Dexamethasone Suppression Test Response Research Articles

Diurnal Cortisol Patterns and Dexamethasone Suppression Test Responses in Healthy Young Adults Born Preterm at Very Low Birth Weight.

BackgroundEarly life stress, such as painful and stressful procedures during neonatal intensive care after preterm birth, can permanently affect physiological, hormonal and neurobiological systems. This may contribute to altered programming of the hypothalamic-pituitary-adrenal axis (HPAA) and provoke changes in HPAA function with long-term health impacts. Previous studies suggest a lower HPAA response to stress in young adults born preterm compared with controls born at term. We assessed whether these differences in HPAA stress responsiveness are reflected in everyday life HPAA functioning, i.e. in diurnal salivary cortisol patterns, and reactivity to a low-dose dexamethasone suppression test (DST), in unimpaired young adults born preterm at very low birth weight (VLBW; <1500 g).MethodsThe participants were recruited from the Helsinki Study of Very Low Birth Weight Adults cohort study. At mean age 23.3 years (2.1 SD), 49 VLBW and 36 controls born at term participated in the study. For cortisol analyzes, saliva samples were collected on two consecutive days at 0, 15, 30 and 60 min after wake-up, at 12:00 h, 17:00 h and 22:00 h. After the last salivary sample of the first study day the participants were instructed to take a 0.5 mg dexamethasone tablet.ResultsWith mixed-effects model no difference was seen in overall diurnal salivary cortisol between VLBW and control groups [13.9% (95% CI: -11.6, 47.0), P = 0.31]. Salivary cortisol increased similarly after awakening in both VLBW and control participants [mean difference -2.9% (29.2, 33.0), P = 0.85]. Also reactivity to the low-dose DST (awakening cortisol ratio day2/day1) was similar between VLBW and control groups [-1.1% (-53.5, 103.8), P = 0.97)].ConclusionsDiurnal cortisol patterns and reactivity to a low-dose DST in young adulthood were not associated with preterm birth.

Probing the association between dexamethasone-induced cortisol suppression and serotonin transporter availability among drug-free patients with major depressive disorder—A small-sample SPECT study with [123I]ADAM

The association between hypothalamo-pituitary-adrenal (HPA) axis function and the serotonergic system could be involved in the mechanism of depression. However, neuroimaging evidence is scarce. The aim of the present study was to probe the association between dexamethasone suppression test response and serotonin transporter (SERT) availability in drug-free patients with major depressive disorder (MDD). Seventeen MDD patients (five males and twelve females) were recruited. SPECT with [(123)I] ADAM was used to measure the midbrain SERT availability, and HPA axis function was measured by the dexamethasone suppression test (DST). The association was significant when considering all participants (ρ=0.69, p=0.002). This association may have clinical implications for the treatment of MDD.

A follow-up of cognitive performance and diurnal salivary cortisol changes in former burnout patients

The purpose of this study was to determine whether recovery from burnout is associated with improved cognitive functioning, and whether such improvement is associated with changes in hypothalamic–pituitary–adrenal axis activity and return to work. Forty-five former burnout patients were followed up after 1.5 years with a neuropsychological examination, diurnal salivary cortisol measurements, dexamethasone suppression test (DST), and self-ratings of cognitive problems. At follow-up, improved cognitive performance was observed on several tests of short-term memory and attention. Self-rated cognitive problems decreased considerably, but this decrease was unrelated to the improvement on neuropsychological tests. Diurnal salivary cortisol concentrations at awakening, 30 min after awakening, and in the evening, did not change from baseline to follow-up, nor did the cortisol awakening response. However, slightly, but significantly, stronger suppression of cortisol in response to the DST was observed at follow-up. Improvements in subjective or objective cognitive functioning and changes in diurnal cortisol concentration were unrelated to the extent of work resumption. However, a decreased DST response at follow-up was partially related to improved cognitive performance and work resumption. The clinical implications are that burnout seems to be associated with slight and significantly reversible cognitive impairment, and that self-rated cognitive change during recovery poorly reflects objective cognitive change.

Retrospective Evaluation of the Dexamethasone Suppression Test as a Predictor of Response to Electroconvulsive Therapy in Patients With Comorbid Major Depressive Disorder and Posttraumatic Stress Disorder

There is evidence that response to dexamethasone suppression test (DST) can be predictive of treatment outcomes in major depressive disorder (MDD). The purpose of this study was to explore if DST response, at both 1 and 0.5 mg of dexamethasone doses, is predictive of the effectiveness of electroconvulsive therapy (ECT) in depression symptom reduction in patients with comorbid posttraumatic stress disorder (PTSD) and MDD who are treated with ECT. We performed a chart review of all patients with both PTSD and MDD receiving ECT from January 2002 through December 2008, who had DST performed before starting ECT. A total of 32 patients meeting these criteria were identified. Those patients were divided into 3 groups based on their response to the DST: enhanced suppressors (n = 13), normal suppressors (n = 14), and nonsuppressors (n = 5). Posttraumatic stress disorder and MDD outcomes after completion of the primary ECT treatment series were measured. Results were stratified by pretreatment DST responses. Nonsuppressors showed significantly more response to ECT, in both MDD and PTSD symptom scales, as compared with normal suppressors and enhanced suppressors. Normal suppressors showed significantly more response to ECT than enhanced suppressors. Electroconvulsive therapy did not appear to be effective in depression symptom reduction for enhanced suppressors. This study suggests that DST results may be predictive of depression symptom reduction in response to ECT in patients with comorbid PTSD and MDD, with patients suppressing morning cortisol production in response to 0.5 mg of dexamethasone showing little improvement. In addition, this study lends further evidence that ECT is an effective treatment for some patients with comorbid MDD and PTSD.

Cognitive performance in patients with burnout, in relation to diurnal salivary cortisol

This study investigated cognitive performance in patients with burnout, in relation to the flexibility of the hypothalamic–pituitary–adrenal (HPA) axis. Clinical cases with work stress-induced burnout (n = 65), and demographically matched, healthy reference subjects (n = 65), were given six neuropsychological tests and a self-rating scale for cognitive problems. Diurnal salivary cortisol was measured among burnout cases and an external reference group (n = 174), including a dexamethasone suppression test (DST) among burnout cases. Compared with referents, the burnout group under-performed in a cognitive speed test (Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol), but not in any other test of sustained attention, episodic memory, or vocabulary. Burnout cases had considerably more subjective cognitive problems, but ratings were unrelated to test performance. Compared with referents, burnout cases had similar morning salivary cortisol levels and similar awakening response, but lower evening cortisol. Among burnout cases, lower diurnal cortisol variability was related to slower performance in several tests. The DST response showed no consistent relationship with any cognitive parameter. Hence, despite considerable subjective cognitive problems, the burnout group showed only a partial, mild deviation in cognitive performance. A flatter diurnal cortisol profile was related to lower cognitive processing speed, but diurnal cortisol pattern and DST response were normal, suggesting a maintained HPA axis flexibility.

Personality pathology, depression and HPA axis functioning.

Hypothalamic pituitary adrenal (HPA) axis functioning, as measured by the dexamethasone suppression test (DST), has been extensively investigated in major depressive disorder (MDD). Evaluating DST response in MDD patients while simultaneously considering clinically relevant personality disorders may further clarify the contribution of both personality pathology and HPA axis function to depressive symptoms. The present study measured personality pathology by administering the revised version of the Millon Clinical Multiaxial Inventory (MCMI-II) in a sample of 25 patients diagnosed with MDD. Analyses revealed that suppressors (n = 19) scored significantly higher than non-suppressors (n = 6) on six of the 13 MCMI-II personality disorder scales: Avoidant, Schizoid, Self-Defeating, Passive-Aggressive, Schizotypal and Borderline. Increased personality pathology was associated with normal suppression of cortisol following the DST. This suggests that suppression of the DST may be associated with depressive states linked with personality pathology while the more biologically based depression is associated with abnormal HPA pathophysiology. Copyright 2001 John Wiley & Sons, Ltd.

Mixed anxiety–depressive disorder and major depressive disorder: comparison of the severity of illness and biological variables

Mixed anxiety–depressive disorder (MADD) is a new diagnostic category defining patients who suffer from both anxiety and depressive symptoms of limited and equal intensity accompanied by at least some autonomic features. Patients do not meet the criteria for specific anxiety or depressive disorders. The emergence of the symptoms is independent of stressful life events. There are many issues presently under investigation about the validity of this clinical entity. In this study, a group of 29 patients with MADD was compared with a group of 31 patients with major depressive disorder (MDD) to assess the differences and similarities between these two disease categories in terms of severity measures and biological variables. The dexamethasone suppression test (DST) was employed, and thyroid hormones and thyrotropin (TSH) levels were measured for the evaluation of hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–thyroid (HPT) axes, respectively. The patients with MADD were found to be less depressive and more anxious compared to those with MDD. DST responses and thyroid functions were found to be similar in the two groups. When severity of depression was controlled, k max and 2300-h cortisol values were found to be significantly higher in the MADD group. Although the patients with MDD and MADD presented with relatively different clinical features, there is not enough biological evidence indicating that MADD represents a discrete diagnostic category. However, there may be relatively higher HPA activity in MADD patients.

The lower limits of dexamethasone window in Chinese depressives

Background: Previous studies have shown wide variation in plasma dexamethasone (DEX) concentrations following a standard 1-mg dexamethasone suppression test (DST), and significantly lower DEX concentrations in DST nonsuppressors compared with suppressors, suggesting that DEX pharmacokinetics/bioavailability is an important variable associated with DST nonsuppression. Methods: To determine the effect of plasma DEX levels on the DST in Chinese depressives, we measured plasma DEX and post-DEX cortisol levels at 4:00 pm in a group of 50 depressed outpatients, 28 anxiety outpatients, and 33 normal subjects during the course of 1-mg oral overnight DST. Results: We found a significant difference in the plasma DEX levels between DST nonsuppressors and suppressors in the depression group and overall subject population, and a significant negative correlation between the plasma DEX and cortisol levels in the depression, anxiety, and total groups. Within a DEX “window”, the DST performance was enhanced, whereas the relationships between plasma DEX and post-DEX cortisol levels remained equally strong. Conclusions: Our findings support a relationship between plasma DEX and post-DEX cortisol levels, a relationship that might be superimposed on the hypothalamic–pituitary–adrenal axis. Comparing our “window” range with those of previous studies, we suggest that Chinese depressives may have lower limits of plasma DEX window, and that ethnicity may be an intervening variable in both DST response and pharmacokinetics of DEX.

The dexamethasone suppression test and treatment outcome in elderly depressed patients participating in a placebo-controlled multicenter trial involving moclobemide and nortriptyline

The dexamethasone suppression test (DST) was conducted in 95 elderly DSM-III-R depressed patients randomized for treatment with moclobemide (MOC; 400 mg daily), nortriptyline (NT; 75 mg daily), or placebo (PBO) in a 7-week double-blind multicenter study. Patients were assessed weekly using various clinical scales, including the 17-item Hamilton Depression Rating Scale. The DST was administered at baseline and at the end of treatment. At baseline, no relationship was found between DST status and the various clinical scales used. At the end of treatment, suppressors (DST-) had significantly improved clinical ratings compared to nonsuppressors (DST+), and were mostly found among those treated with NT (71%) as compared to MOC (41%) or PBO (33%) (p < .03). On the other hand, baseline DST measures influenced treatment outcome; DST+ patients had a greater number of treatment responders to NT (48%) than MOC (19%) or PBO (20%) (p < .07). For DST- patients, the situation was reversed: NT, 7%; MOC, 31%. Postdexamethasone cortisol levels were lower in MOC responders (p < .07). An interaction was found between DST and drug-specific response. The DST may be a useful adjunct for predicting and evaluating the outcome of antidepressant therapy.

The predictive value of hypothalamic-pituitary-adrenal axis dysfunction in Alzheimer's disease

Up to 58% of Alzheimer's disease (AD) patients are dexamethasone nonsuppressors (McKeith 1984: Ferrier et al 1991). In addition, a significant proportion of AD patients are high basal cortisol secretors (Raskind et al 1982; Davis et al 1986). The glucocorticoid cascade hypothesis proposes that hippocampat degeneration in AD might result in hypercortisolism, while simultaneously this overactive hypothalamic-pituitary-adrenal (HPA) system could act as an etiological factor in further neuronal degeneration (Sapolsky and McEwen 1986). If the glucocorticoid cascade hypothesis is relevant to the pathophysiology of AD, then hypercortisolemia and nonsuppression on the dexamethasone suppression test (DST) might be expected to predict the rate of progression. Although Miller et al (1994) reported significantly greater mortality in DST nonsuppressors, two studies have reported findings that are inconsistent with the glucocorticoid cascade hypothesis. Ferrier et al (1991) reported that DST nonsuppression did not predict clinical outcome. Weiner et al (1993) demonstrated that basal cortisol did correlate with subsequent cognitive decline, but when the data from 1 patient with extreme values were excluded the relationship became insignificant. The aim of this study was to determine if basal cortisol levels or DST response might provide a predictive marker for the rate of progression in AD.

Neuroendocrine and sleep variables in major depressed inpatients: role of severity

To evaluate the reliability of the endogenous concept of depressive illness according to the Newcastle Endogenous Depression Diagnostic Index (NEDDI), 155 major depressive inpatients with NEDDI scores ≥ 6 (endogenous) were matched for gender and age (± 5 years) to 155 major depressive inpatients with NEDDI scores ≤6 (nonendogenous). When sleep polygraphic variables, neuroendocrine parameters (dexamethasone suppression and thyrotropin-releasing hormone tests), and various clinical variables (unipolar/bipolar status, psychotic/nonpsychotic subtype, and severity of the depressive episode) were examined, statistically significant differences between endogenous and nonendogenous patients emerged for three variables: the thyroid-stimulating hormone response to the thyrotropin-releasing hormone test, the dexamethasone suppression test response at 16:00 h, and the percentage of time awake during the night. However, when the effects of age and severity of depression were controlled, those differences disappeared.

Dexamethasone suppression test in mentally handicapped subjects

AbstractObjective:This study investigated the frequency of abnormal Dexamethasone Suppression Test (DST) in a randomly selected group of mentally handicapped subjects.Method:Forty three subjects living in the community were selected and assessed on a variety of clinical rating scales including Hamilton Rating Scale for Depression (HDS) and Wessex Case Register Form (WCRF). DST was conducted on all the patients and the findings correlated with demographic and clinical variables. Groups defined by DST status were also compared using t-test. In subjects who showed an abnormal response, clinical assessments and DST was repeated after 3 months.Results:Only 7 of 43 subjects showed an abnormal response which did not correlate with either the severity of affective symptoms or the presence or absence of behavioural difficulties. Six of the 7 DST positive subjects were either severely or profoundly impaired on DSM-III criteria indicating that the underlying brain pathology may be pathogenetically important. This was supported by the observation that abnormal DST response was enduring at follow up.Conclusions:The findings suggest that DST may be of little value as a diagnostic tool in the mentally handicapped.

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

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.

Dexamethasone suppression test and response to cognitive therapy and antidepressant medication

This study utilized 43 female subjects, diagnosed with Major Depression, with 20 showing an abnormal pre-treatment response to the dexamethasone suppression test (DST) and 23 showing a normal pre-treatment DST response. Half of the subjects in each group were randomly assigned to receive eight weekly sessions of cognitive therapy or eight weeks of tricyclic medication. The main conclusions were: (a) the DST did not predict differential treatment responsiveness, with both groups of subjects improving with either cognitive therapy or tricyclics; (b) the DST was useful prognostically in that depressives with an abnormal DST had a poorer response to either treatment; (c) both treatments produced a normalization of post-treatment DST responses; (d) both treatments produced a reduction in post-treatment dysfunctional thoughts with cognitive therapy producing a greater reduction; (e) there was a high correlation (0.74) between pretreatment DST response and presence versus absence of melancholic symptoms; (f) all results found when subjects were classified by DST response were replicated when subjects were re-classified as to presence or absence of melancholic symptoms.

The Dexamethasone Suppression Test in Alzheimer's Disease and Major Depression: Relationship to Dementia Severity, Depression, and CSF Monoamines

Patients with Alzheimer's disease (AD) have been reported to have a rate of nonsuppression on the dexamethasone suppression test (DST) comparable to that of patients with major depression. With symptoms of depression being increasingly recognized in patients with AD, studying their DST response may provide clues to the etiology of the abnormal response in both diagnostic groups. A correlation between dementia severity and post-dexamethasone cortisol was found within the group of male, but not female AD patients. Within the group of elderly depressives, a correlation between post-dexamethasone cortisol and ratings of depression was found. Serum dexamethasone levels were not significantly lower in the nonsuppressors as compared with suppressors in either diagnostic group. Within the AD group, dexamethasone levels themselves correlated significantly with ratings of dementia severity and with the Wechsler Memory Scale score. Cerebrospinal fluid (CSF) 3-methoxy-4-hydroxyphenylglycol (MHPG) correlated positively with 4:00 pm post-dexamethasone cortisol level and with ratings of dementia severity in the AD patients. Findings are discussed in light of the known clinical and other biological similarities between AD and major depression, followed by a review of theories regarding the etiology of the hypothalamic-pituitary-adrenal abnormalities in these two illnesses.

Dexamethasone kinetics in depressed patients before and after clinical response

Dexamethasone pharmacokinetics were measured in 19 depressed patients, 10 dexamethasone suppression test (DST) nonsuppressors and nine suppressors, following a 1 mg oral dose in tablet form at 2300h. Median dexamethasone concentrations were significantly lower in the nonsuppressors from 3–16 hr post-administration. Nonsuppressors had a significantly lower area under the curve than suppressors, and plasma clearance was significantly faster in the nonsuppressors than in the suppressors. Eleven patients, six nonsuppressors and five suppressors, agreed to a repeat DST after clinical improvement when all six nonsuppressors had normal DST responses. There were no significant differences between the median dexamethasone concentrations, or any of the pharmacokinetic parameters measured, of the “normalising” nonsuppressors and the suppressors. Dexamethasone kinetics were altered in depressed nonsuppressors but became normal with remission of depressive symptoms and normalisation of the DST response.

The dexamethasone suppression test in chronic alcoholics with and without depression and its relationship to their hepatic status

Fifty consecutively admitted male alcoholics (mean age = 42.8 ± 8.5 years) were selected. This study shows objectively that 31 50 chronic alcoholics (62%) were found to be severely depressed (Hamilton Depression Rating Scale (HRS) > 22); 12 50 (24%) moderately depressed (HRS = 16–22); and 7 50 (14%) were not depressed (HRS < 15). According to dexamethasone suppression test (DST) results, 8 out of 50 patients showed escape from suppression with 2 mg dexamethasone while 42 50 showed normal suppression. Depression in alcoholics may be of neurotic type or it may be ethanol-induced reactive depression. Raised cortisol levels and abnormal DST response showed a definite tendency towards normalisation after total abstinence accompanied by clinical improvement of depressive symptomatology. The DST showed improvement on improvement of mood and sleep in these patients during total abstinence. An abnormal DST response in chronic alcoholics seems to be state-related and not trait-dependent; it seems to be a non-specific test for depression in alcoholics. Hepatic status was affected equally in both suppressors and non-suppressors of DST. It is therefore suggested that abnormal DST in alcoholics may be due to the abnormality of the hypothalamo-pituitary-adrenocortical (HPA) axis and not due to abnormal hepatic function or histological status.

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.

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.

Is the dexamethasone suppression test predictive of response to specific antidepressant treatment in major depression?

The authors attempt to correlate the response to dexamethasone suppression test (DST) with a clinical response to antidepressant drugs in 68 patients with major depression. Antidepressants that influence noradrenergic or serotonergic transmission with relative different potencies were selected and used in standard doses for 6 weeks. The response was evaluated weekly by raters blind to DST results and to antidepressant medications prescribed. The retrospective analysis failed to correlate DST response with outcome of treatment. Therefore the present results suggest that this laboratory test does not help to identify subgroups of depressed patients responding preferentially to various antidepressant drugs.