Psychiatry Research, 25, I23- I33 Elsevier

123

The Dexamethasone Suppression Test in Relation to Symptomatology: Preliminary Findings Controlling for Serum Dexamethasone Concentrations

Jay Smith, Vaughan Carr, Howard Morris, and JudyBilliland

Received May 8, 1987; revised version received February 5, 1988; accepted March 26, 1988.

Abstract. A diagnostically heterogeneous sample of psychiatric inpatients (n = 52) was administered the I mg dexamethasone suppression test (DST) shortly after hospital admission. Each was also assessed using the Hamilton Rating Scale for Depression (HRSD) and selected items of the Present State Examination (PSE) representing psychomotor retardation and anxiety. A potent determinant of postdexamethasone serum cortisol concentrations was found to be the level of serum dexamethasone concentration achieved following the oral dose. No relationship was found between postdexamethasone cortisol concentration and the scores on either the HRSD or an anxiety scale derived from selected PSE items. However, symptoms of psychomotor retardation were significantly related to postdexamethasone serum cortisol concentration, particularly when the serum dexamethasone concentrations were taken into account. It may be that DST nonsuppression in psychiatric patients is in part a reflection of the presence of psychomotor retardation, a phenomenon that cuts across diagnostic categories.

Key Words. Dexamethasone, cortisol, symptomatology.

Reports of abnormal dexamethasone suppression test (DST) results in a range of psychiatric disorders have cast doubt on the diagnostic specificity of the DST. For instance, while finding about a 70% incidence of nonsuppression in depressed patients, Coppen et al. (1983) reported a significant frequency of abnormal response in other psychiatric disorders. This ranged from 2 I .7% in patients with schizophrenia to 43.8% in neurotic nondepressive illness and 46.7% in senile dementia. Berger et al. (1984) also examined 23 1 patients with mixed psychiatric diagnoses and found that neither the 1 mg nor the 1.5 mg DST discriminated between patients with endogenous depression and those with nondepressive psychiatric disorders. Two further studies by Klein et al. (1984) and Keitner et al. (19856) have confirmed the lack of diagnostic specificity of the test in large heterogeneous psychiatric samples.

Jay Smith, M.B., B.S., F.R.A.N.Z.C.P., was Psychiatry Registrar at the Royal Adelaide Hospital, Adelaide, South Australia, 5000, at the time this research was conducted. Her most recent appointment was Registrar in Psychiatry at the Maudsley Hospital, Denmark Hill, London, SE5 8AZ. Vaughan Carr, M.B., B.S., F.R.C.P.(C.), F.R.A.N.Z.C.P., is Senior Lecturer in the Department of Psychiatry, University of Adelaide, Adelaide, South Australia, 5000. Howard Morris, B.Sc., Ph.D., is a Principal Hospital Scientist, and Judy Gilliland, B.Sc., is a Senior Hospital Scientist in the Division of Clinical Chemistry, Institute of Medical and Veterinary Science, Adelaide, South Australia, 5000. (Reprint requests to Dr. V. Carr, University of Adelaide Dept. of Psychiatry, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia.)

Ol65-1781/88/$03.50 @ 1988 Elsevier Scientific Publishers Ireland Ltd.

124

In endogenous depressive illness, rates of dexamethasone nonsuppression between 44% and 70% have been reported with, on average, 45% of depressed patients failing to exhibit cortisol suppression after dexamethasone (Sternberg, 1984). In addition, investigators have reported a significant incidence of DST abnormalities in schizo- phrenia, dementia, mania, bulimia, chronic pain, and borderline personality disorder (Dewan et al., 1982; Graham et al., 1982; Coppen et al., 1983; Sternberg, 1984).

This lack of diagnostic specificity within heterogeneous patient samples suggests that DST nonsuppression may be related to particular patterns of symptomatology which cut across traditional diagnostic boundaries. This theme was first pursued by Reus (1982) who used DST responses as the independent variable in a study of psychiatric symptoms. He proposed that DST nonsuppression was not specific to melancholia, but to a subset of symptoms that may be present in a number of different diagnostic groups. In his study of 118 patients, nonsuppressors showed more symptoms related to sleep disturbance, attentional difficulty, anxiety, and anergia than did suppressors. Sleep disturbance was also noted to be more common among nonsuppressors in a study by Nasr et al. (1983). More specifically, late insomnia rather than middle insomnia characterized the nonsuppressor group. Rapid eye movement (REM) latency and the DST were studied in 20 patients with chronic pain by Blumer et al. (1982) who reported a close correlation between postdexamethasone cortisol levels and shortened REM latency.

Other investigators have examined the relationship between cognitive function and DST results. Caine et al. (1984) administered neuropsychological tests covering 30 variables to a group of 20 depressed patients. No relationship was found between results on the DST and cognitive impairment. In contrast, Silberman et al. (1985) who administered tests of memory and cognition related to conditions of learning, type of retrieval, and stimulus properties to a sample of depressed patients, found that DST suppressors were more cognitively impaired than nonsuppressors.

Similar uncertainty surrounds the role of appetite and weight loss in DST nonsuppression. Berger et al. (1982) noted that, in a group of depressed patients, nonsuppressors differed significantly from suppressors with regard to weight loss. A significant correlation between decreased appetite and DST nonsuppression was reported by Zimmerman et al. (1984) who failed to find differences between suppressors and nonsuppressors with regard to reported weight loss. Coppen et al. (1984) also found no difference in DST results between patients with a history of weight loss and those without such a history. A similar result was reported by Keitner et al. (1985a), again using patients’ reports of weight loss. However, Berger et al. (1985) found that over half of a group of depressed patients with positive DSTs demonstrated documented weight loss.

Two early reports (Coryell and Schlesser, 1981; Targum et al., 1983) noted the presence of abnormal DST results in patients who later attempted or completed suicide. On the other hand, Secunda et al. (1986) found no relationship between DST nonsuppression and suicide attempts.

Two other symptoms identified by the Present State Examination (PSE)- slowness and general anxiety-were noted to be associated with DST non- suppression by Calloway et al. (1984). Symptoms of anxiety have not clearly been reported to relate to DST results. Some investigators have noted a significantly

125

higher level of anxiety in DST nonsuppressors (Ceulemans et al., 1985) while others have found no relationship (Sangal et al., 1984). The symptom complex of

psychomotor retardation has not been thoroughly studied in regard to the DST. Zimmerman et al. (1986) in their literature review of psychomotor retardation in the context of the DST, reported an association between psychomotor retardation and nonsuppression in some studies while no such association was evident in others. Small patient samples in the work reviewed and insufficiently comprehensive measurement of the symptom dimension in question may account for these conflicting findings.

An increasing number of studies have reported that serum concentrations of dexamethasone are significantly lower in cortisol nonsuppressors than suppressors (Berger et al., 1984; Holsboer et al., 1984; Johnson et al., 1984). These observations, which seem to undermine the reliability of the DST, have been confirmed by others (Arana et al., 1984; Morris et al., 1986). The importance of taking this factor into account is underlined by our own earlier finding that when serum dexamethasone concentrations are controlled, a modest increase in diagnostic specificity appears to occur (Carr et al., 1986).

A recent pharmacokinetic study has shown no significant difference in dexamethasone kinetics between suppressors and nonsuppressors in the early distribution phase but enhanced elimination of dexamethasone in nonsuppressors in the 9- to 24-hour period after ingestion (Holsboer et al., 1986; Wiedemann and Holsboer, 1987). On the basis of their findings in the early biophase with oral and intravenous DST, they conclude that plasma dexamethasone concentrations at the conventional sampling times following oral dexamethasone do not reflect the biopotency of the drug to suppress hypothalamic-pituitary-adrenal (HPA) axis activity (Wiedemann and Holsboer, 1987). This conclusion is based on the assumption that the sensitivity of pituitary corticotropic cells to the action of dexamethasone is maximal around midnight. Apart from the fact that the evidence supporting this assumption (Nichols et al., 1965; Krieger et al., 1971) is open to alternative interpretations, the suppressive action of dexamethasone on pituitary cells does continue at a biologically significant level beyond the first 9 hours after ingestion. Dexamethasone availability in the later biophase, as reflected in plasma concentrations at the conventional sampling times, can therefore be expected to act as a significant determinant of cortisol concentrations at these times. This deduction is supported empirically by the findings in several different laboratories of a statistically significant relationship between serum dexamethasone and cortisol concentrations at the later times of 16OOh and 2300h (Arana et al., 1984; Berger et al., 1984; Holsboer et al., 1984; Johnson et al., 1984; Morris et al., 1986) and the improved diagnostic specificity of the DST obtained when the dexamethasone levels at these times are taken into account (Carr et al., 1986; Johnson et al., 1987). These lines of evidence suggest that the conclusions of Wiedemann and Holsboer (1987) may be premature at this stage. It is clear, however, that further elucidation of the feedback control of the HPA axis is required before this issue can be clarified.

The present report represents the preliminary findings of a longer study designed to test the hypothesis that an abnormal DST in psychiatric patients is determined by two factors other than a diagnosis of depression. These are (1) the serum

126

dexamethasone concentrations obtained following oral administration of dexa- methasone and (2) the presence of the specific symptom groups of anxiety and/or psychomotor retardation. A diagnostically heterogeneous sample of psychiatric inpatients was therefore chosen to explore the possibility that DST nonsuppression may be a function of a diagnostically nonspecific biological process which is reflected in a certain symptom cluster that, likewise, cuts across diagnostic categories.

Methods

Subjects. The sample (n = 52) was drawn from consecutive admissions to an inpatient psychiatric unit in a general teaching hospital. Exclusion criteria defined by Carroll et al. (I 98 I) were used in patient selection. The 52 patients included 26 males and 26 females with a mean age of 48.5 years (range 16-73). DSM-IIIdiagnoses (American Psychiatric Association, 1980) were assigned by consensus between a consultant psychiatrist (V.C.) and a senior psychiatry trainee (J.S.) on the basis of clinical interview and case-note information. Physical examination and appropriate investigations were ordered on admission to exclude significant physical illness.

Procedure. Dexamethasone I mg was administered at 2300h within 48 hours of hospital admission, and blood samples for estimation of serum cortisol and dexamethasone concentrations were drawn at I200h and I6OOh the following day. These sampling times were selected on the basis of previous work indicating that the correlation between dexamethasone and cortisol concentrations is highest at 16OOh (Morris et al., 1985). Serum cortisol and dexamethasone concentrations were determined by radioimmunoassay, cortisol with Amerlex reagents (Amersham International plc. Amersham, United Kingdom) and dexamethasone as described previously (Gilliland and Morris, 1986). The locally determined criterion for abnormal DST response was failure to suppress the serum cortisol concentration below 160 nmol/ I (5.8 pg/dl).

All clinical assessments were completed by the first author within 48 hours of hospital admission and before the results of the DST became available. Thus, biological and clinical variables were collected at the point of greatest likelihood of maximal psychopathology and/or subjective distress. Clinical ratings included items l-17 on the Hamilton Rating Scale for Depression (HRSD) (Hamilton, 1960) and the Present State Examination (PSE) (Wing et al., 1974). With respect to the latter, only selected items were rated and these were divided into two groups, anxiety (score range O-16) and psychomotor retardation (score range O-30). The specific PSE items used for each symptom group are displayed in the Appendix. Each item was rated on a three-point scale (0, I, and 2) and the rating obtained added to yield a score for each symptom group. The psychomotor retardation scale drawn from the PSE was composed of items similar to those in the Depressive Retardation Rating Scale devised by Widliicher (1983) for the measurement of psychomotor retardation.

Results

Major depressive disorder was present in 17 of the 52 subjects. Diagnoses for the remainder were schizophrenia (7); adjustment disorder (6); panic disorder (3); psychogenic pain disorder (3); conversion disorder (2); multi-infarct dementia (2); dysthymic disorder (2); and bipolar disorder, manic (3), mixed (I), and atypical (1). There was one patient in each of the following five categories: atypical psychosis, borderline personality disorder, uncomplicated bereavement, cannabis abuse, and alcohol abuse.

As statistical analyses revealed similar results for both the 12OOh and 16OOh samples, only the 1600h samples are described in this report. A series of stepwise

127

multiple regression analyses was performed in each of which the 16OOh cortisol concentration was held as the dependent variable and varying combinations of the following were entered as the independent variables: serum dexamethasone concentration (DEX), Hamilton score (HRSD), PSE anxiety score (ANX), and PSE psychomotor retardation score (PMR).

As can be seen in Table 1, the major variance in serum cortisol was found to be due to variability in serum dexamethasone concentrations (equations #1 to #3). The relationship between cortisol and dexamethasone concentration was negative, curvilinear, and could be expressed by the equation:

[Cortisol] = 105.8 [Dexamethasone]4.62.

Cortisol concentrations were found to be unrelated either to the HRSD score (equation #3) or the anxiety score derived from the PSE items (equation #2). However, the psychomotor retardation score derived from the selected PSE items correlated positively with serum cortisol concentration when entered into a multiple regression analysis with dexamethasone concentration (equation #I).

The relationship between serum cortisol and dexamethasone concentrations was controlled statistically by means of partial correlation analyses. Dexamethasone concentration was entered as the partial correlate and the correlation coefficients between cortisol concentration and each of the HRSD, anxiety, and psychomotor retardation scores were then computed in turn. The HRSD and anxiety scores remained unrelated to cortisol concentration, while the magnitude of the correlation coefficient between cortisol concentration and psychomotor retardation increased modestly from that obtained when dexamethasone concentration was not controlled (r = 0.28, p < 0.05) by a factor of about 35% (r = 0.38, p < 0.01).

Table 1. Determinants of serum cortisol at 1600h as indicated by multiple regression analysis

t 0

#l cortisol = 9.24 PMR 2.432 <0.020

-38.04 DEX -3.203 <0.005

+145.5 K

Multiple R = 0.480; df = 1, 50; p < 0.001

#2 Cortisol = -3.5 ANX 4.620 NS

-33.7 DEX -2.670 <0.020 +223.0 K

MultipleR=0.380;df=1,50;p<0.010

#I3 cortisol = 1.6 HRSD 0.558 NS

-35.7 DEX -2.850 <O.Ol 0

+182.4 K

Multiple R = 0.378; df = 1,50; p < 0.010

PMR = psychomotor retardation score on the Present State Examination. DEX = serum dexamethasone cowentrath. ANX = anxiety score on the Present State Examination. HRSD = Hamilton Rating Scale for Depression score. K = constant,

128

In summary: (1) Serum dexamethasone concentration was found to be an important determinant of serum cortisol concentration in the dexamethasone suppression test. (2) No relationship was found between serum cortisol concen- trations and severity of depression (HRSD score) or level of anxiety (ANX score), even when dexamethasone levels were taken into account. (3) A significant relation- ship was found in this clinically heterogeneous sample between the severity of psychomotor retardation (PMR score) and postdexamethasone cortisol concen- trations, and the strength of this relationship increased when serum dexamethasone concentrations were controlled statistically.

Discussion

This study is consistent with recent reports that serum dexamethasone concentration is an important variable in determining postdexamethasone cortisol concentrations and, hence, DST suppressor status in psychiatric patients (Arana et al., 1984; Johnson et al., 1984; Carr et al., 1986; Morris et al., 1986). The significant inverse relationship between dexamethasone and cortisol concentrations during the DST strongly suggests that this factor needs to be taken into account in future applications of the test in psychiatric research.

High postdexamethasone cortisol concentrations have not consistently been found to be related to HRSD scores in the majority of reports, and the findings of the present study indicate a lack of association. Klein et al. (1984), Maes et al. (1986), and Zimmerman et al. (1986) have reported a significant relationship between HRSD score and postdexamethasone cortisol concentrations. These reports concerned patients who were defined as depressed on the basis of diagnostic classification (Maes et al., 1986; Zimmerman et al., 1986) or HRSD score (Klein et al., 1984). The statistically significant differences in HRSD scores between suppressors and nonsuppressors tend to be small and are probably not clinically meaningful. These studies stand in contrast to the comparatively small majority of studies that report no association between depression, as reflected by the HRSD score, and DST result. In a group of subjects with major depression, Brown and Shuey (1980) found no relationship between HRSD score and DST nonsuppression. Similarly, Targum et al. (1983) found no significant difference in DST results between patients with HRSD scores below 30 and those with scores above 30. Two other studies of patients with depressive symptoms (Sangal et al., 1984; Silberman et al., 1985) found no relationship between HRSD score and postdexamethasone cortisol concentrations. This lack of association between severity of depression, as measured by the HRSD, and DST nonsuppression has also been reported in bulimia (Lindy et al., 1985), borderline personality disorder (Beeber et al., 1984), and schizophrenia (Dewan et al., 1982).

Likewise, anxiety symptoms have not been consistently reported to be associated with DST results. Calloway et al. (1984) reported an association between DST nonsuppression and anxiety, but they noted that this association was relatively weak. Ceulemans et al. (1985), in 40 nonpsychiatric patients, found a significantly higher level of anxiety in nonsuppressors than suppressors. However, Sangal et al. (1984), using both observer-rated and self-rated anxiety scales, found no difference between

129

suppressors and nonsuppressors. This finding was corroborated by Krishnan et al. (1985), who found that anxiety symptoms did not discriminate between suppressors and nonsuppressors. In addition, a number of authors have reported low frequencies of DST nonsuppression in anxiety disorders such as panic disorder (Roy-Byrne et al., 1985), agoraphobia (Curtis et al., 1982), and obsessive-compulsive disorder (Montiero et al., 1986). The present study confirms this trend in the literature which suggests that DST nonsuppression is not related to anxiety.

Psychomotor change has long been recognized to be a central feature of the depressive syndrome. Charles Darwin, in 1872, expressed this when he characterized depressed patients as those who “no longer wish for action, but remain motionless and passive . ...” A century later, Nelson and Charney (198 1) reviewed the literature regarding major depressive illness and concluded that psychomotor change-in particular, retardation-is the symptom most strongly associated with “autonomous” depression. It is therefore of considerable interest that this study has demonstrated a relationship between psychomotor retardation and HPA axis disinhibition as measured by the DST.

Two other points are noteworthy in this context: (I) The relationship between psychomotor retardation and postdexamethasone cortisol concentration was strengthened when the variability in serum dexamethasone concentration was taken into account. (2) This relationship was found in samples of psychiatric inpatients regardless of diagnosis. It remains to be seen whether the observed correlation is maintained in separate samples of patients with and without major depressive disorders. It may be that in major depressive disorder more severe degrees of depression would result in greater degrees of psychomotor retardation and hence, perhaps, a greater frequency of DST nonsuppression. To address this question, a larger number of subjects would be required than were available in the present study in which only 17 in the sample of 52 had a diagnosis of major depressive disorder. A larger sample of depressed patients may also reveal a significant relationship between DST status and HRSD score, which was not obtained in the present instance.

The measurement of psychomotor retardation has received some attention in recent years (Greden and Carroll, 1981; Widlocher, 1983) but this symptom group has not been specifically studied in regard to possible underlying neurophysiological alterations. The results of the present study suggest that further research within this framework may be useful in elucidating the psychobiology of HPA axis disinhibition.

Most definitions of psychomotor retardation include the central concept of slowing of both psychic and motor activity which may be expressed in a myriad of symptoms or signs, ranging in severity from fatigue and loss of interest to stupor. Widlocher (1983) provides a comprehensive description of the manifestations of psychomotor retardation, and comments that retardation is an unsatisfactory name for what is essentially a “freezing” of activity in several spheres. Although predominantly described in depressive illness, psychomotor retardation may be observed in other psychiatric syndromes. The symptom groups of “negative schizophrenia” (Andreasen, 1982) and “Type II schizophrenia”(Crow, 1982) share a number of similarities with psychomotor retardation. In chronic pain, psychomotor changes of lesser severity, such as fatigue, loss of interest, poor concentration, and so

130

on, have been described (Blumer et al., 1982). Slowness of movement, impaired ability to act, apathy, and personal neglect also form an important part of the syndrome of dementia (Trimble, 1981). Thus, the relationship of postdexamethasone cortisol concentration to the presence and severity of psychomotor retardation may begin to explain the frequency of DST nonsuppression both in depressive illness and in other psychiatric disorders.

The precise pathophysiology of psychomotor retardation is not known. It has been postulated that mesolimbic-nigrostriatal pathways may form the anatomical substrate for the connection between affective and neuroendocrine functions and motor functions (Greden and Carroll, 1981). Further research may help to define more precisely the anatomical and biochemical characteristics of this area, and shed more light on the relationship between HPA axis disinhibition and psychiatric illness.

References

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

Andreasen, N.C. Negative symptoms in schizophrenia: Definition and reliability. Archives af General Psychiatry, 39,784 ( 1982).

Arana, G.W., Workman, R.J., and Baldessarini, R.J. Association between low plasma levels of dexamethasone and elevated levels of cortisol in psychiatric patients given dexamethasone. American Journal of Psychiatry, 141, I6 I9 ( 1984).

Beeber, A.R., Kline, M.D., Pies, R.W., and Manring, J.M. Dexamethasone suppression test in hospitalized depressed patients with borderline personality disorder. Journal q/ Nervous and Mental Disease, 172,30 I ( 1984).

Berger, M., Doerr, P., Lund, R., Bronisch, T., and von Zerssen, D. Neuroendocrinological and neurophysiological studies in major depressive disorder: Are there biological markers for the endogenous subtype? Biological Psychiatry, 17, I2 I7 ( 1982).

Berger, M., Pirke, K.-M., Doerr, P., Krieg, J.-C., and von Zerssen, D. The limited utility of the dexamethasone suppression test for the diagnostic process in psychiatry. British Journal of Psychiatry, 145, 372 (I 984).

Berger, M., Pirke, K.-M., Krieg, J.-C., and von Zerssen, D. The effect of weight loss and inappropriate plasma dexamethasone levels on the DST. Psychiatry Research, 15,35 I (1985).

Blumer, D., Zorick, F., Heilbronn, M., and Roth, T. Biological markers for depression in chronic pain. Journal of Nervous and Mental Disease, 170,425 (1982).

Brown, W.A., and Shuey, I. Response to dexamethasone and subtype of depression. Archives of General Psychiatry, 37,747 (1980).

Caine, E.D., Yerevanian, B.I., and Bamford, K.A. Cognitive function and the dexamethasone suppression test in depression. American Journal of Psychiatry, 141, I I6 (1984).

Calloway, S.P., Dolan, R.J., Fonagy, P., DeSouza, V.F.A., and Wakeling, A. Endocrine changes and clinical profiles in depression: I. The dexamethasone suppression test. Psychological Medicine, 14, 749 (1984).

Carr, V., Morris, H., and Gilliland, J. The effect of serum dexamethasone concentrations in the dexamethasone suppression test. Biological Psychiatry, 21, 735 (1986).

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 General Psychiatry, 38, I5 (I 98 I).

Ceulemans, D.L., Westenberg, H.G., and Van Praag, H.M. The effect of stress on the dexamethasone suppression test. Psychiatry Research. 14, I89 (I 985).

131

Coppen, A., Abou-Saleh, M., Milln, P., Metcalfe, M., Hat-wood, J.,-and Bailey, J. Dexamethasone suppression test in depression and other psychiatric illness. British Journal of Psychiatry. 142,498 (I 983).

Coppen, A., Harwood, J., and Wood, K. Depression, weight loss and the dexamethasone suppression test. British Journal of Psychiatry, 143,88 (1984).

Coryell, W., and Schlesser, M.A. Suicide and the dexamethasone suppression test in unipolar depression. American Journal of Psychiutry, 138, I I20 (I 98 I).

Crow, T.J. Two syndromes in schizophrenia. Trends in Neuroscience, October, p. 351 ( 1982).

Curtis, G.C., Cameron, O.G., and Nesse, R.M. The dexamethasone suppression test in panic disorder and agoraphobia. American Journal of Psychiatry, 139, 1043 (1982).

Darwin, C. The Expression of the Emotions in Man and Animals. (1872). University of Chicago Press, Chicago (1965).

Dewan, M.J., Pandurangi, A.K., Boucher, M.L., Levy, B.F., and Major, L.F. Abnormal dexamethasone suppression test results in chronic schizophrenic patients. American Journal of Psychiatry. 139, 1501 (1982).

Gilliland, J.M., and Morris, H.A. A radioimmunoassay for urinary and serum dexamethasone. Communicutions in Luboratory Medicine, 2,6 (I 986).

Graham, P.M., Booth, J., Baranga, G., Galhenage, S., Myers, C.M., Teoh, C.L., and Cox, L.S. The dexamethasone suppression test in mania. Journul of Affective Disorders, 4, 201 (1982).

Greden, J.F., and Carroll, B.J. Psychomotor function in affective disorders: An overview of new monitoring techniques. American Journal of Psychiatry, 138, 1441 (198 I).

Hamilton, M. A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry. 23,56 (1960).

Holsboer, F., Haack, D., Gerken, A., and Vecsei, P. Plasma dexamethasone concentrations and differential suppression response of cortisol and corticosterone in depressives and controls. Biological Psychiutry, 19,28 I (1984).

Holsboer, F., Wiedemann, K., and Boll, E. Shortened dexamethasone half-life in depressed dexamethasone nonsuppressors. (Letter) Archives of General Psychiutry, 43,8 I3 (I 986).

Johnson, G.F., Hunt, G., Kerr, K., and Caterson, I. Dexamethasone suppression test (DST) and plasma dexamethasone levels in depressed patients. Psychiatry Research. 13,305 (1984).

Johnson, G.F., Hunt, G., Kerr, K., and Caterson, 1. The plasma dexamethasone “window” and the dexamethasone suppression test in depression. Biotogicut Psychiatry, 22, 1035 (1987).

Keitner, G.I., Brown, W.A., Quails, C.B., Haier, R.J., and Barnes, K.T. Results of dexamethasone suppression test in psychiatric patients with and without weight loss. American Journal of Psychiatry, 142, 246 (1985~).

Keitner, G.I., Haier, R.J., Quails, C.B., Brown, W.A., and McKendall, M.J. Diagnostic heterogeneity and the DST in consecutive psychiatric admissions. Psychiatry Research, 14, 215 (19856).

Klein, H.E., Bender, W., Mayr, H., Niederschiveiberer, A., and Schmauss, M. The DST and its relationship to psychiatric diagnosis, symptoms and treatment outcome. British Journal of Psychiatry, 145,59 I ( 1984).

Krieger, D.T., Allen, W., Rizzo, F., and Krieger, H.P. Characterization of the normal temporal pattern of plasma corticosteroid levels. Journal of Clinical Endocrinology, 32,266 (1971).

Krishnan, K.R., France, R.D., Pelton, S., McCann, U.D., Manepalli, A.N., and Davidson, J.R.T. What does the dexamethasone suppression test identify? Biological Psychiatry, 20,957 (1985).

Lindy, D.C., Walsh, B.T., Roose, S.P., Gladis, M., and Glassman, A.H. The dexamethasone suppression test in bulimia. American Journul of Psychiatry, 142,1375 (1985).

Maes, M., De Ruyter, M., Hobin, P., and Suy, E. The dexamethasone suppression test, the Hamilton Depression Rating Scale and the DSM-III depression categories. Journal of Affective Disorders, 10,207 (1986).

132

Monteiro, W., Marks, LM., Noshirvani, H., and Checkley, S. Normal dexamethasone suppression test in obsessive-compulsive disorder. British Journal of Psychiatry, 148, 326 ( 1986).

Morris, H., Carr, V., Gilliland, J., and Hooper, M. Dexamethasone concentrations and the dexamethasone suppression test in psychiatric disorders. British Journal of Psychiatry, 148, 66 ( 1986).

Morris, H.A., Gilliland, J.M., and Carr, V. Methodological variables affecting the DST. Proceedings of the Australian Society for Psychiatric Research, 5, 22 (I 985).

Nasr, S.J., Pandey, G., Altman, E.G., Gibbons, R.D., Gaviria, F.M., and Davis, J.M. Symptom profile of patients with positive DST: A pilot study. Biological Psychiatry, 18,57 I (1983).

Nelson, J.C., and Charney, D.S. The symptoms of major depressive illness. American Journal of Psychiatry, 138, I ( I98 I).

Nichols, T., Nugent, C.A., and Tyler, F.H. Diurnal variation in suppression of adrenal function by glucocorticoids. Journal of Clinical Endocrinology, 25, 343 (1965).

Reus, V.I. Pituitary-adrenal disinhibition as the independent variable in the assessment of behavioral symptoms. Biological Psychiatry, 17, 3 I7 (1982).

Roy-Byrne, P., Burer, L.M., and White, T.W. The dexamethasone suppression test in panic disorder: Comparison with normal controls. Biological Psychiatry, 20, 1234 (1985).

Sangal, R., Correa, E.I., and De Paulo, J.P. Depression and anxiety inventories and the dexamethasone suppression test. Biological Psychiatry, 19, I207 (I 984).

Secunda, S.K., Cross, C.K., Koslow, S., Katz, M.M., Kocsis, J., Maas, J.W., and Landis, H. Biochemistry and suicidal behavior in depressed patients. Biological Psychiatry. 21, 756 ( 1986).

Silberman, E.K., Weingartner, H., Targum, S.D., and Byrnes, S. Cognitive functioning in biological subtypes of depression. Biological Psychiatry, 20,654 (1985).

Sternberg, D. Biologic tests in psychiatry. Psychiatric Clinics of North America, 7, 639 ( 1984).

Targum, S.D., Rosen, L., and Capodanno, A.E. The dexamethasone suppression test in suicidal patients with unipolar depression. American Journal of Psychiatry, 140, 877 (1983).

Trimble, M.R. Neuropsychiutry. John Wiley & Sons, Chichester (1981). Widlocher, D.J. Psychomotor retardation: Clinical, theoretical and psychomotor aspects.

Psychiatric Clinics of North America, 6,27 ( 1983). Wiedemann, K., and Holsboer, F. Plasma dexamethasone kinetics during the DST after

oral and intravenous administration of the test drug. Biological Psychiatry, 22, 1340 (I 987). Wing, J.K., Cooper, J.E., and Sartorius, N. Measurement and Classification of Psychiatric

Syndromes: An Instruction Manualfor the PSEand Catego-Program. Cambridge University Press, London (1974).

Zimmerman, M., Pfohl, B.M., and Coryell, W.H. Appetite and weight change and the dexamethasone suppression test. Biotogicuf Psychiatry, 19,923 (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 (1986).

133

Appendix. Present State Examination items that form the enxiety and psychomotor retardation

Anxiety Item No.

4 Worrying

5 Tension pains

7 Muscular tension

10 Nervous tension

11 Free floating autonomic anxiety

12 Anxious foreboding with autonomic accompaniments

14 Panic attacks with autonomic symptoms

120 Observed anxiety

Psychomotor retardation Item No.

6 Tiredness or exhaustion

19 Inefficient thinking

20 Poor concentration

22 Loss of interest

28 Social withdrawal

36 Anergia and retardation

38 Loss of libido

51 Dulled perception

54 Lost emotions

102 Stupor

108 Self-neglect

110 Slowness and underactivity

128 Blunted affect

120 Slow speech

133 Muteness

134 Restricted quantity of speech