The clinical use of the dexamethasone suppression test in DSM-III affective disorders: Correlation with the severe depressive subtypes of melancholia and psychosis

The utility of the dexamethasone suppression test (DST) as an adjunct in the diagnosis of major depression remains controversial. While the research utility of the DST has been confirmed, the clinical utility has been questioned. We studied 166 consecutive admissions to a general, non-research unit who either met DSM-III criteria for major depression or had depressive symptoms associated with other DSM-III diagnoses. Using a 5 μg/dl criterion, non-suppression of serum cortisol after dexamethasone was observed in 63% of patients with DSM-III major depression. Patients with the most severe subtypes of major depression (melancholia and psychosis) showed both the highest rate of serum cortisol non-suppression and the highest post-DST serum cortisol concentrations. These findings from the clinical setting where the test, if found useful, will be used ultimately suggest that the DST is both sensitive and specific for the diagnosis of major depression. Future research will determine the potential role of the DST as an adjunct to the clinical assessment and management of patients with major affective disorder.     

Inositol treatment has no effect on the dexamethasone suppression test.

The dexamethasone suppression test (DST) is a widely studied state marker for endogenous depression. Several drugs cause false positives or negatives in this test. Since inositol is a new treatment for depression it is important to determine if it causes artifacts in the DST. Five patients with major depression diagnosed according to DSM-IV underwent a dexamethasone suppression test before and after one and two weeks of 12 grams daily inositol treatment. Three normal subjects underwent the same procedure before and after one week of inositol treatment. Four depressed patients and all three normal subjects demonstrated pretreatment dexamethasone suppression of plasma cortisol. One or two weeks of inositol treatment had no effect on post-dexamethasone cortisol plasma levels in patients or subjects. One depressed patient was a non-suppressor before treatment and continued to show elevated post dexamethasone cortisol levels after one week of inositol treatment. However, after two weeks on inositol, when substantial clinical improvement was noted, he converted to a normal DST. Chronic inositol treatment does not seem to induce false positive DST results.     

The dexamethasone suppression test as a monitor of clinical recovery

To evaluate the dexamethasone suppression test (DST) as an aid in monitoring clinical recovery, the authors evaluated 127 outpatients with major depression who received the DST during depression and after clinical recovery. Although DST response varied among the 73 patients who met the Research Diagnostic Criteria for definite endogenous depression, their mean postdexamethasone plasma cortisol level was significantly higher during depression than after recovery. However, the DST's utility in monitoring long-term outcome was not great, as there was a high chance of remaining stable for 6 months after recovery regardless of cortisol value during depression or after recovery.     

The dexamethasone suppression test in depressive illness: Clinical correlates

Clinical correlates of endogenous depression which may be associated with dexamethasone resistance have been evaluated by many investigators and found to be inconclusive. The authors investigated in 40 endogenously depressed patients the relationship of the dexamethasone suppression test (DST) and various clinical correlates - SADS scales, Research Diagnostic Criteria (RDC) depressive subtypes, family history from the FHRDC, responsivity to antidepressant treatment, etc. Dexamethasone resistance was found to be significantly associated with psychotic and bipolar depression but unrelated to the other clinical correlates examined. These findings are limited to the 2 mg DST; clinical correlates associated with non-suppression to dexamethasone may be related to the dose of dexamethasone.     

Weekly monitoring of dexamethasone suppression response in depression: its relationship to change of body weight and psychopathology

Weekly dexamethasone suppression tests (DST) were performed in 19 hospitalized patients with major depressive disorder, endogenous subtype, and who had an abnormal DST at admission. Depression scores (Hamilton Rating Scale) and weight changes were collected by investigators who were blind to the test results. Major findings were: (1) the DST gradually normalized 3-4 weeks prior to full resolution of clinical symptomatology; (2) weight loss was an important patient variable which may have contributed to false positive DST results; however, the positive correlation between changes in DST results and changes in depression scores in all our patients with or without weight loss suggests that psychopathological factors other than weight change participate in the development of dexamethasone resistance in depression; (3) the low dose (1 mg) version of the test requires careful control of minor medical disturbances, which can make the test result ambiguous. The data suggest that after resolution of some methodological issues the DST may serve as a valuable laboratory test to monitor clinical progress during drug treatment.     

Cortisol suppression per nanogram per milliliter of plasma dexamethasone in depressive and normal subjects

It has been suggested that dexamethasone pharmacokinetics may affect cortisol suppression during the Dexamethasone Suppression Test (DST). In depressed patients the cortisol response has been shown to negatively correlate with dexamethasone plasma concentrations, which also influence the sensitivity and specificity of the DST. These findings have been interpreted as weakening the utility of the DST. However, the analysis of pre- and post-1 mg DST cortisol concentrations corrected for plasma dexamethasone concentrations suggest that compared with normals (n = 52), patients with major depressive disorder (MDD) as a group (n = 71) had less suppressibility of cortisol to the same plasma dexamethasone concentrations. Moreover, when the MDD patients were evaluated based on DST status, the suppressors had cortisol/dexamethasone ratios (micrograms/dl of cortisol per ng/ml of plasma dexamethasone) similar to the normal controls, whereas the nonsuppressors had ratios that were significantly higher. These data suggest that DST non-suppression, as well as sensitivity and specificity of the DST in depression, is not only attributable to altered dexamethasone disposition, but indeed, there is a genuine reduced sensitivity of cortisol to dexamethasone that still points to an abnormality of the delayed feedback mechanism of the hypothalamic-pituitary-adrenal system in some depressed patients.     

Serial dexamethasone suppression tests in psychiatric illness: Part III. The influence of intervening variables

The effects of different intervening variables on dexamethasone suppression test (DST) results were evaluated in depressed, schizophrenic, and manic patients. There was a significant correlation between age and DST results in major depression. Some "isolated peaks" of DST nonsuppression were explained by low dexamethasone serum levels. In schizophrenic and manic patients, the dexamethasone concentrations increased to above the normal range during the study period. A significant negative correlation between dexamethasone concentrations and DST results was found in schizophrenia and mania, but not in depression. Dexamethasone levels were generally higher in men than in women. Weight loss and hospital admission affected the DST in individual cases, whereas length of episode and drug withdrawal did not. Thus, the intervening variables accounted for some of the abnormal DST results, but other factors such as severity of illness, nonspecific stress, or possibly depression itself emerged as the main causes of abnormal DST results.     

Cortisol and corticosterone response after syn-corticotropin in relationship to dexamethasone suppressibility of cortisol

The current study was designed to investigate whether glucocorticoid output after syn-ACTH stimulation is different in depression associated with dexamethasone suppression test (DST) nonsuppression from the euthymic state and DST suppression. We gave 28 depressives a DST and an adrenocortical challenge with synthetic ACTH. Fourteen patients were nonsuppressors on the DST. After successful drug treatment, the subjects were reinvestigated by both tests; all DSTs revealed plasma cortisol concentrations below the criterion value of 50 ng/ml. Cortisol and corticosterone responses after syn-ACTH tended to be higher during depression. After clinical remission, higher cortisol and corticosterone responses occurred in those patients who were DST nonsuppressors during depression. This finding suggests that patients who suffer from a depression which is linked to an abnormal pituitary--adrenocortical regulation develop an enhanced sensitivity of the adrenal cortex to ACTH.     

Plasma ACTH levels in depression before and after recovery: relationship to the dexamethasone suppression test

Sixteen patients with major depressive disorder who were nonsuppressors on the dexamethasone suppression test (DST) on hospital admission were studied for plasma levels of adrenocorticotropic hormone (ACTH). Eight patients reverted to normal suppression with clinical recovery, while eight remained nonsuppressors. There was a significant reduction of ACTH levels in those who normalized on their DST, while ACTH levels remained high in the group that continued to be nonsuppressors. The results favored the hypothesis that dexamethasone nonsuppression in depression is mediated by high ACTH levels.     

Dexamethasone suppression test, TRH test and Newcastle II depression rating in the diagnosis of depressive disorders

The dexamethasone suppression test (DST), the thyrotropin releasing hormone (TRH) test and the Newcastle II depression rating (NII) were compared with the clinical diagnosis and evaluated in 61 patients fulfilling the criteria of an affective disorder according to the DSM-III classification. A statistically significant correlation between clinical diagnosis and DST as well as NII, but not between clinical diagnosis and TRH test, was found. There was no correlation between DST and the severity of depression according to the Hamilton depression rating. The nosographic and the diagnostic specificities and sensitivities for the DST, TRH test and NII and DST and NII, a nosographic sensitivity of 50% and a nosographic specificity of 84% were found. Correspondingly, the diagnostic sensitivity was 43% and the diagnostic specificity was 88%. The DST and the TRH test were found of no value in the prediction of the response to antidepressive treatment. Mainly because of a low diagnostic sensitivity the NII, the DST and the TRH test are of limited value in the diagnosis of depressive disorders.     

The dexamethasone suppression test in affective disorders. A review

The Dexamethasone Suppression Test (DST) is a new tool to help in the diagnosis of depression. The authors present the clinical methodology for in- and out-patients and review the current literature on the DST. Some show a correlation between cortisol non-suppression after dexamethasone and the diagnosis of endogenous or primary depression. The authors illustrate the interest of the DST by providing there personal experience of this test. The influence of clinical state, severity of depression and other variables, such as age, sex, menopause and family history, are reviewed in reference to the neuro-transmitters control of the DST.     

Dexamethasone suppression test abnormalities in multiple sclerosis: relation to ACTH therapy

We studied the 1-mg overnight dexamethasone suppression test (DST) in patients with MS. In about 50% of patients, serum cortisol did not fall below 5.0 micrograms/dl. This percentage was similar in patients with major depression, but contrasted to 11% in normal controls. MS nonsuppressors were not more depressed than suppressors; dexamethasone bioavailability may have contributed because nonsuppressors had lower serum dexamethasone levels than suppressors. Suppressors improved in the week following ACTH therapy; nonsuppressors did not. Furthermore, serum dexamethasone values correlated positively with clinical response to ACTH treatment. The DST may be a useful neuroendocrine test of glucocorticoid sensitivity in MS patients.     

Neuroendocrine aspects of primary endogenous depression. II. Serum dexamethasone concentrations and hypothalamic-pituitary-adrenal cortical activity as determinants of the dexamethasone suppression test response

To determine the contribution of serum dexamethasone concentrations and hypothalamic-pituitary-adrenal cortical activity before dexamethasone administration to the dexamethasone suppression test (DST) response, a series of stepwise discriminant function analyses were performed for 40 patients with definite endogenous depression and 40 matched normal control subjects. The 24-hour serum cortisol concentration before dexamethasone administration and the serum dexamethasone concentrations at 8, 16, and 24 hours after administration served as the independent variables, and the DST "escaper"/"suppressor" dichotomy served as the dependent variable. While both types of independent variables significantly influenced the DST response, the major factor that contributed to the discrimination of escapers from suppressors was the 24-hour cortisol concentration before dexamethasone administration. Sixteen hours after dexamethasone administration, when the DST had the highest positive predictive value, serum dexamethasone concentrations significantly influenced DST outcome only when they were below a certain threshold level. At this time, hypothalamic-pituitary-adrenal cortical hyperactivity before dexamethasone administration accounted for approximately two thirds of the incidence of DST nonsuppression.     

The dexamethasone suppression test in elderly, non-depressed patients with dementia

Attempts have been made to use the dexamethasone suppression test (DST) to distinguish patients who have a primary depressive disorder from those suffering a degenerative cerebral disorder. It has been suggested however, that organic brain damage reduces neuroendocrine sensitivity and can be associated with failure to suppress on the DST. This study investigates the DST in 21 patients, over 65 years, with dementia but no evidence of depression on a variety of clinical criteria. Seven patients had abnormal DSTs.     

Depression after minor closed head injury: role of dexamethasone suppression test and antidepressants

The results of dexamethasone suppression test (DST) and the effectiveness of amitriptyline and phenelzine in treating depression with melancholia after minor closed head injury in 10 patients were compared to those in 12 control patients with primary depression and melancholia. Prevalence of abnormal DST results was higher in the control group (91%) than in the closed head injury group (10%). Results of the DST corresponded with clinical improvement. Amitriptyline produced significant and consistent improvement in all control patients at the end of 4 weeks of treatment. No patient in the closed head injury group showed significant improvement with amitriptyline. The closed head injury patients were treated with phenelzine after a 3- to 7-day washout period. No statistical improvement after 4 weeks of treatment with phenelzine was seen in any of these patients. The DST may be useful as an adjunct to the diagnostic and monitoring process in primary depression with melancholia. Depression after minor closed head injury did not correlate with the DST. Amitriptyline and phenelzine have limited use (if any) in depression with melancholia after minor closed head injury.     

Dexamethasone suppression test and response to antidepressants in depressed mentally handicapped subjects

ABSTRACT. Nineteen mentally handicapped subjects who were referred to the service with clinically significant depression were assessed with a view to determining the value of the dexamethasone suppression test (DST) in clinical diagnosis and in predicting response to antidepressant treatment. They were assessed initially and then 3 months after they had been treated with a tricyclic antidepressant. It was found that a significant proportion had an abnormal DST response which reversed after recovery in some but not in others. Non-reversal was more likely to occur in the more severely handicapped patients. It was concluded that DST was of little value as a diagnostic tool for the detection of depression in mentally handicapped subjects.     

Use of the dexamethasone suppression test in an inpatient setting: a replication and new findings

The dexamethasone suppression test (DST) was administered to 131 depressed and 109 nondepressed psychiatric inpatients. The depressed patients were categorized according to DSM-III as minor depression, major depression without melancholia, and major depression with melancholia and/or with psychotic features. The nondepressed patients were stratified over several DSM-III subcategories. DST nonsuppression was nonspecific for major depression: the mean post-dexamethasone cortisol value and the number of nonsuppressors were not significantly different between the major depressives and the nondepressed psychiatric controls. Within the depressive sample the DST was a significant (p less than 0.01) discriminator between major and minor depression. Postdexamethasone plasma greater than or equal to 3.5 micrograms/dl at 0800h was the most sensitive (39%) and specific (94%) criterion; cortisol values at 1600h and 2300h showed no significant discriminating power for major vs. minor depression. The diagnostic utility of the DST thus appears to be limited to confirming the diagnosis of major depression, once the clinical diagnosis of depression is made. There was no significant influence of age or gender on postdexamethasone cortisol values.     

Cerebrospinal fluid biochemical examinations: do they reflect clinical or biological differences?

5-Hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), cortisol (CS), tryptophan (TRY), and calcium (Ca) concentrations were measured in the spinal fluid of 85 female psychiatric inpatients in a drug-free state; 32 women suffered from major depression, another 32 had schizophrenic (or schizophreniform) disorder, and 21 had alcohol dependence as defined by DSM-III criteria. A dexamethasone suppression test (DST) was carried out following lumbar punctures in all patients. Biochemical results were analyzed by two-way analysis of variance to test the effect of diagnosis and dexamethasone nonsuppression. CS concentration proved to be significantly higher in dexamethasone nonsuppressors, independent of the diagnosis. HVA was lower in nonsuppressors, particularly in alcohol-dependent patients; 5HIAA showed a tendency to be higher in nonsuppressor depressed patients. TRY was again higher in nonsuppressors, significant only in schizophrenic patients. Ca concentration was higher in depression and lower in alcohol dependence, and within the depression group it was higher in normal DST patients. The results indicate that the primarily biological dysfunction, i.e., the limbic-hypothalamic disinhibition reflected in the DST, may be more closely related to spinal fluid biochemistry than clinical syndromes.     

Psychopathological correlates of plasma cortisol after dexamethasone suppression: A polydiagnostic approach

Seventy-seven consecutively admitted inpatients with depressive syndromes were examined with the Present State Examination and classified according to eight different operational diagnoses of endogenous depression. All patients received a 1.5 mg dexamethasone suppression test (DST). Sensitivity, specificity and the corrected predictive values of DST nonsuppression (50 or more ng/ml at 0800 hr, 1600 hr, or 2300 hr), adjusted to a 50% prevalence of endogenous and nonendogenous depression, varied considerably depending on the diagnostic definition used. The highest predictive value (89.9%) was found with the Taylor-Abrams criteria (sensitivity = 43.9%, specificity = 95.0%), and the lowest predictive value (53.3%) with DSM-III (sensitivity = 37.7%, specificity = 68.1%). Eliminating the patients with dexamethasone levels of less than 2000 pg/ml improved the diagnostic specificity of the DST for most of the eight definitions of endogenous depression. This further indicates that plasma dexamethasone levels should be analyzed in studies designed to explore the diagnostic utility of the DST. A significant, chance-corrected association between DST nonsuppression and the diagnosis of endogenous depression was found with clinical diagnosis (according to the International Classification of Diseases), and for four out of eight operational diagnoses (Newcastle Scale 1, Newcastle Scale II, Taylor-Abrams Criteria, and Vienna Research Criteria). For the other diagnoses (Research Diagnostic Criteria, DSM-III, Michigan Discriminant Index, and Hamilton Endogenomorphy Index), no significant association was found. The RDC criterion “early or intermittent awakening” was the only one out of 28 diagnostic criteria tested which was significantly associated with DST nonsuppression.     

Dexamethasone effects on numbers of cells in lymphocyte subpopulations: Changes associated with major depression and DST nonsuppression

1. 1. The authors studied the effects of administration of 1 mg of dexamethasone on the number of cells in discrete subpopulations of lymphocytes in major depressed and psychiatric control patients with depressive symptoms.

2. 2. Dexamethasone significantly decreased the total lymphocyte count and numbers of T and helper T lymphocytes in control patients.

3. 3. In contrast, dexamethasone failed to significantly decrease the numbers of cells in any of the subpopulations of lymphocytes studied in major depressed patients.

4. 4. Among major depressed patients both DST suppressors and nonsuppressors were insensitive to the suppressive effects of dexamethasone on lymphocyte numbers.

5. 5. However, in DST nonsuppressors, but not in DST suppressors, dexamethasone administration significantly the number of cytotoxic/suppressor T lymphocytes and natural killer cells.

6. 6. The authors conclude that insensitivity to the suppressive effects of dexamethasone on lymphocyte numbers is specific to major depression and is not associated with DST status. However, DST nonsuppression is associated with a facilitating effect of dexamethasone on the number of cells in some subpopulations of lymphocytes.