Abnormal Dexamethasone Suppression Test Results Research Articles

Platelet MAO activity and the dexamethasone suppression test in bipolar depression

The correlation between postdexamethasone cortisol levels after the dexamethasone suppression test (DST) and platelet monoamine oxidase (MAO) activity was studied in 31 depressed female inpatients with Research Diagnostic Criteria primary, endogenous, bipolar depression (12 bipolar I and 19 bipolar II). Out of the 31 patients, 25 showed abnormal DST results. Platelet MAO activity did not differ significantly from the matched control group. There was a trend that patients with higher MAO activity had lower postdexamethasone cortisol levels, but it was significant only for the 0800 hr cortisol levels.

The validity of DSM-III axis IV (severity of psychosocial stressors).

One hundred thirty depressed inpatients were rated on DSM-III axis IV on the basis of information collected from a comprehensive life events interview. Axis IV scores were more highly correlated with undesirable than desirable events, with exits than entrances, and with time-limited than chronic events. Higher axis IV scores were associated with a lower rate of abnormal dexamethasone suppression test results, a higher morbid risk for alcoholism, a greater frequency of personality disorders, and a greater likelihood of attempted suicide during the index episode.

The dexamethasone suppression test and suicidal patients.

The dexamethasone suppression test (DST) was used in an in-patient crisis unit to determine whether the test could identify suicidal patients who might benefit from tricyclic antidepressants. DST results, DSM-III diagnoses, and measures of symptom levels were obtained for 72 patients admitted for a 3-5 day period; 31 were non-suppressors. Abnormal DST results were not related to DSM-III diagnosis or to scores on measures of depression and symptom levels. Only three patients met DSM-III criteria for major depression with melancholia; 26 patients had a diagnosis of alcohol or substance abuse. The poor specificity of the DST in this patient population suggests that its routine use in such patients could be highly misleading.

Cortisol secretion in endogenous depression. I. Basal plasma levels.

Plasma levels of cortisol were sampled for 24 hours in 32 endogenously depressed (ED) patients and 72 normal controls who also underwent the dexamethasone suppression test. The ED patients had significantly higher mean 24-hour plasma levels of cortisol (means 24h PC). However, means 24h PC values of subjects in both groups were normally distributed, with a marked overlap between the two. Only seven ED patients had means 24h PC values higher than 2 SDs from the normal mean (greater than 10 micrograms/dL). An abnormal dexamethasone suppression test result was only partially related to basal cortisol levels. The mean plasma level of cortisol between 1 and 4 PM was found to be highly correlated with the means 24h PC value in ED patients, as has been previously reported in normal subjects and patients with various other diseases (in which it also powerfully discriminated between hypersecretors and normosecretors). This finding supports the use of mean cortisol levels between 1 and 4 PM as a reliable and convenient indication of cortisol secretion.

Cortisol escape from morphine suppression

Twenty-one unmedicated, sequentially admitted psychiatric patients of either sex and four male healthy volunteers were given an intravenous injection of 2.5 mg morphine. Blood samples were drawn immediately before and at 30-minute intervals for 3 hours after the injection and assayed for cortisol. Morphine suppressed cortisol secretion. Early resumption of cortisol secretion (escape) was more frequent in patients with a diagnosis of major depressive disorder and with abnormal dexamethasone suppression test results. The sensitivity of this infusion paradigm for the diagnosis of major depressive disorder was 40%, and the specificity was 82%. The implications of these findings for the pathophysiology of depression are discussed.

The dexamethasone suppression and metyrapone tests in depression

The dexamethasone suppression test (DST) and the metyrapone test (MT), a useful and reliable procedure for assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, were performed in 28 patients suffering from major depressive illness with melancholia. The relationship between the DST and MT appeared to be complex. Patients who failed to suppress cortisol secretion after dexamethasone administration had higher postmetyrapone cortexolone levels and cortexolone/cortisol ratios than suppressors. However, there was a wide range of metyrapone responses in patients exhibiting abnormal DST results. This suggests that failure of adequate suppression after 1 mg of dexamethasone in depressed patients does not necessarily reflect homogeneity in the HPA axis disturbances of such patients.

Effect of TRH on TSH and prolactin levels in affective disorders

The thyrotropin-releasing hormone (TRH) test was studied in 32 patients with acute major depressive disorder, 16 patients with recurrent unipolar ( n=8) or bipolar ( n=8) affective disorder in remission, and 22 healthy control subjects. Twenty-six of the 32 acutely ill patients were also studied when in remission. Outcome in these patients was correlated to serum levels of triiodothyronine (T 3), 3,3',5'triiodothyronine (reverse T 3), thyroxine (T 4), thyroid-stimulating hormone (TSH), prolactin (PRL), melatonin, dexamethasone suppression test (DST) results, and clinical symptoms assessed by the Comprehensive Psychopathological Rating Scale (CPRS). The TSH response to TRH (δTSH) was decreased in the acutely ill patients, but no difference was found between patients in remission and controls. The δTSH was correlated to TSH but not to T 3 and T 4 levels in both acutely ill and control subjects. In the acutely ill group, δTSH did not distinguish between patients with normal and abnormal DST results. Thus, abnormalities in the hypothalamic-pituitary-thyroid (HPT) axis are not correlated to abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, δTSH did not differentiate between melancholic ( DSM-III) and nonmelancholic patients or between patients with primary and secondary depression. No correlation was found between δTSH and CPRS scores. Patients with observable agitation>0.25 points (item range 0–3) had higher levels of δTSH than patients with lower levels. No significant correlation was found between δTSH and seven specific symptom clusters on the CPRS. However, there was a possible relation between low δTSH and violent suicide attempts or suicide. PRL levels did not distinguish acutely ill patients from controls. Finally, there was no significant regression between δTSH and melatonin levels. The decrease in δTSH seen in the acutely ill patients was too small to be of diagnostic value as a laboratory measure differentiating acutely ill and healthy subjects. The mechanism underlying the HPT alterations in acute major depressive disorder may be a desensitization of the TRH receptor in the thyrotrophs secondary to an increased endogenous TRH stimulation.

Opioid Regulation of Hypothalamic-Pituitary-Adrenal Function in Depression

A morphine infusion paradigm was used to investigate opioid mechanisms in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression. The subjects were unmedicated psychiatric inpatients and healthy volunteers. Morphine suppressed cortisol secretion. Early resumption of cortisol secretion was associated with a diagnosis of major depression and abnormal dexamethasone suppression test results. Our data suggest that the hyperactivity of the HPA axis observed in depression is abnormally resistant to opioid inhibition as well as glucocorticoid feedback.

Limited Utility of the 1-mg Dexamethasone Suppression Test as a Measure of Hypercortisolism

To the Editor.— In their multicenter investigation of the dexamethasone suppression test (DST), Stokes et al 1 found that nonsuppression (NS) was more frequent among healthy normal persons than has previously been reported, and that, among depressed patients, abnormal DST results were not significantly more frequent in endogenous, melancholic, or psychotic subtypes. In placing their results in the context of the DST literature, Stokes et al reviewed only three other studies of the DST in healthy control subjects. 2-4 They attributed the low nonsuppression rates found by Carroll et al 2 and McHardy-Young et al 3 to the fact that these investigators used 2 mg of dexamethasone. In contrast, Amsterdam et al 4 used only 1 mg of dexamethasone and found a relatively high nonsuppression rate in healthy control subjects, similar to data obtained by Stokes et al. 1 Based on their own study and their limited literature review, Stokes et

Dexamethasone suppression test in alcoholism.

The hypothalamic-pituitary-adrenal function was investigated in alcoholic patients using the dexamethasone suppression test (DST). Seventy-two patients were studied when they had been abstinent from alcohol for 3 to 6 weeks. Eight patients undergoing detoxification and 79 control subjects were investigated for comparison. Alcoholic patients after a 3- to 6-week abstinence period showed significantly higher prevalence of abnormal DST results (28%) than control subjects (11%). Patients undergoing detoxification showed even a higher prevalence of abnormal DST results (62%). Abnormal DST status was not associated with the presence of depression in these patients but was associated with abnormal liver function. It is supposed that abnormal DST responses in alcoholic patients are not diagnostic of depression but appear to be related to effects of alcohol either on liver metabolism or on the hypothalamic-pituitary-adrenal function or both.

Study of the diagnostic value of the dexamethasone suppression test in endogenous depression

The diagnostic value of the dexamethasone suppression test (DST) in “endogenous” depression was evaluated in 209 psychiatric inpatients. A high incidence of abnormal DST results was observed in “endogenous” depressives (52%), schizo-affective (69%) and borderline patients (38%). However, 25% of the patients with other psychiatric disease also failed to suppress on the DST. Diagnostic criteria, previous history of alcoholism, psychiatric drug treatment, age and sex did not significantly affect DST performance. The present data do not indicate that the DST represents a highly specific marker of “endogenous” depression.

Dexamethasone suppression test in masked depression

The dexamethasone suppression test (DST), family history, response to antidepressant medication and short-term course were investigated in 16 female patients with masked depression. Twelve patients showed abnormal DST results, 3 patients had positive family history of affective illness in first-degree relatives, 11 responded well to antidepressant drug treatment and 3 showed definite hypomanic episodes during follow-up. The results suggest that masked depression is a special form of primary (endogenous) depressive illness, and that the DST is a good diagnostic aid not only in the ‘classical’ but also in masked forms of depressive disorders.

The dexamethasone suppression test in demented outpatients with and without depression

The dexamethasone suppression test (DST) was given to 33 elderly, male outpatients, previously diagnosed by DSM-III criteria as having dementia. Fifteen of these patients also had signs and symptoms of depression and, except for the presence of organic mental syndrome, would have met DSM-III criteria for major depressive episode. Of these 15 depressed, demented patients, 40% had abnormal DST results. None of the 18 patients who had dementia alone had abnormal DSTs. Our data suggest that in elderly, demented outpatients, an abnormal DST may be associated with concomitant depression.

The dexamethasone suppression test in depressed patients: Clinical and biochemical aspects

Endogenous depression (ED) is regarded as a psychiatric disease with a biological pathogenesis. Consequently patients with ED respond favourably to somatic treatment, whereas for non-endogenously depressed patients drug-treatment would be often inappropriate. Until now, psychopathologists have failed to define precisely the endogenous subtype of depression on clinical features alone. It is well established that a subgroup of depressed patients shows hypersecretion of cortisol and consequently inadequate suppression of cortisol after a test dose of dexamethasone. This dexamethasone suppression test (DST) was introduced as a laboratory marker, specifically identifying endogenously depressed individuals. This survey illustrates the present dispute about the diagnostic confidence and clinical value of the DST in a psychiatric population, and related biochemical aspects. The following conclusions are stated: (a) use of the DST to validate a theory of nosology is premature. (b) Influence of psychoactive drug medication, diet and weight loss have to be established. (c) Preliminary data suggest that abnormal DST results frequently normalize before clinical recovery and abnormal DST results may be observed before a relapse into depression is clinically apparent. From this it was concluded that the DST might be useful as predictor of clinical outcome. (d) From the association of depressive episodes with disinhibited HPA-activity, a causative role of corticotropin and glucocorticoids in the development of psychiatric illness can be hypothesized. Beside some pharmacological data no supportive evidence for this hypothesis is available. (e) Multisteroid analysis after dexamethasone has provided promising results indicating increased sensitivity of the test when based upon cortisol/11-deoxycortisol ratios and disturbed mineralocorticosteroid secretion in endogenously depressed patients.

Effects of chronic medical illness and dementia on the dexamethasone suppression test.

The dexamethasone suppression test (DST) was performed on 26 elderly male outpatients in a geriatric medical clinic. Patients with depression were excluded. All patients had two or more medical diagnoses. Fourteen patients also met DSM-III criteria for dementia. No patient had an abnormal DST result. The authors suggest that neither chronic medical illness nor dementia causes false-positive DST results in this patient population in an outpatient setting, and discuss the findings in relation to previous reports.

Escape from dexamethasone suppression: Possible role of an impaired inhibitory opioid mechanism

1. 1. Several lines of evidence indicate that the activity of the hypothalamus-pituitary-adrenal (HPA) axis in depression is disinhibited. 2. 2. Escape from dexamethasone suppression, although not limited to is more frequent in patients with endogenous depression compared to normals or patients with other psychiatric diagnoses. 3. 3. Norepinephrine, serotonin and acetylcholine have been implicated in the pathophysiology of this neuroendocrine abnormality. 4. 4. Morphine, 5 mg intravenously, suppressed Cortisol secretion in healthy volunteers (n = 4) and the majority of 32 psychiatric inpatients. 5. 5. However, patients with endogenous depression and abnormal dexamethasone suppression test results show early resumption (escape) of cortisol secretion following the initial suppression induced by morphine. 6. 6. It is concluded that the pathophysiology of this neuroendocrine abnormality is not limited to classical neurotransmitter-HPA axis interaction but that it also involves opioid inhibitory mechanisms.

Mood, vegetative disturbance, and dexamethasone suppression test after stroke.

Assessments of mood disturbance and "vegetative" (appetite or sleep) disturbance as well as a single-dose dexamethasone suppression test (DST) were carried out in 25 randomly selected stroke patients and in 13 nonstroke control patients hospitalized in a rehabilitation center. Prevalence rates of moderate-to-serve depression of mood and vegetative disturbance were significantly higher in stroke patients than controls (48% and 52% versus 0% and 8%, respectively), as was the prevalence of abnormal DST results (52% versus 8%). Abnormal DST results were associated with the occurrence of moderate to severe mood, appetite, and sleep disturbances among all patients. in 2 stroke patients, repeated DST results paralleled the clinical course. The DST may be useful as an adjunct to the diagnosis and in monitoring the progress of the common and potentially reversible mood and vegetative disturbances occurring after stroke.

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.

Hypothalamic-pituitary-adrenal axis abnormality and ECT response

Response to electroconvulsive therapy (ECT) was assessed in 42 depressed patients grouped by dexamethasone suppression test (DST) response. Patients with initially abnormal DST results had better outcomes according to global ratings that did patients with initially normal DST results; final Hamilton Rating Scale scores did not distinguish these two groups, however. No group had an outcome that was clearly poor; only three (14.3%) patients with initially normal DST results were rated as unimproved at discharge. The results of this and other studies attempting to predict response to ECT are sensitive to the heterogeneity of patients referred for ECT, the timing and type of outcome assessment, and the differential action of placebo effects.

The dexamethasone suppression test in prepubertal depressed children.

The authors evaluated 18 dysphoric children aged 6--12 years by structured clinical assessments and an overnight dexamethasone suppression test (DST) administered on an outpatient basis. Nine children met diagnostic criteria for major depressive disorder, and 8 of the 9 also met the Research Diagnostic Criteria for endogenous depression. Of the 9 depressed children, 5 had abnormal DST results; 8 of the 9 nondepressed children had normal test results. The results suggest that endogenous depression in childhood is not a rare condition and that it is clinically and neuroendocrinologically similar to the adult disorder. The DST may be useful as a diagnostic aid with depressed children.