obsessive-Compulsive

NIMH Global Obsessive-Compulsive

4.8 (4.5) 0

# (%) with current major depression Scale, mean (SD) Scale score, mean (SD)

25.5 (4.9) 9.8 (2.0)

(SD = 4.6)(t= 7.0,df= 4,p = 0.002), but baseline and final postdexamethasone cortisols were almost identical-2.9 pg/dl (SD = 3.1) and 2.8 pg/dl (SD = 3.5), respectively. The five patients given placebo showed very little clinical change; baseline and final Y-BOCS scores were 26.2 (SD = 3.9) and 23.6 (SD = 5.9), respectively. They likewise showed little change in postdexamethasone cortisol values; baseline and final values were 2.0pg/dl (SD = 2.2) and 1.2pg/dl (SD = 0.4), a nonsignificant difference. Instead, baseline and final postdexamethasone cortisol values were highly correlated (Table 4) in contrast to the corresponding values among the previously studied panic disorder patients. Of the two OCD patients with baseline values > 5 pg/dl, one exceeded that threshold 10 weeks later; none of the patients with baseline values d 5 pug/d1 were nonsuppressors IO weeks later. We selected diagnosis, sampling time, dexamethasone plasma level, age, and sex as independent variables in a series of regression analyses undertaken to test the relative importance of diagnosis to postdexamethasone cortisol values. When OCD and never-ill control groups were merged, these dependent variables were, over all, not predictive of postdexamethasone cortisol (model F= 1.6; df = 5,5 1; R2 = 0.14; p = 0.18). We then merged the panic disorder and OCD groups and included an additional independent variable-the HRSD score. The overall model was highly significant (F = 5.5; df = 6, 88; R2 = 0.27; p = O.OOOl), but only diagnosis was a significant predictor after the other variables had entered the model (l= -2.5, df = 1, p = 0.01).

Discussion An earlier study of panic disorder patients found associations between an abnormal escape from dexamethasone and greater clinical severity at baseline, a lower likelihood of placebo response, and an increased likelihood that medication withdrawal would be unsuccessful 6 months later (Coryell et al., 1989). We undertook the present study to determine whether these relationships generalized to another of the anxiety illnesses-OCD. Results suggest that escape from dexamethasone suppression is no more likely in OCD patients than in never-ill controls and is thus too rare to be of practical value. The low rate of nonsuppression reported here concurs with the results of Lieberman et al. (1985) and Jenike et al. (1987) (Table I) but stands in marked contrast to those of &berg et al. (1982), Cameron et al. (1986), Cottraux et al. (1984), and Perse et al. (1987). Unfortunately, there is no obvious reconciliation.

20

1.9 (2.1)

n Coriisol, pggidl,

mean (SD) # (%) with

1 (5.0)

> 6 /Ig/dl

1392 (245)

mean (SD)

1288 (252)

2.1 (1.3)

13 (15.9)

21 (25.6)

37 (45.1)”

1.8 (0.8) 1300 12081

1556 (39)

1 (9.1)

5 (13.2)

1.7 (0.9)

1 (9.1) 1 (9.1)

6 (15.8)

2.0 (2.6)

3.1 (2.7)

4.5 (2.2)’

5 (13.2)

11

38

82

2. 3. 4. 5. 6. 7. 8

Significantly Significantly Significantly Signlflcantly

different different different different

from from from from

OCD, OCD. OCD. OCD,

1263 (2581

2.5 (1.3)

5 (10.0)

9 (18.0)

20 (40.0)5

4.2 (2.1)2

50

(8)

Panic disorder

After treatment

Fisher’s exact test, p = 0.048. x2 = 9.7, df = 1, p < 0.005. x2 = 3.6, df = 1,p = 0.05. Wilcoxon rank sum test (x2 approximation); x2 = 13.7, df = 1, p = 0.0002.

1. Significantly different from OCD, t = -4.8, df = 100, p < 0.0001. Significantly different from OCD, t = -3.0, df = 59, p < 0.005. Significantly different from OCD, t = -4.6, df = 100. p < 0.0001. Significantly different from OCD, x2 = 6.1, df = 1, p = 0.01.

2.2 (1.7)

mean (SD) Sampling time,

ng/dl,

methasone

Plasma dexa-

3 (15.0)

2 (10.0)

> 4 pg/dl

> 5 j.igldl

corlisol

(A)

((3

W

(A)

OCD

Panic disorder

OCD

Never-ill controls

Baseline

1529 f231s

1.5 (0.9)

4 (11.1)

4 (11.1)

4(11.1)

3.0 (2.4)

36

(Cl

Never-ill controls

44 (53.7)6 26 (31 .7)7 17 (20.7)

1 (5.0)

4.9 (2.5)3

2.1 (2.3)

3 (15.0)

82

2 (10.0)

W

20

Panic disorder

(A)

OCD

5 (13.2)

5 (13.2)

6 (15.8)

3.5 (3.1)

38

(C)

Never-ill controls

Baseline or after treatment

Table 3. Dexamethasone suppression test (DST) results at baseline and after treatment among obsessivecompulsive disorder (OCD), panic disorder, and never-ill controls

249

Table 4. Postdexamethasone assorted variables by group

cortisol

Obsessivecompulsive disorder (n = 20)

at baseline: Correlations

Panic disorder (n = 82)

with

Never-ill controls (n = 38)

r

P

r

D

r

D

0.05

-0.13

0.83 0.60

-0.08 -0.26

0.48 0.02

-0.10 -0.03

0.53 0.84

0.41

0.07

0.17

0.14

-

-

Yale-Brown Obsessive-Compulsive DisorderScale score

0.31

0.18

-

-

-

-

NIMH GlobalObsessive-Compulsive Scale score

0.38

0.10

-

-

-

-

0.74 In= 111

0.009

Age Weight/height Hamiltondepression score

Final postdexamethasone cortisol

0.10 In = 501

0.49

0.86 In = 36)

0.0001

lnsel et al. (1985) found that inpatients with OCD were much more likely to be nonsuppressors than were outpatients and suggested that severity might be an important factor. There were no correlations between postdexamethasone cortisol and severity in the present study, but this relationship may not hold at the less severe end of the clinical continuum. Only one study has described inpatients and, unfortunately, very few have used the same scales to quantify obsessive-compulsive symptoms. Thus, severity comparisons between studies with high nonsuppression rates and those with low nonsuppression

rates are not possible.

According to some authors (Jenike et al., 1987) but not others (Cottraux et al., 1984; Lieberman et al., 1985; Cameron et al., 1986), depressive symptoms are associated with higher postdexamethasone cortisol values among OCD patients. The

present study found a nonsignificant correlation between HRSD scores and postdexamethasone cortisol values, but the sample had very little depression over all (none had major depression at baseline), and the spectrum of possible depressive symptoms may have been inadequate to expose such a relationship. At the present time there is far too little consistency to attribute nonsuppression among OCD patients to coexisting depression. DST parameters such as the timing and frequency of postdexamethasone sampling, dexamethasone doses, and thresholds used to define nonsuppression are all potentially important in study comparisons. However, none of these appear to explain the differences across these studies. Most, including those reporting the lowest (Lieberman et al., 1985) and the highest (Cameron et al., 1986) rates, have used a single sampling at 4 p.m. and a threshold of 5 pg/dl.

250 Of course, other less obvious nonclinical variables can influence nonsuppression rates. The appropriate threshold for nonsuppression may vary by the assay and assay standard used, and present data show that minor shifts in threshold can result in markedly different nonsuppression rates. The use of within-study control groups therefore becomes important. In the only other study with such a group (Lieberman et al., 1985), OCD patients had markedly lower nonsuppression rates than did the comparison group of patients with major depression (Table 1). In the present study, OCD patients had nonsuppression rates markedly lower than those of panic disorder patients. These rates were also more stable over time, suggesting that state effects have more influence on manifest HPA function in panic disorder. Finally, noncompliance can clearly produce spuriously high nonsuppression rates, and none of the previous studies have monitored dexamethasone plasma levels. Since sample sizes were modest in most cases, only a few occultly noncompliant individuals could have substantially raised apparent nonsuppression rates. Dexamethasone plasma levels supplied evidence that compliance was uniform in the present study. The possibility remains that the samples with higher nonsuppression rates have been more heterogeneous than those with lower rates. If so, then nonsuppression within the more mixed samples may have useful meaning. Future studies should go beyond a simple report of rates and search for such meaning. Only studies which find the higher rates can determine whether OCD patients with abnormal DST results differ in meaningful ways from those with normal DST results-are they more prone to depression and are they more likely to relapse with medication withdrawal’? Acknowledgment.

This research

Pharmaceuticals,

was supported

in part

by a grant

from

Ciba-Geigy

Inc.

References American

Psychiatric Association. DSM-III: f)iu~nostic~ ard Slotistkul Mutttrol (!f Mm/u/ 3rd ed. Washington. DC: APA. 19X0. American Psychiatric Association. DSM-//l-R: fktgttm/ic~ utid .Sluti.rlic~ul Muntrol (f Mental Disordws. 3rd ed., revised. Washington. DC: APA. 19X7. Arana, G.W.: Raldessarini, RJ.; and Orensteen. M. The dexamethasone suppression test far diagnoses and prognosis in psychiatry. Archiws 01’ Gc~twrul f.s.l~c~/riu/r.l~. 42: I I 93- 1204. 1985. s erg, M.; ThorCn, P.; and Rertilsson. I.. Clomipramine treatment olohscssive diwrdcl .&,b Biochemical and clinical aspects. f.s,,c,hot/thurtttut,(t/~t~.l, Rdk/it~ IX: 13-2 I. 19X2. Cameron, O.G.; Kerber, K.; and C’urtis, (;.C. Obsessive-compulsive disorder and the IIST. f.s_whiurr_v Rrscwwh. I9:329-330, 19X6. Carr, V.; Morris, H.; and Gilliland, .I. The effect of serum dcxamcthasone concentrations in the DST. Biological f.v~~chiu/r,,, 2 I :735-743. 19x6. Carroll, R.J.; Feinberg, M.; Greden. J.F.; Tarika. .I.; Albala. AA.: Haskett, K.F.: .lames. N.Mcl.; Kronl’ol, Z.; I.ohr, N.; Steiner. M.; de Vigne. .I.[‘.: and Young. F. A specific laboratory test for the diagnosis of melancholia. Arc~/~i~~.s 01’ Gcrwrul P.v.l~c~hiu/rl~. 3X: I S-22. Disordws.

19x1. Carson. per

S.W.;

nanogram

Biologic~~l Coryell.

Halbreich. per

mililiter

t?sychiu/r,~. W.

The

II.; Yeh. C.M.; of

plasma

24:569-577,

use of laboratory

Es_i~c~hiu/ric~ /)c,~,c,/o/“tt’,tt/,

Asnis.


dexamethasone

and (;oldstcin.

S. Cortisol

in depressive

and

suppression

normal

sub.iccts.

19Xx. tests

3: I39- 159. 19X4.

in psychiatric

diagnosis:

The

1)Sl’

as an example.

251

Coryell, W.; Noyes, R., Jr.; and Schlechte, J. The significance of HPA axis disturbance in panic disorder. Biological Psychiatry, 25:989-1002, 1989. Coryell, W., and Schlesser, M.A. Dexamethasone suppression test response in major depression: Stability across hospitalizations. Psychiurry Research. 8: 179-l 89, 1983. Coryell, W.; Smith, R.; Cook, B.; Moucharafieh, S.; Dunner, F.; and House, D. Serial dexamethasone suppression test results during antidepressant therapy: Relationship to diagnosis and clinical change. Psychiatry Research, IO: I65- 174, 1983. Coryell, W., and Zimmerman, M. HPA-axis abnormalities in psychiatrically well controls. Psychiatry Research, 201265-273, 1987. Cottraux, J.A.; Bouvard, M.; Claustrat, B.; and Juenet, C. Abnormal dexamethasone suppression test in primary obsessive-compulsive patients: A confirmatory report. Psychiuny Research, I 3: l57- 165, 1984. Gerner, R.H., and Gwirtsman, H.E. Abnormalities of dexamethasone suppression tests and urinary M H PC in anorexia nervosa. American Journal of Psychiatry, I38:650-653, I98 I. Godwin, C.D. The dexamethasone suppression test in acute mania. Journal of Affective Disorders, 7:28 I-286, 1984. Goodman, W.K.; Rasmussen, S.A.; Price, L.H.; Mazure, C.; Heninger, G.; and Charney, D.S. Yale-Brown Obsessive-Compulsive Scak (Y-BOCS). New Haven, CT: Yale University Department of Psychiatry, 1986. Greenwald, B.S.; Math& A.A.; Mohs, R.C.; Levy, M.I.; Johns, C.A.; and Davis, K.L. Cortisol and Alzheimer’s disease: II. Dexamethasone suppression, dementia severity and affective symptoms. American Journal of Psychiatry. 143:442-446, 1986. Hamilton, M. Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology. 61278-296, 1967. Hudson, J.I.; Pope, H.G.; Jonas, J.M.; Laffer, P.S.; Hudson, M.S.; and Melby, J.C. Hypothalamic-pituitary-adrenal axis hyperactivity in bulimia. Psychiatry Research. 8: I I I117, 1983. Insel, T.R.; Mueller, E.A.; Gillin, J.C.; Siever, L.J.; and Murphy, D.L. Tricyclic response and obsessive-compulsive disorder. Progress in Neuropsychopharmucology and Biological Psychiatry, 9:25-3 I, 1985. Jenike, M.A.; Baer, L.; Brotman, A.W.; Gaff, D.C.; Minichiello, W.E.; and Regan, N.J. Obsessive-compulsive disorder, depression, and the dexamethasone suppression test. Journal of Clinical Psychopharmacology. 7: I82- 184, 1987. Lieberman, J.A.; Kane, J.M.; Sarantakos, S.; Cole, K.; Howard, A.; Borenstein, M.; Novacenko, H.; and Puig-Antich, J. Dexamethasone suppression tests in patients with obsessive-compulsive disorder. American Journal of Psychiarry. 142:747-75 I, 1985. Montiero, W.; Marks, I.M.; Noshirvani, H.; and Checkley, S. Normal dexamethasone suppression test in obsessive-compulsive disorder. British Journal of Psychiatry. 148:326-329, 1986. Murphy, D.L.; Pickar, D.; and Alterman, I.S. Methods for the quantitative assessment of depressive and manic behavior. In: Burdock, E.; Sudilovski, A.; and Gershon, S., eds. The Behavior of Psychiatric Patients. New York: Marcel Dekker, inc., 1982. pp. 355-391. Perse, T.; Greist, J.; Jefferson, J.; Rosenfeld, R.; and Dar, R. Fluvoxamine treatment of obsessive-compulsive disorder. Americun Journal of Psychiarry, 144:1543-l 548, 1987. Schlesser, M.A.; Winokur, G.; and Sherman, B.M. Hypothalamic-pituitary-adrenal axis activity in depressive illness. Archives of General Psychiatry, 37:737-743, 1980. Sharma, R.P.; Pandey, G.N.; Janicak, P.G.; Peterson, J.; Comaty, J.E.; and Davis, J.M. The effect of diagnosis and age on the DST: A meta-analytic approach. Biological Psychiatry. 24:555-568, 1988. Spitzer, R.L.; Endicott, J.; and Robins, E. Research Diugnosric Criteria. 3rd ed. New York: New York State Psychiatric Institute, 1978. Willenbreng, M.L.; Morlay, J.E.; Niewoehner, C.B.; Heilman, R.O.; Carlson, C.H.; and Shafer, R.B. Adrenocortical hyperactivity in newly admitted alcoholics: Prevalence, course and associated variables. Psychoneuroendocrinology, 9:4 15-422, 1984. Zimmerman, M.; Coryell, W.; and Pfohl, B. The validity of the dexamethasone suppression test as a marker for endogenous depression. Archives of General Psychiatry. 43:347-355, 1986.