Dexamethasone Suppression Test Results Research Articles

Liver function, plasma dexamethasone, and DST results in detoxified alcoholics

Alcohol abuse, alcohol withdrawal, and deterioration of hepatic function have been associated with abnormal dexamethasone suppression test (DST) results. Chronic alcohol abuse may also directly alter the pharmacokinetic disposition of dexamethasone. Plasma dexamethasone concentrations following a DST were determined in 53 detoxified alcoholics. Those with abnormal liver function had higher 4 p.m. plasma dexamethasone concentrations and lower DST cortisol concentrations. Those with normal liver function had lower plasma dexamethasone and higher DST cortisol concentrations consistent with induction of hepatic metabolic enzymes from chronic use of alcohol. The data indicate that liver function is one of the variables influencing dexamethasone disposition and DST cortisol suppression.

Neuroendocrine probes as biological markers of affective disorders: new directions.

Numerous endocrine abnormalities are found in depressive illness and, among these, several have been proposed as useful markers in diagnosis, prediction of treatment response, monitoring treatment outcome or in understanding of etiology. This paper reviews five endocrine systems--the hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-thyroid axis, growth hormone regulation, prolactin regulation and pineal function, in which such abnormalities have been reported. The dexamethasone suppression test (DST) results are affected by a variety of other diseases and confounding conditions. Furthermore, variability in dexamethasone availability has recently been shown to be an important factor, influencing post-DST cortisol levels. Refined tests, taking into account all these factors, or alternative tests of hypothalamic-pituitary-adrenal function may lead to improved clinical utility. Pineal function is now the focus of considerable investigation. Low nocturnal output of melatonin is found in unipolar and bipolar affective disorder and is normalized by treatment with antidepressant drugs which block re-uptake of noradrenaline. These findings support the hypothesis of noradrenergic abnormality in depression. In seasonal affective disorder there is evidence for a phase delay in the melatonin rhythm which may be a key factor in the seasonal disorder. Effective light therapy causes a phase advance in the abnormal melatonin rhythm. Whether the normalization of the melatonin rhythm is instrumental in producing the antidepressant effect is yet to be determined. There are wide spread neuroendocrine abnormalities in depressive illness. These abnormalities encompass many different pituitary hormones, as well as the pineal.(ABSTRACT TRUNCATED AT 250 WORDS)

DST status and blood chemistries in prepubertal children

Cholesterol, sodium, potassium, and serum glucose were examined to determine if they could predict status on the dexamethasone suppression test (DST) in 59 depressed prepubertal psychiatric inpatients and 21 nondepressed psychiatric inpatients. Multivariate analyses found that none of these variables, alone or combined, were predictive of DST results.

3H-imipramine binding to freshly prepared platelet membranes in depression

3H-Imipramine binding was measured in freshly prepared platelet membranes from 47 drug-free major depressives and 46 healthy controls. Where possible, platelet binding in depressed subjects was repeated following treatment. A significant negative correlation was found between B max and assay protein concentration and B max values were corrected for this effect. Adjusted B max was significantly lower (by 14%) in female depressed patients than in female control subjects, and the difference was of similar magnitude premenopausally and postmenopausally. No such difference was found in males. K d did not differ significantly between depressed and control subjects. Multiple regression analysis confirmed significant effects on B max of presence of depressive illness, age (positive correlation), and season (higher in summer). Wirhin the depressed sample, B max was significantly lower in those subjects with obsessional features. Endogenicity (Research Diagnostic Criteria or Newcastle), dexamethasone suppression test result, drug-free interval, family history of depression, depressive psychosis, suicidal ideation, and past history of suicide attempts were not significantly related to B max. Paired comparisons revealed no significant effect on B max of 6 weeks' treatment with imipramine, maprotiline, or BRL 14342 or of a course of electroconvulsive therapy.

The significance of HPA axis disturbance in panic disorder

Agoraphobic and panic disorder patients underwent 1-mg Dexamethasone Suppression Tests (DST) before, during, and after an 8-week trial of diazepam, alprazolam, or placebo. Previously described, never-ill controls underwent similar testing. At baseline, 21 of 82 (25.6%)panic disorder and 5 of 38 (13.2%) controls were nonsuppressors. This difference grew more marked with multiple testing over a 2-month period; 18 of 44 (40.9%) panic disorder patients were nonsuppressors on at least 1 of 3 tests compared with only 5 of 35 (14.3%) controls ( p = 0.006). DST results were related to severity, but not to the presence or absence, of depressive syndromes. Control for plasma dexamethasone levels left highly significant differences in postdexamethasone cortisol across diagnostic groups. Neither DST results nor plasma dexamethasone levels changed in concert with clinical change, and type of treatment had little differential effect on these measures. Nor did DST results predict subsequent course when active treatment was extended by 6 months. However, DST results during the initial 8 weeks of treatment were strongly related to relapse when medications were tapered, even though this occurred 6 months after the last DST.

Major depression with psychotic features in adolescence

Major Depression with psychotic features remains a poorly-defined entity in adolescents. The diagnostic differentiation from schizophrenia can be difficult and the implications for treatment have not been studied. Of 81 hospitalized adolescents studied with semistructured interviews GADS), 12 had schizophrenia and six had major depression with psychotic features (MD-psychotic; DSM-III). Analysis of SADS results, dexamethasone suppression test results, and hospital course suggests that those with MD-psychotic were differentiated from those with schizophrenia by better premorbid function, family history of affective disorder, more acute onset, onset with nondelusional depression, more severe guilt, worthlessness and hopelessness, more severe psychomotor retardation and delayed insomnia, and more suicidal ideation and behavior. Consistent with studies in adults, cross-sectional mental status parameters did not differentiate well between groups and were heterogeneous within the MD-psychotic group. Dexamethasone nonsuppression appeared to distinguish the two groups. Implications for diagnostic dilemmas, treatment, and the design of prospective studies are discussed.

The dexamethasone suppression test and suicide attempts.

We examined covariations between results of the dexamethasone suppression test (DST) and suicidal behaviour for 44 patients who had attempted suicide at least once; the suicide methods, diagnoses and time factors were controlled for. The control groups comprised 82 psychiatric patients and a sample of 69 patients with endogenous depression. In spite of hypotheses suggesting the contrary, there was no significant relationship between DST results and acute suicide attempts. Although patients who had used "soft" methods were often suppressors, chi-square tests using the suicide classification of the ICD-9 as well as tests employing more precise subcategories failed to reveal any significant covariation. In groups of patients with an identical diagnosis of endogenous depression, the sensitivity of the DST with regard to suicide attempts was 52%. The difference between suppressors and nonsuppressors in previous suicide attempts was insignificant. Further, the Hamilton Rating Scale for Depression profiles of DST suppressors and nonsuppressors showed no significant differences with regard to either different symptoms or the evaluation of acute suicide risk.

The plasma dexamethasone window: Evidence supporting its usefulness to validate dexamethasone suppression test results

Two doses of dexamethasone (DEX) (0.5 and 1.0 mg) were administered in a randomized crossover design to 31 patients with major depression, 9 healthy controls, and 14 nondepressed psychiatric patients. Using this modified Dexamethasone Suppression Test (DST), minimum DEX levels of 6 nmol/liter at 8:00 am and 2.0 nmol/liter at 4:00 pm were required to achieve reliable suppression of cortisol in healthy controls and nondepressed psychiatric patients. Failure to achieve these minimum plasma DEX levels was associated with similar rates of nonsuppression in both depressed and nondepressed patients, thereby reducing the specificity of the DST. Conversely, high DEX levels greater than 13 nmol/liter at 8:00 am or 4.0 nmol/liter at 4:00 pm were associated with abnormal “suppressibility” in depressed patients, thereby reducing the sensitivity of the test. Controlling for plasma DEX concentrations by selecting a test result that fell within a plasma DEX window at 8:00 am and 4:00 pm increased the sensitivity and specificity of the DST. Significant differences in plasma DEX between suppressors and nonsuppressors were no longer evident when comparing patients with adequate DEX levels, thus ensuring that cortisol escape reflected HPA axis changes associated with depression and not peripheral mechanisms responsible for the availability of DEX. These results suggest that the clinical utility of the DST would be significantly enhanced by extending the standard 1.0-mg DST and retesting those patients with levels outside the DEX window with a higher or lower dose. The data also indicate that the measurement of plasma DEX is essential to validly interpret DST status and highlight the need to standardize DEX assays to compare DST results between research centers.

Evening urine cortisol excretion and DST results in depression and Anorexia Nervosa

Cortisol determination in a single one-hour urine sample collected between 2200 h and 2300 h has been shown to identify accurately patients with Cushing's disease. To examine the usefulness of this procedure for identifying psychiatric patients with a pituitary-adrenal disturbance, we studied 17 drug-free depressed patients, 6 euthymic anorectic patients and 10 healthy volunteers. We found that there was good agreement between DST results and evening urine cortisol excretion in this sample (when cortisol levels were expressed as ng of cortisol per mg of creatinine), and that adopting as a criterion a urine cortisol value two standard deviations above the mean cortisol value of the controls predicts 74% of the dexamethasone suppression test (DST) results. We would like to suggest that this measure deserves further study as a potentially useful and simple alternative to the DST for identifying psychiatric patients with a pituitary-adrenal disturbance.

Plasma dexamethasone and cortisol levels in depressed outpatients

We investigated the 1-mg dexamethasone suppression test (DST) in 41 outpatients with major depressive disorder assessing the role of dexamethasone blood level, age and basal cortisol on DST results. Non-suppressors (approximately 25% of patients) had lower dexamethasone levels, and post-dexamethasone cortisol was negatively correlated with plasma dexamethasone; these findings were more significant after covarying out age and basal cortisol, factors that were also significantly associated to non-suppressors. A subgroup of patients ( n = 19) also had 0.75-mg and 2.0-mg DST to evaluate whether a threshold dexamethasone blood level existed; a dexamethasone blood level greater than 1.5 ng/ml converted all non-suppressors to suppressors. Implications of these findings are discussed.

The dexamethasone suppression test: Its relationship to diagnoses, severity of depression and response to treatment

1. The dexamethasone suppression test (DST) was applied to 40 depressed patients, 40 healthy volunteers and 40 patients with other psychiatric disorders. 2. The post-dexaniethasone cortisol level, adopted as the non-suppres sion criterion and established locally, was 3.0 μg/dl. 3. The DST sensitivity in depression was 45%, with a specificity of 95% and a positive predictive value of 90%. 4. There was a significant correlation (r = 0.38, p<0.05) between HDRS scores of depressed patients and their post-dexamethasone cortisol levels. 5. A prospective study of the depressed group, which was assessed with three depression rating scales, showed differences between non-suppressors and suppressors regarding to the symptoms severity and response to the treatment. It suggests that an abnormal DST result could have a prognostic value to antidepressant drugs and ECT. 6. The DST specificity in depression was also calculated from its performance in the group with other psychiatric disorders, and their diagnoses as well as the abnormal DST results were critically discussed.

Plasma cortisol and depression in pathological gamblers.

Basal serum cortisol and dexamethasone suppression test (DST) results were studied in 21 pathological gamblers who varied on the Beck Depression Inventory and selected scales of the Minnesota Multiphasic Personality Inventory, which had previously been shown to be related to depression in gamblers. All subjects were suppressors on the DST. There was a significant relationship between fluctuation in 08.00 h and 16.00 h basal cortisol levels and the psychological measures, suggesting a subtype of pathological gambler with potential clinical significance.

Comparison of in vivo and in vitro glucocorticoid sensitivity in depression: Relationship to the dexamethasone suppression test

The effect of in vivo (1 mg) and in vitro (10 −7−10 −10 m) dexamethasone administration on mitogen-induced lymphocyte proliferation was examined in drug-free depressed patients, nondepressed psychiatric patients, as well as normal controls, and was related to the results of a standard overnight Dexamethasone Suppression Test (DST). The effect of oral dexamethasone administration was also examined for its effect on lymphocyte cytosolic glucocorticoid receptor content. Oral dexamethasone administration significantly decreased both phytohemagglutinin (PHA) and concanavalin A (Con-A) induced lymphocyte proliferation, as well as glucocorticoid receptor number in suppressors, whereas dexamethasone failed to decrease these responses in nonsuppressors. Nonsuppressors had significantly lower serum dexamethasone levels compared to suppressors at both 8:00 am and 4:00 pm. However, when differences in serum dexamethasone levels were covaried out, there were still significant differences between suppressors and nonsuppressors on the dexamethasone-induced mitogen changes, but the changes in glucocorticoid receptor content were no longer significant. In vitro incubation of lymphocytes with dexamethasone produced a dose-related decrease in mitogenesis, which was not different between the depressed and nondepressed groups. However, at physiologically relevant concentrations of dexamethasone (10 −9−10 −10 m, nonsuppressors as compared to suppressors were more resistant to the immunosuppressive effects of in vitro dexamethasone on the Con-A response. The inhibitory effect of in vitro dexamethasone on Con-A-stimulated lymphocytes was positively correlated with basal 4:00 pm cortisol values. In conclusion, in vitro techniques are useful probes to assess glucocorticoid sensitivity in depression. The present results also further support the hypothesis that glucocorticoid insensitivity is associated with DST nonsuppression.

The effect of diagnosis and age on the DST: A metaanalytic approach

The authors present new data on the results of the pretreatment Dexamethasone Suppression Test (DST) in 164 drug-free inpatients, as well as on the effects of age on postdex-amethasone cortisol values. Nonsuppression rates were 18% in schizophrenic patients ( n = 44), versus 46% in patients with a major depression ( n = 56). In addition, a significant correlation was found between age and the 4:00 PM postdexamethasone cortisol value among the depressed patients ( r = 0.33). The authors then applied a metaanalysis to summarize 25 other studies that have addressed the schizophrenia/major depression dichotomy as it relates to the DST outcome. Nonsuppression rates were consistently different in schizophrenic patients (19%) when compared to patients with a major depression (51 %) or normal controls (7%). These differences were highly significant as measured by the Mantel-Haenszel chi-square statistic. A metaanalysis applied to a series of correlations obtained from 14 other studies reporting an agei'postdexamethasone cortisol relationship in affective patients indicated a modest, but significant correlation ( r = 0.24) in a total of 1284 patients ( p < 1 × 10 −8).

Past and present strategies of research on the HPA-axis in psychiatry.

Hypercortisolism in depression has been extensively studied during the last three decades. The main hypothesis regarding origin and clinical relevance of this phenomenon, however, has changed significantly. Up to the mid-seventies hypercortisolism was conceived as consequence of stress modified by the degree of unconscious defense mechanisms in different forms of depressive or non-depressive psychiatric disorders. At the end of the seventies this point of view changed considerably. Hypercortisolism was regarded as a biological statemarker of the endogenous subtype of depression with clinical differential-diagnostic relevance. An abnormal dexamethasone suppression test (DST) was assumed to be the best indication of increased activation of the cortisol system. These conclusions turned out to be wrong. DST results are not specific for melancholia and the test seems to be of limited value for measuring the function of the HPA-axis. Intervening variables, such as weight loss, drug and alcohol withdrawal or situational stress, influence the test results significantly, independent of the nosological classification. Additionally, interindividual differences in the susceptibility of the HPA-axis may decisively influence the the activation of the HPA-axis as well in healthy subjects under stress as in psychiatric patients.

Lack of correlation between DST results and urinary MHPG in depressed inpatients.

Abnormalities of noradrenaline metabolism and of the activity of hypothalamic-pituitary adrenal axis (HPA) have been reported in depression. To study the possible relationship between these 2 parameters, urinary excretion of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and Dexamethasone Suppression Test (DST) were analyzed in 58 depressed patients. A positive correlation was found between the age of depressed patients and 24-h urinary excretion of MHPG. Twenty-two patients (38%) were DST non suppressors. Pre-DST plasma cortisol levels were significantly higher in non suppressors than suppressors. No difference was found however between urinary MHPG levels in suppressors and non suppressors. There was no correlation between pre-DST plasma cortisol and levels of urinary excretion of MHPG. These results do not support the hypothesis of a relationship between these 2 parameters. However, when depressed patients were separated into two groups according to urinary excretion of MHPG ("high MHPG" and "low MHPG"), the "high MHPG" group included significantly more non suppressors then the "low MHPG" one. This result is not sufficient to demonstrate of link between HPA system activity and central noradrenaline metabolism.

Drugs and the DST: need for a reappraisal.

It has generally been assumed that psychotropic drugs do not influence results on the dexamethasone suppression test (DST), except in some specific situations. Yet they directly affect the activity of many neurotransmitter systems, which in turn regulate hypothalamic-pituitary-adrenal (HPA) axis functioning. Several reports have shown correlations between the intake of or recent withdrawal from psychoactive substances and changes in DST results. A review of the DST literature reveals that these effects have not been controlled in most DST studies. It is therefore possible that the consequences of intake of psychotropic agents may have contributed to the debate surrounding the DST by producing unappreciated spurious DST results.

Pre- and postdexamethasone cortisol and prolactin levels in sexual dysfunction and normal controls

Initially, the Dexamethasone Suppression Test (DST) was reported to be a specific marker for endogenous depression (Carroll 1982). Recent studies however suggest that supposedly abnormal DST results may also occur in healthy controls (Stokes et al. 1985) and in a number of other psychiatric disorders (Holsboer and Benkert 1985), though the rate of nonsuppressors is higher in major depressive disorder (Stokes et al. 1985). Dexamethasone has also been shown to decrease prolactin levels, an effect that is more often found in normal controls and in nonendogenous depression than in endogenous depression (Rupprecht et al. 1987). Hyperprolactinemia may induce sexual dysfunction (Braunstein 1983), whereas in psychogenic sexual dysfunction, Benkert and Witt (1980) and Miller et al. (1980) reported normal prolactin levels, and others even lowered prolactin levels (Natoli et al. 1985). As no data are available

Neuroendocrine Aspects of Suicidal Behavior

To assess biologic risk factors in suicidal behavior accurately, it is necessary to distinguish prospective from retrospective design. The former studies are more likely to elicit information concerning possible risk factors in suicide, whereas the latter may be better indicators of biologic traits. In both types of investigations, measures taken close to the suicide attempt are more likely to reflect the biologic state of the individual at the time of the behavior. Although the abnormalities present in suicidal individuals are not entirely clear, most evidence to date suggests an overactivity of the hypothalamic-pituitary-adrenal axis and a dysregulation of both serotonin and adrenergic metabolism. These systems are interrelated. Both animal and human studies have established that a multivariate biologic approach is necessary to the understanding of the pathophysiology of suicide.

Neuroendocrine Aspects of Suicidal Behavior

To assess biologic risk factors in suicidal behavior accurately, it is necessary to distinguish prospective from retrospective designs. The former studies are more likely to elicit information concerning possible risk factors in suicide, whereas the latter may be better indicators of biologic traits. In both types of investigations, measures taken close to the suicide attempt are more likely to reflect the biologic state of the individual at the time of the behavior. Although the abnormalities present in suicidal individuals are not entirely clear, most evidence to date suggests an overactivity of the hypothalamic-pituitary-adrenal axis and a dysregulation of both serotonin and adrenergic metabolism. These systems are interrelated. Both animal and human studies have established that a multivariate biologic approach is necessary to the understanding of the pathophysiology of suicide.