Dexamethasone suppression test in female patients with endogenous depression: determinations of plasma corticosterone, 11-deoxycorticosterone, 11-deoxycortisol, cortisol and cortisone

Investigation of the plasma concentrations of five adrenal steroids—corticosterone (B), 11-deoxycorticosterone (DOC), 11-deoxycortisol (S), cortisol (F) and cortisone (E)—before and after an overnight dexamethasone suppression test (DST) revealed that the sensitivity of the DST can be increased by using a multisteroid analysis. None of the individual plasma steroids was superior in discriminating between six normal and six endogenously depressed (ED) women. The ratios of F/S and B/DOC were markedly increased in most of the ED patients in comparison to the healthy controls, indicating an activation of adrenal 11β-hydroxylase in ED. Thus after an overnight DST, more specific indicators of adrenal activity derived from multisteroid analysis may increase the sensitivity of this valuable laboratory test.     

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.     

Dexamethasone suppression in depressed elderly outpatients

The dexamethasone suppression test (DST) was performed as part of the preliminary workup in 85 previously untreated outpatients with major affective disorder, unipolar depressive type, who were over age 60. All patients were given a systematic structured interview (NIMH-DIS), and all had scores over 20 on the 21-item Hamilton Depression Rating Scale (HAM-D). Only 12 patients (14%) had positive DSTs; more of the non-melancholic (6 of 25; 24%) than melancholic (6 of 60; 10%) patients failed to suppress serum cortisol following standard dexamethasone challenge (p less than .10). DST results did not correlate with patients' HAM-D or Zung depression scores, gender, response to treatment, or any other variable studied. These findings suggest that, in comparison to previous reports, a positive DST may be 1) less common in major depressive disorders, 2) no more common in more severely depressed patients, and 3) less relevant to indications for specific treatment.     

Factors interfering with the 1 mg dexamethasone suppression test in depression

The 1 mg dexamethasone suppression test (DST) was performed in 50 depressive inpatients in order to investigate factors which might interfere with its sensitivity and specificity for endogenous depression: improvement within one week after the test, recent admission to a psychiatric ward, and weight loss. Four out of five endogenous depressive patients whose depression improved within one week after the test had normal suppression, thus supporting the assumption that normalization of the DST may precede the improvement in depression. Nonendogenous depressive patients had an accumulation of pathologic test results on the day after admission that may be due to "admission stress". However, in endogenous depressives this effect was not observed. An influence of weight loss on the percentage of suppressors and nonsuppressors was not demonstrable. It is concluded that in the evaluation of DST results time parameters should be considered to a greater degree.     

ACTH and multisteroid responses to corticotropin-releasing factor in depressive illness: relationship to multisteroid responses after ACTH stimulation and dexamethasone suppression

One hundred micrograms of ovine-corticotropin releasing factor (o-CRF) was administered intravenously to eight unmedicated patients with severe endogenous depression. Responses of immunoreactive (ir)-ACTH and the adrenal glucocorticosteroids corticosterone (B), 11-deoxycortisol (S), cortisol (F) and cortisone (E) were measured and compared with those following synthetic corticotropin stimulation and dexamethasone suppression. A comparative evaluation of the three pituitary--adrenal function tests suggests that hypersecretion of ir-ACTH and adrenal corticosteroids (B, S, F, and E) in depression reflects a central dysfunction rather than an altered responsiveness of the pituitary or adrenal glands. The data illustrate that the o-CRF paradigm is a valuable instrument to further support the hypothesis that a limbic--hypothalamic overdrive is the basic mechanism underlying exaggerated adrenocortical output in the endogenous subgroup of depressed patients.     

Pretreatment dexamethasone suppression test as a predictor of response to phenelzine

Twenty inpatients who met Research Diagnostic Criteria and DSM-III criteria for depression underwent a 2-week washout period before the administration of a pretreatment dexamethasone suppression test (DST); the patients then received the monoamine oxidase inhibitor (MAOI) phenelzine. The mean MAO inhibition level achieved during treatment was greater than 80%. On the basis of clinical global evaluation and changes in Hamilton Rating Scale for Depression scores, 7 of the 9 baseline DST suppressors were classified as responders, 1 as a partial responder, and 1 as a nonresponder; of the 11 baseline DST nonsuppressors, 3 were responders, 1 a partial responder, and 7 nonresponders. The Mann-Whitney U test yielded p less than .02, indicating that an abnormally high pretreatment level of cortisol in response to the DST appeared to be predictive of nonresponse to phenelzine.     

The dexamethasone suppression test and the diagnosis of depression in adults with severe and profound developmental disabilities

The dexamethasone suppression test (DST) was administered to 40 adults with severe and profound mental retardation. All participants were free from known conditions which may have given misleading results from cortisol assay. Of nine participants who showed symptoms possibly indicating depression the DST results concurred in two cases (i.e. there were two true-positives). However there were four or five (depending on criteria adopted) false-positive DST results. There did not appear to be a consistent behavioural profile for positive DST responders. With sensitivity to possible depression estimated at 22%, and a diagnostic confidence of <35%, these data do not support recommendations that the DST is useful for assisting in diagnosis of depression in this population.     

Effect of hospital admission on DST results

The authors examined the dexamethasone suppression test (DST) responses of 41 patients with primary major depressive disorder and 40 patients with other psychiatric disorders who were tested within 2-6 days of hospital admission. Significantly more patients with primary depression who were tested on day 2 demonstrated abnormal cortisol suppression than those who were tested on days 3, 4, or 3-6 and than patients with other psychiatric disorders regardless of test day. These results suggest that patients with primary depression may be sensitive to psychophysiologic stresses associated with hospital admission and that the utility of the DST may require further evaluation vis-à-vis the day of DST administration.     

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.     

Clinical investigations into antidepressive mechanisms. II. Dexamethasone suppression test predicts response to nomifensine or amitriptyline

This prospective study investigates the possibility of a central noradrenergic-cholinergic imbalance in subgroups of depressed inpatients using the dexamethasone suppression test (DST) as one peripheral indicator. The DST was performed in 43 depressed inpatients. Subsequently, a group (n = 20) of DST suppressors (DST-) and a group (n = 23) of DST nonsuppressors (DST+) were treated under double blind conditions with either nomifensine (NOM) a noradrenaline potentiating drug, or amitriptyline (AMI) a noradrenaline potentiating and strong anticholinergic compound. DST+ depressives responded favorably to AMI, but not to NOM. Conversely, DST- depressives responded favorably to NOM but less well to AMI. Together with other biochemical findings this data suggests: 1) a hypofunction of the noradrenergic system in DST- patients who may, from a clinical point of view, usually show minor or 'neurotic' depressions; 2) a hypofunction of the noradrenergic and a hyperfunction of the cholinergic system in DST+ patients who may present a more severe or 'endogenous' depression. These data suggest a biochemical heterogeneity of depression and offer an aid for a more specific antidepressive drug therapy.     

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.     

The dexamethasone suppression test as a predictor of sleep deprivation antidepressant effect

An abnormal dexamethasone suppression test (DST) result, a sensitive and specific marker for endogenous depression, was found to be associated with an antidepressant response to sleep deprivation in patients who met DSM-III criteria for Major Depressive Episode regardless of whether they met criteria for melancholia or psychotic subtypes of this disorder. These findings support previous reports of an association between an abnormal DST result and antidepressant effects of sleep deprivation in depressed patients. Our results extend the positive association between an abnormal DST result and the antidepressant response to sleep deprivation to include depressed patients who are clinically nonmelancholic during thair current episode but who have an abnormal DST result.     

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.     

Adrenocortical hyperactivity in depression: effects of agitation, delusions, melancholia, and other illness variables

In an attempt to determine the relative contributions to adrenocortical hyperactivity in depression of agitation, delusions, and melancholic subtype, we measured cortisol levels before and after dexamethasone in 93 unipolar major depressed inpatients. Stepwise multiple regression showed that agitation predicted 22% of the variance in a.m. cortisol level after dexamethasone. Addition of the variables melancholia and delusionality to the regression model accounted for 27% and 34%, respectively, of the variance in the same cortisol variable. Age, illness severity, and weight loss added no further significant predictive value. Age, weight loss, and illness severity did affect cortisol levels when examined separately from the other variables. Rate of nonsuppression on the dexamethasone suppression test (DST) differed between the nonmelancholic major depressive group and any other group with melancholia. These results suggest why some discrepancies may exist between studies of the DST in delusional depression and indicate that agitation merits careful assessment in future studies of DST response.     

The effect of weight loss and inappropriate plasma dexamethasone levels on the DST

Recent studies from different research groups have raised fundamental questions about the postulated specificity of the dexamethasone suppression test (DST) for endogenous depression. Findings in 116 psychiatric inpatients and 24 semi-starved healthy volunteers underline the importance of weight loss as a factor affecting DST results. A study of 160 DSTs in 93 psychiatric inpatients further revealed a significant negative correlation of plasma cortisol and plasma dexamethasone levels 10 hours after oral administration of 1 mg of dexamethasone. These results suggest a decisive effect of the pharmacokinetics of dexamethasone, at least on the 1-mg DST.     

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.     

The dexamethasone suppression test in patients with alcoholism

It is unknown whether the dexamethasone suppression test (DST) can be used to help identify patients with major depressive disorder if they have recently been abusing alcohol. We evaluated 38 male alcoholics with Research Diagnostic Criteria (RDC), the Beck Depression Inventory (BDI), and the standardized overnight 1-mg DST, administered after 3-4 weeks of detoxification. Eighty-two percent had a normal suppressive DST response. The DST may be useful in aiding identification of patients with a profile of major depressive disorder and continued depression after alcohol detoxification. The test might facilitate a rational selection of alcoholics who may benefit from antidepressants. However, the possibility of false positive results must be further investigated.     

Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome

Maximum nocturnal serum melatonin level (MTmax) in relation to some clinical variables was studied in 32 patients with a major depressive episode and in 33 healthy subjects with reference to the outcome of the dexamethasone suppression test (DST). Significant regressions were found between MTmax levels and clinical rating scores in CPRS, interpreted as retardation symptoms. Four healthy subjects with disposition for dysthymic reactions had subnormal MTmax levels, which differed from MTmax levels in subjects without such disposition. Patients but not the healthy subjects, who reported parental loss before 17 years of age, had subnormal MTmax levels and differed from patients with no reported parental loss. Patients with no reported suicidal behaviour in clinical history had significantly lower MTmax levels than patients with reported suicide attempts. No relations were found between low MTmax levels and diagnoses, duration of illness, reported inheritance for depressive illness or sleep disturbances. A hypothetical low melatonin syndrome in depression is proposed: low nocturnal melatonin, abnormal dexamethasone suppression test, disturbed 24-h rhythm of cortisol, less pronounced daily and annual cyclic variation in depressive symptomatology.     

Serial dexamethasone suppression tests in psychiatric illness: Part II. A study in major depressive disorder

Weekly dexamethasone suppression tests (DSTs) were performed in 35 patients with major depressive disorder until clinical response. At initial evaluation, 65% of the patients showed nonsuppression, and 85.7% showed nonsuppression at least once during the treatment period. Normalization of the DST results usually coincided with or occurred before clinical recovery, although isolated "peaks" of DST nonsuppression occurred in 45.7% of the patients, irrespective of the clinical course. The test was not useful as a predictor of clinical recovery or relapse. Moderately ill depressed patients had significantly higher nonsuppression rates than schizophrenic or manic patients with corresponding severity scores, indicating that different factors might be associated with nonsuppression in different diagnoses. However, many abnormal DST results could neither be related to the course of the depression nor to the severity of illness; thus other factors must also be responsible for DST nonsuppression.